The rising global incidence of acute and chronic kidney diseases has increased the demand for renal replacement therapy. This issue, compounded with the limited availability of viable kidneys for transplantation, has propelled the search for alternative strategies to address the growing health and economic burdens associated with these conditions. In the search for such alternatives, significant efforts have been devised to augment the current and primarily supportive management of renal injury with novel regenerative strategies. For example, gene- and cell-based approaches that utilize recombinant peptides/proteins, gene, cell, organoid, and RNAi technologies have shown promising outcomes primarily in experimental models. Supporting research has also been conducted to improve our understanding of the critical aspects that facilitate the development of efficient gene- and cell-based techniques that the complex structure of the kidney has traditionally limited. This manuscript is intended to communicate efforts that have driven the development of such therapies by identifying the vectors and delivery routes needed to drive exogenous transgene incorporation that may support the treatment of acute and chronic kidney diseases.

Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)₂-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI+Veh (infarcted, treated with vehicle); and AMI+PY (infarcted, treated with the cholinesterase inhibitor pyridostigmine bromide (PY) - 40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. Clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI+PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI+Veh group. Furthermore, there was a notable downregulation of pro-inflammatory gene expression and an upregulation of anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers indicative of subclinical kidney injury. Conclusion: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Cadmium (Cd) is a pervasive, toxic environmental pollutant that preferentially accumulates in tubular epithelium of the kidney. Current evidence suggests that the cumulative burden of Cd here leads to progress loss of the glomerular filtration rate (GFR). In this study, we have quantified changes in estimated GFR (eGFR) and albumin excretion (Ealb) in according to levels of blood Cd ([Cd]b) and excretion of Cd (ECd) after adjustment for confounders. ECd and Ealb were normalized to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr. Among 482 residents of Cd-polluted and non-polluted regions of Thailand, 8.1% had low eGFR and 16.9% had albuminuria, (Ealb/Ccr)×100 ≥ 20 mg/L filtrate. In the low Cd burden group, (ECd/Ccr) ×100 < 1.44 µg/L filtrate, eGFR did not correlate with ECd/Ccr (β = 0.007), while an inverse association with ECd/Ccr was found in the medium (β =−0.230) and high-burden groups (β =−0.349). Prevalence odds ratios (POR) for low eGFR were increased in the medium (POR 8.26) and high Cd burden groups (POR 3.64). Also, eGFR explained a significant proportion of Ealb/Ccr variation among those with middle (η2 0.093) and high [Cd]b tertiles (η2 0.132), but did not with low tertile (η2 0.001). With adjustment of eGFR, age and BMI, POR values for albuminuria were increased in the middle (POR 2.36) and high [Cd]b tertiles (POR 2.74) and those with diabetes (POR 6.02) and hypertension (2.05). These data argue that ECd/Ccr of 1.44 µg/L filtrate (0.01−0.02 µg/g creatinine) could determine a Cd threshold level from which protective exposure guidelines should be formulated.

Myeloperoxidase (MPO) belong to the family of heme containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kD) is the product of MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications like removal of introns and signal peptide and leads to the formation of enzymatically inactive glycosylated apoproMPO which complexes with chaperons, producing active proMPO by the insertion of heme moiety. The active enzyme is a homodimer of heavy and light chain protomers. This enzyme is released into extracellular fluid after oxidative stress and different inflammatory responses. MPO is the only type of peroxidase using H2O2 to oxidize several halides and pseudohalides to form different hypohalous acids. So the antibacterial activities of MPO involve the production of reactive oxygen and reactive nitrogen species. Controlled MPO release at the site of infection is of prime importance for its efficient activities. Any uncontrolled degranulation exaggerates the inflammation that can also lead to tissue damage even in absence of inflammation. Several types of tissue injuries and pathogenesis of several other major chronic diseases like rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes and cancer have been reported to be linked with myeloperoxidase derived oxidants. So the enhanced level of MPO activity is one of the best diagnostic tool of inflammatory and oxidative stress biomarkers among these commonly occurring diseases.

Migraine is a primary headache disorder with a prevalence of 11.6% globally and 27% in Saudi Arabia. Irritable bowel syndrome has a prevalence of 9.2% worldwide. The prevalence of IBS has not been established nationally. However, provincial studies for both migraine and IBS have been conducted across the nation. There is a significant link between migraines and IBS globally. This identifies an association that needs to be investigated in a nationwide manner. This study aims to observe the association and the relationship between migraine and irritable bowel syndrome in Saudi Arabia. A cross-sectional study was conducted between March 2021 to June 2021 among the general population of Saudi Arabia, whose ages are 15 years old or greater. The data collection tools included MS-Q for migraine symptoms, MIGSEV scale for severity of migraine, and The IBS module of the Rome IV Diagnostic Questionnaire (R4DQ) for IBS symptoms and its subtype. With a total of 2802 participants, the majority of the study sample were males, who constituted 52.5%. Among the study's sample, the prevalence of migraine consisted of 27.4%, and the prevalence of IBS was 16.4%. The odds of having IBS in migraineurs were much higher than in those without migraines (OR 4.127; 95% CI 3.325-5.121), and the association was statistically significant (P<0.001). In conclusion, there is a strong association between migraine and irritable bowel syndrome in Saudi Arabia.

Depression, anxiety, and pain are part of a common phenomenon that requires to be studied together when evaluating patients with chronic pain. The aim of the study was to examine the correlations between depression, anxiety and pain intensity in patients with chronic pain and how they change when a depressive episode was added. A sample of 120 patients with chronic pain (age: 51.90±11.94; 81.7% female; 18.3% male) was studied in two stages with a three-month period between them. Patients with a depressive episode (n=61) were treated with antidepressants and analgesics, while a patient without depression (n=59) was treated only with analgesics. The scales used to achieve the objectives were: HAM-D-17, Spielberger‘s STAI and VAS. Insignificant correlations were found between depression, state and trait anxiety, and pain intensity (p<0,05) in the group without depression, except for a significant one between depression and state anxiety (p<0,01) in the second stage. Significant correlations were identified between all indicators (p<0,01) in the group with depression at the two stages. Those in the second stage were stronger. The interrelations between sensory and affective aspects of pain were stronger when a depressive episode occurs, the severity of which determines their dynamics.

Obesity has become a global epidemic, contributing to the development of numerous chronic diseases, including diabetes, chronic kidney disease (CKD) and cardiovascular disorders. MicroRNAs (miRNAs) have emerged as key regulators in various biological processes, including metabolism, inflammation, and tissue remodeling, making them pivotal players in obesity-related pathologies. This review aims to provide comprehensive insights into the roles of miRNAs in obesity, with a particular emphasis on their involvement in the pathogenesis of CKD and cardiovascular disorders. We highlight the involvement of specific miRNAs in adipose tissue development, energy homeostasis, inflammation, and insulin resistance, contributing to the pathogenesis of obesity. Moreover, we explore the impact of miRNAs on renal fibrosis, and inflammation, giving clues on their roles in the development and progression of CKD. Additionally, we discuss the influence of miRNAs on endothelial dysfunction, atherosclerosis, and cardiac remodeling, emphasizing their contribution to obesity-related cardiovascular disorders. Understanding the regulatory functions of miRNAs in these interconnected conditions holds promise for improved diagnosis, prognosis, and therapeutic interventions. Indeed, miRNAs are potential diagnostic biomarkers for obesity-related diseases although challenges remain to be elucidated before their clinical translation. Furthermore, we highlight the emerging strategies that target miRNAs as therapeutic interventions to mitigate the detrimental effects of obesity on kidney and cardiovascular health.

Chronic pancreatitis (CP) is an irreversible and progressive inflammation of the pancreas that can involve both pancreatic parenchyma and pancreatic duct. CP results in morphological change in the gland in the form of fibrosis and calcification along with functional impairment in the form of exocrine and endocrine insufficiency. Studies on the natural history of CP reveal the irreversibility of the condition and the resultant plethora of complications of which pancreatic adenocarcinoma is the most dreaded one. (1,2) In Japanese population-based studies by Otsuki and Fuzino et al, CP was clearly shown to reduce lifespan among males and females by 10.5 years and 16 years, respectively. (3) Most of these patients had occult pancreatic malignancies which were diagnosed late and were detected to be the commonest cause of mortality among these patients with a standardized mortality rate of 7.33. (3) This dismal prognosis is superadded with significant morbidity due to pain and poor quality of life rendering a significant burden on health and health-related infrastructure. These factors have led researchers to conceptualize early CP which theoretically is a reversible stage in the disease spectrum characterized by ongoing pancreatic injury with the presence of clinical symptoms and absence of classical imaging features of CP. Subsequently, the disease is thought to go through a compensated stage, a transitional stage, and culminating into decompensated stage with florid evidence of functional impairment of the gland. (4) In this focused review, we will discuss the definition and concept of early CP, risk factors and natural history of the development of CP, and the role of various modalities of EUS in the timely diagnosis of early CP.

Patients with chronic (CM) and high frequency episodic migraine (HFEM) report cognitive complaints that contribute to migraine burden. Although, there is little evidence about the ef-fects of migraine treatments on these symptoms. Objective: To evaluate the effect of preventive treatment on the impact of cognitive symptoms, specifically the ability to concentrate, in individuals with CM and HFEM. Methods: Prospective cohort study in patients with CM and HFEM initiating treatment with botulinum toxin (BT) or anti-CGRP/R monoclonal antibodies (mAbs). Patients were evaluated at baseline and after 3 months of treatment, using a headache diary and a question about the im-pact of migraine attacks on concentration (never, rarely, sometimes, often, and always). Results: 108 patients (105 females, 44.3 years of age on average), 75% with CM and 27% with HFEM were included, 55 received a first session of BT and 53 received 3 injections of a monthly mAb. In both groups, there was a significant decline on the impact of migraine in concentration (related samples Wilcoxon signed rank test <0.001) compared to baseline. Reduction in monthly headache days was the main predictor of any concentration improvement, while treatment group, age, ongoing medication with topiramate or baseline medication overuse were not sig-nificant. Conclusion: Preventive treatment of HFEM or CM with drugs not acting on central nervous sys-tem is associated with a decrease of the impact of migraine attacks on concentration, predicted by the decline in headache days. These results indicate that migraine preventive treatment also improves non-pain symptoms, which is relevant given the contribution of cognitive complaints to the impact of headache attacks

Chronic renal failure (CRF) is a major public health problem worldwide. In this work, we investigated the effects of a purified Laminaria japonica polysaccharide (LJP61A) on the renal function using adenine-induced CRF mice model. Results exhibited that adenine treatment caused serious renal pathological damages and elevation of serum creatinine and blood urea nitrogen of mice. However, these changes could be significantly reversed by the administration of LJP61A in a dose-dependent manner. Additionally, LJP61A could dramatically reduce the weight loss, improve the urine biochemical index, and regulate the electrolyte disturbance of CRF mice. These results suggested that the renal functions of adenine-induced CRF mice could be improved by LJP61A, which might be developed to a potential therapeutic agent for CRF patients.

Aim: To analyze a single center's experience with Short Bowel Syndrome/ Chronic Intestinal Failure (SBS/CIF) in adult patients treated with Home Parenteral Nutrition (HPN). Materials and methods: In the last thirty years, 13 patients with SBS/CIF were included in an HPN program. Results: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of the starting HPN was 44 years old. Most are submitted to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients have died while on HPN for a median of 42 months. The causes of death HPN-related were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide, with good tolerance, and need reduction of HPN support. All these eight patients have a satisfactory quality of life (parenteral support needs range between five to two nutrition bags per week). Conclusion: HPN remains the gold standard of SBS/CIF treatment, although Teduglutide may reduce HPN needs and HPN complications and provide a better quality of life. An HPN multidisciplinary healthcare group support is essential to ensure these patients' survival and quality of life. Keywords Short bowel Syndrome, Chronic Intestinal failure, Home Parenteral Nutrition, Teduglutide, Complications of Parenteral Support.

In 2011, it was reviewed that there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS. Moreover, the comorbidity between both conditions may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear. This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies that are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicate that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue. In conclusion, based on our review we may posit that shared immune-inflammatory pathways and activated microglia underpin comorbid depression and CFS and that activated microglia are the main orchestrators of this comorbidity. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

A subset of patients with schizophrenia experience physio-somatic symptoms reminiscent of chronic fatigue and fibromyalgia. In schizophrenia, these symptoms contribute to impaired quality of life, and are strongly related to neuro-cognitive deficits, and increased IgA responses to tryptophan catabolites. Negative and PHEM (psychosis, hostility, excitation, mannerism) symptoms, psychomotor retardation (PMR) and formal thought disorders, appear to be manifestations of a single trait reflecting overall severity of schizophrenia (OSOS). In this study, 120 patients with deficit schizophrenia (DEFSCZ) and 54 healthy subjects were assessed with the FibroFatigue (FF) rating scale, and the above-mentioned symptom domains as well as neuro-cognitive tests and biomarkers were measured. In DEFSCZ, there were robust associations between the FF score and all above-mentioned symptom domains, and impairments in semantic and episodic memory and executive functions. Furthermore, the FF score loaded highly on an OSOS latent vector (LV), which showed adequate convergent validity, internal consistency reliability and predictive relevance and fitted a reflective model. Soft Independent Modelling of Class Analogy (SIMCA) showed that the FF items discriminated DEFSCZ from controls with an overall accuracy of 100%. Interleukin IL-1β, IL-1 receptor antagonist (sIL-1RA), tumour necrosis factor (TNF)-α and CCL-11 (eotaxin) explained 66.8% of the variance in the FF score and 59.4% of the variance in OSOS. In conclusion, these data show that physio-somatic symptoms are a core component of the phenomenology of DEFSCZ and are largely mediated by neurotoxic effects of activated immune pathways, including aberrations in CCL-11, IL-1β and TNF-α signalling.

Nutrition is crucial for the management of patients affected by chronic kidney disease (CKD) to slow down disease progression and to correct symptoms. The mainstay of the nutritional approach to renal patients is protein restriction coupled with adequate energy supply to prevent malnutrition. However, other aspects of renal diets, including fiber content, can be beneficial. This paper summarizes the latest literature on the role of different types of dietary fiber in CKD, with special attention to intestinal microbiota and the potential protective role of renal diets. Fibers have been identified based on aqueous solubility, but other features, such as viscosity, fermentability, and bulking effect in the colon should be considered. A proper amount of fiber should be recommended not only in the general population but also in CKD patients, to achieve an adequate composition and metabolism of intestinal microbiota and to reduce the risks connected with obesity, diabetes, and dyslipidemia.

The association between the choice of general anesthetic agents and the risk of acute kidney injury (AKI) and long-term renal function after nephrectomy has not yet been evaluated. We reviewed 1087 cases of partial or radical nephrectomy. The incidence of postoperative AKI, new-onset chronic kidney disease (CKD) stage 3a and CKD upstaging were compared between different general anesthetic agent groups: propofol, sevoflurane, and desflurane. Four different propensity score analyses were performed to minimize confounding for each pair of comparison (propofol vs sevoflurane; propofol vs desflurane; sevoflurane vs desflurane; propofol vs volatile agents). Study outcomes were compared before and after matching. Kaplan-Meier survival curve analysis was performed to compare renal survival determined by the development of CKD stage 3a between groups up to 36 months after nephrectomy before and after matching. Propofol was associated with a lower incidence of AKI, CKD upstaging and a higher three-year renal survival after nephrectomy compared to sevoflurane or desflurane group after matching (AKI: propofol 23.2% vs. sevoflurane 39.5%, P=0.004, vs. desflurane 34.3%, P=0.031; CKD upstaging: propofol 27.2% vs. sevoflurane 58.4%, P<0.001, vs. desflurane 48.6%, P=0.017; Log-rank test propofol vs. sevoflurane P<0.001, vs. desflurane P=0.015). Propofol was also associated with a lower incidence of new-onset CKD after nephrectomy compared to sevoflurane after matching (P<0.001). However, there were no significant differences between sevoflurane and desflurane. In conclusion, propofol, compared to volatile agents, may be the reasonable choice of general anesthetic agent for nephrectomy to attenuate postoperative renal dysfunction. Randomized prospective trials are warranted to test this hypothesis.

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

Objectives: This study was undertaken to reveal therapeutic effects and the preliminary mechanism of Chinese medicine formula Qianlie Tongli decoction (QTD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: A total of 50 male C57BL/6 mice were randomly divided into five groups. All groups except the control group were injected subcutaneously T2 peptide emulsion, which induced the CP/CPPS model. After the induction of CP/CPPS, the model group was given 0.9% NaCl by oral gavage while low-dose, medium-dose, and high-dose groups were treated with Chinese medicine formula. Micturition habits and pain behavior of mice were analyzed for each group. Hematoxylin and eosin staining were used to investigate prostate inflammation. The serum level of tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA) kit. Key findings: Chinese medicine formula significantly reduced the number of urine spots and improved pain response frequency in the medium-dose and high-dose group. The high-dose group showed reduced considerably inflammatory lesion and inflammatory cell infiltration than the low-dose and medium-dose groups. Serum levels of TNF-α in the high-dose group were significantly reduced compared with the model group. Conclusions: The results demonstrated the therapeutic effects of Qianlie Tongli decoction in CP/CPPS mice by analyzing clinically relevant symptoms (urinary tract system, pelvic pain, and prostate inflammation), and preliminary explored the inflammatory-related treatment mechanisms by measuring TNF-α.

Obesity induces inflammation in the hypothalamus and adipose tissue, resulting in metabolic disorders. A novel hypothalamic neuropeptide, neurosecretory protein GM (NPGM), was previously identified in the hypothalamus of vertebrates. While NPGM plays an important role in lipid metabolism in chicks, its metabolic regulatory effects in mammals remain unclear. In this study, a novel Cre driver line, NPGM-Cre, was generated for cell-specific manipulation. Cre-dependent overexpression of Npgm led to fat accumulation without increased food consumption in NPGM-Cre mice. Chemogenetic activation of NPGM neurons acutely promoted feeding behavior and chronically resulted in a transient increase in body mass gain. Furthermore, the ablated NPGM neurons exhibited a tendency to be glucose intolerant, with infiltration of proinflammatory macrophages into the adipose tissue. These results suggest that NPGM neurons may regulate lipid storage and inflammatory responses, thereby maintaining glucose homeostasis.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with 1-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n=136) and by pain perception for second class patients (n=62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

Exposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging, angiogenesis, and atherosclerosis-based cardiovascular disease (ACVD). Dipeptidyl peptidase-4 (DPP-4) is a complex enzyme (also called CD26) that acts as a membrane-anchored cell surface exopeptidase. DPP4 is upregulated in metabolic and inflammatory cardiovascular disorders. The widespread expression of DPP4 macrophages and immune cells and the noncatalytic function of DPP4 (also called CD26) as a signaling and binding protein across a wide range of species suggest a teleological role for DPP4 in inflammation and immune response. DPP-4 exhibits many physiological and pharmacological functions by regulating its extremely abundant substrates [e.g., stromal cell-derived factor-1α/ C-X-C chemokine receptor type-4, glucagon-like peptide-1 (GLP-1), etc.]. Over last ten year, emerging data demonstrated unexpected roles for GLP-1 and DPP-4 in extracellular and intracellular signaling, immune activation, inflammation, oxidative stress production, cell apoptosis, insulin resistance, and lipid metabolism,. This mini review has focuses on recent novel findings in this field, highlighting an imbalance between GLP-1 and DPP4 as a potential therapeutic molecular target in treatments of chronic psychological stress-related atherosclerotic cardiovascular disease in humans and animals.

Long-term health consequences are influenced by circumstances that occur during pregnancy. The confluence of the maternal and fetal circulations occurs at the placenta, which is the first or-gan to develop. Placental pathology can provide an accurate diagnosis of inflammation inside the amniotic sac. The pathological alterations of preterm placentas provide evidence for the causes of numerous perinatal pathologies, including spontaneous preterm births. This retrospec-tive study aimed to re-examine placentas regarded as normal by the Obstetrics and Gynecology Department in our institution so that grading and staging of any evident inflammatory response could be evaluated and associated with baby gender. Eighty-four full-term placentas were col-lected after delivery. Placentas that were considered normal and were not sent to the histo-pathology department were taken. Morphological examination of fresh placenta was conducted. Full thicknesses of placenta samples were taken from central and marginal regions of placental disc. Fetal and maternal inflammatory responses syndrome were assessed. Villitis of unknown etiology (VUE) and chronic deciduitis also were evaluated in the placenta. Immunohistochemis-try (IHC) was also performed to evaluate patterns of inflammation in the placenta using an-ti-CD8 and anti-CD68 antibodies. The correlation between the silent pathologies and clinical complications or involvement of developing fetal inflammatory response syndrome was meas-ured. In this study, seventeen (20%) maternal inflammatory samples and ten (12%) fetal inflam-matory samples showed inflammatory responses. The frequency of chronic deciduitis and villi-tis of unknown etiology was more remarkable among Saudi pregnant women than the previ-ously reported findings in the literature of placental pathology. The prevalence of fetal and ma-ternal inflammatory response was greater in the placentas of mothers of males than in placentas of female mothers. Grading placental inflammation usually predict the degree of maternal an-ti-fetal cellular rejection. Fetal inflammatory response syndrome usually goes unnoticed in Sau-di Arabia. There are differences in the inflammatory response in the placenta based on the sex of the newborn. Increasing the number of placental samples that must be sent for microscopic in-spection may be preferable due to their significance in identifying the causes of chronic disor-ders.

Background and Objectives: There is a need to effectively manage the healthy aging of the rapidly increasing number of elderly people in an ultra-elderly society. The purpose of this study was to analyze the mediating effects of social networks and wisdom on the relationship between lifestyle habits and healthy aging in older adults with chronic diseases. Materials and Methods: Participants were 120 community-dwelling older adults aged 65 and older with at least one chronic disease. Data were collected from elderly people who met the criteria by visiting nursing care worker training centers, senior centers, social gatherings, and home welfare centers in D, G, and S cities from May 24 to June 23, 2023, with a questionnaire consisting of lifestyle habits, social networks, wisdom and healthy aging, and general characteristics. Results: The degree of healthy aging of the subjects was 3.56 out of 5, and there were differences in the degree of healthy aging according to age (F=3.76, p=0.026), spousal relationship (t=3.11, p=0.002), education (F=9.08, p&lt;0.001), number of diseases (F=8.65, p&lt;0.001), and economic level (t=-2.45, p=0.016). The most common diseases among the subjects were hypertension, hyperlipidemia, joint diseases and diabetes mellitus. Healthy aging was highly correlated with lifestyle habits (r=0.63, p&lt;0.001), social networks (r=0.65, p&lt;0.001), and wisdom (r=0.73, p&lt;0.001). Social networks (β=0.46, p&lt;0.001) and wisdom (β=0.55, p&lt;0.001) had partial mediating effects (z=4.15, p&lt;0.001; z=5.11, p&lt;0.001) on the relationship between subjects' lifestyle habits and healthy aging. Conclusions: In order to increase the degree of healthy aging of the subjects, it is necessary to establish a mediating intervention program that manages to have a good lifestyle habits in daily life, increase social networks, and become wise.

Ankle sprains are exceedingly common injuries in both athletes and general population. They account for 10 to 30% of all sports injuries. Although the vast majority of lateral ankle ligamentous injuries respond successfully to conservative management, the absolute number of those that progress to chronic lateral ankle instability (CLAI) remains considerably important. This condition is characterized by persistent symptoms and may be associated with short-term and long-term complications and functional deficits. There is still a lack of ideal postoperative management of CLAI patients. Furthermore, an evidence-based rehabilitation phasing does not exist and most of the published studies regarding this subject suggest some protocols based on a wide variety of functional assessment scores and other modalities which are not accurate enough. Moreover, the literature that assesses the ability to return to work (RTW) and return to sport (RTS) in general population and athletes operated for CLAI shows most commonly aggregated results with global rates of RTW or RTS without describing a detailed timeline based on the readiness of patients to return to each level of activity. Although stress radiographs and MRI have been assessed as potential tools to improve postoperative management of CLAI patients, the first modality is limited by its low sensitivity to detect laxity and the second one by its static character and its inability to predict the healing process phase nor the mechanical properties of the repaired/reconstructed ligaments. Bioelectrical impedance, mechanical impedance and near-infrared spectroscopy are non-invasive methods of measurement that could be potential assessment tools to help surgeons improve the postoperative management of patients after CLAI surgery.

Background: Overall survival is the most important outcome for treatment response in feline chronic kidney disease (CKD). Beraprost has been shown to reduce the kidney function decline in cats with International Renal Interest Society (IRIS) stage 2 and 3 CKD. However, association with prolonged survival has not yet been examined. Objective: To assess the relationship between beraprost and overall survival in cats with CKD in real clinical practice. Animals: Client-owned cats with IRIS stage 3 CKD (n = 134), evaluated between 2017 and 2020. Methods: Retrospective cohort study based on data from electronic medical records of one hospital. Results: Multivariable Cox regression models on all treatment effects showed that beraprost only was related to better survival (P = 0.028). The cohort was divided into “beraprost therapy” and “no beraprost therapy” groups, and survival analyses revealed that overall survival was significantly longer in the beraprost therapy group, using Kaplan-Meier curves (P = 0.004). However, baseline phosphate is known to be an important prognostic indicator and was not well balanced between the two groups. Therefore, a subcohort of 97 cats was selected (those having baseline phosphate < 6.0 mg/dL) that allowed for this parameter to be balanced between groups. The survival data in this subcohort was consistent with that of the overall study cohort. Conclusions: In feline patients with CKD, beraprost therapy was associated with better overall survival.

Microbiota-based strategies are a novel auxiliary therapeutic and preventative way of moderating chronic kidney disease. Lactobacillus mixture (Lm) was previously demonstrated to exert a renal-protective function in the CKD mice model. The efficacy of probiotics in pet foods is a relatively new area of study, and thus verifying the potential health benefits is necessary. This study evaluated the efficacy of Lm treats in feline CKD and elucidated the mechanisms underlying host-microbe interactions. CKD cats (2 and 3 stages) were administrated probiotic pet treats daily (10 g) for 8 weeks. The results demonstrated that during the eight weeks of Lm administration, creatinine was reduced or maintained in all cats with CKD. Similarly, gut-derived uremic toxins (GDUT), IS, and TMAO were significantly downregulated in the serum (confidence intervals = 90%). The life quality of the cats also improved. Feline gut microbiome data, KEGG pathway, and renal function indicator analyses revealed the possible mechanisms involved in modulating CKD feline microbial composition. Further regulation of the microbial functions in amino acid metabolism after Lm administration contributed to downregulating deleterious IS, PCS, and TMAO. The current study provides potential adjuvant therapeutic insights into probiotic pet foods or treats for pets with CKD.

Background: COVID-19 is associated with neuropsychiatric symptoms including increased depressive, anxiety and chronic fatigue-syndrome (CFS)-like physiosomatic (previously known as psychosomatic) symptoms.Aims: To delineate the associations between affective and CFS-like symptoms in COVID-19 and chest CT-scan anomalies (CCTAs), oxygen saturation (SpO₂), interleukin (IL)-6, IL-10, C-Reactive Protein (CRP), albumin, calcium, magnesium, soluble angiotensin converting enzyme (ACE2) and soluble advanced glycation products (sRAGEs).Method: The above biomarkers were assessed in 60 COVID-19 patients and 30 heathy controls who had measurements of the Hamilton Depression (HDRS) and Anxiety (HAM-A) and the Fibromyalgia and Chronic Fatigue (FF) Rating Scales. Results: Partial Least Squares-SEM analysis showed that reliable latent vectors could be extracted from a) key depressive and anxiety and physiosomatic symptoms (the physio-affective or PA-core), b) IL-6, IL-10, CRP, albumin, calcium, and sRAGEs (the immune response core); and c) different CCTAs (including ground glass opacities, consolidation, and crazy paving) and lowered SpO2% (lung lesions). PLS showed that 70.0% of the variance in the PA-core was explained by the regression on the immune response and lung lesions latent vectors. Moreover, one common “infection-immune-inflammatory (III) core” underpins pneumonia-associated CCTAs, lowered SpO2 and immune activation, and this III core explains 70% of the variance in the PA core, and a relevant part of the variance in melancholia, insomnia, and neurocognitive symptoms.Discussion: Acute SARS-CoV-2 infection is accompanied by lung lesions and lowered SpO2 which both may cause activated immune-inflammatory pathways, which mediate the effects of the former on the PA-core and other neuropsychiatric symptoms due to SARS-CoV-2 infection.

Temporomandibular joint disorders (TMD) are characterized by their multifactorial etiology and pathogenesis. A 3-year prospective study was conducted in a Portuguese TMD department to study the prevalence of different TMD signs and symptoms and their association with risk factors and comorbidities. Five hundred ninety-five patients were included using an online database: EUROTMJ. Most patients were female (80.50 %), with a mean age of 38.20±15.73 years. The main complaints were temporomandibular joint (TMJ) clicking (13.26%), pain (12.49%), and masticatory muscle tension (12.15%). The main clinical findings were myalgia (74%), TMJ clicking (60-62%) and arthralgia (31-36%). Risk factors such as clenching (60%) and bruxism (30%) were positively associated with TMJ pain and myalgia. Orthodontic treatment (20%) and wisdom tooth removal (19%) were positively associated with TMJ clicking, while jaw trauma (6%) tracheal intubation (4%) and orthognathic surgery (1%) were positively associated with TMJ crepitus, limited man-dibular range of motion and TMJ pain, respectively. 42.88% of TMD patients had other associated chronic diseases, most of them were mental behavioral or neurodevelopmental disorders (33.76%), namely, anxiety (20%) and depression (13%). The authors also observed a positively association of mental disorders with the degree of TMJ pain and myalgia. Online database seems to be a relevant scientific instrument for healthcare providers who treat TMD. The authors expect that EUROTMJ database can serve as a milestone for other TMD departments.

Introduction. This retrospective study aimed to compare the risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Methods. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF23, fetuinA, sclerostin, and VC scores (Adragao method). Multivariable linear regression identified VC predictors. Results: The prevalence of VC was similar in both groups, but HD patients had more pronounced VC scores ≥6. Pre-HD patients were older, with higher prevalence of Balkan endemic nephropathy, hypertension, and less frequent use of calcium phosphate binders. Both groups exhibited similar patterns of hyperphosphatemia, low vitamin D, and iPTH levels. In HD group normal phosphate was significantly common in patients with VC, whereas hyperphosphatemia was significantly common in patients without VC. Fetuin-A levels were higher in pre-HD patients, while FGF23 was elevated in HD patients. In pre-HD patients, male gender was associated with reduced VC risk, while in HD patients, malignancies and serum phosphate levels were negative VC predictors. Conclusion: Effective monitoring and tailored treatment of VC in CKD are still focused on phosphate regulation. Besides, mineral disturbances, hormones and biomarkers regulation, and patient-specific variables need to be considered.

Contrary to popular belief, we have known for many years that the endometrium is not a sterile environment and is considered to be a low-biomass milieu compared to the vagina. Numerous trials and studies have attempted to establish a valid sampling method and assess its physiological composition, but no consensus has been reached. Many factors such as ethnicity, age and inflammation, can influence the microbiome. Moreover, it possesses a higher alpha-diversity and therefore contains more diverse bacteria than the vagina. For instance, Lactobacillus has been shown to be a predominant genus in the vaginal microbiome of healthy women. Consequently, even if a majority of scientists postulate that a predominance of Lactobacillus inside the uterus improves reproductive outcomes, vaginal contamination by these bacteria during sampling cannot be ruled out. Certain pathologies, such as chronic endometritis, have been identified as inflammation perpetrators that hinder the embryo implantation process. This pro-inflammatory climate created by dysbiosis of the endometrial microbiota could induce secondary inflammatory mediators via Toll-like receptors, creating an environment conducive to the development of endometriosis and even promoting carcinogenesis. However, studies to this day have focused on small populations. In addition, there is no clearly defined healthy uterine composition yet. At most, only a few taxa have been identified as pathogenic. As sampling and analysis methods become increasingly precise, we can expect the endometrial microbiota to be incorporated into future diagnostic tools and treatments for women’s health.

There is a pressing need for more precise biomarkers of chronic kidney disease (CKD). Plasma samples from 820 subjects [231 with CKD, 325 with end-stage kidney disease (ESKD) and 264 controls] were analyzed by LC-MS/MS to determine a metabolic profile of 28 aminoacids (AA) and biogenic amines to test their value as markers of CKD risk and progression. The Kynurenine/Tryptophan ratio showed the strongest correlation with estimated glomerular filtration rate values (coefficient=-0.731, P&lt;0.0001). Models created with Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) containing the metabolic signature showed high goodness of fit and predictability for controls/CKD (R2X:0.73;R2Y:0.92;Q2:0.92) and lower for CDK/ESKD (R2X:0.56;R2Y:0.59;Q2:0.55). Based on generated VIP scores, the most relevant markers for segregating samples into control/CKD or CKD/ESKD groups were citrulline (1.67) and tryptophan (1.59), respectively. ROC analysis showed that the addition of the metabolic profile to a model including CKD classic risk factors improved AUC from 86.7% (83.6-89.9) to 100% (100-100) for CKD risk (P&lt;0.0001), and from 63.0% (58.2-67.8) to 96.5% (95.3-97.8) for the risk of progression from CKD to ESKD (P&lt;0.0001). Plasma concentrations of AA and related amines may be useful as diagnostic biomarkers of kidney disease, both for CKD risk and for progression of CKD patients to ESKD.

Chronic unpredictable environmental stress (CUES) may induce predisposition to diabetes mellitus. This study investigates the role of CUES on impaired homeostasis. Stressed group mice (n = 20) were exposed to CUES for 16 weeks. Weekly body weight, feed consumption, feed efficiency ratio, fasting blood glucose were monitored. Plasma HbA1c, plasma cortisol, plasma epinephrine and plasma insulin, serum lipids, antioxidants and carbohydrate metabolizing enzymes activity were assessed along with DNA damage and histopathological examination of liver, kidney, pancreas, spleen and skeletal muscles. Fasting blood glucose levels & HbA1c in the stressed were significantly higher compared to control (p < 0.001). Serum lipids were found insignificantly higher in stressed mice compared to control. Body weights of the stressed mice and feed efficiency ratio were found significant (p < 0.001). Plasma corticosterone, plasma epinephrine, HOMA-IR was found to be significantly higher in the stressed group (p < 0.001). Plasma insulin level was found to be significantly lower in the stressed group (p < 0.001). Significant changes were observed in antioxidants level, carbohydrate metabolizing enzymes activity, peripheral tissues and DNA integrity. CUES initiates pathogenesis of diabetes.

Objective: A previous study showed that schizophrenia is accompanied by lowered levels of trace/metal elements including cesium. There are no data whether changes in cesium, rubidium and rhenium are associated with activated immune-inflammatory pathways, cognitive impairments, and the symptomatology of schizophrenia. Methods: This study measured cesium, rubidium, and rhenium, cognitive impairments (using the Brief Assessment of Cognition in Schizophrenia) and the cytokines/chemokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and CCL11 (eotaxin) in 120 schizophrenia patients and 54 healthy controls. Severity of illness was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale and the Hamilton Depression Rating Scale (HAM-D). Results: Serum cesium was significantly lower in schizophrenia patients as compared with controls. Serum cesium was significantly and inversely associated with CCL11 and TNF-α, but not IL-1β. Moreover, there were significant inverse associations between serum cesium levels and the BPRS, FF, HAM-D and SANS scores and positive correlations between cesium and neurocognitive probe results including the Tower of London, Symbol Coding, Controlled Word Association, Category Instances, Digit Sequencing Task, and List Learning tests. Conclusion: The results suggest that lowered serum cesium levels may play a role in the pathophysiology of SCZ, specific symptom domains including negative, depressive and fatigue symptoms, neurocognitive impairments (spatial working, episodic and semantic memory and executive functions) and neuro-immune pathways as well.

Background: Coronary tortuosity is a common angiographic finding. Scarce data is available on clinical profile of patients with coronary tortuosity (CT) and its relation with coronary artery disease (CAD). Method: A total 224 patients undergoing angiography for suspected CAD were included in the study. CT was defined by the presence of ≥3 consecutive bends of > 45 degree measured at end-diastole in an epicardial artery ≥2 mm in diameter. CT was present in 45(20.08%) patients in the study and another 45 patients without CT was randomly selected as control (NCT group). Clinical profile of CT and NCT group was compared. Results: Incidence of CT was significantly higher in females (p=0.000) and hypertensives (p=0.001) patients. CT was most commonly seen in Left circumflex coronary artery. Incidence of CAD was significantly lower in CT group as compare to NCT group (0.02). Risk factors for CAD was associated with reduced incidence of CT. Majority (88.46%) patient with CT without CAD presented with chronic stable angina out of which (65.21%) had an objective evidence of myocardial ischemia. Conclusion: CT is more commonly seen females and hypertensive patients. It has negative correlation with CAD. Risk factors of CAD do not predict CT. CT itself can lead to myocardial ischemia.

RNA epigenetics is perhaps the most recent aspect of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combination whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes into RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

Chronic graft-versus-host disease (cGvHD) occurs in 20-50% of recipients following allogeneic haematopoietic stem cell transplantation (allo-HSCT). Corticosteroids (CS) remain the first line treatment but have suboptimal efficacy and carry the risk of long-term side effects. New agents with a better safety profile and higher efficacy, ideally combining immunomodulatory and antifibrotic properties, are urgently needed. From 2016 to 2020, we conducted a phase 2 clinical trial with ATO in chronic GvHD (ClinicalTrials.gov ID NCT02966301 - GMED16-001). This study aimed to evaluate the efficacy and safety of a first-line combination of arsenic trioxide (ATO) and CS in adult patients with cGvHD who require systemic therapy after a first allo-HSCT for a haematological disease. In this prospective, national, multicenter, single-arm, open-label phase II study, conducted in 5 university hospital centers in France, ATO was initiated within 10 days of starting CS at 1 mg/kg/day. Patients received 11 infusions of ATO per 4-week cycle, at a dose of 0.15 mg/kg per infusion. Patients received 1 or 2 cycles of treatment depending on the clinical response and the assessment of the treating physician. The results were published in July 2022 in a paper entitled "High Response Rate and Corticosteroid Sparing with ATO-Based First-Line Therapy in Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation". The GMED16-001 study demonstrated convincing efficacy and safety characteristics of the intravenous drug (Trisenox^®/Arscimed^®): the first-line use of ATO in addition to corticosteroids was associated with a high clinical response rate and correlated with rapid corticosteroid (CS) sparing in moderate to severe cGvHD after allo-HSCT. We performed a post-hoc analysis of the data to determine the best schedule for treating cGvHD patients with ATO. Our post-hoc analysis leads us to the conclusion that two cycles of ATO, at 0.15 mg/kg/day, 5 days per week for 4 weeks each, separated by a 4-week therapy-free interval, appears to be the most promising treatment schedule.

Introduction: Wound healing is a complex cascade involving the orchestration of inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. These cells achieve tissue repair through an interchange of cytokines and growth factors through a controlled inflammation, angiogenesis, and remodeling process. Disruptions in the wound-healing process by comorbid conditions lead to significant morbidity and mortality. Stem cell therapy has emerged as a new strategy to facilitate the wound healing process. Stem cells harvested from different sources can be used for wound repair and regeneration (endothelial progenitor cells, bone marrow, adipose tissue, dermal and inducible pluripotent stem cells). We aimed to review clinical, translational, and primary literature on stem cell therapies in chronic wounds and summarize practical clinical applications to dermatological care. Materials and Methods: A comprehensive search of Pubmed, Embase, Web of Science, Google Scholar, and Cochrane Library was conducted for studies relating to stem cells and wound healing. Duplicate results were removed using Covidence. Titles and abstracts were screened by two independent researchers (BF and KR), with discrepancies resolved through discussion and mutual agreement. Articles were excluded if they were review-type or commentary-type articles. Results: A total of 22,454 articles were retrieved from the search. Deduplication removed 905, and automation removed an additional 18,363 articles. After an initial screening of titles and abstracts, 170 articles remained. Full-text screening resulted in an additional 126 articles being removed, leaving 44 included studies. Discussion: Stem cells used for wound repair and regeneration include endothelial progenitor stem cells and adult stem cells, in the forms of bone marrow-derived mesenchymal stem cells, adipose tissue stem cells, and inducible pluripotent stem cells. Among these sources, adipose tissue-derived mesenchymal stem cells (AD-MSCs) are ideally used due to the abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic factors. AD-MSCs have been used to enhance wound healing in peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and postsurgical wounds after Mohs micrographic surgery. These cells have been delivered to the tissue topically, with scaffolds, combined with plasma-rich proteins, and through atelocollagen in various human studies. These approaches, when combined with local wound care practices, resulted in decreased pain, shorter wound healing times, and better cosmesis. Conclusions: Stem cell transplantation is a potential therapeutic approach in the wound healing process. Transplanted stem cells do not only differentiate into multiple skin cell types but also provide cytokine and growth factors required for wound healing resulting in increased angiogenesis. Thus, this approach may be regarded as an attractive option for intractable wounds that cause major clinical problems, especially chronic lower leg wounds. It can also be used after Mohs micrographic surgery for defects left to heal by secondary intention. Stem cell application may reduce the overall cost burden on the healthcare system and improve the quality of life for patients.

Fibromyalgia is a complex and often misunderstood chronic pain disorder. It is characterized by widespread musculoskeletal pain, fatigue, and heightened sensitivity, and has evolved in diag-nostic criteria and understanding over the years. Initially met with skepticism, fibromyalgia is now recognized as a global health concern affecting millions of people, with a prevalence trans-cending demographic boundaries. The clinical features and diagnosis of fibromyalgia encompass a range of symptoms beyond pain, including sleep disturbances and cognitive difficulties. The study emphasizes the importance of a comprehensive evaluation for accurate diagnosis, considering the shift from tender point reliance to a more holistic approach. Etiology and pathophysiology involve genetic predisposition, neurotransmitter dysregulation, central sensitization, and immune system involvement. Risk factors such as gender, age, family history, and comorbid conditions contribute to susceptibility. The impact on quality of life is profound, affecting physical and social aspects, often accompanied by mood disorders. Management approaches include pharmacological interventions, non-pharmacological therapies, lifestyle modifications, and alternative treatments. The study also delves into emerging research, exploring advances in neurobiological understanding, brain imaging, genetic markers, glutamate modulation, cannabinoids, gut microbiome, and digital health tools for fibromyalgia manage-ment. Overall, this study provides a nuanced and up-to-date overview of the complexities sur-rounding fibromyalgia, aiming to enhance understanding and support for individuals grappling with this challenging condition.

.Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of β-galactosidase at pH 6 (SA-β-Gal) is a classic maker of senescence in cellular biology. However the predictive role of kidney tissue SA-β-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectively studied the expression of SA-β-Gal in kidney biopsies obtained in a cohort [n=29] of incident patients who were followed up for 3 years as for standard of care. SA-β-Gal staining was approximately 4-fold higher in the tubular compartment of patients with CKD vs. controls [26.0 ± 9 vs. 7.4 ± 6% positive tubuli in patients vs. controls; p < 0.025]. Tubular expressions of SA-β-Gal, but not proteinuria at the time of biopsy correlated with eGFR loss at follow-up; moreover, SA-β-Gal expression in more than 30% of kidney tubules was associated with fast progressive kidney disease. In summary, our study shows that SA-β-Gal is upregulated in the kidney tubular compartment of adult patients affected by CKD, and suggests that tubular SA-β-Gal is associated with accelerated loss of renal function.

Real-time quaking-induced conversion (RT-QuIC) assays have become common in the detection of chronic wasting disease (CWD) and are very sensitive provided the assay duration is sufficient. However, a prolonged assay duration may lead to non-specific signal amplification. The wide range of pre-defined assay durations in current RT-QuIC applications presents a need for optimization of the RT-QuIC assay duration. In this study, receiver operating characteristic (ROC) analysis was applied to optimize assay duration for detection of CWD in obex and retropharyngeal lymph node (RLN) tissue specimens. Two different fluorescence thresholds were used: a fixed threshold based on background fluorescence (Tstdev) and a max-point ratio (maximum/background fluorescence) threshold (TMPR) to determine CWD positivity. The optimal assay duration was 27 h for both obex and RLN based on Tstdev, and 27 and 28 h for obex and RLN, respectively, based on TMPR. The optimized assay durations were then evaluated for screening CWD in white-tailed deer from an affected farm. Results by RT-QuIC using optimized duration based on Tstdev and TMPR were in 100% and 92.3 % or higher agreement with those by the widely used screening assay, ELISA. In comparison, when using a 40 h assay duration, the agreement between RT-QuIC and ELISA reduced to 89.2% or higher, and the RT-QuIC results were significantly (p < 0.05) different from those using optimum durations. These findings demonstrated that the application of ROC analysis for the optimization of assay duration could improve the RT-QuIC assay for screening CWD in white-tailed deer.

Crohn's disease (CD) is a chronic, relapsing disorder belonging to inflammatory bowel diseases (IBD). It is manifested by relapsing transmural inflammation found in any segment of the gastrointestinal tract. Chronic fatigue is a common and underrecognized symptom of CD, which prevalence is much higher in the population of CD patients as compared to healthy population. It stems from an intricate web of interactions between various risk factors, and its pathophysiology is still not fully understood. Implementation of routine screening and holistic, multidisciplinary approach involving psychological support may be crucial in management of CD patients with chronic fatigue. There is currently no single intervention aimed at decreasing fatigue alone, and its treatment is especially difficult in patients with fatigue persisting despite clinical and endoscopic remission. Extensive research is still needed in order to be able to predict, prevent, identify and ultimately treat fatigue associated with CD. The aim of this review is to summarize the knowledge on the etiology, diagnosis, and treatment of chronic fatigue in CD patients.

In the present research, chronic viral hepatitis in children is approached from a multidisciplinary point of view, considering social status, economic and medical aspects. We conducted a 4-year observational prospective study. A questionnaire regarding the socio-economic status of pediatric patients diagnosed with chronic viral hepatitis B or C was applied. In total, 159 patients were included, 52 % from urban areas, 2.5 % coming from centres for abandoned children. Among 119 school-aged children, 66% were attending classes. All patients are registered with a general practitioner. Regarding the monthly income per family, 49% had less than 1000 RON (5 RON = 1$), of which 17% had no income, 28% had an income ranging between 1000 and 2000 RON and in only 23% of cases the income exceeded 2000 RON (5% had more than 4000 RON). There were between 3 and 12 members per family. Concerning parents` educational level, the average years of study for mothers was 7.8, while for fathers, it was 8.2. For 17 % of children, at least one of the parents was illiterate, and for 5.6 %, both parents were illiterate. For a third of patients, both parents were unemployed. Regarding social living conditions, 38.4% did not have water facilities or sewerage, and 32 % used personal objects (scissors, nail clippers) in common. The socio-economic level can have a significant impact on disease epidemiology (infectiousness) and access to treatment, and it is tightly related to educational level and access to information, which are critical factors in disease prevention through general and specific measures and in disease management (treating infected patients and limiting the transmission).

Background: Chronic kidney disease (CKD) is a common complication of non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. Methods: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD), increased serum creatinine ≥50%, renal replacement therapy (RRT), and death in pre-transplant, peri-transplant and post-transplant period. Results: 74 patients were studied (7 heart transplant, 34 liver transplants, and 33 lung transplant). Patients who were not followed-up by nephrology in the pre-transplant (p&lt;0.027), peri-transplant (p&lt;0.046), and the longest time until outpatient clinic follow-up (HR 1,032) were associated with a higher risk of creatinine increase ≥50%. Receiving a lung transplant conferred higher risk than liver or hear transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxic and the number of hospital admissions were significantly associated to present a creatinine increase ≥50% and develop ESKD. Conclusion: An early follow-up by the nephrology department was associated with a decrease in the worsening of renal function.

There is growing interest in the application of fecal microbiota transplants (FMTs) in small animal medicine, but there are few published studies that have tested their effectiveness in the domestic cat (Felis catus). Here we use 16S rRNA gene sequencing to examine fecal microbiome changes in 68 domestic cats with chronic digestive issues that underwent FMT treatment using lyophilized stool that was delivered in oral capsules. Fecal samples were collected from FMT recipients before and two weeks after treatment, as well as from their stool donors, and healthy animals. We found that according to their owners, 77% of cats were reported to show improvement in their clinical signs (termed ‘Responders’), and 23% were reported to exhibit no change or a worsening of their clinical signs (termed ‘Non-Responders’). Variation in the fecal microbiomes of FMT recipients most strongly correlated with host clinical signs, diet, and IBD diagnosis. The relative abundances of Collinsella, Negativibacillus, Parabacteroides, and Peptoclostridium changed differentially in FMT recipients. Overall, on average 13% of the bacterial amplicon sequence variants (ASVs) were shared between stool donors and FMT recipients (excluding ASVs already present in FMT recipients prior to treatment). The most commonly shared ASVs were classified as Prevotella 9, Peptoclostridium, Bacteroides, Collinsella and unclassified Lachnospiraceae. Lastly, FMT recipients that had recently taken antibiotics exhibited increases in microbiome similarity to an age-matched healthy reference set compared to other cats. Cats that had diarrhea or diarrhea with vomiting became more similar to healthy cats than did cats exhibiting other clinical signs. Overall, our results suggest that oral capsule FMT treatment was effective in this group of cats and microbiome responses may be modulated by the FMT recipient’s initial presenting clinical signs, prior IBD diagnosis, recent antibiotic use, and their diet.

Background: Diabetes Mellitus is a metabolite disorder with parameters of high blood sugar levels. In the management of diabetes can be used the drug metformin is the gold of choice to achieve a therapeutic effect and rarely causes side effects of the drug, but it still has debate view. However, if used in excessive doses for patients with kidney disease, it will be contraindicated with side effects such as lactic acidosis. Objective: This study aims to evaluate the side effect of Metformin for diabetic kidney diseases (DKD) patients. Method: This study used the Narrative Review Method that was obtained from 2011 to 2021, in the English language from PubMed, Google Scholar, and Cochrane Library. Results: Metformin is at the forefront of the treatment of type 2 diabetes mellitus (DM2). Metformin is likely to have lactic acidosis-related adverse effects in chronic kidney disease (CKD) patients, such as increased arterial lactate. Lactic acidosis is defined as an increase in arterial lactate with an indicator of more than five mmol/L and an arterial blood pH of less than 7.35. Metformin-induced lactate levels are considered to be below the parameters. DKD risk factors can be conceptually classified as several susceptibility factors, initiation factors, and developmental factors. The two most prominent risk factors are hyperglycemia and hypertension. Conclusion: Metformin can increase lactate levels in CKD patients but is still below the parameters of lactic acidosis. This study may have some weaknesses and requires further prospective research to validate the results.

Uremic toxins are the compounds that emerge in the blood when kidney excretory function is impaired. The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually death during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes rise during uremia; however, the exact origin for most of them is still discussable. There are 3 main sources for such compounds: exogenous ones are consumed with food, whereas endogenous are produced by host metabolism or by symbiotic microbiota metabolism. In this article, we identified uremic toxins presumably of gut microbiota origin. We analyzed various databases to get information on enzymatic reactions in bacteria and human organism potentially yielded uremic toxins and to determine what toxins could be synthetized in bacteria residing in human gut. We selected biochemical pathways resulting in uremic toxins synthesis related to specific bacterial strains, and revealed links between toxin concentration in uremia and the proportion of different bacteria species, which can synthesize it. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of a particular toxin synthesis by the human metabolism. Finally, we analyzed which bacteria are potentially producing the biggest number of uremic toxins as well as which bacteria are decomposing them. Our study presents a bioinformatics-based approach for both elucidation of the origin of uremic toxins and search of the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.

Objective: To determine the association of edentulism with different chronic diseases in Mexicans aged 60 years and over. Material and Methods: A cross-sectional study was carried out using data from the World Health Survey for Mexico, which had a probabilistic, multi-stage and cluster sampling. The results of the self-report of chronic diseases (diabetes, arthritis, depression, angina pectoris, asthma and schizophrenia) and of edentulism were analyzed. Dental data were available for 20 of the 32 States of the Mexican Republic. Statistical analysis was performed in Stata 14.0 using the svy module for complex samples. Results: In total, 4213 subjects were included, representing a population of 7,576,057 individuals. The mean age was 70.13 ± 7.82 years (limits 60 to 98). Women represented 56.2%. The chronic diseases analyzed were presented as follows: diabetes 15.0% (N = 1,132,693); arthritis 13.2% (N = 1,001,667); depression 5.5% (N = 414,912); angina pectoris 4.5% (344,315); asthma 3.6% (N = 269,287); and schizophrenia 2.2% (N = 16,988). The prevalence of edentulism was 26.3%, which represents 1,993,463 people aged 60 years and over with this characteristic. For the presence of angina in women aged 60 to 69 years (p &lt;0.05) and depression in men aged 70 years and over (p &lt;0.0001), a higher prevalence of edentulism was observed. Conclusions: In general, there was no observation of association between edentulism was observed on the different chronic diseases included in the study. In the stratified analysis, only in women aged 60 to 69 years, for angina, and in men aged 70 and over, for depression, were associated.

Background: Chronic lower limb ulcers (CLLU) have an important burden to the individual and the healthcare system. However, there is a lack of information about the cost of CLLU in Argentina.Objective: To determinate the number and cost of consultation and hospitalization associated to CLLU in a public hospital in Argentina. Methods: Retrospective observational study. Cost estimation were calculated based on days of stay, treatments and laboratory tests in a inpatient population and the number of consultations, treatments and laboratory tests, in a outpatient population. Results: In 2013 and 2014, the overall number of consultation with ICD-10 codes was 7,224 and the number of inpatient was 359. The mean age for male and female outpatient consultations was 59.53(±13.06) years and 59.04(±10.93), respectively. For CLLU male and female inpatient, the mean age was 63.9(±10.4) years and 54.5(±8.6) years, respectively. The length of stay was 22.88 days. There was a mean of 0.41 surgeries per patient where 25% were amputations. The mean annual cost in a single public hospital was US$4,053.65 per inpatient and US$3,589.24 per outpatient. Conclusion: Cost information allows new public health policies to reduce socioeconomic burden due to CLLU.

In the world, migraine is one of the most common cause of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers, in combination with a genetic predisposition. Among factors related to the migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this contest, in addition to migraine conventional pharmacological treatments, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, like diabetes mellitus, arterial hypertension, obesity, cancer and chronic kidney diseases, whose link is represented by gut dysbiosis.

Background and objectives: Since 2013, highly effective direct-acting (DAA) chronic hepatitis C (CHC) antiviral therapy became available, which has cure rates of over 95%. For choice of optimal CHC treatment, assessment of hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage are necessary. Information about distribution of these parameters among CHC patients in Baltic states and especially in Ukraine is scarce. This study was performed to obtain epidemiological data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (Baltic states) and lower-middle income (Ukraine) countries. Materials and Methods: This was an epidemiological, retrospective, cross-sectional study that included 1451 CHC patients. Demographic and disease information from medical charts was collected for each patient during a single visit. Results: Most frequent suspected mode of viral transmission was blood transfusions (17.8%), followed by injection drug use (15.7%); however, in 50.9% of patients exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%) transmission by the injection drug use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1 - 66.4%; GT3 - 28.1; and GT2 - 4.1%. The prevalence of GT1 was the highest in Latvia (84%), and the lowest in Ukraine (63%, p<0.001). Liver fibrosis stages were distributed as follows: F0 - 12.2%, F1 - 26.3%, F2 - 23.5%, F3 – 17.1% and F4 - 20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p <0.001). Conclusions: This study contributes to the knowledge of epidemiological characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation is Science and Technology (COST) (https://www.cost.eu/cost-actions/what-are-cost-actions/ ) - COST action 15111 - from 2016 to 2020. The main goal of the Cost Action was to assess the existing fragmented knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report on the recommendations for clinical diagnosis, heath services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS (https://www.cost.eu/actions/CA15111/#tabs|Name:overview).

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic method. The multitude of different etiological factors, the diversity of the clinical picture and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated diseases that in their natural course can lead to myocardial involvement, but also the iatrogenic cause of myocarditis due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, changes in ECG and echocardiography has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive diagnostic gold standard for diagnosis and clinical follow-up of thses patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening patients with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Background. Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms.Aim. To examine the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), and CFS-like (Fibro-fatigue Scale) symptoms and immune-inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylceramide in RA. Methods. The serum biomarkers were assayed in fifty-nine RA and fifty-nine patients without increased psychopathology (PP) and fifty healthy controls.Results. There were highly significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tenders and swollen joints, and patient and evaluator global assessment scores. A common latent vector (reflective model) could be extracted from the PP and RA-severity scales, which showed excellent psychometric properties. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning PP and RA symptoms could be explained by the regression on immune-inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. Conclusions. Depression, anxiety, and CFS-like symptoms due to RA are reflective manifestations of the phenome of RA and are mediated via the effects of the same immune-inflammatory, autoimmune, and EOS pathways and lactosylceramide that underpin the pathophysiology of RA. These PP symptoms are clinical manifestations of the pathophysiology of RA.

Introduction: The relation between physical well-being and chronic pain is complex and involves several subjective and objective covariates. We aimed to assess the role of media-tor, confounder, or interactor played by covariates, including sleep quality, physical activity, perceived stress, smoking, and alcohol drinking in the relation between physical well-being and chronic pain. Method: We used Poisson regression to obtain incidence rate ratios (IRR) of the associa-tion between physical well-being and chronic pain in a cohort study carried out among uni-versity students. We applied General Structural Equation Modeling (GSEM) to assess me-diation, and stratum-specific analysis to distinguish confounding from interaction. We computed Relative Excess Risks due to Interaction (RERI), Attributable Proportion (AP), and Synergy index (S) to measure additive interaction. Results: High physical well-being is related to a large decrease in the risk of chronic pain (IRRTotal Effect= 0.58; 95%CI 0.50-0.81). Perceived stress mediates 12.5% of the total effect of physical well-being on chronic pain. The stratum-specific IRRs of current smokers and non-current smokers were different from each other and were larger than the crude IRR (IRR=1.49; 95% CI: 1.24-1.80), which indicates that smoking could be both confounder and interactor. Interaction analyses showed that physical activity could act as a potential interactor (RERI=0.25; 95% CI: 0.13, 0.60). Conclusion: Perceived stress is an important mediator of the relation between physical well-being and chronic pain, while smoking is both a confounder and an interactor. Our findings may prove useful in distinguishing high-risk from low-risk groups, in the interven-tions aimed at reducing chronic pain.

The kidney and the heart work together in balancing the body circulation and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidney physiology is primarily designed to maintain a stable metabolic rate and has limited capacity to cope with any steep increase in renal metabolism. In the kidneys the glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of renal glucose transport in disease states is providing better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over-exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.

COPD is currently the fourth leading cause of death in the world. Globally, due to continued exposure to COPD risk factors and an aging population, the burden of COPD is expected to increase in the coming decades. The BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index is a practical and multidimensional predictor for prognosis of COPD, and better than FEV1.We used the database of Kaohsiung Chang Gung Memorial Hospital medical center, Taiwan to analyze the correlation between BODE index, healthcare resource utilization, and Charlson comorbidity index (CCI). This retrospective study to collect COPD patients with complete BODE index data who had undergone a 6-minute walk examination in our hospital from January 2015 to December 2016. The medical cost and comorbidities database were analyzed from January 1, 2015, to August 31, 2017. Of 396 patients, 382 (96.5%) were male, with an average age of 71.3 ± 8.4 years. There was a significant association between the BODE index and the CCI of COPD patients (p < 0.001). Healthcare resource utilization was positively correlated with the BODE index during the 32 months of retrospective clinical outcomes: positively correlated with the number of hospitalizations (p<0.001), hospitalization days (p<0.001), hospitalization expenses (p=0.005), and total medical expenses (p=0.024), respectively. Our findings provide the crucial information for clinician to predict medical burden and comorbidities in patients with COPD by using BODE index.

: Over time, we have come to recognize a very complex network of physiological changes enabling wound healing. An immunological process enables the body to distinguish damaged cells and begin a cleaning mechanism by separating damaged proteins and cells with matrix metallopro-teinases, a complement reaction, and free radicals. A wide variety of cell functions help to rebuild new tissue, dependent on energy provision and oxygen supply. Like in an optimized "biorector," disturbance can lead to prolonged healing. One of the earliest investigated local factors is the pH of wounds, studied in close relation to the local perfusion, oxygen tension, and lactate concentration. Granulation tissue with the wrong pH can hinder fibroblast and keratinocyte division and pro-liferation, as well as skin graft takes. Methods for influencing the pH have been tested, such as occlusion and acidification by the topical application of acidic media. In most trials, this has not changed the wound's pH to an acidic one, but it has reduced the strong alkalinity of deeper or chronic wound. Energy provision is essential for all repair processes. New insights into the metabolism of cells have changed the definition of lactate from a waste product to an indispensable energy provider in normoxic and hypoxic conditions. Neovascularization depends on oxygen provision and lactate, signaling hypoxic conditions even under normoxic conditions. An appropriate pH is necessary for successful skin grafting; hypoxia can change the pH of wounds. This review describes the close interconnections between the local lactate levels, metabolism, healing mechanisms, and pH. Furthermore, it analyzes and evaluates the different possible ways to support metabolism, such as lactate enhancement and pH adjustment. The aim of wound treatment must be the optimization of all these components. Therefore, the role of lactate and its influence on wound healing in acute and chronic wounds will be assessed.

Hepatitis B virus (HBV) infection remains a global public problem despite the availability of effective vaccine. In the past decades, nonalcoholic fatty liver disease (NAFLD) has surpassed HBV as the most common cause of chronic liver disease worldwide. The prevalence of concomitant chronic hepatitis B (CHB) and NAFLD, thus, reaches endemic in geographic regions where both conditions are common. Patients with CHB and NAFLD are at increased risk of liver disease progression to cirrhosis and hepatocellular carcinoma. Due to complexity of the pathogenesis, accurate diagnosis of NAFLD in CHB patients can be challenging. Liver biopsy is considered the gold standard for diagnosing and determining the disease severity, but it is an invasive procedure with potential complications. There is a growing body of literatures on the application of novel noninvasive serum biomarkers and advanced radiological modalities to diagnose and evaluate NAFLD, but most have not been adequately validated especially for patients with CHB. Currently, there is no approved therapy for NAFLD though many new agents are in different phases of development. This review provides a summary of the epidemiology, clinical features, diagnosis and management of the NAFLD and highlights the unmet needs in the areas of CHB and NAFLD coexistence.

Background: Elucidation of epigenetic mechanisms correlating with neuropathic pain in humans is crucial for the prevention and treatment of this treatment-resistant pain state. In the present study, associations between neuropathic pain characteristics and DNA methylation of the transient receptor potential ankyrin 1(TRPA1) gene were evaluated in chronic pain patients and preoperative patients. Methods: Pain and psychological states were prospectively assessed in patients who suffered chronic pain or were scheduled for thoracic surgery. Neuropathic characteristics were assessed using the Douleur Neuropathique 4 (DN4) questionnaire. DNA methylation levels of the CpG island in the TRPA1 gene were examined using whole blood. Results: Forty-eight adult patients were enrolled in this study. Increases in DNA methylation rates at CpG -51 showed positive correlations with increases in the DN4 score both in preoperative and chronic pain patients. Combined methylation rates at CpG -51 also significantly increased together with increase in DN4 scores. Conclusions: Neuropathic pain characteristics are likely associated with methylation rates at the promoter region of the TRPA1 gene in human peripheral blood.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p=0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically ‘exhausted’ in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

Critically the paper argues that a truly people-centered technology supported chronic care system can only be designed by understanding and responding to the needs, attributes and capabilities of the most vulnerable in society. The paper suggests innovative ways of supporting interactions with these ‘end-users’ and highlights how reflection on these approaches can contribute to emancipating both the health system to move towards more socially inclusive e-health solutions.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic condition characterized by exacerbation of symptoms after exertion (post-exertional malaise or “PEM”), and by fatigue whose severity and associated requirement for rest are excessive and disproportionate to the fatigue-inducing activity. There is no definitive molecular marker or known underlying pathological mechanism for the condition. Increasing evidence for aberrant energy metabolism suggests a role for mitochondrial dysfunction in ME/CFS. Our objective was therefore to measure mitochondrial function and cellular stress sensing in actively metabolising patient blood cells. We immortalized lymphoblasts isolated from 51 ME/CFS patients diagnosed according to the Canadian Consensus Criteria and an age- and gender-matched control group. Parameters of mitochondrial function and energy stress sensing were assessed by Seahorse extracellular flux analysis, proteomics, and an array of additional biochemical assays. As a proportion of the basal oxygen consumption rate (OCR), the rate of ATP synthesis by Complex V was significantly reduced in ME/CFS lymphoblasts, while significant elevations were observed in Complex I OCR, maximum OCR, spare respiratory capacity, nonmitochondrial OCR and “proton leak” as a proportion of the basal OCR. This was accompanied by a reduction of mitochondrial membrane potential, chronically hyperactivated TOR Complex I stress signalling and upregulated expression of mitochondrial respiratory complexes, fatty acid transporters and enzymes of the β-oxidation and TCA cycles. By contrast, mitochondrial mass and genome copy number, as well as glycolytic rates and steady state ATP levels were unchanged. Our results suggest a model in which ME/CFS lymphoblasts have a Complex V defect accompanied by compensatory upregulation of their respiratory capacity that includes the mitochondrial respiratory complexes, membrane transporters and enzymes involved in fatty acid β-oxidation. This homeostatically returns ATP synthesis and steady state levels to “normal” in the resting cells, but may leave them unable to adequately respond to acute increases in energy demand as the relevant homeostatic pathways are already activated.

Anthocyanins are among the best-known phenolic compounds and possess remarkable biological activities, including antioxidant, anti-inflammatory, anticancer, and antidiabetic effects. Despite their therapeutic benefits, they are not widely used as health-promoting agents due to their insta-bility, low absorption, and thus, low bioavailability and rapid metabolism in the human body. Recent research suggests that the application of nanotechnology could increase their solubility and/or bioavailability, and thus, their biological potential. Therefore, in this review, we decided to provide, for the first time, a comprehensive overview of in vitro and in vivo studies on nanocarriers used as delivery systems of anthocyanins, and their aglycones, i.e., anthocyanidins alone or com-bined with conventional drugs to the treatment or management of chronic diseases.

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection by HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms have generated the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFN-, then IFN-α plus ribavirin (IFN-RBV); then, pegylated-IFN--RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing the patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced SVR (&gt; 90%); the compounds were able to inhibit HCV replication without significant side effects, even in pediatric populations. The management of coinfected patients HBV-HCV and HCV-HIV has also improved based on DAA and PEG-IFNα-RBV (HBV-HCV). CD4 cells are crucial for an effective antiviral response. IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research focuses on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection to different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These pa-tients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmaco-logic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infec-tious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and modalities of vaccination in SOT adult candidates and recipients.

Background: A meaningful part of schizophrenia patients suffer from physiosomatic symptoms (formerly named psychosomatic) which are reminiscent of chronic fatigue syndrome and fibromyalgia (FF) and are associated with signs of immune activation and increased levels of tryptophan catabolites (TRYCATs). Aims: To examine whether FF symptoms in schizophrenia are associated with breakdown of the paracellular pathway, zonulin, lowered natural IgM responses to oxidative specific epitopes (OSEs); and whether FF symptoms belong to the behavioral-cognitive-physical-psychosocial-(BCPS)-worsening index consisting of indices of a general cognitive decline (G-CoDe), symptomatome of schizophrenia, and quality of life (QoL)-phenomenome. Methods: FF symptoms were assessed using the Fibromyalgia and Chronic Fatigue Rating scale in 80 schizophrenia patients and 40 healthy controls and serum cytokines/chemokines, IgA levels to TRYCATs, IgM to OSEs, zonulin and transcellular/paracellular (TRANS/PARA) molecules were assayed using ELISA methods. Results: A large part (42.3%) of the variance in the total FF score was explained by the regression on the PARA/TRANS ratio, pro-inflammatory cytokines, IgM to zonulin, IgA to TRYCATs (all positively) and IgM to OSEs (inversely). There were highly significant correlations between the total FF score and G-CoDe, symtopmatome, QoL phenomenome and BCPS-worsening score. FF symptoms belong to a common core shared by G-CoDe, symtopmatome, and QoL phenomenome. Discussion: The physio-somatic symptoms of schizophrenia are driven by various pathways including increased zonulin, breakdown of the paracellular tight-junctions pathway, immune activation with induction of the TRYCAT pathway, and consequent neurotoxicity. It is concluded that FF symptoms are part of the phenome of schizophrenia and BCPS-worsening as well.

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have been attracted attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. This review explores the emerging role of omega-3 FAs and their specialized pro-resolving mediators (SPMs) in the context of macrophage polarization, with a focus on chronic liver diseases. Omega-3, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have promising effects in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. SPMs, such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties. These mediators modulate the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLD, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3 and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. However, the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment require further investigation. Understanding the intricate relationship among SPM and macrophage polarization holds unlimited potential for the development of novel therapeutic strategies for chronic liver diseases.

Background and Objectives: To evaluate the effectiveness and safety of balloon pulmonary angio-plasty in patients with inoperable chronic thromboembolic pulmonary hypertension in Vilnius Pulmonary Hypertension Referral centre and provide comparative analysis with other centres. Materials and Methods. This study included all balloon pulmonary angioplasty procedures per-formed between 2019 and 2024 in a single tertiary centre. Invasive haemodynamic parameters and clinical variables were assessed at baseline, at the end of invasive treatment, and at the con-clusion of follow-up (average 8.6 months) following the last balloon pulmonary angioplasty. Ad-ditionally, respective literature review was performed. Results. Twenty-six patients with inoper-able chronic thromboembolic pulmonary hypertension were enrolled. The mean age of the pa-tients was 61.6 (40-80) years. Each patient underwent an average of 4.2 (1-9) procedures. Fol-low-up data were available for 12 patients. Mean pulmonary arterial pressure decreased by 38.8% (p

Variations in liver metabolism as a result of hepatitis C virus have been established by numerous clinical trials. The use of antioxidants supplements has been reported to minimize the implication of this disease. In this regard, we examined the suitability of Solanum fruit juice, a natural source of vitamin C and citrus flavoniod as a precursor for the treatment of patients with chronic hepatitis C. Forty adult patients who were diagnosed with chronic hepatitis C and were under antiviral therapy were divided into two equal groups. Group 1 patients received their antiviral therapy with normal food and water and served as the control group while patients in group 2 were supplemented with Solanum fruit juice for eight consecutive weeks. Measurements for Anthropometric data, C reactive protein (CRP), atherogenic indices, biochemical parameters and activities of liver marker enzymes were recorded before and after eight weeks. No alterations were found in waist circumference, body mass and body fat following regular use of Solanum fruit juice. The serum levels of oxidative stress markers, LDL-cholesterol, total cholesterol, CRP and atherogenic indices decreased in the Solanum fruit juice group when compared to the control group. Moreover, the activities of the liver marker enzyme AST decreased in those who had high levels before the intervention. These results underscore the benefits of Solanum fruit juice in the diet of patients with HCV as a result of decreased cholesterol in blood serum, decreased inflammation, and increase in antioxidant capacity as well as maintaining body mass index. This clinical trial is registered at Pan African Clinical Trial Registry (www.pactr.org) with unique identification number PACTR201802003092138.

Many people in the USA have lost their lives or become addicted to opioids via prescription opioids given for chronic pain. The chronic pain epidemic has emerged due to a convergence of factors, including the medicalization of pain as well as injuries happening in the workplace, in the home, or during recreation. Opioid prescriptions rose precipitously from the late 1990’s through to approximately 2020, and despite public awareness, still are increasing. This review examines literature on integrative approaches to chronic pain as delineated by pain type. The review is organized by the most common causes of chronic pain, and randomized controlled trials, meta-analyses and systematic reviews are extracted for each cause of chronic pain. Several promising interventions may alleviate chronic pain of some causes, and some interventions may work across pain causes. Lowering inflammation through dietary or lifestyle regimens may be a general way of reducing pain. Pain can be alleviated through several adjunctive and integrative treatment approaches, which may serve to lower the need for opioid medication.

Laboratory analyses reveal significant differences between vaccinated and unvaccinated patients in parameters like C-reactive protein, ferritin, and white blood cell counts. Univariate and multivariate Cox proportional hazards regression analyses identify several factors influencing mortality, including comorbidities, pneumonia development, and various inflammatory markers.

Chronic rhinosinusitis (CRS) is a significant health problem. It affects 5%–12% of the general population. The causes that underlie the onset of CRS are not yet well known. However, many factors may contribute to its onset, such as environmental factors and the host’s condition. Medical treatment mainly uses local corticosteroids, nasal irrigation, and antibiotics. In recent years, a new therapeutic approach that employs the use of probiotics emerged. Probiotics have been extensively studied as a therapy for dysbiosis and inflammatory pathologies of various parts of the body . We aimed to examine the studies in the existing literature to update probiotics’ role in rhinosinusitis chronic medical treatment.

Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes; however, its involvement in the regulation of cardiomyocyte autophagy under chronic intermittent hypoxia (CIH) remains largely unknown. Here we showed that CIH induced calcineurin activity in H9C2 cells, resulting in the attenuation of adenosine monophos-phate-activated protein kinase (AMPK) signaling and inhibition of H9C2 cell autophagy. Au-tophagy, LC3-II levels, and AMPK phosphorylation were significantly elevated in response to CIH in H9C2 cells by day 3; however, these effects were reversed, and calcineurin activity and apoptosis were significantly increased by day 5. The calcineurin inhibitor, FK506, restored AMPK activation and LC3 protein levels, and reduced CIH-induced H9C2 cell apoptosis, while calcineurin overexpression significantly attenuated the increase in LC3 levels and enhanced H9C2 cell apop-tosis. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9C2 cells ex-pressing a dominant negative K45R AMPK mutant. Autophagy downregulation abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicated that calcineurin suppressed adaptive autophagy during CIH by downregulating AMPK activation. Our findings showed the underlying mechanisms of calcineurin and autophagy regulation during H9C2 cell survival in response to CIH, and suggested a new strategy for preventing CIH-induced cardiomyocyte damage.

(1) Background: Research has shown that thoughts about pain are important for the management of chronic pain in children. In order to monitor changes in thoughts about pain over time and evaluate the efficacy of treatments, we need valid and reliable measures. The aims of this study were to develop a questionnaire to assess a child’s concept of pain and to evaluate its psychometric properties; (2) Methods: This is a cross-sectional, two-phase, mixed-method study. A total of 324 individuals aged 8 to 17 years old responded to the newly created questionnaire. The Survey of the Concept of Pain (SOCOPA) was calibrated using the Rasch model. The chi-square test was used for the fit statistics. Underfit and overfit of the model were determined and a descriptive analysis of infit and outfit was conducted to identify who responded erratically. Internal consistency was measured using the Person Separation Index (PSI); (3) Results: Fit to the Rasch model was good. Suitable targeting indicated which items were simple to answer; Person Fit identified 9.56% children who responded erratically; PSI=0.814; (4) Conclusions: The findings suggest that SOCOPA is a measure of a child’s concept of pain that is easy to administer and respond to. It has a good fit and a good internal consistency.

Chronic diseases are characterised by cell’s autophagy and proteins disarrangement resulting in sarcopenia, hypoalbuminemia and hypo-haemoglobinaemia. Hypo-haemoglobinaemia couses worse prognosis independentely of the principal disease. Currently, the cornerstone of therapy of anaemia is iron supplementation, with or without erythropoietin for the stimulation of hematopoiesis. However, treatment strategies should incorporate the addition of heme, the principal biochemical constituent of haemoglobin. Heme synthesis follows a complex biochemical pathway. The limiting step of heme synthesis is D-ALA availability which, for its synthesis, requires Glycine and Succinil-CoA. Consequently, treatment of anaemia should not be based only on iron availability, but also on the availability of the molecules fundamental for heme synthesis. Therefore, an adequate clinical therapeutic strategy should integrate the standard iron infusion and the supply of essential amino acids and vitamins involved in the heme synthesis. We report preliminary data in selected elderly anaemic patients with congestive heart failure (CHF) and catabolic disarrangement, who, in addition to standard iron therapy, received personalized therapy with essential-AAs and vitamins involved in the maintenance of heme. Notably, such individualized therapy resulted in a significant increase in the serum concentration of haemoglobin after 30 days of treatment compared to standard iron therapy.

(1) Background: Chronic musculoskeletal pain (CMP) in adolescents can negatively affect physical, psychological and social functioning, resulting in functional disability. This study aims to evaluate the effectiveness of an outpatient rehabilitation program based on graded exposure in vivo (EP) compared with care as usual (CAU) in a RCT. The aim of the interventions (EP and CAU) is to improve functional ability in adolescents with CMP, CAU is interdisciplinary outpatient rehabilitation care, based on graded activity. (2) Methods: A pragmatic multicenter randomized clinical trial with a 12-month follow-up was used. Adolescents (12-21 years) with musculoskeletal pain were invited to participate. Primary outcome was functional disability (Functional Disability Inventory). Most important secondary measures: perceived harmfulness, pain catastrophizing and intensity. Data analysis was performed by intention-to-treat linear mixed model analysis. (3) Results: Sixty adolescents were randomized to EP or CAU and data of 53 adolescents (93% female) could be analyzed (25 EP, 28 CAU). Mean age was 16.0 years (SD=1.87). Adolescents in EP showed a clinically relevant and statistically significant decrease in functional disability (estimated mean difference at least -8.81,p-values≤0.01) compared with CAU at all time points. Significant differences in favor of EP were found for perceived harmfulness at all time points (p-values≤0.002), for pain catastrophizing (PCS) at 2 months follow-up (p-value=0.039) and for pain intensity at 4 and 10 months follow-up (p-values≤0.028). (4) Conclusion: The effectiveness of the trial is in favor of the EP and leads to a significant and clinically relevant decrease in functional disability compared to usual care.

Assessment of cardiac function is the leading parameter when evaluating the state of the cardiovascular system of patients undergoing chronic hemodialysis. The aim of the paper: to assess the state of the cardiovascular system of these patients using new sensitive echocardiography and Doppler techniques and thus advance the prevention of cardiovascular disease.Method: Twenty children with end-stage renal insufficiency on chronic hemodialysis and twenty healthy controls underwent echocardiographic monitoring using standard Doppler and tissue Doppler imaging. Structural and functional changes in the left ventricle were evaluated.Results: Patients on hemodialysis had significantly greater left ventricular mass indices compared to the controls (p<0.001). The patients on hemodialysis had preserved systolic function – their fractional shortening, ejection fraction and Sm (systolic myocardial velocity) did not differ significantly compared to the controls (p>0.05). Early diastolic function in children on hemodialysis was also preserved: the E/A and Em/Am ratio did not differ significantly from the control group (p>0.05). Children on hemodialysis exhibited impaired late diastolic function (compliance index), that is, considerably higher E/Em compared to controls (p<0.00). Myocardial Performance Index values showed statistically significant elevation in children on hemodialysis compared to the control group (p<0.001).Conclusion: Tissue Doppler in tandem with conventional Pulsed Doppler can provide additional information on left ventricular filling pressures (E/Em) in children on hemodialysis. It is therefore recommended to perform routine measuring of Em waves and the E/Em ratio, not only in order to evaluate myocardial relaxation and ventricular filling pressures, but primarily to stratify risk and provide a prognosis.

Chronic heat stress (HS), aggravated by global warming, reduces the production efficiency of the buffalo dairy industry. Here, we conducted a proteomic analysis to investigate the adaptation strategies used by buffalo in response to heat stress. Seventeen differentially abundant proteins with known functions were detected using label-free quantification (LFQ), and five of these differentially expressed proteins were validated with parallel reaction monitoring (PRM). These five proteins were associated with various aspects of heat stress, including decreased heat production, increased blood oxygen delivery, and enhanced natural disease resistance. Lipase (LPL), glutathione peroxidase 3 (GPX3), cathelicidin-2 (CATHL2, LL-37), ceruloplasmin (CP), and hemoglobin subunit alpha 1 (HBA1) were shown to play cooperative roles in the tolerance of chronic HS in dairy buffalo. We found that high levels of HBA1 increased blood oxygen transport capacity. Our results increase our understanding of the adaptation of dairy buffalo to chronic heat stress.

Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed by transient elastography No patient had cirrhosis at baseline (LSM≥12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected by HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR)=1.14; p=0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM≥5 kPa) [adjusted odds ratio (aOR)=2.37; p=0.029], and greater than 7 kPa (ΔLSM≥7 kPa) [aOR=3.24; p=0.032], after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR=2.18; p=0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.

The aim of this cross-sectional study was to assess the perceived medication-related burden among patients with multiple non-communicable diseases (NCDs), and to investigate the association between perceived burden and adherence to medication therapy. Medication-related burden was measured in three primary care clinics in Qatar using the Living with Medicines Questionnaire (LMQ) among adults with diabetes, with or without other comorbidities. Adherence was measured using the Adherence to Refills and Medications Scale (ARMS). Two hundred ninety-three eligible patients participated in the study. Majority of participants reported experiencing minimum (66.6%) to moderate (24.1%) medication-related burden. There was a significant positive correlation between the medication-related burden (measured by the LWQ) and medication adherence (measured by ARMS) (rs (253) = 0.317, p <0.0005). The duration of diabetes diagnosis, adherence score, marital status, employment status, and presence diagnosis of hypertension were significant predictors of medication burden. A considerable proportion of the patients in this study have reported experiencing medication-related burden. Healthcare providers should seek strategies to address this burden especially among patients with risk factors of cardiovascular diseases, non-adherent to their medication therapy, living alone, or non-employed.

Given their severity and non-healing nature, diabetic chronic wounds are a significant concern to the 30.3 million Americans diagnosed with diabetes mellitus (2015). Peripheral arterial diseases, neuropathy, and infection contribute to the development of these wounds, which lead to an increased incidence of lower extremity amputations. Early recognition, debridement, offloading, and controlling infection are imperative for timely treatment. However, wound characterization and treatment are highly subjective and based largely on the experience of the treating clinician. Many wound dressings have been designed to address particular clinical presentations, but a prescriptive method is lacking for identifying the particular state of chronic, non-healing wounds. The authors suggest that recent developments in wound dressings and biosensing may allow for the quantitative, real-time representation of the wound environment, including exudate levels, pathogen concentrations, and tissue regeneration. Development of such sensing capability could enable more strategic, personalized care at the onset of ulceration and limit the infection leading to amputation. This review presents an overview of the pathophysiology of diabetic chronic wounds, a brief summary of biomaterial wound dressing treatment options, and biosensor development for biomarker sensing in the wound environment.

Objective: To estimate for the first time the burden of serious fungal infections in Romania; Methods: Data derived from the World Health Organization (WHO), National Institute of Statistics, Romanian public health agencies and non-profit health organizations and published annual reports on local epidemiology were used in the present study. When no data was available, specific at-risk populations were used to calculate frequencies of serious fungal diseases, using previously published epidemiological parameters. All data refer to the year 2016; 3) Results: The estimated number of serious fungal infections in Romanian population was 435,930 in 2016. Recurrent vulvovaginal candidiasis accounts for up to 80% of total cases (more than 350,000 women annually). Concerning the HIV related infections, among 14349 infected persons, Pneumocystis pneumonia occurred in about 10% of late presenters (30 cases in 2016), while cryptococcal meningitis is rarely diagnosed (less than 20 cases). Annually, the total number of oesophageal candidiasis and oral thrush cases in HIV-positive patients may be as high as 1229 and 3066, respectively. In immunocompromised and cancer patient population, the annual incidence of candidaemia is 295, and at least 158 invasive aspergillosis cases and 4 mucormycosis cases occur yearly. With 4,966 critical care beds and approximately 200,000 abdominal surgeries performed, the estimated annual incidence of candidaemia and Candida peritonitis is 689 and 344, respectively. The annual incidence of pulmonary tuberculosis is still high in Romania (12,747 cases). Thus, the prevalence of post-TB chronic pulmonary aspergillosis is estimated to be 8.98/100,000 (1768 cases). The prevalence of chronic obstructive pulmonary disease (COPD) and asthma in adults is 6% and 6.5%, respectively. Therefore, allergic bronchopulmonary aspergillosis prevalence is estimated at 29,387 and severe asthma with fungal sensitisation at 38,731 cases annually. 4) Conclusions: Not being on the list of reportable diseases, the number of patients presenting with severe mycoses in Romania can only be roughly estimated. Based on local reports and prevalence estimation, we consider that at least 2.2% of Romanians suffer a serious form of fungal disease.

Initially, renal resistive index (RRI) was investigated to improve diagnosis in kidney diseases, but failed to meet this goal. Recently many papers highlighted the prognostic significance of RRI in chronic kidney disease, in the estimation of revascularization success of renal artery stenoses or the evolution of the graft and recipients in renal transplantation. Moreover, RRI gained importance in prediction of acute kidney injury in critically ill patients. Along with RRI study in renal pathology have been revealed correlations of this index with parameters of systemic circulation. The theoretical and experimental premises of this connection were reconsidered, and studies for analyzing the link between RRI and arterial stiffness, central and peripheral pressure or left ventricular flow were conducted with this purpose. A high amount of data is currently indicating that RRI is influenced more by pulse pressure and vascular compliance than by renal vascular resistance – assuming that RRI reflects the complex interplay between systemic circulation and renal microcirculation and should be considered as a marker of systemic cardiovascular risk beyond its prognostic relevance for kidney disease. In this review we will go through clinical research that revealed the implications of RRI in renal and cardiovascular disease.

Chronic pain is an unpleasant sensory and emotional experience that persists or recurs more than three months and may extend beyond the expected time of healing. Recently nociplastic pain has been introduced as a descriptor of mechanism of pain, which is due to disturbance of neural processing without actual or potential tissue damage, appearing to replace a concept of psychogenic pain. An interdisciplinary task force of the International Association for the Study of Pain (IASP) compiled a systematic classification of clinical conditions associated with chronic pain, which was published in 2018 and will officially come into effect in 2022 in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) by the World Health Organization. ICD-11 offers the option for recording the presence of psychological or social factors in chronic pain; however, cognitive, emotional, and social dimensions in the pathogenesis of chronic pain are missing. Earlier pain disorder was defined as a condition with chronic pain associated with psychological factors, but it was replaced with somatic symptom disorder with predominant pain in Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in 2013. Recently clinical nosology is trending toward highlighting neurological pathology of chronic pain, discounting psychological or social factors in the pathogenesis of pain. This review article discusses components of the pain pathway, the component-based mechanisms of pain, central and peripheral sensitization, roles of chronic inflammation, and the involvement of tryptophan-kynurenine pathway metabolites, exploring participations of psychosocial and behavioral factors in central sensitization of diseases progressing into development of chronic pain, comorbid diseases that commonly present a symptom of chronic pain, and psychiatric disorders that manifest chronic pain without obvious actual or potential tissue damage.

Considering the relevance of the pathogenesis research of different liver diseases, in our study we investigated the possible activity of IL-23/IL-17 axis on the im-munohepatotoxicity of two etiologically different CLD. A total of patients with CHC infection, 19 with NASH and 20 healthy controls (CG) were recruited. After histological verification from liver tissue obtain by liver biopsy, patients with CHC were divided into two groups: CHC-NSF (F0/F1/F2)-non-significant fibrosis, 20 patients, and CHC-SF (F3/F4)-significant fibrosis/cirrhosis, 16 patients. All anthropometric, biochemical, immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed accordance to standard procedure. The plasma levels of IL-6, Il-17A and IL-23 were significantly higher in CHC-SF and NASH in compared with CG. Also, plasma levels of IL-23/IL-17A were significantly higher in NASH in compared to CHC-SF. In CHC-SF we had significantly lowest IL-10 level in compared with all three groups. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in compared with NASH. IN CHC-SF and NASH, IL17-A and IL-23 in liver tissue were significantly higher in compare to plasma levels. In conclusan, proinflammatory response of IL-23/17A axis is dominant in plasma and liver tissue in CHC with higher levels of liver fibrosis and in NASH patients.

Malassezia are lipid-dependent basidiomycetous yeast of the normal skin microbiome, although Malassezia DNA has been recently detected in other body sites and has been associated with cer-tain chronic human diseases. This new perspective raises many questions. Are these yeasts truly present in the investigated body site or were they contaminated by other body sites, adjacent or not? Does this DNA contamination come from living or dead yeast? If these yeasts are alive, do they belong to the resident mycobiota or are they transient colonizers which are not permanently established within these niches? And, finally, are these yeasts associated with certain chronic diseases or not? In an attempt to shed light on this knowledge gap, we critically re-viewed the 31 published studies focusing on the association of Malassezia spp. with chronic human diseases, including psoriasis, atopic dermatitis (AD), chronic rhinosinusitis (CRS), asthma, cystic fibrosis (CF), HIV infection, inflammatory bowel disease (IBD), colorectal cancer (CRC), and neurodegenerative diseases.

Background Sarcopenia is a state with progressive and generalized loss of skeletal muscle mass and strength. It is a serious complication occurring in chronic kidney disease (CKD) patients which increases morbidity and mortality rate. Sarcopenia is diagnosed when loss of both compartments - muscle strength and skeletal muscle quality or quantity are present. However, there are still numerous patients, also with CKD, diagnosed as pre-sarcopenic individuals with low muscle strength and normal skeletal muscle quality or quantity and conversely, with correct muscle strength and decreased skeletal muscle mass, who are prone to develop sarcopenia in future life. It is crucial to examine numerous variables possibly associated with changes of skeletal muscle mass and muscle strength in terms of preventing the development of sarcopenia. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in advanced stages of CKD. Methods The study sample consisted of 84 non-dialysis dependent patients of both sexes (including 45.2% of women) with eGFR < 45 ml/min/1.73m2: 26.2% with eGFR 30-44 mL/min/1.73 m2, 65.5% with eGFR 15-29 mL/min/1.73 m2 and 8.3% with eGFR < 15 mL/min/1.73 m2. Muscle strength was estimated by measuring hand grip strength (HGS) with the use of handheld hydraulic dynamometer. Muscle quantity was measured by bioimpedance spectroscopy using Body Composition Monitor. Appendicular skeletal muscle mass (ASM) was calculated according to Lin’s formula. Serum creatinine, urea, uric acid and albumin were measured. Results In bivariate analysis we found that ASM significantly and positively correlated with anthropometric variables such as body mass (r=0.903, p

One of the most common complications of neurogenic bladder secondary to spinal cord injury (SCI) is urinary incontinence, possibly related to bladder-emptying methods and changes in quality of life. This study aimed to identify the occurrence of this complication in adults with SCI and analyze its relationship with bladder-emptying methods, satisfaction, and lifestyle. This is a quantitative, exploratory, cross-sectional study. The variables were collected using the Bowel and Bladder Treatment Index during a telephone interview with 290 participants from February to November 2021. According to the results, 70% of the participants were male and 74.1% performed clean intermediate catheterization (CIC) as the main bladder-emptying method. Moreover, 55.6% were considered incontinent in the last year. Emptying by normal urination and bladder reflex triggering had a statistically significant relationship with urinary incontinence. A statistical association was observed between all the variables of satisfaction and lifestyle with urinary incontinence. Although CIC reduced urine leakage, a considerable number of participants still presented with frequent urine leakage. Urinary incontinence negatively altered satisfaction with the bladder-emptying method, effectiveness of bladder management, quality of life, and personal and social relationships.

Background: Initial phases of molecular and cellular maladaptive bone response at early CKD remain mostly unknown. Methods: We induced mild CKD in SHRs by either arterial hypertension lasting six months (sham-operated rats, SO6) or in its’ combination with 3/4 nephrectomy lasting two and six months (Nx2 and Nx6, correspondently). Sham operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. We measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact PTH and FGF23, Klotho, dickkopf-1, sclerostin. And assessed bone response by static histomorphometric indices and gene expression profiles. Results: Mild CKD groups had no increase in renal Pi excretion, FGF23 and PTH levels. Serum Pi, dickkopf-1, and sclerostin were higher in Nx6. Decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast number. The decline in eroded perimeter was only apparent in Nx6. Significant downregulation of genes related to Pi transport, MAPK, WNT, and BMP signaling accompanied histological alterations in Nx2 and Nx6. Conclusions: We found an association of mild CKD with histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.

Neutrophil elastase (NE) is taken up by macrophages, retains intracellular protease activity and induces a pro-inflammatory phenotype. However, the mechanism of NE-induced pro-inflammatory polarization of macrophages is not well understood. We hypothesized that intracellular NE degrades histone deacetylases (HDAC) and Sirtuins, disrupting the balance of lysine acetylation and deacetylation, and resulting in nuclear to cytoplasmic translocation of a major alarmin, High Mobility Group Box 1 (HMGB1), a pro-inflammatory response in macrophages. Human blood monocytes were obtained from healthy donors, or from subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Monocytes were differentiated into blood monocyte derived macrophages (BMDM) in vitro. Human BMDM were exposed to NE or control vehicle and the abundance of HDACs and Sirtuins was determined by western blotting of total cell lysates or nuclear extracts, or determined by ELISA. HDAC, Sirtuin, and Histone acetyltransferase (HAT) activities were measured. NE degraded most HDACs and Sirtuin (Sirt)1, resulting in decreased HDAC and sirtuin activities, with minimal change in HAT activity. We then evaluated whether the NE-induced loss of Sirt activity or loss of HDAC activities would alter the cellular localization of HMGB1. NE-treatment or treatment with Trichostatin A (TSA), a global HDAC inhibitor, both increased HMGB1 translocation from the nucleus to the cytoplasm, consistent with HMGB1 activation. NE significantly degraded Class I and II HDAC family members and Sirt 1 which shifted BMDM to a pro-inflammatory phenotype.

Cadmium (Cd) is a metal with no nutritional or physiological value, but is found in most people because it is a contaminant in nearly all food types. The intestinal absorption rate determines the body burden of Cd because humans lack a physiologic mechanism for excretion of the metal. Most acquired Cd accumulates in the kidneys, in which the Cd content increases through age 50 but falls thereafter. The decline from maximal kidney content is probably due to release of Cd from injured tubular cells into urine and replacement of destroyed nephrons by scar tissue. Chronic kidney disease is diagnosed when the estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2, or when albuminuria is present. Albuminuria is defined as an albumin-to-creatinine ratio ≥ 30 mg/g creatinine in women or ≥ 20 mg/g creatinine in men that persists for at least 3 months. Generally, Cd-induced reductions in eGFR are not reversible, and Cd nephropathy may progress to end-stage kidney disease. There is no evidence that elimination of current environmental exposure can reverse Cd nephropathy, and no theoretical reason to believe that such a reversal is possible. This review provides an update of knowledge concerning CKD in population environmentally exposed to Cd. Special attention is devoted to mechanisms of Cd-induced albuminuria concurrently with eGFR reductions, and the difficult challenge of exposure guidelines sufficient to eliminate the risk of Cd-induced CKD is addressed.

After reviewing cancer theories, cancer treatment development histories, randomized clinical trial's performance, cancer treatment strategy, trial follow-up times, and conducting numerous simulations using existing data, the authors found: (1) medical treatments come with three to four lethal factors: treatment side-effects, emotional distress and chronic dress, lack of exercises or physical inactivity, and excessive nutrition in some cases; (2) clinical trial exaggerates the benefits of fast-acting treatments and underestimates the slow-delivering adverse side effects as a result of statistical averaging, interfering effects of personal lifestyle factors, and insufficient follow-up times; (3) the benefits of medical treatments are limited by chain comparison, where surgery sets up a negative standard relative to the best way for resolving cancer; (4) the strategy of destroying the tumor is unworkable; (5) medical treatments can turn natural cancer growth curve into approximately doubly exponential curve; (6) multiple factor non-medical measures are much more powerful than medical treatments in controlling cancer growth and metastasis rates; and (7) cancer early diagnosis and over treatments are bad strategies that have great adverse impacts on cancer patients. Based on huge increases in cancer growth rate constants, substantial of loss of organ functional capacity, and severe systemic aging-like cellular damages, the authors concluded that medical treatments promote cancer growth and metastasis rates and shorten patient lives in most cases, and the claimed benefits are caused by triple biases of clinical trials. The authors believe that the better strategy for ending the global cancer epidemic is abandoning clinical trails as the research model, changing caner treatment strategy from killing cancer cells to slowing down cancer growth rates by using multiple factors optimization approach in personalized medicine.

Cyanobacteria (blue-green algae) may rapidly propagate under favorable conditions, forming dense blooms. As water blooms deteriorate, blue-green algae can generate potent toxins, potentially harmful to companion animals, wildlife, and even humans. One widely recognized cyanobacterial toxin is microcystin. This algal toxin has been implicated in surface waters globally, increasing liver cancer and/or disease risk amongst those who depend on sources prone to microcystin contamination. Interestingly, no study looked at weather conditions when connecting liver health outcomes to freshwater cyanotoxins. The purpose of this study was to determine if climate was an important determinant of liver mortality and total microcystins at the ecological level. Secondary data was used to evaluate the proposed hypothesis. Environmental data (CDC WONDER) and toxin data (USEPA) were used in multivariate regression analysis. Mean daily sunlight and total microcystins were significant predictors of age-adjusted chronic liver disease and cirrhosis death rates. Mean annual precipitation and mean daily max temperature were non-significant predictors. This study demonstrated how microcystins in combination with climate may increase liver mortality. The results can prompt others to study environmental exposures of terminal liver diseases, guiding environmental health and the water industry of human survival needs.

Background. There is limited evidence on the relationship between chronic kidney disease (CKD) and frailty in older people in Vietnam. This study aimed to examine the prevalence of frailty and its impact on mortality in older patients with end-stage renal disease. Method. This is a prospective, observational study at two large Dialysis Centres in Vietnam from November 2020 to June 2021. Consecutive older patients diagnosed with end-stage renal disease and on dialysis were recruited. Participants’ frailty status was defined by the Clinical Frailty Scale (CFS). The study outcome was all-cause mortality at 6th month. Results. A total of 175 participants were recruited (mean age 72.4 years, 58.9% female). Using the cut-point of CFS ≥4, 87.4% of the participants were frail. Mortality at 6th month was 14.9%, 31.9% in participants with CFS ≥7, 12.8% in participants with CFS=6, 7.5% in participants with CFS from 4 to 5, and 4.5% in participants with CFS ≤3 (p=0.001). Cox regression analysis showed that compared to the non-frail participants, the probability of death over 6 months was nearly 2-fold higher in the mildly frail, 3-fold higher in the moderately frail, and 9-fold higher in the severely frail participants. Conclusion. This study demonstrated a very high prevalence of frailty in older patients with end-stage renal disease and dialysis and the significant impact of frailty severity on mortality. Healthcare providers should consider incorporating frailty screening into routine care for older patients with end-stage renal disease and dialysis.

There is evidence that chronic fatigue spectrum disorders (CFAS-D) including Myalgic Encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue with physiosomatic symptoms including when due to comorbid medical disease are characterized by neuroimmune and neuro-oxidative biomarkers. The present study was performed to delineate the protein-protein interaction (PPI) network of CFAS-D and to discover the pathways, molecular patterns and domains enriched in their PPI network. We performed network, enrichment and annotation analysis using differentially expressed proteins and metabolics, which we established in CFAS-D patients. PPI network analysis revealed that the backbone of the highly connective CFAS-D network comprises NFKB1, CTNNB1, ALB, peroxides, NOS2, TNF, and IL6, and that the network comprises interconnected immune-oxidative-nitrosative and Wnt/catenin subnetworks. MultiOmics enrichment analysis shows that the CFAS-D network is highly significantly associated with cellular (antioxidant) detoxification, hydrogen peroxide metabolic process, peroxidase and oxidoreductase activity, IL10 anti-inflammatory signaling, and neurodegenerative, canonical Wnt, the catenin complex, cadherin domains, cell-cell junctions and TLR2/4 pathways; and the transcription factors NF-κB and RELA. The top-10 DOID annotations of the CFAS-D network include four intestinal, three immune system disorders, cancer and infectious disease. Custom GO term annotation analysis revealed that the CFAS-D network is associated with a response to a toxic substance, lipopolysaccharides, bacterium or virus. In conclusion, CFAS-D may be triggered by a variety of stimuli and their effects are mediated by aberrations in the cross-talks between redox, NF-κB, and Wnt/catenin signaling pathways leading to dysfunctions in multicellular organismal homeostatic processes.

Natural cycles underpin the very stuff of life. In this commentary we consider unnatural cycles: that is, anthropogenic activities which have a circularity, but whose nature is to have a detrimental effect on human health, exacerbating existing problems. Natural cycles have feedback loops, some of which have recently come to light, with an understanding that everything is connected in some way. In health, feedback loops are imperative in homeostatic mechanisms. However, in the unnatural cycle the feedback loops serve to reinforce (and in some cases amplify) negative problems. We offer a commentary on an unnatural cycle moving from air quality to lung function and back to air quality; we call this the lung disease unnatural cycle. We suggest where links occur, and where wider consideration of interactions between various disciplines can lead to breaking this unnatural (or vicious) cycle, changing it to a healthy cycle where individual health can be improved, along with better global scale outcomes. We suggest that many activities within this unnatural cycle occur within silos. However, the improved cycle incorporates joint activities at geological, health, and financial levels, to the mutual benefit of all, breaking the unnatural cycle, and improving health, life and financial costs.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable disease. The first PREM (Patient Reported Outcome Measure) type questionnaire that has been dedicated to asses experience of care in COPD is the PREM-C9. Aim: To create a Polish version of the PREM-C9 and determine its the psychometric characteristics. Methods: The validation procedure involved forward and back translation and included 42 COPD patients. The psychometric properties were assessed using Cronbach's alpha, Bartlett's test, Kaiser-Meyer-Olkin and Spearman correlation coefficient. The validity of the questionnaire was assessed using Principal Component Analysis for the extracted principal components. The validity of the factor analysis was demonstrated by the Bartlett's sphericity test and the Kaiser-Meyer-Olkin (KMO). Factor analysis was performed using the Oblimin and Varimax rotation. The reliability of the questionnaire was assessed using the Cronbach's alpha. Results: The Polish version of the PREM-C9 questionnaire met all validation criteria: face, translation, psychometric, functional and reconstruction equivalence. The Spearman correlation results between Polish PREM-C9&amp;CAT: rho= 0,44, p=0,003539; HADS-Anxiety: rho= 0.370864, p=0,015612, HADS-Depression: rho= 0,387405, p=0,011253. Conclusion: The developed Polish PREM-C9 questionnaire is a reliable and valid tool that assesses Polish COPD patients' experiences of their disease and the care they receive.

Chronic heat stress (CHS) has been exerting great pressure on the poultry industry due to the global warming. CHS-induced negative impacts deeply change the physiology, metabolism, egg production and meat quality of ducks. To reduce the increasing economic loss, different environmental strategies have been adopted. Here, we comprehensively compared three rearing modes for Cherry-Valley ducks (CVds) mainly by changing the environmental temperature. Plus, the transcriptome analysis and physiological anatomy were implied to investigate the underlying molecular biology and pneumonocyte dynamics. It turns out that the CVds affected by CHS have poor growth performance and bad carcass traits. In addition, the irreversible damage caused by CHS in the lung tissue of CVds was observed. Furthermore, several potential genes related to CHS have been found, such as HSPA8, IGF1, FGFR1, ACSL3, ACSL6, NR1H3 and GAPDH. This study strongly indicates the severe injury of CHS from the high-temperature environment and points out one of the adopting directions for duck rearing.