Chronic Myeloid Leukemia (CML) is one of the most commonly found types of myeloproliferative neoplasms, characterized by increased proliferation of granulocytic cells without losing their differentiation ability. Imatinib, a Tyrosine Kinase Inhibitor (TKI), can be effectively used as therapy for CML. However, imatinib can affect bone turnover, thus having clinical implications on the bones of CML patients undergoing long-term imatinib therapy. However, parameters that can accurately describe the bone condition in CML patients receiving imatinib still need further study. A combination of imaging techniques such as Bone Mineral Density (BMD) and bone turnover activity markers such as C-terminal telopeptide of type I collagen (CTX-1) and Osteocalcin has the potential to be used as monitoring parameters for bone density abnormalities in CML patients receiving imatinib. This article explains the rationale for using BMD, CTX-1, and Osteocalcin as monitoring parameters of bone remodeling in CML patients receiving imatinib. First, the physiological process of bone turnover will be explained. Then, we describe the role of tyrosine kinase in bone metabolism. Next, the impact of imatinib on BMD, CTX-1, and Osteocalcin will be explained. In conclusion, the assessment of bone health of CML patients on Imatinib should include both BMD tests and bone turnover marker assays such as CTX-1 and Osteocalcin.

This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) its impact on quality of life (QoL) and chronic fatigue in adult seven years after the 2014-2015 CHIKV outbreak in Piedecuesta, Colombia. We evaluated 78 adults (median age: 30 years, IQR: 21.0; women 60.3%) with confirmed CHIKV infection. In 2022, participants underwent a GALS examination and completed surveys on disability, stiffness, health status, and fatigue. A rheumatologist evaluated patients who reported arthralgia, morning stiffness, and abnormal GALS examination. Chronic fatigue was defined as fatigue persisting for over six months. Seven years after infection, 14.1% of participants were classified as pCHIK-CR cases, 41.0% as having non-inflammatory pain likely degenerative (NIP-LD), and 44.9% without rheumatic disease (Wo-RM). Patients with pCHIK-CR and NIP-LD exhibited significantly worse QoL compared to Wo-RM cases. Chronic fatigue prevalence increased from 8.6% in Wo-RM patients to 25.0% in NIP-LD and 54.6% in pCHIK-CR cases. This study implemented a comprehensive clinical as-sessment to objectively estimate and characterize the incidence of chronic rheumatological disease attributed to CHIKV infection. One in seven cases with CHIKV infection develops pCHIK-CR, which impacts both QoL and chronic fatigue. This study contributes to understanding the burden of these arboviruses in the medium term.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today we are talking about a new paradigm - cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies.

Myalgic Encephalomyelitis (ME), sometimes called Chronic Fatigue Syndrome (CFS), is a complex, debilitating condition characterised by symptoms such as profound fatigue, autonomic dysfunction, gastrointestinal problems, unrefreshing sleep, cognitive problems, exercise intolerance and post-exertional malaise (PEM) (a worsening of symptoms after mild physical or mental effort). The pathophysiology of ME remains poorly understood. This paper proposes a novel hypothesis centred on norepinephrine dysregulation and insulin signaling as the underlying mechanisms contributing to distinct subtypes of ME. I hypothesise that ME can be categorised into three subtypes based on variations in norepinephrine transport and insulin signaling: ME1, ME2, and ME3. In ME1, a higher than normal rate of insulin secretion during the first phase insulin response and/or hypersensitive insulin receptors leads to reduced neuronal norepinephrine reuptake, resulting in elevated extracellular norepinephrine and subsequent down-regulation of beta-2 adrenergic receptors. ME2 is characterised by prolonged insulin release and insulin resistance, which may contribute to the development of postural orthostatic tachycardia syndrome (POTS) and microclot formation. ME3 is marked by reduced norepinephrine synthesis and a resultant deficiency of norepinephrine within neurons. All three subtypes involve a deficiency of norepinephrine inside the noradrenergic neuron which is worsened by physical and mental exertion. There are many similarities between ME and Long COVID. Both have their onset after a virus and have a similar symptom profile, as well as having the same co-occurring conditions such as mast cell activation and POTS. It is quite possible that a subset of Long COVID patients have ME, and so I will be referring to both ME and Long COVID research papers throughout this hypothesis paper. This hypothesis integrates genetic, metabolic, and neuroendocrine data to delineate these subtypes and suggests tailored diagnostic and therapeutic approaches for each. This hypothesis aims to guide future research into the distinct pathophysiological mechanisms of ME and enhance understanding and management of this debilitating condition.

Ribavirin and its analogues exhibit an in vitro antiproliferative effect in cancer cells. In this work we studied the biological activities of a number of oxymethyl derivatives of ribavirin’s aglycon – 1,2,4-triazole-3-carboxamide. Oxymethyl derivatives of 1,2,4-triazole-3-carboxamide with substitu-tions at the fifth or first position of the triazole ring, were synthesized and their antiproliferative and antimicrobial effects were assessed. For both series the presence of an antiproliferative effect was inves-tigated and in the case of 1-oxymethyl derivatives was shown an antimicrobial potential against a Gram-positive bacteria Micrococcus luteus and Gram-negative bacterium Pseudomonas aeruginosa. The obtained results showed that the n-decyloxymethyl derivatives induced leukemia cell death at low mi-cromolar concentrations. We confirmed that n-decyloxymethyl derivatives of ribavirin inhibited cell cy-cle progression and induced accumulation of leukemia cells in subG1-phase. The molecular docking results suggest that oxymethyl derivatives may act by inhibiting translation initiation due to interfering with eIF4E assembly. The outcome results relived that active derivatives (1- or 5-n-decyloxymethyl-1,2,4-triazole-3-carboxamides) can be considered as a lead compound for anti-cancer treatments.

Mesenchymal Stem Cells (MSCs) secretions, usually containing growth factors, cytokines, and chemokines, have improved wound healing via a paracrine mechanism. This makes them particularly valuable as potential cell therapeutics. Similarly, wound healing is mainly regulated via paracrine signaling of growth factors, cytokines, and chemokines. Chronic wound healing has prolonged inflammatory, proliferative, or remodeling phases, resulting in tissue fibrosis and non-healing ulcers. The growth factors, cytokines, and chemokines secreted by MSCs can be applied to wounds by transplanting cells or using the secretome/conditioned medium (CM) of MSCs, which contains these secreted bioactive molecules. For their success in increasing the wound healing rate, MSCs offer a promising option for treating chronic wounds. This review provides a concise summary of current knowledge of the biological properties of MSCs and describes the use of MSCs for wound healing. In particular, the scope of this review focuses on the role of MSCs in wound healing by increasing wound healing rate with the secretion of growth factors, cytokines, and chemokines. In addition, the function and type of MSCs also have been discussed.

Introduction: Migraine is a highly disabling neurological condition with substantial variability in its clinical presentation. This study aimed to explore the influence of familial transmission of comorbid medical conditions on the phenotype of chronic and episodic migraine. Methods: A total of 500 patients who presented to a private tertiary headache clinic were categorized into episodic and chronic migraine groups based on the International Classification of Headache Disorders-3 criteria. Data on demographics, clinical symptoms, and familial medical history were collected. Statistical analysis included chi-square and independent sample t-tests to evaluate the impact of familial comorbidities on migraine phenotypes. Results: Of the participants, 63% were diagnosed with episodic migraine and 37% with chronic migraine. Significant findings included higher rates of medication overuse (63.31%) and allodynia (58.82%) in patients with chronic migraine. Notably, patients with a maternal history of hypercholesterolemia showed a higher prevalence of chronic migraine (78.6%), whereas those with both parents affected tended to have episodic migraine. Educational levels are inversely correlated with the prevalence of chronic migraine, suggesting a socioeconomic influence on migraine chronification. Discussion: This study highlights significant associations between familial health conditions and migraine phenotypes. The findings suggest that the maternal transmission of comorbidities, particularly hypercholesterolemia, may influence the development of chronic migraine. These results underscore the importance of considering familial medical history in the management and understanding of migraine.

Chagas disease, caused by Trypanosoma cruzi, leads to severe complications in 30% of infected individuals, including acute myocarditis and chronic fibrosing cardiomyopathy. Despite the significant burden of the disease, there is currently no licensed vaccine available to prevent it. This study aimed to evaluate the mucosal and systemic immunogenicity as well as the prophylactic efficacy of a mucosal vaccine and its impact on both acute and chronic cardiomyopathy. The results showed that nasal administration of Trans-sialidase (TS) plus c-di-AMP (TS+A). TS+A vaccine elicited NALT expression of IFN-γ, IL-17a, and IL-4 mRNA, and nasal-specific IgA production. Ex vivo challenge with TS also triggered enhanced proliferation of lymphocyte from the NALT, sentinel cervical lymph node and spleen. TS+A immunization increased plasma levels of Th1/Th2/Th17 cytokines and an evident cellular response to judge enhanced delayed-type hypersensitivity responses following TS footpad challenge. After oral infection, TS+A-vaccinated mice showed significantly reduced parasitemia and parasite load in heart, muscle and intestine, while markers of hepatic and muscle damage as well as clinical manifestations of acute infection are strongly diminished. TS+A also attenuated acute myocarditis and heart expression of inflammatory markers. The protection conferred by TS+A extended into the chronic phase, where it resulted in a clear reduction in chronic myocarditis, fibrosis, and functional electrocardiographic abnormalities, associated with decreased expression of the pro-fibrotic TGF-β. These results revealed that it is possible to develop a mucosal vaccine against T. cruzi based on TS and c-di-AMP, capable to reduce the development of Chagas cardiomyopathy, the hallmark of Chagas disease.

Introduction: Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are susceptible to viral infections, including varicella-zoster virus (VZV) reactivation due to both disease-related and treatment-induced immunosuppression. The recombinant adjuvanted herpes zoster vaccine (RZV) has shown high efficacy in immunocompetent adults, but immunogenicity data in CLL and MM patients is limited. This study evaluates the immunogenicity and safety of RZV in this population. Methods: Patients with CLL and MM vaccinated with RZV (administered in two doses at least one month apart) were included in the study. Pre- and post-vaccination anti-VZV IgM and IgG antibody levels were measured to assess immunogenicity, and adverse events (AEs) were captured for safety evaluation. Results: Seventy-eight patients received both vaccine doses, and 71 had post-vaccination samples. Most of the patients were IgM seronegative and IgG seropositive before vaccination. Pre-vaccination IgG levels were higher in CLL compared to MM patients (p=0.001), while post-vaccination IgG levels significantly increased in both CLL (p<0.0001) and MM (p<0.0001) patients. In actively treated CLL patients, the pre-vaccination IgG levels were significantly lower than in not actively treated patients (p=0.002). Post-vaccination IgG levels were lower in MM patients receiving antiviral prophylaxis concurrently with the vaccination (p=0.013). AEs were reported in 49.4% after the first dose and 48.7% after the second dose, mostly mild (local or low-grade systemic). One case of immune thrombocytopenia was noted. Conclusion: RZV demonstrated strong immunogenicity and acceptable safety in CLL and MM patients, significantly boosting IgG levels, even in actively treated or heavily pretreated patients.

This literature review focusses on diagnostics of Equine Asthma (EA), possible influencing factors on diagnostic techniques and latest developments in diagnosing horses during EA remission or in case of subclinical disease. Routine EA diagnostics include clinical examination of the respiratory system including percussion and auscultation, clinical pathology including white blood cells and arterial blood gas analysis, bronchoscopy to evaluate the amount and viscosity of respiratory secretion, bronchoalveolar lavage and cytology of tracheal aspirates (TA) and bronchoalveolar lavage fluid (BALF). Grading of EA severity and inflammatory subtype is based on BALF cy-tology, while TA cytology helps to rule out previous bacterial infections. Different factors have an impact on the airways regarding structure of the epithelium, cytology and inflammatory markers possibly influencing the diagnosis of EA. Short-term exercise increases the total cell count and inflammatory mediators in BALF of men, asymptomatic horses and other species. Further factors involve cold or chlorinated air, long-term training effects and the co-incidence of further respir-atory disease, in particular exercise-induced pulmonary hemorrhage. As BALF cytology may be unremarkable during EA remission and low-grade disease, exercise and other factors stressing the bronchial epithelium may help to diagnose these patients.

Anxiety-based cognitive distortions pertaining to somatic perception (ABCD-SP) - primarily catastrophizing, fear avoidance and kinesiophobia- have been repeatedly linked to worsening chronic, non-cancer pain (CNCP) outcomes of increased disability, amplified pain, ineffective opioid use, and opioid misuse. Several studies have suggested that treating ABCD-SP can improve pain outcomes, yet identification and targeting of ABCD-SP is not part of the standard medical pain assessment and treatment plan. Utilizing a narrative review of proposed mechanisms, published patient perspectives, and study correlates connecting these cognitive distortions with CNCP outcomes, a better practice approach to the delivery of standard medical CNCP care can be deduced and formulated into a Belief and Behavior Action Plan (BBAP) for medical clinicians treating CNCP to implement into initial and maintenance care planning. These recommendations require relatively few resources to implement and have the potential to disseminate more effective CNCP treatment on a large scale now, and into the new frontier of cognitive computing within medicine.

No consensus exists on whether acute aerobic exercise alters the glomerular filtration rate in older adults. Objective: To assess the immediate effects of three aerobic exercise intensities on the estimated glomerular filtration rate (eGFR) in healthy, sedentary older adults. Methods: Eighteen healthy, sedentary older adults (12 men and eight women) voluntarily participated in the study. The participants underwent three standardized aerobic exercise tests (100%, 80%, and 60% of the maximal heart rate) on a bicycle ergometer. Blood samples were collected to determine cholesterol, triacylglycerol, glucose, serum creatinine (Cr), Cystatin C (CysC) concentrations, and eGFR. Results: eGFR and serum concentrations of Cr and CysC were not modified at any exercise intensity. There was a negative correlation between blood total cholesterol vs. eGFR (R= -0.512, R= -0.582, R= -0.531; p &lt;0.05) at rest, 60%, and 100% of the maximal heart rate, respectively. Besides, a negative correlation existed between age vs. eGFR at 60% of the maximal heart rate (R= -0.516; p &lt;0.05). Conclusion: Short-time aerobic exercise of low, moderate, and vigorous intensity did not significantly affect eGFR and is considered safe for kidney function in healthy, sedentary older adults.

Chronic inflammation alters lipoprotein metabolism and causes changes in serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, and immunomodulator. However, unlike in people with inflammatory bowel disease, scarce information is available in dogs with protein-losing enteropathy secondary to chronic inflammatory enteropathy (iPLE). The first aim was to describe and compare the lipid profile, CRP concentrations and PON-1 activity in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data, and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides, and lipoprotein classes obtained by electrophoretic separation. There was a significant difference of all serum analytes between iPLE and healthy dogs. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. Some lipoprotein classes correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. Lipoproteins, CRP and PON-1 activity are altered in dogs with iPLE. Results need to be confirmed in further studies.

Background/Objectives: Habituation and sensitization are opposite phenomena that play a role in the pathophysiology of episodic migraine and its progression to chronic migraine (CM). There have been just a few studies that have investigated these phenomena in patients with medication overuse headache (MOH) in comparison to those with chronic migraine (CM) and healthy controls (HCs), and the findings have been inconsistent. Methods: We measured and examined visual evoked potentials (VEPs) in 81 patients with MOH and 24 patients with CM, as well as 24 HCs. The VEPs were used to assess sensitization by analyzing the amplitude of the first block (100 sweeps), and to evaluate habituation by measuring the amplitude response decrement after 6 blocks. We further examined patients diagnosed with MOH based on their acute medication type and after a 3-week acute medication withdrawal program. Results: There were no significant differences between groups in terms of the first N1-P1 VEP amplitude block and its habituation. It was found that patients with MOH had a greater drop in the amplitude of the VEP P1-N2 complex after repeated stimulation than patients with CM or HC. The VEPs parameters showed no significant differences based on the specific overused drug and after a 3-week acute medication off. Conclusions: We propose that the results obtained in patients with MOH indicate an abnormal activation of inhibitory circuits in the parieto-occipital region in response to repeated modulatory stimuli.

Objective: To develop and validate the short version of the JAEN Scale for use in women with Fibromyalgia Syndrome (FMS) to make the balance disorder measurement process more efficient. Methods: A Cross-sectional observational validation study was conducted. Fifty-six women with FMS and 44 healthy control were included. Certain items of the original tool were selected with the aim of 1) Improving internal consistency by reducing item redundancy 2) Obtaining a diagnostic capacity with an Area Under the ROC Curve (AUC) greater than 0.70 for discriminating FMS patients and fallers. The internal consistency, factorial validity, concurrent validity and diagnostic capacity of the new tool were analyzed. Results: Factorial analysis showed a two-factor structure that explained 72% of variance. Cronbach alpha coefficients of 0.904 were obtained for the total score of the JAEN-10 items. Concurrent validity analysis showed strong correlations of the JAEN-10 with other instruments that measured quality of life, postural balance or disability related to dizziness. The score of the JAEN-10 items showed an AUC of 0.858 with a sensitivity of 64.29 and a specificity of 95.45 for discriminating between FMS and healthy controls, and an AUC of 0.835 with a sensitivity of 90.48 and a specificity of 67.24 for discriminating between fallers and non-fallers.; Conclusions: The 10-item JAEN scale is a valid instrument for discriminating between subjects with or without FMS and between fallers and non-fallers. Its psychometric properties are good and similar to those of the original 20-item scale. Moreover, it is quicker to complete, which may be relevant in subjects with a tendency to experience fatigue.

Background/Objectives: The anesthetic block of the sensory branches of the superficial cervical plexus (SCP) renders a specific area of the face, head, and anterior neck insensible and painless. Chronic pain in these areas can be difficult to diagnose and treat. In this report, we briefly review the existing evidence on the topic of the SCP block (SCPB) to set the context for our research. We then share our own clinical experience with the SCPB for managing chronic pain syndromes from both cancerous and non-cancerous etiologies. Methods: We first performed a comprehensive literature search and narrative review of clinical cases and studies that utilized the SCPB as an analgesic technique. We then conducted a retrospective case series of all patients who received a SCPB at our pain clinic since 2020. Results: Our literature review found only a few cases reported, with most of them focusing on acute painful emergencies and perioperative pain syndromes and only very few addressing chronic pain. In our pain clinic, 14 patients received one or more SCPBs for chronic pain management. In 42% of these cases, the pain was related to cancer. The most common areas of pain corresponded to the regions supplied by the transverse cervical and greater auricular nerves. The procedures were uneventful in all cases, and patients rated them as effective and worthwhile 71% of the time. Conclusions: Despite the lack of high-quality studies on SCPBs in pain management, the authors’ experience suggests that it is a valid minimally invasive alternative for managing chronic face, head and neck pain.

Objectives: Chronic pulmonary aspergillosis (CPA) is a fungal lung infection characterized by slowly progressive destruction of the lung parenchyma and has four main subtypes. The objective of this work was to evaluate the epidemiology of CPA in our area and evaluate the involvement of the different subtypes in mortality. Methods: This was a descriptive longitudinal retrospective study developed in three tertiary hospitals in Spain. Among all patients admitted with a pulmonary aspergillosis diagnosis, we selected those who fulfilled the criteria for chronic aspergillosis according to the criteria of Denning, excluding those with a haematological disorder. Results: Among 409 inpatients recorded as having pulmonary aspergillosis infection, only 76 (18.5%) fulfilled the criteria for CPA, with an estimated incidence of 0.67 cases/100,000 inhabitants/year. The subtypes detected were subacute invasive aspergillosis (SAIA) in 33 (43.4%) patients, simple aspergilloma (SA) in 25 (32.9%) patients, cavitary chronic aspergillosis (CCPA) in 13 (17.1%) patients and chronic fibrosant (CFAP) in 5 (6.5%) patients. The overall three-month mortality was 23%, which was higher in SAIA patients. The predictors of early mortality were age >65 years (OR 3.0 CI 95 1.0–9.5 0.043) and SAIA subtype vs. other subtypes (OR 3.1 CI 95 1.0–9.5 p 0.042). Conclusions: The incidence rate estimated was inferior to that previously reported. Three-month mortality in patients with CPA was high, with older age and SAIA subtype being the variable independent predictors of a worse prognosis.

Cardiovascular (CV) morbidity and mortality are markedly increased in non-dialysis patients with chronic kidney disease (CKD). Thus, the precise management of CV risk factors involved in CKD is crucial to improving outcomes. Serum phosphate (Pi) and FGF-23 levels have been linked with a higher risk of CV events in CKD. However, the exact thresholds of Pi and FGF-23, at which the risk of adverse events increases, remain unknown. We evaluated the expression of intact FGF-23 (iFGF-23) and Pi in a non-dialysis CKD patient population (n=82; 42M:40F; median age 61 years) and investigated their association with CV and renal outcomes, in a 5-year follow-up period. At baseline, the median estimated glomerular filtration rate (eGFR), iFGF-23, and Pi were 45 ml/min/1.73m² (IQ 26.6-73.1), 69.9 µg/ml (IQ 33-117) and 3.4 mg/dL (IQ 3.3-3.9), respectively. Univariate analysis showed a strong association of both iFGF-23 and Pi with age, Charlson Comorbidity Index, hypertension, and diabetes. In addition, iFGF-23 and Pi were both associated with the composite outcome (major CV and cerebrovascular events – MACCEs, hospitalizations, and all-cause mortality) during follow-up. Moreover, Pi was independently associated with all-cause mortality during follow-up. The segmentation of the population in terciles, according to Pi (<3mg/dL; 3-3.6 mg/dL; ≥3.7 mg/dL) within reference serum levels, showed a distribution of the fatality of 0%, 20% and 80% (p =0.034), respectively. Our results reinforce the association of both iFGF-23 and Pi with composite CV outcomes in non-dialysis CKD patients and further suggest that Pi, within current reference levels, may behave as an independent risk factor for mortality in this population. It is suggested that a reassessment of Pi reference levels for early therapeutic intervention in this population may be justified.

Accumulating psychedelic research has demonstrated potential for improving mental health and wellbeing, yet studies in the context of eating disorders (EDs) are limited. This study explores the subjective effects of psychedelic experiences to gain insight into the benefits and risks for people with EDs. Semi-structured interviews were conducted with 11 eligible adults. A purposive sample of eight adults aged 25-54 (M =  36.9) with chronic EDs, diagnosed (N = 7) and undiagnosed (N = 1) were thematically analysed. Reports of cessation or reduction of ED symptoms were unanimous, with two participants reporting recovery, attributed to psychedelic use. Thematic analysis resulted in two superordinate themes, each comprising three subordinate themes. The first superordinate theme, ‘Exploring’ via the ‘gateway to healing’, illustrates mental, emotional, and transcendental elements of psychedelic experiences. The second superordinate theme, ‘Transformation’ and being ‘able to do the work’, illustrates cognitive and behavioural outcomes, with retrospective safety perceptions. This research presents an account representative of the ED population for the therapeutic potential for psychedelic experiences to reduce symptoms and improve wellbeing. Findings provide evidence of therapeutic feasibility to support larger scale research, emphasising the therapeutic use of psychedelics as a potentially promising avenue for chronic and treatment resistant EDs.

Background/Objectives: interpretation of evidence on de-escalation of triple therapy with with-drawal of inhaled corticosteroids (ICS) to dual bronchodilator therapy with a long-acting musca-rinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstruc-tive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discon-tinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: we searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov and CENTRAL for RCTs and observational studies from inception to March 22, 2024, investigating the effect of triple therapy de-escalation with withdrawal of ICS to dual therapy on the risk of COPD exacerbation, pneumonia and lung function. This study was registered with PROSPERO, CRD42024527942. Results: 3335 studies were screened; three RCTs and three real-world non-interventional studies were ultimately identified as eligible. Analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80 to 1.15; I²=77%) for ICS withdrawal compared with triple therapy continuation. Analysis according eosinophil levels showed that COPD subjects with ≥300 eosino-phils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated from ICS/LABA/LAMA to LABA/LAMA (pooled HR: 1.35, 95% CI 1.00-1.82; I2: 56%). The ICS withdrawal in favour of LABA/LAMA did not significantly affect the risk of mortality and pneumonia. Conclusions: the main findings of this meta-analysis are consistent with current recommendations and suggest that the use of eosinophil counts may be of help in guiding maintenance therapy. However, methodological heterogeneity between the included studies is evident.

Sleep disturbances and chronic pain are prevalent and interrelated conditions that significantly impact individuals' quality of life. Understanding the intricate dynamics between sleep and pain is crucial for developing effective treatments that enhance the well-being of affected individuals and reduce the economic burden of these debilitating conditions. This narrative review examines the complex relationship between sleep disturbances and chronic pain. We describe the prevalence and types of sleep disturbances and sleep disorders in chronic pain patients. Posteriorly we critically review the clinical and experimental evidence investigating the relationship between sleep disturbances and chronic pain aiming to clarify the impact of chronic pain on sleep and, conversely, the impact of sleep disturbances on pain perception. We conclude that a bidirectional relationship between chronic pain and sleep disturbances is almost a consensus in the literature, however, the strength of each direction of the association is less clear. As of now, the literature suggests that sleep impairment is a stronger predictor of pain than pain is a predictor of sleep impairment. Additionally, addressing sleep disturbances in chronic pain patients is crucial, as poor sleep has been linked to higher levels of disability, depression, and pain-related catastrophizing.

Background/Objectives: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease (CVD). Carotid intima-media thickness (C-IMT) is a non-invasive marker of atherosclerosis. Low omega-3 polyunsaturated fatty acids (PUFA) intake and vitamin D deficiency are potential cardiometabolic risk factors in patients with CKD. The aim of this study was to evaluate dietary intake and status of omega-3 PUFA and vitamin D in pre-dialysis and hemodialysis patients and to examine the link of dietary α-linolenic acid (ALA) and fish consumption with blood pressure and C-IMT in CKD patients. Methods: All 77 selected patients (36 pre-dialysis, 41 on hemodialysis) underwent standardized clinical, nutritional, and laboratory assessments. Repeated 24-hour recalls were performed to assess dietary intake. The fatty acid profile was determined by gas-liquid chromatography. Results: Inadequate vitamin D intake and vitamin D status were found in 95% of patients. PUFAs profiles did not differ between hemodialysis and pre-dialysis participants. Dietary intake of ALA was negatively correlated with systolic blood pressure (SBP) (p=0.007), C-IMT (p=0.002), serum CRP (p=0.044), iPTH (p=0.01) and 25(OH)D3 (p=0.006). ALA intake of more than 0.23 g/daily was associated with lower SBP (p=0.001), serum 25(OH)D3 (p=0.004), and C-IMT (p=0.002). Conclusions: This study contributes to a better understanding of the relationship between dietary ALA intake and C-IMT in CKD. The results of this study could emphasize the significant role of the high prevalence of vitamin D deficiency and inadequate omega-3 PUFA intake and status considering CVD health in CKD patients.

Our previous study demonstrated that the acute high-dose rate (3.3 Gy/minute) gamma irradiation of postnatal day 3 (P3) mice with 5Gy induced depression and drastic neuropathological changes in the dentate gyrus of the hippocampus of the adult mice. The present study investigated the effects of chronic low-dose-rate (1.2mGy/h) gamma irradiation from P30 to P180 with a cumulative dose of 5Gy on animal behaviour, hippocampal cellular change, miRNA and mRNA expression in the hippocampus and blood in female mice. The radiation exposure did not significantly affect the animal's body weight and neuropsychiatric changes such as anxiety and depression examined by neurobehavioural tests including open field, light-dark box, elevated plus maze, tail suspension test and forced swim test. Immunohistochemical staining did not detect any obvious loss of mature and immature neurons (NeuN and DCX) or any inflammatory glial response (IBA1, GFAP, and PDGFR1). Nevertheless, r-H2AX foci in the stratum granulosum of the dentate gyrus were significantly increased, suggesting the chronic low dose rate irradiation induced persistent DNA damage foci in mice. miRNA sequencing and qRT-PCR indicated an increased expression of miR-448-3p and miR-361-5p, but decreased expression of miR-193a-3p in the mouse hippocampus. Meanwhile, mRNA sequencing and qRT-PCR showed a reduced expression of Ccn1, Fli1, Fosb, Ets1, Hs3st5, and Eif4ebp1, but enhanced expression of Cort, Foxh1, and Opalin. Database searching by miRDB and TargetScan predicted that FLI1 and HS3ST5 are the targets of miR-448-3p, and Eif4ebp2 is the target of miR-361-5p. miRNA/mRNA sequencing and qRT-PCR results in blood showed the increased expression of miR-6967-3p and the decreased expression of its target S1pr5. The interactions of these miRNAs and mRNAs may contribute to the chronic low dose rate radiation-induced persistent DNA damage.

Background. National surveys reported on variable prevalence of chronic kidney disease (CKD) due to differences in characteristics of population, design, equations used to estimate glomerular filtration rate (eGFR) and definitions. The EH-UH 2 survey is the first study evaluating CKD prevalence, characteristics and awareness in Croatia. Methods. This was a cross-sectional nationwide observational study designed to assess the prevalence and cardio-kidney-metabolic risk factors in Croatia which included 1765 randomly selected subjects. We estimated the prevalence of CKD by means of albumin-to-creatinine ratio (ACR) and eGFR (CKD EPI equation). Comorbidities, anthropometric and social factors related to the prevalence of CKD were analyzed, and CV risk profile was evaluated. Results. The weighted prevalence of CKD (any stage), CKD stage ≥ G3A A2, and CKD defined only as eGFR < 60 ml/min/1.73 m2 were estimated at 17.1%, 9.8% and 7.9%, respectively. The prevalence was higher in men than in women (11.8% vs. 7.9%; p 30 mg/g was 15.1%. Older age, male gender, diabetes, ePWV, and uric acid were independently associated with CKD prevalence. The awareness of CKD of 9.5%. Unaware were older with lower income, less educated, having more frequently diabetes, hypertension (less frequently controlled) and milder renal impairment. Conclusion. In Croatia, the estimated prevalence of CKD is high, being more frequently presented in men than in women. CKD patients have unfavorable CV risk profile. The awareness of CKD is very low reflecting poor health literacy in general population but also in health care workers.

Hepatitis B Virus (HBV) infection carries a significant health burden worldwide. It is a leading cause of acute and chronic liver disease resulting in cirrhosis and hepatocellular carcinoma (HCC). This virus affects millions globally, and despite several medical advancements, research, and efforts to develop curative treatment, the persistence of HBV in infected individuals by cccDNA and integration pose formidable challenges. This review aims to provide a broad-based overview of HBV persistence, integration and the implications for chronic infection and tumorigenesis. By considering these points, we bring forth insights into the advancement of therapies that aim to disrupt the chronicity of HBV infection and improve clinical outcomes.

Bioimpedance analysis (BIA) is a validated non-invasive technique already proven to be useful for the diagnosis, prognosis, and management of body fluids in subjects with heart failure (HF) and chronic kidney disease (CKD). Although BIA has been widely employed for research purposes, its clinical application is still not fully widespread. The aim of this review is to provide a comprehensive overview of the state of art of BIA utilization by analysing the clinical benefits, limitations, and the potential future developments in this clinically unexplored field.

This brief report investigates the potential correlation between manual labor and opioid addiction, focusing on contributing factors such as chronic pain, regular exercise, healthcare access, and housing stability. Although manual labor is associated with higher rates of work-related injuries and chronic pain, the review finds no strong, direct correlation between manual labor and increased opioid addiction rates. The relationship is complex and influenced by a range of socio-economic factors. The findings highlight the need for further research, particularly longitudinal studies, to explore these dynamics in depth and develop targeted interventions for at-risk populations.

Globally, 77\% of the elderly aged 65 and above suffer from multiple chronic ailments, according to recent research. However, several barriers within the healthcare system in the developing world hinder the adoption of home-based patient management. IoMT is beneficial for healthcare personnel, but its application raises security concerns, particularly in authentication. Several authentication techniques have been proposed which, however, lack a balance of security and usability. By analyzing the shortcomings of the existing authentication methods and the available sensors on smartphones, this paper proposes to explore the possibility of using a smartphone’s embedded sensors for elderly user identification process in IoMT. We proposed an adaptive authentication technique for the elderly patients using the MAPE-K$_{\text{HMT}}$ framework by developing an android application that takes as input, the user’s contextual information including device fingerprint, location, network, and user data to monitor the user and estimate the risk associated with a user using the Naïve Bayes algorithm. The risk score was then used as input to the rule-based module that assigned authenticators according to user age, health condition and available authenticators. The model demonstrated high accuracy in distinguishing between authorized and unauthorized access attempts and supported the usable security goal for the elderly users.

Esophageal cancer (EC) is one of the most common malignant tumors worldwide, and its two major types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) present a severe global public health problem with an increasing incidence and mortality. Established risk factors include smoking, alcohol consumption, and dietary habits, but recent research highlights the substantial role of oral microbiota in EC pathogenesis. This review explores the intricate relationship between microbiome and esophageal carcinogenesis, focusing on eight significant mechanisms: chronic inflammation, microbial dysbiosis, production of carcinogenic metabolites, direct interaction with epithelial cells, epigenetic modifications, interaction with gastroesophageal reflux disease (GERD), metabolic changes, and angiogenesis. Certain harmful bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are specifically implicated in sustaining irritation and tumor progression through pathways including NF-κB and NLRP3 inflammasome. Additionally, the review explores how microbial byproducts, including short-chain fatty acids (SCFAs) and reactive oxygen species (ROS), contribute to DNA harm and disease advancement. Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target microbiota-immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.

Background: The implementation of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has brought a significant improvement in the prognosis for CML patients and a decrease in the number of patients requiring allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, the impact of TKIs on allo-HCT outcomes have not been thoroughly explored. Objectives: The main endpoint of our research was to assess the impact of prior TKI treatment on acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD). Methods: In our retrospective analysis we included 240 patients treated between 1993 and 2013, and divided them into 3 groups according to the therapy administered prior to matched related or matched unrelated donor allo-HCT (imatinib group n=41, dasatinib/nilotinib group n=28, TKI naïve group n=171). Results: Both the cumulative incidence of aGvHD (p=0.044) and cGvHD (p&lt;0.001) in individuals receiving second generation TKIs (2G-TKIs) prior to allo-HCT compared to patients receiving no TKIs or imatinib (IMA) (40.7% vs 61.4% vs 70.7%, p=0.044; 25.0% vs 76.4% vs 51.2%, p&lt;0.001, respectively). In case of the 2G-TKI cohort, the number of low-grade aGvHD and cGvHD was significantly lower compared to the IMA and TKI-naïve groups (p=0.018, p=0.004; p&lt;0.001 versus TKI-naïve, respectively). In terms of 3-year overall survival (OS) there were no important variations between TKI-naïve, IMA and 2G-TKI (55% vs 49.9% vs 69.6%, p=0.740). Conclusions: The results of our study suggest that TKI treatment prior to allo-HCT may have protective impact on immune-mediated outcomes.

Introduction: Diagnosing and managing Borrelia miyamotoi disease (BMD) is challenging due to its symptom overlap with Lyme disease (LD) and the lack of reliable laboratory diagnostics for BMD. This case study demonstrates the use of phage-based PCR (phb-PCR) to identify B. miyamotoi in a patient who had been bitten by ticks. Case presentation: A female patient aged 46 presented with joint and muscle pain, myalgic encephalomyelitis/chronic fatigue syndrome, and cognitive impairment after multiple tick bites in Europe. The patient was assessed for LD at the National Reference Centre in Strasbourg using Enzyme-linked immunosorbent assay (ELISA) and immunoblot. Additional diagnostics involved screening for Bartonella and Anaplasma antibodies using indirect immunofluorescence, and tests for antinuclear antibodies to check for autoimmune conditions. All serological and immunological tests yielded negative results. However, the phb-PCR identified B. miyamotoi. Consequently, the patient received treatment for BMD with a regimen of intravenous ceftriaxone, oral azithromycin, and additional intravenous vitamin and mineral therapy. Post-treatment evaluations showed significant improvements in pain levels, cognitive abilities, and fatigue. Conclusion: This case highlights the importance of direct diagnostic methods like phb-PCR for identifying BMD when serological tests fail. Clinicians should consider B. miyamotoi testing for accurate and timely management of complex TBDs.

Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regula-tory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to en-tail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA-FOXP3high activated Treg (aTreg) subset differs, it is critical to analyse homeostatic sig-naling in Treg subsets. Therefore, in this study, by using conventional and imaging flow cytome-try, we monitored STAT5 signaling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and disease course during follow-up of 37 patients with CLL. aTreg percentage was significantly increased among CD4+ T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4+FOXP3+ T cells at the start of therapy was character-ized by more frequent episodes of severe infections during follow-up, suggesting that aTreg frac-tion could represent a possible marker of severe disease course with infectious complications. Augmented homeostatic STAT5 signaling could support aTreg expansion, as higher pSTAT5 lev-els were significantly corelated with increased aTreg frequency among CD4+FOXP3+ T cells during follow-up of patients on therapy as well as following SARS-CoV-2 antigen-specific stimulation in vitro.

Hamstring muscle (HM) flexibility is frequently compromised in people with chronic low back pain (CLBP), contributing to disability and leading to a less favorable recovery. In a previous article, we presented the results of a study on the immediate effect of passive HM stretching on flexibility in 90 people with CLBP. There was considerable variability in the changes after stretching. The objective of this supplementary analysis was to compare the clinical characteristics of individuals who experienced a significant improvement in flexibility with those who did not. We fixed a threshold of 7° to indicate an improvement in passive Straight Leg Raise (SLR) angle and differentiate between 'Responders' and 'Non-responders' to passive HM stretching. Only Body Mass Index differed between groups; it was significantly smaller in Responders (p=0.007). The majority of Non-responders experienced workplace accidents, but this was of marginal difference compared to Responders (p=0.056). Further studies should consider a broader clinical analysis with a larger sample size to understand which factors influence the HM stretching response in CLBP patients.

This study evaluated changes over time in skeletal muscle atrophy, expressions of skeletal muscle anabolic and catabolic genes, and mitochondrial activity by skeletal muscle type in an adenine-induced chronic kidney disease (CKD) model. A CKD model was successfully established by feeding male Wistar rats a 0.75% adenine diet for 4 weeks starting at 8 weeks of age. Control and CKD groups were sacrificed at 12 and 20 weeks of age. Back muscles were analyzed histologically, and succinate dehydrogenase (SDH) staining was performed to evaluate mitochondrial activity. Gene expressions of myogenic determination gene number 1 and myogenin as indicators of muscle anabolism, atrogin-1 and muscle RING-finger protein-1 (MuRF1) as indicators of muscle catabolism, and peroxisome proliferator-activated receptor-γ coactivator-1-α as a marker of mitochondrial biogenesis were assessed. Type I and type II muscle cross-sectional areas (CSAs) were decreased at 12 weeks, but type I muscle CSA recovered at 20 weeks. SDH staining was lower in CKD than control rats at 12 weeks, but no significant difference was observed at 20 weeks. Increased expressions of myogenin, atrogin-1, and MuRF-1 were observed only at 12 weeks, but no differences were observed at 20 weeks. The adenine-induced CKD rat model appears to show changes in muscle atrophy over time.

The immune system is central in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, developing a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyses the critical variables related to the safety, efficacy, and effectiveness of CHB treatments. HeberNasvac's experience is revisited to address the challenges and potentialities of therapeutic vaccines, as well as the current roadblocks in research and development, registration, and large-scale implementation.

Background/Objectives: The latest WHO classification underscores the importance of the complete blood count (CBC) and cell morphology assessment in diagnosing lymphoid neoplasms. This study evaluated the diagnostic role of Research Use Only (RUO) parameters from the BC-6800 Plus Mindray analyzer in differentiating cell chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and other lymphoproliferative disorders. Methods: CBCs were performed on 90 patients (66% male, median age 67 years) with pathological blood counts (ALL, n=14; CLL, n=47; other lymphoproliferative disorders, n=29) at Novara’s University Hospital. Univariable and multivariable logistic regression assessed the association of basic (WBC, Hb, RDW, NE#, LY#, MO#, PLT) and research cell parameters (NLR, NMR, LMR, NeuX, NeuY, NeuZ, LymX, LymY, LymZ, MonX, MonY, MonZ). Results: In multivariable analysis, Hb (p=0.02), NeuY (p=0.04), and MonY (p=0.01) independently predicted CLL versus ALL, correctly classifying 93.4% of cases (AUC 0.91, 95% CI 0.81-1.0). MO# (p=0.003), LymY (p&lt;0.0001), and MonY (p=0.004) were independent predictors of CLL versus other lymphoproliferative disorders, classifying 77.6% of cases (AUC 0.86, 95% CI 0.78-0.95). NeuZ (p=0.01) and NeuY (p=0.04) independently predicted ALL versus other lymphoproliferative disorders, classifying 93% of cases (AUC 0.98, 95% CI 0.95-1.0). Conclusions: The use of RUO parameters offers valuable, cost-effective support in the early diagnosis of ALL, CLL, and other lymphoproliferative disorders.

Background and Aims: Sustained virologic response (SVR) lead to the decrease of portal hypertension, the regression of fibrosis, the improvement of the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in HCV cirrhotic patients treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological and coagulation tests were collected at baseline, EOT and SVR12/24. Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVR. The MELD score decrease at EOT (13.48 ± 4.273; p =0.001), and SVR (9.88 ± 2.774; p = 0.000), compared to baseline (14.92 ± 4.707). Fibroscan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT) there was a trend towards improvement during treatment, changes that were statistically significant for the majority of patients. Factor II low at baseline (75.40 ± 7.506), increases at EOT (87.40 ± 9.587), and later at SVR (99.12 ± 11.695; p = 0.000). FVIII values increased at baseline (175.52 ± 16.414) decrease at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). FvW values decreased during treatment (146.84 ± 9.428 – baseline, 141.32 ± 9.690; p =0.000 – EOT, 126.68 ± 17.960 – SVR). In regards to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the “reset” of the coagulopathy might be due to the improving of the liver function due to viral eradication secondary to AAD therapy.

Background and Objectives: Zonulin is a molecule that has been identified as an intestinal permeability marker in recent years. Zonulin previously linked to Diabetes Mellitus, Obesity and Cardiovascular Disease but but its role in chronic kidney disease (CKD) was unclear. This study aims to investigate the relationship between Zonulin and systemic inflammation (SI), endothelial dysfunction (ED), especially renal functions, in patients with CKD. Materials and Methods: One hundred sixty-three participants were enrolled in this study. All participants were divided into two groups, patient and control groups, according to the presence of CKD (eGFR <60 mL/min/1.73m²). Results: A total of 104 patients with CKD (mean age 58.9 ±1.4) and 59 control subjects (mean age 59.0 ±1.1 ) were included, and age (p =0.934) and gender (p =0.196) were similar between the groups. In the comparison analysis, plasma zonulin levels in the CKD group (166.16 ± 53.54) were significantly higher than the controls group (143.30 ± 60.92) (p <0.001). In the correlation analysis, serum zonulin level showed positive correlation with claudin-3 (r =0.612, p <0.001), IL-6 (r =0.307,p <0.001), creatinine (r =0.313, p <0.001) and negative correlation with eGFR (r =-0.320, p <0.001) and TC (r =-0.074, p =0.047). Additionally, in linear regression analysis, zonulin level was significantly associated to eGFR, after adjustment for age and SBP (β value =-0.918, p =0.012). Conclusion: High serum zonulin levels in patients with CKD reflect increased intestinal permeability and were associated with impaired renal function. Moreover, it was thought that zonulin level could be associated with SI, but novel clinical studies were needed to elucidate its relationship with ED.

Background/Objectives: Bacterial infections (BI) are a major cause of mortality in patients with alcohol-associated hepatitis (AH); however, only a few studies have investigated BI in AH in the last decade. Therefore, we aimed to assess the features and outcomes of BI in patients with AH. Methods: This observational descriptive study included patients with AH admitted to a tertiary academic hospital between 2016–2021. Clinical and complete microbiological data were recorded and complications, including acute-on-chronic liver failure (ACLF), and mortality over 90-days were compared between infected and non-infected patients. Results: Overall, 115 patients with AH were recruited and 75 had severe AH; among them, 66 started corticosteroid treatment. We identified 69 cases of BI in 44 patients; the incidence of BI at hospital discharge was 32.2%, which reached 38.2% at 90 days. The predominant infection site was the chest (35%). Among the identified bacteria (52.1%), half were gram-positive and half gram-negative. A low rate of multidrug-resistant bacteria (14%) was also noted. Infected patients during hospitalization (n=37) exhibited higher rates of hepatic decompensation and ACLF p=0.001) and lower survival (81.8% vs. 95.8%, p=0.015) than did non-infected patients (n=78). In-hospital infected patients (n=22) exhibited worse survival (72.7%) than did those infected upon admission (93.3%) or non-infected patients (94.9%) (p=0.009). Corticosteroid-treated patients displayed a nonsignificant increase in the total number of BI; however, without greater mortality. Conclusions: BI were common in our cohort of patients with AH. Patients with in-hospital infections commonly experienced serious complications, including high ACLF and death rates. Infections diagnosed upon admission were treated without affecting survival.

Background: Current treatment for Chronic Kidney Disease (CKD) focuses on improving manifestations and delaying progression. Nutritional approaches play a crucial role in CKD management, and various supplements have become available. Ketoanalogues of amino acids (KA), calcum citrate, and inulin have been proposed as suitable supplements, yet their widespread use has been limited due to insufficient evidence. This study aimed to generate general guidance statements on the appropriateness of these supplements through a RAND/UCLA consensus process; Methods: A RAND/UCLA consensus panel was convened to evaluate the appropriateness of these supplements in different clinical scenarios. In this study, we present a subgroup analysis focusing on a panel of eleven clinical nephrologists from among the experts; Results: Supplementation of low protein diets (LPD) and very low protein diets (VLPD) with KA was considered appropriate to reduce manifestations and delay CKD outcomes, supplementation with calcium citrate is considered appropriate to reduce CKD manifestations, and supplementation with inulin is considered appropriate to delay CKD outcomes and manage comorbidities; Conclusions: Based on a combination of clinical experience and scientific evidence , the panel reached a consensus that KA supplementation of LPD and VLPD, calcium citrate, and inulin are appropriate in patients with CKD across various scenarios.

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), facilitation of short-chain fatty acids (SCFAs) production, activation of the glucagon-like peptide 1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we have discussed research in other disease models that use probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

The RECONNECT project tackles the fragmentation in Ireland's public healthcare systems, aiming to improve service planning and delivery. It integrates complex systems within the Health Service Executive (HSE) for chronic disease management, prioritizes data privacy, and supports future digital resource integration. The methodology includes: (1) structural integration via a Federated Database design to maintain system autonomy while ensuring privacy; (2) semantic integration through a Record Linkage module to enable integration without individual identifiers; and (3) adoption of the HL7-FHIR framework for high interoperability, aligning with the national electronic health record (EHR) and the Integrated Information Service (IIS). The RECONNECT system is unique in Ireland, featuring a generic architecture for loosely coupled systems, adherence to HL7-FHIR for interoperability, efficient reuse of digital assets, and a robust privacy layer. A demonstration system using synthetic data from the Hospital Inpatient Enquiry (HIPE) and Chronic Disease Management (CDM) systems is implemented on Neo4j for visualization.

Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage or metabolic insult. Senescence is associated with aging and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) is not fully understood however, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated aging. This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases as controls. We show that senescence proteins CKAP4 and PTX3 are upregulated in AKI and CKD patients compared with controls with chronic diseases suggesting they may play in a role in overall kidney disease development. Additionally, CKAP4 was found to be differentially expressed in both AKI and CKD when compared to unhealthy controls hence this biomarker could be prognostic senescence biomarker of both AKI and CKD.

Fibromyalgia (FM), classified by ICD-11 with code MG30.0, is a chronic debilitating disease characterized by wide-spread pain, fatigue, cognitive impairment, sleep and intestinal alterations, among other. FM affects a large proportion of the world-wide population, with increased prevalence among women. The lack of understanding of its etiology and pathophysiology hampers the development of effective treatments. Our group had developed a manual therapy (MT) pressure-controlled custom manual protocol on FM showing hyperalgesia/allodynia, fatigue and patient’s quality of life benefits in a cohort of 38 FM cases (NCT04174300). With the aim of understanding the therapeutic molecular mechanisms triggered by MT, this study interrogated PBMC transcriptomes from FM participants of this clinical trial using RNAseq and RT-qPCR technologies. The results showed that the salt-induced kinase SIK-1 was consistently downregulated by MT in FM, correlating with improvement of patient symptoms. In addition, the study compared the findings in a non-FM control cohort subjected to the same MT protocol evidencing that the changes in SIK1 with MT only occurred in individuals with FM. This positions SIK-1 as a potential biomarker to monitor response to MT, and as a therapeutic target of FM, to be further explored by continuation studies.

Chronic kidney disease (CKD) is a growing public health issue with significant morbidity and mortality rates. Traditional diagnostics, with about 70% accuracy, often delay CKD detection, highlighting the need for more efficient methods. Recent studies indicate a potential link between CKD and auditory health, yet this relationship remains underexplored due to methodological challenges and the complexity of establishing causality. Our research utilizes data spanning from 2000 to 2020 from the National Health and Nutrition Examination Survey (NHANES), covering 12,392 participants, including 2,060 diagnosed with CKD. Through meticulous analysis employing logistic regression and Mendelian randomization, we have unearthed novel insights into the bi-directional associations between hearing impairment and CKD. Furthermore, we developed and validated a machine learning model that surpasses traditional diagnostic approaches in terms of accuracy and predictive power. These findings highlight the innovative integration of auditory examinations with demographic data to enhance CKD detection. Our approach demonstrates the potential of machine learning in transforming diagnostic methodologies, thus offering a significant advancement in the field of nephrology and public health.

Abstract: Epidemiological, experimental, and ecological data have indicated the controversial effect of in utero chronic low dose rate (100 mGy) dose radiation exposure. Our main goal of this study was to examine if different low dose rates of chronic pre- or/and post-natal radiation exposure with accumulative high doses could induce hippocampal cellular, mRNA, and miRNA changes leading to neuropsychiatric disorders. The comprehensive mouse phenotypic traits, organ weight pathological, blood mRNA and miRNA changes were also studied. Using different approaches including SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA), neurobehavioral tests, pathological examination, immunohistochemistry, mRNA and miRNA sequencing, and real-time quantitative polymerase chain reaction ( qRT-PCR) validation, we found that in prenatally irradiated (100 mGy/d for 18 days with an accumulative dose of 1.8 Gy) 1-year-old mice, no cellular changes including neurogenesis, mature neurons and glial cells in the hilus of the dentate gyrus and development of cognitive impairment, neuropsychiatric disorders occurred. However, a significant reduction in body weight and mass index (BMI) was indicated by the SHIRPA test. A reduced exploratory behavior was shown by an open field test. Organ weight measurement showed a significant reduction of the testes, kidneys, heart, liver, and epididymides although no abnormal changes from pathological examination. mRNA and miRNA sequencing and qRT-PCR validation revealed the upregulation of Rubcnl, Abhd14b and downregulation of Hspa1b, P4ha1, and Banp genes in both hippocampus and blood of mice prenatally irradiated with 100 mGy/d. Meanwhile, downregulation of miR-448-3p, miR1298-5p in the hippocampus, miR-320-3p, miR-423-5p, miR-486b-5p, miR-486b-3p, miR-423-3p, miR-652-3p, miR-324-3p, miR-181b-5p, miR-let-7b and miR-6904-5p in the blood was induced. The target scan revealed that Rubcnl is one of the miR-181b-5p targets in the blood. We, therefore, concluded that prenatal chronic irradiation with a low dose rate of 100 mGy/d and accumulative dose of 1.8Gy or below may not induce significant adverse health effects on the offspring. Further study of different low dose rate radiation exposure with accumulative high doses may provide threshold doses for authorities or regulators to set new radiation safety guidelines to replace those extrapolated from acute high dose/dose rate irradiation to reduce unnecessary emergency evacuation or expanding once a nuclear accident or leakage occurs.

Dent disease type 1 is a rare inherited renal disorder affecting mainly young males, generally leading to end-stage renal failure and for which there is no cure. It is caused by inactivating mutations in the gene encoding ClC-5, a 2Cl-/H+ exchanger found on endosomes in the renal proximal tubule. This transporter participates in reabsorbing all filtered plasma proteins which justifies why proteinuria is commonly observed when ClC-5 is defective. In the context of Dent disease type 1, a proximal tubule dedifferentiation was shown to be accompanied by a dysfunctional cell metabolism. However, the exact mechanisms linking such alterations to chronic kidney disease are still unclear. In this review, we gather knowledge from several Dent disease type 1 models to summarize the current hypotheses generated to understand the progression of this disorder. We also highlight some urinary biomarkers for Dent disease type 1 suggested in different studies.

Background: beta blockers of three generations are first-line drugs in the treatment of chronic heart failure (CHF). However, to date there is no clear understanding of the effect of beta blockers on myocardial energy metabolism disorders in CHF. The aim of the study: to conduct a study of beta-blockers of different generations on myocardial energy metabolism in the experimental CHF. Methods: CHF was modeled in white outbred rats by administering doxorubicin. The study drugs were administered intragastrically – new drug Hypertril (1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide)-3.5 mg/kg, metoprolol - 15 mg/kg, Nebivolol -10 mg/kg, Carvedilol 50 mg/kg, Bisoprolol, 10 mg/kg. In the myocardium, the main indices of energy metabolism were determined - ATP, ADP, AMP, malate, lactate, pyruvate, succinate dehydrogenase (SDH) activity, NAD-dependent malate dehydrogenase (NAD-MDH) activity. Results: traditional second-generation beta-blockers (Metoprolol and Bisoprolol) did not affect the studied indices of energy metabolism, and third-generation beta-blockers with additional properties - Carvedilol and, especially, Nebivalol and Hypertril improved myocardial energy metabolism. Conclusions: obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF.

Percutaneous coronary intervention (PCI) to chronic total occlusion (CTO) is still a subject of debate. The primary goal of revascularization is to provide symptomatic relief and enhancing left ventricular (LV) functions. Global longitudinal strain (GLS) is proven to be more sensitive than ejection fraction (EF), especially for subtle ischemic changes. The purpose of this study was to investigate the improvement in LV GLS after revascularization of symptomatic stable coronary patients with single-vessel CTO, categorized according to their collateral supply grades. 69 patients with successful CTO PCI were grouped according to their collateral supply grades, as well-developed (WD) and poor collateral groups and followed-up for 3 months. Basal characteristics were similar for both groups, except for lower EF (p=0.04) and impaired GLS (p<0.0001) in the poor collateral group. At the end of 3 months follow-up symptomatic relief was similar in both groups (p=0.101). GLS improvement reached statistical significance only for the poor collateral, not for the WD group (p<0.0001 and p=0.054, respectively). EF did not change significantly in both groups. Poorly collateralized CTO lesion may not only result in baseline LV dysfunction, but also appear to carry potential for recovery after revascularization. This may not be the case for WD collaterals.

The present study examined metabolites in Northern wild rice (WLD), the impact of WLD supplemented high fat (HF) diet on gut microbiota, short chain fatty acids (SCFAs) and correlation with metabolism or inflammation versus HF+white rice (WHR) in mice. C57BL/6J mice received HF diet supplemented with 26g% WHR, 26g% WLD, or 13g% WHR+13g% WLD (WTWD) for 12 weeks. The levels of fasting plasma glucose, total cholesterol, triglycerides, insulin resistance, inflammatory cytokines and monocyte adhesion were lower, and the abundances of fecal Lactobacillus gasseri species bacteria and propionic acid were higher in HF+WLD diet-fed mice compared to HF+WHR diet-fed mice (p<0.05). The anti-inflammatory effects of HF+WTWD diet were weaker than that in HF+WLD diet, but were greater than that in HF+WHR diet-fed mice (p<0.05). Relative abundances of fecal Lactobacillus gasseri and propionic acid in HF+WLD fed-mice were higher than that in HF+WHR fed mice. The abundance of fecal L. gasseri and propionic acid negatively correlated with metabolic and inflammatory markers (p<0.05). The findings suggest that WLD dose-dependently attenuated metabolic and inflammatory disorders in HF diet-fed mice. Interactions between WLD components and gut microbiota may upregulate fecal propionic acid and contribute to metabolic and anti-inflammatory benefits of WLD diet-induced insulin resistant mice.

Background: Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune responses. Body: This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.

The importance of diet shaping the gut microbiota is well known and may help with improving the overall health of an individual. Many other factors also have an influence, such as genetics, age, exercise, antibiotic therapy, or tobacco use. The purpose of this review is to summarize how three distinct dietary types (plant-based diet, Mediterranean diet, and Western diet) affect the composition of gut microbiota and the development of non-communicable diseases (NCDs). PubMed, Web of Science and Scopus databases were used for searching papers with an emphasis on keywords ‘‘dietary pattern’’, ‘‘gut microbiota’’ and ‘‘dysbiosis’’. Plant-based diet and Mediterranean diet promote the production of beneficial bacterial products, and more microbial diversity and therefore are generally considered healthy dietary types. On the other hand, the Western diet is a typical example of an unhealthy approach to nutrition which leads to an overgrowth of pathogenic bacteria. Moreover, understanding the impact of diet on the modulation of gut microbiota may give rise to new therapeutical strategies.

Currently, the primary strategy for addressing polycystic ovarian syndrome (PCOS) involves lifestyle modifications, with a focus on weight loss. The purpose of this meta-analysis was to assess the impact of weight loss through dietary interventions on inflammatory status and hyperandrogenism in PCOS women. A comprehensive search was conducted to identify randomised controlled trials (RCTs) and cohort studies assessing the impact of diet-induced weight loss on circulating inflammatory markers (CRP, IL-6, IL-1β, TNF-α), androgens (testosterone, SHBG, androstenedione) and luteinising hormone (LH) in PCOS women. The quality and risk of bias of the included studies were assessed using the Cochrane Collaboration's tool for RCTs and the Newcastle–Ottawa Scale for cohort studies. Data were entered into RevMan software v5.9 for the calculation of standard mean difference (SMD) and 95% confidence interval (95%CI) of circulating inflammatory markers, androgens and LH between baseline and post-weight loss values. Eleven studies (n=323) were eligible for the systematic review, of which nine (n=286) were included in the meta-analysis. Pooled analysis of data revealed a statistically significant decrease in circulating CRP (SMD 0.39, 95%CI 0.22, 0.56; 9 studies, n=286), IL-6 (SMD 0.37, 95%Cl, 0.12, 0.61; 3 Studies, n=140), TNF- α (SMD 0.30, 95%Cl, 0.07, 0.53; 4 Studies, n=162), androstenedione (SMD 0.36, 95%Cl, 0.13, 0.60; 4 studies, n=147) and LH (SMD 0.30, 95% Cl, 0.09, 0.51; 5 studies, n=197) after weight loss compared to baseline levels among PCOS women. Meta-analysis of five studies (n=173) showed a statistically significant increase in circulating SHBG after weight loss compared to baseline levels (SMD -0.43, 95%Cl, -0.65, -0.21). These findings suggest that weight loss induced by dietary interventions seems to improve PCOS-related chronic inflammation and hyperandrogenism. The possible causative relationship between the improvement in inflammation and hyperandrogenism remains to be determined.

The work and life routine of long-haul truck drivers involves the use of truck stops and rest areas to meet their basic human needs. These extensions of their workspaces while on the road, do not always offer adequate physical structures and services that drivers need for optimal health. Aim: To evaluate long-haul truck drivers’ perceptions about the services of food, safety, physical activity, rest and personal hygiene offered at truck stops and rest areas in Brazil. Method: Quantitative study conducted with long-haul truck drivers from the Southern region of Brazil. For data collection, a sociodemographic questionnaire and a Likert scale on food, rest, personal hygiene, safety and physical activity services were used, offered in general at the truck stops and rest areas along Brazilian roads, from March to August 2023. The data were analyzed with simple frequency descriptive statistics. Results: 175 long-haul truck drivers participated, 70.29% declared that the services of the truck stop and rest areas were charged; more than half (53.59%) of the professionals evaluated the rest service as “good” or “excellent”; the food services, was “good” or “excellent” for 42.24% of the drivers. The spaces for physical activities were the worst evaluated as “bad” or “terrible”, by 41.61%, followed by bathroom service (28.42%) and safety (34.24%), evaluated as “bad” or “terrible”. Conclusions: In the perception of long-haul truck drivers, the rest and feeding services had better evaluations, on the other hand, the services of bathroom, safety and physical activity presented worse evaluations. The perception of drivers demonstrates the lack of investments to improve basic services such as personal hygiene, safe environment and physical exercises, fundamental to the health of the worker, aiming to reduce vulnerability, sedentary lifestyle, and meeting the basic human needs of long-haul truck drivers.

Chronic obstructive pulmonary disease (COPD) is a condition that significantly impacts both patients and healthcare systems. The management of COPD involves various pharmacological intervention strategies, and addressing the issue of low adherence to these strategies has become a subject of significant interest. In response to this concern, there has been a shift towards utilizing telemedicine and mobile applications. The primary objective of this scoping review is to delineate the usage of mobile applications to enhance pharmacological therapeutic adherence in adult patients with COPD. The study involved a search of databases such as Medline, Google Scholar, Cochrane, and ClinicalTrial.gov, focusing on literature published in English and Spanish over the last decade. The selected studies assessed interventions involving mobile applications (mobile apps) designed to improve pharmacological adherence. Four digital aids were identified, available on online platforms, mobile apps, or both: m-PAC, myCOPD, Wellinks mHealth, and Propeller Health. Pro-peller Health, in particular, is an app that directly measures pharmacological adherence through electronic medication monitors attached to participants' inhalers. Opening the app was associated with higher odds of using control medications compared to participants who did not open the app. The findings suggest that these digital interventions serve as valuable tools to enhance patient adherence to treatment. Future research should focus on evaluating the effectiveness of different digital devices, such as digital inhalers and mobile applications, that directly measure pharmacological adherence.

The planar cell polarity (PCP) of epithelial ciliated cells is essential for effective mucociliary clearance (MCC) in the sinonasal mucosa. We hypothesize that MCC coordination is impaired in nasal polyp (NP) mucosae due to suppressed expression of a series of CPLANE (ciliogenesis and planar cell polarity effector) complex proteins in chronic rhinosinusitis (CRS) patients. To inves-tigate this hypothesis, we subjected sinonasal mucosal samples to live video recording to measure mucociliary transport velocity (MCTV) and scanning electron microscopy to evaluate surface morphology. The expression and distribution of a panel of PCP proteins, e.g. WDPCP and FUZ, were investigated in relation to inflammatory cytokine levels and clinical features. The mean MCTV of NP mucosae was significantly lower than that of the inferior turbinate mucosae. The CRS group with NPs (CRSwNP group) (n=28) showed increased expression of IL-13 and CCL26 mRNA compared to CRS patients without NPs (n=25) and controls (n=30). WDPCP and FUZ mRNA levels were significantly decreased in NP mucosae compared to ethmoid sinus mucosae in CRSwNP patients. WDPCP protein distribution was reduced in the cytoplasmic region of ciliated cells in CRSwNP patients. We conclude that suppression of WDPCP in ciliated cells is responsible for the impaired MCC of nasal polyps with type-2 inflammation. This mechanism might explain the decreased clearance and the potential for worsening symptoms of CRSwNP.

Background: Alarming data indicates that low back pain (LBP) affected around 619 million people globally in 2020, that presenting significant health and economic burden. Importantly, the chronic LBP (cLBP) strongly impairs quality of life and leads to disability and premature retirement thus emphasizing the urgent need for providing deeper insight into the factors that affect treatment outcomes and offer thorough guidance for the assessment and management of this disease. Taking into consideration the rising prevalence of cLBP and knowledge gap referring to the overall health benefits of balneotherapy (BT), the aim of this study was to assess the effects of BT on functional status, quality of life and psychological symptoms in patients with cLBP. Methods: A total 210 patients were recruited and divided into two groups: patients receiving conventional pharmacological therapy (CT) and receiving BT. The effectiveness of the treatment was assessed on the basis of Visual Analog Scale for pain intensity, EuroQol (EQ-5D) for the patient’s self-rated health and Work Ability Index Questionnaire to evaluate functional ability. In order to provide deeper insight into the quality of life and also factors associated with the functional status and mental health affected by BT, we also used the Short Form Health Survey Questionnaire and Center of Epidemiologic Studies Depression Scale. Results: Our findings suggest that BT significantly contributed to reduction of pain, better functionality and disability perception status. Conclusions: Understanding the association between individual perceptions of functionality, emotional and social elements provides basis for providing comprehensive guidelines and recommendations for cLBP management.

B-cell lymphoid malignancies is a heterogeneous group of hematologic cancers, where Bruton's tyrosine kinase (BTK) inhibitors have received FDA approval for several subtypes. The first-in-class covalent BTK inhibitor, ibrutinib, binds to the C481 amino acid residue to block the BTK enzyme and prevent the downstream signaling. Resistance to covalent BTK inhibitors can occur through mutations at the BTK binding site (C481S) but also other BTK sites and the phospholipase C gamma 2 (PLCγ2) resulting in downstream signaling. To bypass the C481S mutation, non-covalent BTK inhibitors, such as pirtobrutinib, were developed and are active against both wild-type and the C481S mutation. In this review, we discuss the molecular and genetic mechanisms which contribute to acquisition of resistance to covalent and non-covalent BTK inhibitors. In addition, we discuss the new emerging class of BTK degraders, which utilize the evolution of proteolysis-targeting chimeras (PROTACs) to degrade the BTK protein and constitute an important avenue of overcoming resistance. The moving landscape of resistance to BTK inhibitors and the development of new therapeutic strategies highlight the ongoing advances, that are being made towards the pursue of cure of B-cell lymphoid malignancies.

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, which underpins methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.

Background. Myocardial involvement mediated by chronic obstructive pulmonary disease (COPD) is a common cause of morbidity and mortality. Conventional transthoracic echocardiography (TTE) parameters are poor in the detection of subclinical myocardial dysfunction. Aim.To investigate the contribution of strain in the early detection of cardiac damage in stable COPD patients Methods. Group A and B patients with COPD were enrolled in this study. The COPD assessment test, spirometry, 6-minute walk test, and both conventional TTE and strain were performed in these patients. Results. 80 COPD patients, with a mean age 65.6 ± 8.9 years, were included. The. Left ventricular ejection fraction (LVEF) was 60.7 ± 5.1%. Right atrium and right ventricle (RV) strain were 24.5 ± 6.6% and -19.9 ± 3.7%, respectively. Additionally, left ventricle global longitudinal strain (LV GLS) was -21.1 ± 2. Forty-eight patients had impaired RV strain. Compared to COPD patient with normal RV strain, those with RV reduced starin had a lower 6meter walk distance (6MWD) (p=0.001) and forced expiratory volume in the first second (FEV1) (p=0.012), and a higher CAT score (p=0.012). A reduced RV strain was correlated with a higher risk of hospitalizations for acute exacerbation in the post inclusion year (55% versus 25%; p=0.024). No deaths were recorded during the follow-up period. No significant factors causing neither RA starin alteration nor LV GLS reduction were revealed. Conclusion. Group A and B COPD patients having normal conventional TTE parameters, speckle tracking is a key parameter in the detection of subclinical myocardial dysfunction.

Background: Chronic exposure to severe hypoxia causes an increase in hematocrit (Hct) and hemoglobin concentration ([Hb]), which can lead to Excessive Erythrocytosis (EE), which could impact physical performance. This work aims to determine the differences in the six-minute walking test (6MWT) outputs between EE and healthy subjects residing at more than 5000 meters. Methods: A prospective, cross-sectional study was performed on 71 men (36 healthy and 25 suffering EE) living in La Rinconada, Peru (5100 m). Basal levels of [Hb] and Hct were obtained. All the subjects per-formed the 6MWT, and distance reached, vital signs, dyspnea, and fatigue (Borg scale) at the end of the test were recorded. Results: The average [Hb] and Hct levels in the control group were 18.7 ± 1.2 g/dL and 60.4 ± 7.1%, respectively, contrasting with EE subjects who showed 23.4 ± 1.6 g/dL and 73.6 ± 5.9% (p < 0.001). However, no statistically significant differences were observed in BMI or other anthropometric parameters. At the end of the 6MWT, the distance traveled, and vital constants were similar between both groups, except for arterial oxygen saturation which was consistently lower in subjects with EE along the test. Conclusion: EE does not significantly affect 6MWT performance at high altitudes nor the hemodynamic control during moderate aerobic exercise of subjects who live permanently in a severe hypoxic environment.

Background P53 gene mutation is a very common event in human neoplasia, and genetic mutations in the P53 gene in a single allele are responsible for a hereditary cancer susceptibility syndrome (Li Fraumeni). These variants encode distinct isoforms of the p53 protein, which may disrupt its transcriptional activity. These point mutant proteins are more stable than the normal protein and the mutant product accumulates at a high level that allows obtaining important information about p53 gene expression in malignant cells, especially in Chronic Lymphocytic Leukemia, (CLL). By Enzyme Linked Immune-Absorbent Assay method, (ELISA), was analyzed the frequency of p53 protein expression to 20 eligible patients diagnosed with CLL for to investigate the relationship of this protein in the stages of the disease and the impact on treatment response and survival. In ELISA technique was used the specific antibodies for isoform p53 protein, PAb 240 antibodies. These antibodies bind specifically to denatured p-53 protein. Species reactivity is for human in conformity with the prospect from Manual, Catalog No. LS-F174, Bio-Rad. Results The average concentrations of p53 proteins in 17 of 20 cases were found 16.76 μg / dl, with CV = 0.5% and the probability index p = 0.034. Very high pathological values in the 3 cases of isoform p53 protein were calculated in 2 men, (PM) in the value of 60 µg / dL, respectively at 40 µg / dL and in the case of females, (PW), in 40 µg / dL value, with the transformation into Diffuse Large Lymphoma, (DLL). Conclusion This ELISA method has proven to be a useful prognostic tool for the application of personalized treatment of on-immune therapy, in cases diagnosed with the type B-CLL.

Background:Patients with chronic kidney disease (CKD), especially those undergoing dialysis, encounter complex nutritional challenges. Key dietary factors such as protein and fluid intake, potassium and sodium levels, and co-morbidities significantly influence dietary planning for CKD patients. A standardized approach to dietary recommendations for CKD patients is ineffective due to the diverse needs of individual patients. Social media platforms have become a popular source of dietary information, often advocating low-carb, high-protein diets, and other combinations purported to be universally beneficial. However, these generalized online dietary recommendations lack the individualized approach necessary for CKD patients. Unlike these social media-driven suggestions, established medical guidelines offer a more nuanced view of CKD dietary needs. This study investigates the discrepancies between these sources and their potential impact on patient health. Objective:The primary goal of this study is to identify and analyze the flaws in the dietary recommendation system for CKD patients that might adversely affect their health. By critically evaluating the content of YouTube videos, we aim to compare the dietary advice provided by social media influencers and content creators with established medical guidelines. Our approach combines qualitative and quantitative methods to thoroughly assess the accuracy and reliability of online dietary advice available to CKD patients. Method:We conducted four YouTube searches using keywords related to "diet plan" and "chronic kidney disease (CKD)." From each search, the first 30 videos were selected based on relevance, resulting in an initial pool of 120 videos. A stepwise screening process was used to filter out the most relevant and accessible content, ultimately narrowing the sample to 30 videos for in-depth analysis. The videos were evaluated using two scoring systems: the Journal of the American Medical Association (JAMA) score and the Global Quality Scale (GQS) score, which assess video quality. To ensure impartiality, three independent scorers conducted the evaluations. Additionally, two six-point scorecards were used to evaluate the inclusion and accuracy of information on various foods and eating behaviors affecting CKD risk, with higher scores indicating more comprehensive coverage. Data on video characteristics, such as view count, number of likes, and video age, were also collected to provide context and further insight into their reach and influence. Results:The study included 30 videos, with 60% (18 out of 30) posted by or featuring nephrology health professionals. Scorer 1 reported a mean JAMA score of 2.3 (SD 0.61) out of 4 points and a mean GQS score of 2.5 (SD 0.64) out of 5 points. Scorer 2 found a mean JAMA score of 2.5 (SD 0.62) and a mean GQS score of 2.8 (SD 0.73). Scorer 3 reported a mean JAMA score of 2.6 (SD 0.55) and a mean GQS score of 2.8 (SD 0.69). The dietary six-point scorecards revealed a mean score of 3.6 (SD 0.85) for the presence of information and 2.8 (SD 0.88) for the accuracy of the information. Conclusion:The videos analyzed in this study related to diet plans for CKD patients demonstrated generally low scores, indicating a lack of comprehensive and accurate information. Many videos provided incomplete or partial information, which could mislead viewers and potentially cause harm due to incomplete knowledge. This study highlights the need for careful scrutiny of online content, particularly on platforms like YouTube, due to the potential for contradictory information and its harmful consequences. The findings emphasize the necessity for greater accuracy and vigilance in disseminating health-related information to ensure the safety and well-being of CKD patients.

Osteoarthritis and chronic pancreatitis comorbidity are insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of osteoarthritis and chronic pancreatitis comorbidity, as well as complications associated with this comorbidity. A cohort of 150 patients was categorized into three groups: a control group (n=30), patients with osteoarthritis (n=68), and patients with comorbid osteoarthritis and chronic pancreatitis (n=52). Potential predictors for comorbidity development and associated complications were explored. The study revealed that concurrent osteoarthritis and chronic pancreatitis exacerbate each other's progression and contribute to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for chronic pancreatitis development in osteoarthritis patients. In osteoarthritis patients, fecal elastase-1 levels were identified as potential predictors for exocrine pancreatic insufficiency. Factors such as WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxy vitamin D3, and BMI were found to influence comorbidity development between osteoarthritis and chronic pancreatitis. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors for exocrine pancreatic insufficiency in osteoarthritis patients. In conclusion, the comorbidity of osteoarthritis and chronic pancreatitis exacerbates disease progression and complications, necessitating further investigation.

Background: Chronic pelvic pain is a debilitating condition affecting quality of life. Endometriosis is one of the leading causes of CPP, but recent studies highlighted the role of interstitial cystitis/bladder pain syndrome (IC/PBS) in causing CPP. Only some studies addressed the coexistence between these two conditions, which seems more frequent than what is supposed, leading to diagnostic delays and unnecessary surgeries. This systematic review aimed to evaluate the estimate of the coexistence of endometriosis and IC/PBS. Methods: We performed a systematic review of the literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by “painful bladder syndrome”, “endometriosis”, “interstitial cystitis”, “bladder pain syndrome”. We performed a meta-analysis of the results. Results: Meta-analysis shows that the coexistence of endometriosis and IC/PBS in women with CPP ranges between 15,5-78,3%, which is higher than the prevalence of IC/PBS in the general population. Conclusions: Women with CPP need a multidisciplinary approach and a referral to centers with specific expertise. In cases of endometriosis unresponsive to treatment, other reasons for CPP need to be ruled out, above all in women not responsive to treatment.

Introduction: In Traditional Chinese Medicine (TCM), tongue diagnosis plays an important role. Besides shape, colour and textural attributes of tongue regions have significance due to their association with different organs (viz. heart, lung, kidney-bladder, liver-gallbladder and stomach-spleen) in health and disease. Although numerous quantitative methods have been proposed to reduce inter and intra observer variability in tongue diagnosis, almost all of them considered only global colour/ textural features i.e. from entire body of tongue. In this work, regional colour and texture information of tongue have been analysed for healthy subjects (NOM) and patients suffering from chronic acidity-indigestion (ACD). Methods: Tongue boundaries are marked manually in each image and then tongue bodies are automatically partitioned into five regions linked with said internal organs. Rough assessments of regions’ boundaries are obtained from literature and then they are fine-tuned according to experts’ advice. As boundaries are not well defined, regions near the common boundary of two or more organs, are not assigned to any organ. Several first and second order statistical features based on grey scale intensities and a* values of LAB colour space (indicative of redness) have been extracted from five different regions of tongue images. Intragroup analysis using Wilcoxon signed rank test compared different regions within individual study group. Additionally, intergroup analysis using Wilcoxon rank sum test compared tongues of NOM with ACD for each region separately. Results: Intragroup analysis reveals a* values are statistically different (p&lt;0.01) between stomach-spleen and liver-gallbladder regions for ACD while no significant change of a* are noted between these regions of normal tongue. It was found from intergroup analysis that correlation (one of the second order texture features extracted from grey scale images) of heart region has significantly decreased while correlation of kidney, liver-gallbladder and stomach-spleen regions significantly increased from NOM to ACD. Conclusion: This study sheds light on importance of inclusion of regional textural analysis of tongue in quantitative studies and can be applied to automated tongue diagnosis for other diseases.

Keywords: Chronic Obstructive Pulmonary Disease (COPD), Long Non-Coding RNAs (lncRNAs), Molecular Pathogenesis, Inflammation, Lung Cancer, Diagnostic Biomarkers

Rationale: A wide range of bioactive phytoconstituents from edible fungi, especially therapeutic mushrooms, have the potential to improve health, especially in the case of chronic illnesses. Known for its anti-cancer qualities, ganoderma lucidum has been the focus of multiple clinical studies. Existing systematic reviews imply that more clinical research and methodological refinement are necessary to support its usage as a primary cancer treatment.Objective: The objective of this research is to evaluate the anti-cancer potential of the bioactive phytoconstituents found in mushrooms, specifically Ganoderma lucidum, in a thorough manner. The aim is to conduct a critical assessment of the extant literature, pinpoint any deficiencies, and offer valuable perspectives on the methodological excellence and research requirements in this domain.Method(s): A thorough analysis of published clinical trials was carried out, with a focus on studies that examined the effectiveness of Ganoderma lucidum and other products derived from mushrooms in treating cancer. The study's design, stated results, and methodological rigor were all carefully examined to evaluate the validity and reliability of the conclusions.Results: Despite Ganoderma lucidum's potential against cancer, the evaluation finds insufficient data to support its widespread usage as a primary cancer treatment. Products made from mushrooms, which are frequently sold as dietary supplements, have anti-cancer claims. But since pre-approval is not required under US regulatory framework in order to market food supplements, these statements raise questions regarding their scientific validity.Conclusions/Recommendations: The study's result emphasizes the necessity of more methodological advancement in clinical studies examining Ganoderma lucidum's potential as an anti-cancer agent. It also highlights the significance of thorough scientific validation for goods made from mushrooms that make health claims. To establish accurate claims regarding their anti-cancer effects, recommendations include developing technological methods for the purification of bioactive substances and undertaking thorough studies of mushroom products from different geographical regions. The goal of this thorough analysis is to direct future investigations and support the ethical promotion and use of products derived from mushrooms for medical purposes.

Digital weight-loss services (DWLSs) combining pharmacotherapy and health coaching have the potential to make a major contribution to the global struggle against obesity. However, there is currently no evidence to counter the widespread concern that these services enable large numbers of unsuitable patients to obtain Glucagon-like peptide-1 receptor agonists (GLP-1 RA). This study retrospectively analysed the rate at which the partner pharmacy network of Australia’s largest DWLS provider committed GLP-1 RA dispensing errors over a 6-month period. The analysis found that 191 (0.14%) of the 135131 dispensed Semaglutide orders contained an error. Non-compliant dose escalation (44.5%) and dispatch errors (32.5%) were the two most common error types. Most errors (89%) were deemed to have been of medium urgency, with 6.8% considered high urgency. A disproportionate number of high urgency cases were from wrong medication (31%) and general complaint errors (15%). A Chi-square test revealed a statistically higher dispensing error rate among orders to female patients (0.16%) compared to males (0.076%). The results lay an important foundation in digital pharmacy literature and suggest that comprehensive DWLSs have the potential to safely collaborate with third-party pharmacies in dispensing GLP-1 RAs.

Abstract: Chronic Obstructive Pulmonary Disease (COPD) is a continually advancing respiratory disorder, characterized by enduring airflow limitation along with long-lasting inflammation in the airways. An expanding pool of evidence is emphasizing how mitochondrial dysfunction directly impacts the development and progression of COPD. This comprehensive review delves deeper into the intricate cellular and molecular biology of mitochondria within the framework of COPD, spotlighting significant alterations in structure and function that accompany mitochondrial dysfunction. In this narrative, we delve into the observed changes in mitochondrial shape, behavior, and respiratory chain complex alterations seen in individuals afflicted with COPD. The discussion includes implications on cellular signaling pathways and how this affects the natural process of programmed cellular death (apoptosis) and cellular aging, particularly in reference to COPD. Additionally, we consolidate ongoing therapeutic strategies, honing in on the management of COPD through a focus on mitochondrial dysfunction. Prominent among these strategies is the potential role of antioxidants and mitochondrial biogenesis inducers, which are emerging as promising fields of intervention. Furthermore, we embark on an overview of the possible use of mitochondrial biomarkers as innovative tools in diagnosing COPD, evaluating disease progression, and monitoring the efficacy of COPD treatments. As we unravel the rather complex interplay between mitochondrial biology and COPD, this review highlights the critical importance of formulating treatments that target mitochondrial dysfunction. The ultimate goal of these strategic interventions is to slow down the rate of COPD progression and significantly improve patient outcomes. Lastly, though our understanding of the nexus between COPD and mitochondrial dysfunction has significantly enhanced, ample scope remains for further investigation. Improved insights into the mechanisms of mitochondrial dysfunction, discovered biomarkers, and targeted therapies could encompass a revolutionary step towards comprehensive disease management. The future of COPD treatment seems to lean towards a combination of strategies, prioritizing not only the management of symptoms but also focused on preserving and restoring lung function, improving physical capacity, and enhancing quality of life for COPD patients.

Background: Knowledge of the anatomy of pulmonary arteries is essential in many invasive procedures concerning pulmonary circulation. In the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH), two-dimensional (2D) pulmonary angiography is used. Recognizing the topographic course of the pulmonary arteries and understanding the status in three-dimensions (3D) is paramount. The study aimed to evaluate and describe the branching variant of pulmonary arteries in a single case, as well as morphological parameters of the segmental arteries, like length, diameter and branching angles. Methods: One pair of embalmed human cadaver lungs were dissected by scalpel, surgical forceps and measured until the subsegmental arteries. Results: The diameters (ranging from 3.04 to 9.29 mm) and lengths (ranging from 9.09 to 53.91 mm) of the pulmonary segmental arteries varied. The proximal branching angles were wide and close to perpendicular, while distally, the angles between the segmental and subsegmental arteries were narrower (30-45°). Upon evaluating the branching, rare variations were identified and delineated, notably in the lower lobes of both lungs. Conclusions: Utilizing knowledge and data in clinical settings is instrumental for effectively diagnosing and treating CTEPH. Further research is required to explore the complications in invasive procedures related to various anatomical variations.

The increased life expectancy of PLHIV (People Living with HIV) and the successful highly com-bined antiretroviral therapy (cART) poses new clinical challenges regarding aging and its co-morbid condition. It is commonly believed that HIV infection "accelerates" aging. Human immunodeficiency virus type 1 (HIV-1) infection is characterised by inflammation and immune activation that persists despite cART and that may contribute to the development of co-morbid conditions. Toxicity associated with cART contributes to persistent immune dysregulation. Therefore, we aimed to compare current cART regimens in the light of premature aging to evaluate residual immune activation and inflammation in virologically suppressed patients. We studied a panel of biomarkers (IFN-γ, IL-1β, IL-12p70, IL-2, IL-4, IL-5, IL-6, IL-13, IL-18, GM-CSF, TNF-α, C-reactive protein, D-dimer, soluble CD14), which could provide a non-invasive and af-fordable approach to monitor HIV-related chronic inflammation. The results of the current study do not provide hard evidence favoring a particular cART regimen, although they show less fa-vorable regimen profile containing protease inhibitor. Our data suggests incomplete reduction of inflammation and immune activation in terms of the effective cART. It is likely that the inter-est in various biomarkers related to immune activation and inflammation as predictors of clini-cal outcomes among PLHIV will increase in the future.

In Southeast Asia, the incidence of Leukemia, a malignant blood cancer originating from hema-topoietic progenitor cells, is on the rise, marked by a concerning 54% mortality rate. This study focuses on enhancing early-stage prediction to improve patient recovery prospects significantly. Leveraging Machine Learning and Data Science, we employ protein sequential data from frequently mutated genes such as BCL2, HSP90, PARP, and RB to predict Chronic Myeloid Leukemia (CML). Our approach relies on robust feature extraction techniques, namely Di-peptide Composition (DPC), Amino Acid Composition (AAC), and Pseudo amino acid composition (Pse-AAC), with prior attention to addressing outliers and validating feature selection through the Pearson Corre-lation Coefficient. Data augmentation ensures a well-rounded dataset for analysis. Employing a range of Machine Learning models, including Support Vector Machine (SVM), XGBoost, Random Forest (RF), K Nearest Neighbor (KNN), Decision Tree (DT), and Logistic Regression (LR), we achieve accuracy rates spanning from 66% to 94%. These classifiers undergo comprehensive as-sessment using performance metrics such as accuracy, sensitivity, specificity, F1-score, and the confusion matrix. Our proposed solution, encompassing a user-friendly web application dashboard, presents an invaluable tool for early CML diagnosis with profound implications for practitioners, offering a deploy-able asset within healthcare institutions and hospitals.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, characterized by abnormal growth of mature B cells in the blood, bone marrow, and lymphoid tissues. Although CLL primarily affects the hematopoietic system and lymph nodes, renal involvement is exceptionally rare and presents diagnostic and treatment challenges. Potential causes of renal failure in CLL patients include sepsis, dehydration, tumor lysis syndrome (TLS), compression of the ureter by enlarged lymph nodes, and side effects of cancer therapy. This report presents a case of CLL with renal infiltration leading to severe renal failure, discussing the clinical presentation, diagnostic workup, and management of this condition.

Alpha-methyl-p-tyrosine (AMPT; also referred as metyrosine) is an approved medication for the treatment of pheochromocytoma. As a tyrosine hydroxylase inhibitor AMPT may be a potential candidate for the treatment of diseases involving catecholamine alterations. However, only small-scale clinical trials have tested AMPT repurposing in few other illnesses. Chronic fatigue syndrome (CFS) is an heterogenous disorder with genetically associated vulnerability of catecholamine metabolism (e.g. catechol O-methyltransferase polymorphisms) holding an important impact of environmental factors. The current case report compiles genetic and longitudinal biochemical data for over a year follow-up of one patient sequentially diagnosed with sustained overstress, neurasthenia, CFS, and POTS (postural orthostatic tachycardia syndrome) over a 10-year period, and reports patient’s symptom improvement in response to low-medium doses of AMPT.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology after acute injury and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, Nuclear Magnetic Resonance Imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced-inflammation promote fast loss of muscle mass and reduction of fibers cross sectional area, by inducing muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin expression, that trigger protein breakdown, resulting in acute SkM fibers atrophy. After temporal reduction of inflammation and clearance of infectious viral particles, SkM atrophy persists until the late phase of infection. The genomic CHIKV and MAYV RNAs were still detected in SkM at the late phase, along with increased levels of chemokines and anti-inflammatory cytokines expression. In agreement with the involvement of inflammatory mediators on induced atrophy, neutralization of TNF and the reduction of oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogens expression and atrophic fibers, while increasing weight gain in treated mice. Taken together, these data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphaviruses pathogenesis and with description of potentially new targets of therapeutic intervention.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Background Patients with severe dysphagia are usually fed using a nasogastric tube (NGT). Many patients who receive long-term NGT feeding are unable to obtain sufficient nutrients orally immediately after NGT removal. Thus, a transitional period involving oral diet training is required to transition from NGT feeding to exclusive oral feeding. We aimed to investigate the therapeutic effect of oral diet training in indwelling NGT patients with prolonged dysphagia. Methods A total of 175 patients who were fed using an NGT for more than 4 weeks were enrolled. Their swallowing function was evaluated by a videofluoroscopic swallowing study (VFSS). During the VFSS, patients received thick and thin barium while the NGT was insulted. Then, the patients underwent a VFSS without an NGT thirty minutes after NGT removal. If a patient had no aspiration with NGT inserted during the VFSS, oral diet training combined with NGT feeding was recommended. Results Of the 49 indwelling NGT patients who were recommended to receive oral diet training, 39 (79.6%) transitioned to exclusive oral feeding. A transition period of 2-8 weeks was required for them to achieve full oral feeding. Patients who were eligible for oral feeding trials showed no significant aspiration during the VFSS with an NGT inserted and had sufficient cough function. Patients who required prolonged NGT feeding and who could not complete oral trials showed significant aspiration during the VFSS when an NGT was inserted. Conclusion This study demonstrated that oral diet training combined with NGT feeding was safe in patients with prolonged dysphagia who had sufficient cough function and no aspiration during VFSS. We suggest that if the patient is a proper candidate for NGT removal, direct oral feeding training with an NGT inserted could be a useful therapeutic strategy during the transitional period from long-term NGT feeding to successful oral feeding.

Background: Physiotherapy and chronic low back pain (CLBP) form a broad and fast developing research area. The aim of the article was to holistically, thematically and chronologically analyze and synthesise literature production and identify most prolific research entities and research themes. Methods: The article quantitatively and quantitatively analyzed research literature production harvested from the Scopus bibliometric database. using a triangulation of bibliometric and thematic analysis. For this, Excell and VOSwiever software were used. Results: In the Scopus database, 2843 data sources were found, which were published between 1974 and February 26, 2024. The growth trend has been linearly positive since the beginning of publication, and after 2018, exponential growth began. A review of the most prolific entities showed that the most literature was published in America, Europe and Australasia. The thematic analysis of the information sources identified six main themes, while the chronological analysis revealed three main areas of developments: assessment tools, CLBP processing and study methodology. Conclusions: The results of the bibliometric study presents a good starting point for further research providing Taxonomy and research landscapes as a holistic framework offering multidisciplinary knowledge about CLBP, while chronological analysis provides a basis for identifying prospective research trends.

Background. Chronic kidney disease (CKD) is a progressive condition with limited treatment options that often lead to significant morbidity. Recent studies suggest that oxyhydrogen nanobubbles (HHOnb) may offer therapeutic benefits due to their antioxidative and anti-inflammatory properties. This case series examines the effects of intravenous HHOnb therapy on three patients with varying stages of CKD.Methods. Three patients with CKD underwent a series of ten HHOnb infusions over a period of two to three months. The patients, aged 43 to 70, presented with additional comorbidities including hypertension, diabetes mellitus, and polycystic kidney disease. Clinical parameters, including glomerular filtration rate (GFR), serum creatinine, blood pressure, and uric acid levels, were monitored alongside subjective health improvements.Results. Patient A. A 70-year-old woman with CKD grade 3a experienced a reduction in serum creatinine from 0.98 mg/dL to 0.82 mg/dL and an improvement in GFR from 59 mL/min/1.73 m² to 73.2 mL/min/1.73 m². She reported reduced leg swelling and increased vitality. Patient B. A 52-year-old man with CKD grade 4 and class III obesity showed a decrease in serum creatinine from 3.0 mg/dL to 2.86 mg/dL, an increase in GFR from 23 mL/min/1.73 m² to 24.4 mL/min/1.73 m², and improved sleep quality. Blood pressure reduced from 167/82 mmHg to 145/85 mmHg. Patient C. A 43-year-old man with CKD grade 4 and massive polycystic kidney disease reported reduced fatigue and normalized urination. His serum creatinine decreased from 3.26 mg/dL to 3.09 mg/dL, and his GFR improved from 22 mL/min/1.73 m² to 23.6 mL/min/1.73 m².Conclusion. Intravenous HHOnb therapy demonstrated potential benefits in improving renal function and overall health in CKD patients. These findings suggest that HHOnb could be a promising complementary treatment for CKD, though larger, controlled studies are needed to confirm its efficacy and safety.

Post-acute COVID-19 vaccination syndrome (PACVS) is distinguished from the normal post-vaccination state by altered receptor antibodies (Semmler et al. Vaccines 2023, 11, 1642). Here, we explore the symptoms registry and standard serum markers acquired in the above study to delineate the disease phenotype of PACVS. Symptoms reported by the participants overlapped with established complex dysautonomia syndromes (ME/CFS, POTS, MCAS, SFN). However, many participants were qualified for several (131/191) or none (31/191) of these syndromes. Unbiased clustering (modified Jaccard index) revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (&gt; 80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, vasomotor dysfunction, (ii) cardiovascular impairment, and (iii) cognitive impairment, headache, optic, oculo-motoric and acoustic dysfunctions were also frequently represented. Conspicuous serum markers encompassed increases in interleukins 6 and 8 and low fT3 levels (&gt; 80%), IgG-subclass imbalances and impaired iron-storage (&gt; 50%), and increases in sNFL (&gt; 30%). Serum markers were not correlated to specific symptoms or symptom clusters. A single and unique cause (i. e. SARS-CoV-2 vaccination) is improbable to trigger several distinct etiologies. Therefore, the symptoms and serological features observed in our study cohort probably represent facets of a single complex syndrome.

Concurrent Optical and Magnetic Stimulation (COMS) combines extremely low frequency electromagnetic and light stimulation modalities for enhanced wound healing. In this report, we investigated the potential mechanistic synergism between magnetic and light components by comparing their individual and combined cellular responses. Although each individual stimulation mode was capable of stimulating cell proliferation, magnetic fields exposure alone produced greater proliferation enhancement than light alone, yet their combined effects of were supra-additive of the individual responses. Reactive oxygen species were incrementally reduced by exposure to light, magnetics fields and their combination, where statistical significance was ultimately achieved. On the other hand, ATP production was significantly enhanced in response to magnetic exposure alone or in combination with light. These results suggest that mitochondrial respiratory efficiency was preferentially improved by the combination of the two stimuli. Protein expression related to cell proliferation was preferentially enhanced by the combinatory COMS modality as were the protein levels of the TRPC1 cation channel previously implicated as part of a calcium-mitochondrial signaling axis invoked by electromagnetic exposure and involved in proliferation. These results corroborate that light facilitates functional synergism with magnetic fields that ultimately impinge on mitochondria-dependent developmental responses. The aminoglycoside antibiotics (AGAs) have been previously shown to antagonize TRPC1-mediated magnetotransduction. Streptomycin applied during the exposure to any of the stimulation modes reduced proliferation enhancement, whereas streptomycin added after the exposure did not. Notably, the COMS modality and magnetic field exposure were capable of partially overcoming streptomycin antagonism of proliferation, whereas light alone was not. Transductional antagonism of combinatorial photon-electromagnetic effects by streptomycin thus aligns with previous studies showing that the AGAs block TRPC1-mediated magnetotransduction when applied during exposure. The prophylactic usage of the AGAs (neomycin) should be avoided during COMS therapy to maintain clinical efficacy and would be a common concern with most other electromagnetic regenerative paradigms.

Current Micro-Computed Tomography (Micro-CT) protocols for microvasculature analysis often necessitate organ dissection and non-clearable contrast agents. We describe a non-destructive technique for achieving high-resolution images of the human coronary microvasculature. Formalin-fixed human hearts were cannulated using venogram catheters designed for balloon occlusion. Catheters were anchored at the aortic root. Hearts were placed in sealable, radiolucent containers filled with insulating polyurethane foam. Iodine potassium iodide (IKI, Lugol's solution;6.3% Potassium Iodide, 4.1% Iodide) was injected into the coronary arteries. Contrast distribution was monitored using a North Star Imaging X3000 Micro-CT scanner with low-radiation settings, followed by high-radiation scans (3600 rad, 60 kV, 900 mA). We successfully imaged two intact human hearts with chronic total coronary occlusions of the right coronary artery. The scans enabled detailed analysis of the vasa vasorum surrounding stenosed and occluded segments. After imaging, both hearts were cleared of iodine and excess polyurethane foam and then returned to their initial formalin-fixed state for indefinite storage. Conclusions: This method allows for the non-destructive, high-resolution micro-CT imaging of coronary microvasculature in intact human hearts, paving the way for 3D microvascular reconstruction in a macrovascular context.

We present a case of adult-onset systemic chronic active EBV disease (CAEBV) in a 40-year-old woman with chronic HBV hepatitis. Initial symptoms resembled a viral illness, progressing to recurrent fever, transaminitis, and anasarca. Investigations revealed high-level EBV viremia and an abnormal T-cell population in liver and bone marrow, indicative of CAEBV. Liver biopsy showed CD3+ T-cells lacking TCRbeta and displaying dim/negative CD5, with elevated EBV-infected T-cells. Next-generation sequencing identified rare variants in CREBBP, SPEN, TP73, and PLCG2, suggesting potential contributions to disease pathogenesis. This case underscores diagnostic challenges and management complexities of adult-onset CAEBV, particularly with underlying chronic HBV infection. Genomic profiling offers crucial insights into the molecular landscape of rare lymphoid malignancies, highlighting the importance of personalized treatment strategies. The distinct immunophenotypic features underscore the heterogeneity in EBV-associated T-cell LPDs, urging further research for optimized clinical management

Abstract Sodium glucose cotransporter type 2 inhibitors are a new class of drugs acting on cardiovascular system, renal and metabolism in a multiple way. Indeed, even their principal action is on the transporter of sodium and glucose in the convoluted distal tubule, they have multiple actions as antifibrotic and endothelial protective action. Their principal mechanism consist in the loss of sodium and glucose. Therefore, they have effect on blood pressure and glucose metabolism. In a first period their use has been in the diabetic general population, later on some studies documented their activity in non-diabetic general population, in heart failure in chronic kidney disease. Only in recent years several small studies documented their efficacy in diabetic and non-diabetic kidney transplant patients, larger studies are few and very recent and open new ways for these drugs

Chronic lymphocytic leukemia (CLL) is a distinct category of lymphoproliferative disorder characterized by the clonal expansion of mature B cells, followed by their accumulation in primary and secondary lymphoid organs. Cluster of differentiation (CD) markers such as CD20, CD22, CD23, CD5, and CD81 serve as reliable prognostic indicators and disease progression factors in CLL. The human leukocyte antigen (HLA) system is a critical genetic variable in many diseases, with well-documented associations between HLA and various cancers. This study aims to investigate, for the first time, potential connections between HLA typing and CD marker expression in CLL. Despite being one of the most prevalent neoplasms in developed regions, there is a need for biomarkers that can improve survival predictions and identify possible genetic determinants. Methods: This study included 66 CLL patients and 100 controls, with all samples analyzed using biochemical methods, flow cytometry, and cytomorphology. Next-generation sequencing (NGS) was performed for HLA typing. Results: The results indicate that several CD markers are statistically associated with different HLA alleles. Specifically, CD20 was associated with HLA-DRB1*11:04:01; CD45 with HLA-C*07:01:01; CD79b with HLA-DPA1*02:01:02; CD23 with HLA-B*39:01:01; CD43 with HLA-DRB1*15:01:01; CD22 with HLA-B*49:01:01, HLA-C*07:01:01, HLA-DPB1*02:01:02, and HLA-DRB1*07:01:01; and CD81 with HLA-DPB1*04:02:01, HLA-DQA1*01:04:01, and HLA-DQB1*05:03:01.Conclusion: In conclusion, this research demonstrates significant statistical links between HLA genes and immunophenotypic markers in CLL patients, shedding new light on the immunological context of CLL.

The Interdisciplinary Canadian Collaborative ME Research Network (ICanCME), established in 2019, aims to foster research in Canada and contribute to finding the causes and possible treatments for myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS), thereby reducing the impact of ME/CFS on the health of Canadians. The main objectives of this paper are to suggest standards for ME/CFS research for the collection of data from participants (Recommended Data Elements) and to consider other factors, such as design, language, cultural issues, equity, and diversity. Consensus of the relevant contents of this research guideline was reached during the ICanCME working group meetings and were based on existing guidelines. Members of the working group contributed to guideline development based on their respective expertise. The proposed research guidelines could improve research quality and advance knowledge in the field of ME/CFS, and ultimately benefit ME/CFS patients.

Consumption of ultra-processed foods is associated with abdominal obesity, but this association has not yet been investigated in individuals on hemodialysis. This cross-sectional study, developed with 1014 individuals, aimed to analyze the prevalence of abdominal obesity and its association with the consumption of ultra-processed foods in individuals on hemodialysis. Consumption of ultra-processed foods was measured using a questionnaire, whose list of foods was based on the Surveillance System of Risk and Protective Factors for Chronic Non-Communicable Diseases through Telephone Enquiry. Waist circumference was used to determine the presence of abdominal obesity. The difference in proportions between the independent variables and the outcome was verified using Pearson's chi-square test. Hierarchical logistic regression was used to determine the association between the outcome and the independent variables. The prevalence of abdominal obesity was 77.22%. In the final model, higher consumption of ultra-processed foods, be male and an adult, have between 8 and 11 years of schooling and practice physical activity below the recommended level increased the chances of having abdominal obesity. The research provides a basis for the creation and improvement of public policies that promote improvements in these health determinants.

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.

The prevalence of patients on buprenorphine therapy presenting for elective surgery has increased. Buprenorphine is a widely used medication for management of patients with chronic pain. It is also used for maintenance therapy for patients with a history of opioid use disorder (OUD). Due to lack of standardized protocol for managing patients on buprenorphine peri-operatively, we performed a retrospective analysis to compare pain score outcomes and post-operative opiate requirements between patients who continued versus discontinued buprenorphine. We identified 35 patients, 11 continued buprenorphine and 24 discontinued buprenorphine. The average Post-Anesthesia Care Unit (PACU) pain score was 7.54 for those who discontinued pre-operative buprenorphine and 5.59 for those who continued (P value 0.0339). The average post-operative Morphine Milligram Equivalent (MME) use was 86.13 for those who continued pre-operative buprenorphine and was 107.70 for those who discontinued buprenorphine (P value 0.6439). The results from our study correlate with several previous studies which showed lower PACU pain scores in patients who continued buprenorphine. There is a benefit of decreased pain post-operatively when pre-operative buprenorphine is continued and having a decrease in relapse in those with a history of OUD.

Patients with chronic kidney disease (CKD), particularly those with end-stage kidney disease (ESKD) undergoing dialysis or kidney transplantation, face ongoing challenges in relation to the risk of COVID-19. In addition to their underlying condition, factors such as immune-evasive variants, immunosuppressive therapies, and the need for dialysis contribute to poor COVID-19 outcomes in this population. Severe COVID-19 can lead to the deterioration of CKD/ESKD, resulting in acute kidney injury, septic shock, and respiratory failure. Moreover, patients with CKD/ESKD have shown impaired response to COVID-19 vaccination, with seroconversion failures associated with the burden of immunosuppressive treatments, further heightening their vulnerability to severe disease. Despite the current endemic, it is crucial to acknowledge the ongoing significance of COVID-19 as a serious threat to patients burdened with chronic diseases like CKD and ESRD. Understanding the impact of COVID-19 on these patients is essential, as they remain at risk of severe disease progression. This paper presents the results of a literature review to enhance our understanding of COVID-19-related risks in patients with CKD/ESKD. Expert insights and illustrative scenarios provide practical perspectives and highlight the importance of risk stratification based on clinical factors for guiding targeted measures and treatments to mitigate COVID-19 risks in these vulnerable patients.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

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.

Nutrition therapy is the best solution to human chronic diseases, especially beer and barley which play an important role in human health and civilization. We demonstrated the actional mechanism of functional ingredients in beer and barley to combat chronic diseases, based on PubMed, google, CNKI, and ISI Web of Science databases from 1997 to 2024. Beer is rich in functional ingredients that is a complex of barley malt and hops; the health effect of beer against 26 chronic diseases is highly similar to that of barley, due to molecular mechanism of polyphenols (phenolic acids, flavonoids), melatonin, minerals, bitter acids, vitamins, and peptides. The ancient German Beer Purity Law provides much scientific basis today, especially indirectly supporting the human one cell disease theory. Low purine beer can be produced by enzymatic and biological degradation and adsorption of purines as well as dandelion addition. Functional beer with low purine and high active ingredients made from Beer Purity and barley malt as well as functional foods addition will be the key and important development direction, such as ginger beer and ginseng beer, especially coix-lily beer at the ancestors ca. 9000 years ago. This review paper not only reveals the actional mechanism of beer overcoming human chronic diseases, but also provides scientific basis for the development of functional beer for the prevention and treatment of human chronic 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<0.001), NH weight (r=0.882, p<0.001), height (r=0.694, p<0.001), body mass index (BMI) (r=0.701, p<0.001), lean tissue mass (LTM) (r=0.664, p<0.001), lean tissue index (LTI) (r=0.433, p<0.001), fat mass (r=0.614, p<0.001) and fat tissue index (FTI) (r=0.449, p<0.001), and was negatively associated with clinical variable such as hydration status (p<0.001). HGS significantly and positively correlated with anthropometric parameters such as body mass (r=0.319, p=0.003), NH weight (r=0.315, p=0.004), height (r=0.666, p<0.001), LTM (r=0.490, p<0.001), LTI (r=0.238, p=0.029), and ASM (r=0.501, p<0.001), and was negatively associated with clinical variables like uric acid (p=0.039) and urea (p<0.001). After adjustment for age, sex and height, HGS remained significantly and negatively related with uric acid (β=-1.078, p=0.041) and hydration status (β=-0.805, p=0.042). Conclusions In CKD patients, ASM is determined mainly by anthropometric parameters but HGS - both by anthropometric and clinical variables specific for CKD.

The main goal of our scientific study is to determine the particular characteristics of the endo-scopic image of the otorhinolaryngologic pathology of nasopharynx, which is called chronic rhinosinusitis in association with gastroesophageal acid reflux disease. Background/Objectives: to identify a specific features in the endoscopic picture of chronic rhinosinusitis associated with acid gastroesophageal reflux disease symptoms. Methods: there were selected 521 adult patients, from this sample as a main group we have selected only 95 patients with the highest scores on the Reflux Symptom Index (RSI) (>20) and Reflux Symptom Score-12 (RSS-12) (>130) questionnaires. As a control group we have selected 41 adult patients only with chronic rhinosinusitis and 10 healthy patients. Results: there were significant changes in the nasopharyngeal mucosa. In-creased vascularity of the nasopharyngeal mucosa was noted in 91 patients (95,7%). Hypertrophy of the nasopharyngeal mucosa was found in 83 patients (87,4%). In 77 (81,1%) patients, mucus was found in the nasopharynx with different characteristics of color and consistency, and no mucus or other secretions were found in the middle nasal passages in these patients. In 62 pa-tients (65,3%) asymmetric hypertrophy of the mucosa of the oropharynx was noted. Conclusions: the presence of specific features of the endoscopic picture of the nose and nasopharynx of pa-tients with chronic rhinosinusitis associated with gastroesophageal disease symptoms and pro-posed a method for assessing the degree of influence of gastroesophageal reflux disease on the mucosal layer of the nose and nasopharynx. The possible influence of symptoms of gas-tro-oesophageal reflux disease on the course and severity of clinical manifestations of exacerba-tions of chronic rhinosinusitis needs further investigation.

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&lt;0,05) in the group without depression, except for a significant one between depression and state anxiety (p&lt;0,01) in the second stage. Significant correlations were identified between all indicators (p&lt;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.

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS) and Long COVID are characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and Long COVID, suggesting that use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation, as well as neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and Long COVID.

This review was written with the aim of examining the effects that caused an insult such as a wound to an organ such as the skin. Before examining the cellular mechanisms relating to wound healing, the reader is invited to read the structure of the skin as a necessary basis for understand-ing the final aim of this review. The structure of the skin as a basis for understanding the phe-nomena relating to wound healing is addressed taking into account updated literature that ad-dresses the numerous problems of the skin microenvironment. Starting from this awareness, the paragraph dedicated to wound healing becomes complicated when this phenomenon is not im-plemented and therefore the problems dedicated to chronic wounds, keloids and hypertrophic scars are addressed, pathologies that are still difficult to understand and treat today.