Chronic Chagas Cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilized electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodeling and for examining the potential of anti-parasitic drugs to prevent or alleviate CCC development and progression.

Functional neurological disorders (FND) are relatively frequent disabling conditions. Given their complexity, multidisciplinary rehabilitation is envisaged. Whole-body cryostimulation (WBC) represents a promising adjuvant treatment, mainly because of its anti-inflammatory and exercise-mimicking effects. Here, we propose a novel use of WBC in a wheelchair-ridden 61-year-old woman diagnosed with FND and other comorbidities, who, after several therapeutic and rehabilitation failures, underwent a multidisciplinary rehabilitation program including WBC. The 4-week program included physiotherapy, nutritional intervention, psychological support, and WBC. Questionnaires to assess disease impact, pain level, perceived fatigue and sleep quality were administered. At discharge, improvements in body composition, haematological biomarkers, physical performance, and questionnaire scores were observed. The patient was able to walk with a walker for medium distances, even outdoors. We observed unprecedented improvements, particularly in functional parameters and questionnaire scores. Although we cannot ascertain to which extent WBC per se contributed to the improvements measured, subjective reporting and our clinical observation were that WBC, the only intervention not previously experienced by the patient, acted as a booster for the rehabilitation interventions. Further research will be necessary to rule out any possible placebo effect and to assess the effects of WBC on FND.

Background: This study aimed to compile and analyze an assortment of research findings concerning potential therapeutic strategies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The understanding of the multifaceted nature of ME/CFS and the need for varied and personalized therapeutic approaches were central to this investigation.Methods: A comprehensive review and analysis of various studies conducted on ME/CFS was undertaken. These studies covered a wide array of interventions, including pharmacological treatments, nutritional supplements, dietary changes, physical therapies, and lifestyle modifications. The analysis pertained to the effectiveness of these interventions, potential physiological and biochemical markers, and the response of ME/CFS patients to different treatment strategies.Results: The 22 selected papers investigated demonstrated varied responses to the multitude of interventions. While some interventions showed significant improvement in fatigue and biochemical parameters, others found no significant differences between the treated and control groups. Potential physiological and biochemical markers for ME/CFS, such as impaired T cell metabolism, reduced flow-mediated dilation, and decreased work rate at the ventilatory threshold, were highlighted.Conclusion: The findings underscored the complexity of ME/CFS and the need for personalized treatment strategies. Despite mixed results and several limitations, these studies collectively contributed to understanding ME/CFS's complex pathophysiology and treatment, laying the groundwork for future research towards more effective therapeutic strategies for this debilitating disease.

Leukemia cutis (LC) is defined as leukemic infiltration of the epidermis, the dermis, and the subcutaneous tissue. Leukemia cutis may follow or occur simultaneously with the diagnosis of systemic leukemia. However, cutaneous lesions are occasionally diagnosed as the primary manifestation of leukemia. Leukemic skin infiltrations demonstrate considerable variation regarding number of changes, distribution, and morphology. The highest incidence of LC is observed in chronic lymphocytic leukemia, monocytic and myelomonocytic acute myeloid leukemia, and in T-cell lineage leukemia. Although the pathogenic mechanism of the invasion of leukemic cells into the skin is not well understood, chemokine receptors and adhesion molecules as well as genetic characteristics of leukemia are thought to play a role. Leukemic skin lesions may be localized or disseminated and may occur alone or in combination on any site of the skin, most frequently in the trunk and extremities. The most common clinical presentations of leukemia cutis are papules, nodules, macules, plaques, and ulcers. In most patients, complete or partial resolution of cutaneous infiltrations occurs simultaneously with hematologic remission. However, in patients with resistant disease or recurrent skin infiltration, local radiotherapy can be used. This review presents recent data on the pathogenesis, diagnosis and treatment of leukemic skin involvement in different types of leukemia

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and elderly individuals. DM may accelerate the aging process, and the age-related declines in the estimated Glomerular Filtration Rate (eGFR), can pose a challenge to diagnose diabetic kidney disease (DKD) using standard diagnostic criteria especially with absence of severe albuminuria among the elderly. In the presence of CKD and DM, elderly patients may need multidisciplinary care due to susceptibility to various health issues e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to the elderly. We review the evidence that the benefits from these newer therapies apply equally to elderly and non-elderly patients and propose a framework for the management of DKD by discussing the nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), Sodium Glucose Co-Transporter two inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and Glucagon Like Peptide 1 Receptor Agonists (GLP1-RAs).

Chronic pain has increasingly become a significant health challenge, not just as a symptomatic manifestation but also as a pathological condition with profound socioeconomic implications. Despite the expansion of medical interventions, the prevalence of chronic pain remains remarkably persistent, prompting a turn towards non-pharmacological treatments, such as therapeutic education, exercise and cognitive-behavioral therapy. With the advent of cognitive neuroscience, pain is often presented as a primary output derived from the brain, aligning with Engel's Biopsychosocial Model which views disease not solely from a biological perspective but also considering psychological and social factors. This paradigm shift, brings forward potential misconceptions and over-simplifications. The current review delves into the intricacies of nociception and pain perception. It questions long-standing beliefs like the cerebral-centric view of pain, the forgotten role of the peripheral nervous system in pain chronification, misconceptions around central sensitization syndromes, the controversy about the existence of a dedicated pain neuromatrix, the consciousness of the pain experience and the possible oversight of factors beyond the nervous system. In re-evaluating these aspects, the review emphasizes the critical need for understanding the complexity of pain, urging the scientific and clinical community to move beyond reductionist perspectives and consider the multifaceted nature of this phenomenon.

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

Background Total serum bile acids (TSBA), liver-spleen scan and dynamic liver functional tests, in our case the antipyrine clearance (Ap Cl), have been long adopted. The aim of our study was that of assessing whether some diagnostic tests, scarcely performed due to the novel techniques implementation, were reliable diagnostic tools. Methods Data extracted from records of two well-matched for age and gender populations was retrospectively analysed. Specifically, 17 patients with biopsy-proven chronic hepatitis were confronted with 17 subjects suffering from liver cirrhosis. Clinical, laboratory and instrumental findings, such as the Child-Pugh classification, the number connection test for evaluating hepatic encephalopathy, prothrombin time, serum albumin levels, TSBA concentration, Ap Cl determination, abdominal ultrasound and liver-spleen scan imaging as well as endoscopy features were evaluated. Results Cirrhotics showed a median concentration of TSBA increased respect to that of patients with chronic hepatitis, independently from gender, 20.1 versus 12.24 micromol/L, P= 0.0054. The median AP Cl value of the patients with liver cirrhosis was reduced confronted with that of patients with chronic hepatitis, specifically, 13.92 opposed to 18.3 mcg Ap/dL, P= 0.045. Furthermore, the median liver-spleen scan score was higher in cirrhotics than in chronic hepatitis patients, i.e., 3.47 versus 1.47, P= 0.000. The AUROCs of TSBA levels and of the liver-spleen scan scores for differentiating patients with liver cirrhosis from those with chronic hepatitis were 0.82 and 0.96, respectively. When was applied a new predictive model, combining the previous ones, the AUROC to discriminate patients belonging to the two populations was 0.98. The best cut-off of the new index was 26, with a sensitivity and specificity of 100.00% and 82.35%, respectively, correctly classifying 91.18% of the patients. Discussion Both TSBA and liver-spleen scan were high discriminant as well as their combination, while Ap Cl showed some limitations as reliable diagnostic tool. TSBA and liver-spleen scan have been too soon and unnecessarily overlooked.

Background: Influenza vaccine is a tool for preventing infection and reducing exacerbations in patients with asthma and chronic obstructive pulmonary disease (COPD). Purpose of this study is to investigate dynamics of CRP and serum cytokines (IL-2, IL-6, IL-10, IL-17) in patients with asthma and COPD, as well as to perform a correlation analysis with the clinical parameters of the disease manifestation. Methods: The study included 34 patients with asthma, 20 patients with COPD vaccinated against influenza during a period of remission from 2 to 4 weeks, both groups being under a basic maintenance therapy, and 26 healthy individuals vaccinated with the trivalent polymer-subunit vaccine Grippol® Plus, containing 5 µg of influenza virus strains and 500 µg of azoximer bromide. Results: Observing patients with asthma and COPD, during a year after the vaccination, has revealed a significant reduction in exacerbations frequency (p < 0.05) and duration (p < 0.05) of the bronchial obstructive syndrome (BF). Before the vaccination the IL-6 level in patients with asthma had a direct moderate correlation with duration of exacerbations of the underlying disease (p < 0.05), along with the number of systemic corticosteroids courses during exacerbations (p < 0.05). In 12 months after the vaccination, while assessing cytokine profile of all study groups, a significant reduction in the level of IL-6 was observed, compared to the baseline values (p< 0.05). Conclusion: Conducted analysis of immunological, clinical, and functional parameters of patients with asthma and COPD has proven for influenza vaccine to be effective in BF patients.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia caused by both immune-mediated platelet destruction and impaired platelet production in the bone mar-row, in the absence of any other identifiable cause of low platelets count. ITP in adult patients is a disease that frequently relapses and/or becomes refractory to multiple treatments during its course, with only a small minority of adult patients attaining a sustained complete remission off-therapy. Treatment of refrac-tory ITP can be challenging, due to the unlikeliness of attaining complete response over time. On the other hand, isolated thrombocytopenia may be due to a misdiagnosed clonal myeloid disorder, such as myelodys-plastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), thus mimicking ITP. We here per-form a narrative review on the association between ITP and MDS/CMML and the possibility of overlap and misdiagnosis between these conditions, while we report also the case a patient treated for a severe re-fractory thrombocytopenia which bone marrow examination led to suspect an overlap of MDS and ITP. Our clinical case describes ITP which is refractory to glucocorticoids, high-dose immunoglobulins, Rituxi-mab, splenectomy, thrombopoietin receptor agonists and Fostamatinib, that ultimately attained a short-lived response to a hypometylating agent that was initiated due to bone marrow examination that aroused the suspect of MDS.

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

Objectives: The aim of the study was to evaluate the effects of oral administration of clinical dose of beraprost for feline CKD in healthy cats, and also to examine whether NOS inhibition reversed them. Methods: A placebo-controlled pharmacological sequential design study was carried out to assess plasma aldosterone and renin concentrations, mean blood pressure, heart rate, renal plasma flow, and renal vascular resistance. Results: Beraprost reduced plasma aldosterone when compared to the placebo (P < 0.05); this was reversed when NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was added to beraprost treatment (P < 0.01). No differences in the plasma renin concentration or hemodynamic parameters were detected between beraprost and placebo. The correlation ratios (η2) showed opposite relationships between beraprost and added L-NAME effects on aldosterone concentration, mean blood pressure, heart rate, renal plasma flow, and renal vascular resistance (P < 0.001). Conclusions: In healthy cats, the clinical dose of beraprost suppresses plasma concentration of aldosterone, which can be reversed by inhibition of NOS.

Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is an acquired disease with significant morbidity that affects both children and adults. Effective tools to assess functional capacity (FC) are severely lacking which has significant consequences for timely diagnosis, assessments for patient disability benefits and assessing the impact and effectiveness of interventions. In interventional research the inability to assess FC can result in an incomplete assessment of the potential effect of the intervention. Specifically of concern is that if an intervention is effective in reducing symptom load, patients may increase their activity level to reach a pre-intervention symptom load. Thus, if FC is not accurately assessed, beneficial treatment outcomes may be missed. To address this issue, using extensive, repeated patient feedback we have developed a new questionnaire, FUNCAP, to achieve optimal FC assessment in ME/CFS patients. The questionnaire covers eight domains and activity types: A. Personal hygiene / basic functions, B. Walking / movement, C. Being upright, D. Activities in the home, E. Communication, F. Activities outside the home, G. Reactions to light and sound, and H. Concentration. Through five rounds of anonymous web-based surveys and a further test - retest validation round, two versions of the questionnaire were developed; a longer version comprising 55 questions (FUNCAP55) to improve diagnostic and disability benefit/ insurance FC assessments and a shorter version (FUNCAP27) for interventional research and less extensive FC assessments. FUNCAP may also be useful in other conditions where fatigue and PEM is present, such as Long Covid.

(1) Background: The goal of the study was to evaluate psychological tolerance and health-related quality of life (QOL) in head and neck (HN) cancer patients treated with definitive accelerated radiotherapy (DART); (2) Methods: Seventy-six recurrence-free patients eligible for the study, who were treated with DART in the CAIR-2 phase III clinical study (median of follow-up=47 months), completed EORTC QLQ-C30 with H&amp;N35 module, Hospital Anxiety and Depression Scale (HADS) and Visual–Analog Scales (VAS) of pain in HN and the neck / arm area.; (3) Results: The most dominating symptoms measured with QLQ-C30 were: fatigue (44/100), sleeplessness (39/100), financial problems (38/100) and pain (32/100). Within H&amp;N35 the highest scores were reported on the subscales of sticky saliva (60/100), mouth dryness (65/100) and increased intake of painkillers (50/100). Pain (VAS) was reported by 87% (HN area) and 78% (shoulder) of the patients, with a mean score of 3/10. One-third reported depressive mood (HADS≥15 points) with an average score of 12.5/42 p. The depressed group, who smoked more as compared to non-depressed before DART (96% vs 78%) and required steroids treatment (85% vs 58%) during DART, also scored significantly worse on 23 of 35 subscales of QLQ-C30 and H&amp;N35 and experienced more intense pain (VAS). Women, and less advanced patients scored better in several aspects of the quality of life; (4) Conclusions: Patients treated with DART struggle with low quality of life and persisting treatment-related symptoms including constant pain. HNC survivors, especially those, who are depressed, may require additional psychosocial, rehabilitation and medical intervention programs..

Chronic Kidney Disease (CKD) is a major public health concern with an increasing proportion of sufferers progressing to renal replacement therapy (RRT). Early identification of those at risk of disease progression could be key in improving outcomes. We hypothesise that urinary liver-type fatty acid binding protein (uL-FABP) may be a suitable biomarker for CKD progression and can add value to currently established biomarkers such as urinary protein to creatinine ratio (uPCR) 583 participants with CKD 1-5 (not receiving renal replacement therapy) entered a 2-yr prospective longitudinal study. UPCR and uL-FABP were measured at baseline and CKD progression was defined as either i) a decline in eGFR of >5ml/min/1.73m2 or an increase in serum creatinine by 10% at 1-yr or ii) a decline in eGFR of >6 ml/min/1.73m2, or an increase in serum creatinine by 20% at 2-yrs or iii) the initiation of RRT. A combined outcome of initiating RRT or death was also included. Approximately 40% of participants showed CKD progression. UL-FABP predicted CKD progression at both years 1 and 2 (OR 1.01, p<0.01). Sensitivity and specificity were comparable to those of uPCR (AUC 0.623 v 0.706) and heat map analysis suggested that uL-FABP in the absence of significant proteinuria can predict an increase in serum creatinine of 10% at 1yr and 20% at 2yr. The risk of the combined outcome of initiating RRT or death was 23% higher in those with high uL-FABP (p<0.01) independent of uPCR. UL-FABP appears to be a highly sensitive and specific biomarker of CKD progression. The use of this biomarker could enhance the risk stratification of CKD and its progression and should be assessed further.

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long-considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown by International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-meter walking test with the aid of a walking frame and ankle foot orthoses. The success in the sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.

Endovascular techniques are currently considered as a first line treatment options for lower limb chronic limb-threatening ischemia (CLTI), defined by the presence of ischemic rest pain and severe tissue loss such as ulcers or gangrene. Although the technical success rate of endovascular revascularization is high, in specific patients with advanced infrapopliteal disease and absence of run-off tibial vessels ("desert foot"), the chance of successful revascularization is minimal. In order to avoid primary amputation several treatment option are currently being investigated, including different strategies such as gene therapy or venous arterialization techniques. This review focuses on the percutaneous deep venous arterialization technique, recently introduced in everyday clinical practice, as a promising, minimally invasive treatment option for limb salvage in CLTI patients presenting with “desert foot”.

Rationale: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency. Although most mutations are linked to the X chromosome, therefore affecting males, there are autosomal recessive forms that therefore affect both sexes. Clinically it is characterized by recurrent and severe bacterial and fungal infections, with formation of granulomas, due to the inability of phagocytes to generate reactive oxygen compounds, necessary for the intracellular death of phagocytosed microorganisms. Patient concerns: We reported a 12-year-old boy with pneumonia with pneumatocele of possible staphylococcal etiology at one year of age, bilateral orchitis secondary to Salmonella with hematogenous spread, osteomyelitis due to Salmonella, gastroenteritis due to Salmonella enteritidis, liver abscesses due to Staphycococcus aureus and lymphomatoid papulosis and pyodermititis. Diagnoses: In the biochemical diagnosis, the presence of yellow dye (NBT) and absence of dark bluish black dye (formazan) was evidenced. Regarding the genetic diagnosis, the presence of the mutation in exon 10 of CYBB (OMIM 306400) (Xp21.1) that encodes the gp91phox protein was demonstrated. Interventions and outcomes: Treatment was started with trimethoprim/sulfamethoxazole 400/80 mg every 24 hours via oral, and antifungal prophylaxis with itraconazole 200 mg every 24 hours orally is added, after which he does not present serious bacterial or fungal infections, not being able to administer immunomodulatory treatment with recombinant human Interferon gamma-1b. Lessons: The clinical finding of frequent severe infections associated with granulomas, CGD should be suspected. Treatment of this primary immunodeficiency is trimethoprim/sulfamethoxazole and itraconazole. Importantly, it indicated that the mutation in exon 10 of CYBB (Xp21.1) that encodes the gp91phox might influence the pathogenesis of CGD.

Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia and anemia. Moreover, it is associ-ated with SRSF2 mutations and rarely with CSF3R variants. The presented case is an 84-year-old patient with persistent anemia and monocytosis. Due to the presence of dysmorphic granulocytes, monocyte atypia and myeloid precursors in peripheral blood, the patient was submitted to bone marrow examination. The diagnosis was consistent with CMML type 2. Hemocoagulative test showed an increase of fibrinolysis markers. Next generation targeted sequencing showed TET2 and SRSF2 mutations, along with an unexpected CSF3R germline missense variant, rarely encountered in CMML. The pa-tient started Azacitidine treatment reaching normal hemostatic process values. In con-clusion, we identified a heterozygous germline mutation that, cooperating with TET2 and SRSF2 variants, have been responsible for the hemorrhagic manifestation.

Background: The current review was conducted to determine the effectiveness of atenolol on all-cause mortality rate among Asian patients with chronic progressive diseases, mainly diabetes mellitus, primary hypertension, and coronary artery disease. Methods: We searched the COCHRANE, MEDLINE, TRIP, and EMBASE databases for published articles up to 31 March 2023. Studies that compared all-cause mortality rates among Asian patients who were on atenolol or other medications were included. Results: The review included 79603 Asian patients from three cohort studies. Out of the studied patients, 36046 were atenolol users and 43557 were non-atenolol users. The review revealed that atenolol users recorded lower all-cause mortality rates compared to non-users with a significant difference (OR= 0.57, CI= 0.44-0.75, P<0.001). The pooled estimate of the all-cause mortality rate was also lower among atenolol users (7.02%) compared to metoprolol tartrate users (13.15%) with a significant difference (OR= 0.50, CI= 0.47-0.53, p < 0.0001). Although the included studies were categorized as having a low risk of bias for most of the studied domains, significant heterogeneity was recorded across these studies (I2 =88%, P=0.001). Conclusion: This review found that atenolol when compared to a control or metoprolol tartrate, has a significant effect in reducing the all-cause mortality rate among Asian patients with chronic progressive disease.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common type of leukemia in the Western world. Mutations in different genes, such as TP53 and ATM, and deletions in specific chromosomal regions, including 11q or 17p, have been associated with a worse prognosis for the disease. Recent research from our group has demonstrated that, contrary to the usual cancer development process through missense mutations, B-CLL is driven by the overexpression of the small GTPase RRAS2 in its wild-type form, without activating mutations. While some mouse models of this disease have been developed to date and are commonly used in B-CLL research, they come with various disadvantages, such as a long waiting period until the leukemia fully develops, the need for cell engraftment, or, in some cases, a failure to replicate the alterations found in human patients. We have recently introduced Rosa26-RRAS2fl/flxmb1-Cre as a new mouse model of B-CLL with full disease penetrance. In this work, we have validated this mouse model as a novel tool for the development of new therapies for B-CLL by testing two of the most widely applied targeted agents: ibrutinib and venetoclax. This also paves the way for the development of new targeted agents against R-RAS2 itself, an approach that has not yet been explored in clinical practice.

Background: Recommended CKD first-line diagnostics is based on GFR-determination by Creatinine. Cystatin C-use may provide better assessment. Methods: We compared creatinine- and cystatin C-derived eGFR determination in first-line di-agnostic of 112 hospital patients aged >60 years (median=76 years). Patients were judged kid-ney-sane according to first-line diagnostic recommendations (N=61, eGFR (CKD-EPI) ≥60ml/min/m2, total urine protein <150mg/g creatinine, urinary red and white blood cells not increased) or classified at-risk for kidney insufficiency due to aortic valve dysfunction (N=51). Plausibility of eGFR-values was evaluated retrospectively by final case diagnoses. Results: eGFR (CAPA) was found linearly correlated to eGFR (CKD-EPI) (R2=0.5, slope=0.69, p<0.0001). In 93/112 (>80%) cases, eGFR (CAPA) yielded lower values (on average ≈20%). In 55/112 (49%) cases CKD-stage decreased. CKD-reclassification from kidney-sane to kid-ney-insufficient state (i.e. CKD1/2 to CKD3a/b or 4) or reclassification to more severe kidney in-sufficiency (i.e. CKD3a3b/4 or 3b4) was found in 41/112 (37%) cases. Worsening of CKD-classification (kidney-sanekidney-insufficient) based on eGFR (CAPA) was in 30% of cases plausible in the light of final case-diagnoses. Conclusion: In elderly patients (>60 years), renal function appears systematically overestimated by creatinine-based eGFR (CKD-EPI) heralding for this group employment of cystatin C-based eGFR (CAPA) as first-line diagnostic.

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

Non-alcoholic steatohepatitis (NASH) is a complex disease resulting from chronic liver injury associated with obesity, type 2 diabetes, and inflammation. Recently, multi-target drugs have been proposed to treat complex diseases including NASH; however, their manufacturing pro-cesses remain time- and cost-intensive and inefficient. Therefore, to overcome these limitations, we developed UniStac, a novel enzyme-mediated conjugation platform for multi-specific drug development. UniStac demonstrated high conjugation yields, optimal thermal stabilities, and robust biological activities. Through such platform, we designed a tetra-specific compound, C-192, targeting Glucagon-like peptide 1 (GLP-1), Glucagon (GCG), Fibroblast growth factor 21 (FGF21), and Interleukin-1 receptor antagonist (IL-1RA) simultaneously for the treatment of NASH. The biological activity and treatment efficacy of C-192 were confirmed both in vitro and in vivo using a methionine–choline-deficient (MCD) diet-induced mouse model. C-192 exhibited profound therapeutic efficacies compared to conventional drugs, including liraglutide and dulaglutide. C-192 significantly improved alanine transaminase levels, triglyceride accumula-tion, and the non-alcoholic fatty liver disease activity score. Our results collectively provide clin-ical feasibility of UniStac for developing multi-specific drugs, and C-192 as an innovative thera-peutic opportunity for severe NASH, as it exerts synergistic effects across multiple targets.

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

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

Hemodialysis (HD) patients experience significant psychological stress related HD. Coping strategies are utilized to help these patients cope with this stress. Prevalence of different types of coping strategies in relation with differential levels of HD-related stress scores and by demographics were assessed. HD patients aged 18 years and above who were seeking regular treatment in a specific HD-unit of a hospital in the upper Midwest, were surveyed between March 2020 and July 2020. Descriptive statistics, correlational analyses, and regression analyses were performed. Females could be expected to have emotional coping scores 8 units greater than males, as B = 8.017 for sex in the model, p =.000. Females could be expected to have coping scores 6.4 points higher than males when adjusted for stress levels, as: B = 6.351, p =.001 for sex in the model. For each 1point increase in Stress Score, the Coping Score could be expected to: increase 6.8 points when adjusted for Sex, where B = 6.751 and p =.000. Increased prevalence of emotional pre-occupation was only observed among female patients which increased with the increase in stress. Psychological interventions in female HD patients should be strongly considered in addressing emotional pre-occupation coping.

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

Intestinal microbiota attracts daily attention of a growing number of study which have attempted to link gut dysbiosIs with a variety of disease states: irritable bowel syndrome (IBS), inflamed bowel disease (IBD), Crohn's disease (CD), leaky gut syndrome (LGS), food intolerance, diabetes, metabolic syndrome, cancer, etc.. In our study we analyzed how intestinal dysbiosis may be related to chronic fatigue syndrome (CFS) and depression through the exchange of information through the gut-brain axis (GBA). We studied 33 subjects, 13 males and 20 females, who reported CFS or/and depression: we investigated their salivary cortisol levels, blood serotonin, omega 3/6 ratio, intestinal dysbiosis (calculated on the urinary levels of indoxyl sulfate and skatole), and we looked for the presence of Candida a. or mycetes in the stool; the data accumulated with this research show a correlation between the presence of Candida a./miceti, indoxyl sulfate urine values beyond the physiological and low serotonin levels. In addition, data analysis showed that the EPA/DHA values also show pro-inflammatory levels in case of dysbiosis and low serotonina levels. The relationship, however, with cortisol levels requires further research although this study showed a statistically significant positive correlation between these values, measured at specific times, and serotonin levels. Aims its connections with We investigated the relationship between stress (evaluated through the measurement of salivary cortisol levels) and gastrointestinal efficiency measured as a function of intestinal fermentative and putrefactive dysbiosis, evaluating the levels of urinary indoxyl sulfate in the first case (a possible correlation with the presence of Candida spp or Mycetes in the subjects feces was investigated), urinary skatole levels in the second one, in patients with chronic fatigue syndrome (SFC) and depression. In these patients we also have studied omega 3/6 ratio, and finally we have analized the impact that the alteration of these parameters can have on the serotonin levels. This research attemps to highlight the contact points, in some cases not so obvious, among these topics, contact points that, although they give us interesting indications, show the need to be further deepened by analyzing a larger amount of data.

Patients with advanced chronic liver disease (ACLD) or cirrhosis undergoing surgery have an increased risk of morbidity and mortality in contrast to the general population. Retrospective, observational study of ACLD patients to evaluate the predictive capacity of previous surgical risk scores in a European cohort of patients. ACLD was defined by the presence of thrombocytopenia <150.000/uL and splenomegaly; AST-to-Platelet Ratio Index >2; nodular liver edge by ultrasound; transient elastography >15 kPa and/or signs of portal hypertension. We assessed variables related to 90-day mortality and the discrimination and calibration of current surgical scores (Child-Pugh, MELD-Na, MRS, NSQIP, and VOCAL-Penn). Only patients with ACLD and major surgeries included in VOCAL-Penn were considered (n=512). The mortality rate at 90 days after surgery was 9.8%. Baseline disparities between H. Mar and VOCAL-Penn cohorts were identified. Etiology, obesity, or platelet count not were associated with mortality. The VOCAL-Penn showed the best discrimination (C-statistic90D= 0.876) and overall predictive capacity (Brier90D= 0.054) but calibration was not excellent in our cohort. VOCAL-Penn was suboptimal in patients with diabetes (C-statistic30D= 0.770), without signs of portal hypertension (C-statistic30D= 0.555), or with an abdominal wall (C-statistic30D= 0.608) or urgent (C-statistic180D= 0.692) surgeries. Our European cohort has shown a mortality rate after surgery similar to those described in American studies. However, some variables included in the VOCAL-Penn score were not associated with mortality, and VOCAL-Penn’s discriminative ability decreases in patients with diabetes, without signs of portal hypertension, and with abdominal wall or urgent surgeries. These results should be validated in larger multicenter and prospective studies.

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dis-autonomy tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2-vaccination of healthy controls (N = 89, 71 females, mean/ median age 39/ 49 years) were compared with corresponding values of PACVS-affected persons (N= 191, 159 females, mean/median age: 40/39 years) exhibiting chronic fatigue/dis-autonomy (≥ three symptoms for ≥ five months after last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases of 11 receptor-antibodies (by 25 - 50 %, p < 0.0001), increases in two receptor-antibodies (by 15 - 25 %, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p &lt; 0.0001) by increased angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/ml, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/ml, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/ml, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers

We investigated whether cigarette smoking and dietary acid load (DAL) are associated with the risk of chronic obstructive pulmonary disease (COPD) in middle-aged healthy Korean men. Healthy men without diagnosed chronic disease (40-64 yrs) from the KNHANES-VI (2013–2015) included in the analysis (n=774) were subdivided by smoking status and DAL levels as estimated by the net endogenous acid production (NEAP) quartile. Current smokers tended to have a higher risk of COPD than non-smokers before and after the adjustment. When divided by the DAL quartile, the Q4 tended to have a higher risk of COPD than the Q1. Additionally, current smokers with lower (Q2), modest (Q3), and highest NEAP scores (Q4) showed more than 4-fold higher risks of COPD than the non-smokers with the lowest NEAP scores (Q1). Ex–smokers with higher NEAP scores (Q3 and Q4) showed more than 4-fold higher risks of COPD than the Q1. Interestingly, the risk of COPD was also more than 6-fold higher in non-smokers with the highest NEAP scores compared to the Q1. NEAP scores and smoking status synergistically increased the risk of COPD in middle-aged healthy Korean men. It suggests that DAL levels are an important factor for the prevention and management of COPD.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography dynamic multiple reaction monitoring targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of Chronic Myeloid Leukaemia (CML), we found that intra- and extra-cellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), and extracellular Prostaglandin F_2α (PGF_2α), 5-Hydroxyeicosatetraenoic acid (5-HETE), Palmitic acid (PA, C16:0) and Stearic acid (SA, C18:0) were altered in response to immunomodulation by type I Interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism with potential relevance in the context of cancer inflammation and CML.

Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is the secreted and membrane-associated proteins, which regulate diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence revealed that excess SEMA3A expression and subsequent signaling pathway aggravates kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports demonstrated that inhibition of SEMA3A ameliorated kidney injury via reduction of cell apoptosis, fibrosis and inflammation, thus SE-MA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized current knowledges regarding the role of SEMA3A signaling in kidney pathophysiology and their potential use in kidney diseases.

This study aimed to evaluate the proliferation and migration of fibroblast cells derived from chronic wounds and investigate the impact of low-level laser therapy (LLLT) on their growth and migration. A total of 60 dermal samples were obtained from three sites of chronic pressure ulcers and diabetic ulcers in 20 patients. Following collection in the operating room, the dermal samples were isolated using the procedure described by Freshney RI. Fibroblasts from the wound base (Site 1) exhibited a slow proliferation rate and a decrease in proliferative capacity. Fibroblasts from wound margins (Site 2) and adjacent healing skin (Site 3) could be successfully isolated and maintained for multiple generations without any morphological changes. Fibroblasts from chronic wounds at Sites 2 and 3 showed slower proliferation rates and reduced migration capabilities compared to normal dermal fibroblasts (control samples). The fibroblast cells were exposed to LLLT at different energy levels (2.5, 3, and 3.5 J/cm2). The laser-treated groups demonstrated a significantly higher increase in cell count compared to the control sample, with the highest increase observed at an energy level of 3 J/cm2. These findings suggest that LLLT at an energy level of 3 J/cm2 could effectively enhance fibroblast migration, indicating its potential as a therapeutic intervention for chronic wounds.

Nasal nitric oxide (nNO) is a gas synthesized by the inducible and constitutive NO synthase enzyme in the airway cells of the nasal mucosa. Like lung nitric oxide, it is thought to be associated with airway inflammation in various respiratory diseases in children. The aim of our review was to investigate the current state of use of nasal nitric oxide measurement in children. A comprehensive search was conducted using the Web of Science and PubMed databases specifically targeting publications in the English language, with the following keywords: nasal NO, children, allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). We describe the use of nNO in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, primary ciliary dyskinesia (PCD), and cystic fibrosis (CF) based on the latest literature. CONCLUSION: nNO is a noninvasive, clinically applicable test for use in pediatric allergic rhinitis, chronic rhinosinusitis, acute rhinosinusitis, PCD and CF. It can be used as a complementary method in the diagnosis of these respiratory diseases and as a monitoring method for the treatment of allergic rhinitis, acute and chronic rhinosinusitis.

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

Major depressive disorder (MDD) is one of life-threatening disorders that is prevalent worldwide. The evident etiology of this disease is still poorly understood. Therefore, a possible mechanism is used to evaluate the antidepressant effect. Nowadays, herbal medicine is gaining more interest as an alternative antidepressant. Oroxylum indicum, which is used in traditional medicine and contains a potential antidepressive compound, baicalein, has an antidepressive property. In vitro inhibitory effect on monoamine oxidase-A (MAO-A) enzyme was used to preliminarily screen the antidepressant effect of the O. indicum seed (OIS) extract. Mice were subjected to unpredictable chronic mild stress (UCMS) for 6 weeks and daily administration of the OIS extract started from week 4. The mechanisms involved in antidepressive activity were investigated. The OIS extract significantly alleviated anhedonia and despair behaviors in UCMS-induced mouse model via two possible pathways: (i) normalize the HPA-axis function by restoration of negative feedback (decreased FKBP5 and increased GR expressions) and reduction of glucocorticoid-related negative gene (SGK-1), (ii) improve neurogenesis by escalation of BDNF and CREB expression in the hippocampus and the frontal cortex. HPLC analysis of the extract showed the presence of All the results obtained from this study emphasize its potential as an effective and novel alternative treatment for MDD.

Chronic Limb Threatening Ischemia (CLTI) represents the end stage form of peripheral arterial disease (PAD) and is associated to very poor prognosis with high risk of limb loss and mortality. It can be considered very similar to a terminal cancer disease reflecting a large impact on quality of life and healthcare costs. The aim of this study is to offer an overview of the relationship between CLTI, limb salvage and mortality with a focus on the need of a fast-track team-based management, that’s a driver to achieve better survival results. This review can be useful to improve management of this growing impact disease, and promote standardisation of care and communication between specialist and non-specialist health care professionals.

With enhanced life expectancy and ageing global populations, the prevalence of multimorbidity continues to increase. However, there is a dearth of evidence linked to multimorbidity diagnoses, treatments and health outcomes which remains a concern for future proofing optimal healthcare services. Generating evidence is critical to managing multimorbidity, promoting public health and minimizing health inequalities via effective healthcare policies that improve quality of life for vulnerable populations. This study assessed meta-epidemiology of multimorbidity to report the gaps in scientific knowledge and clinical practice. A systematic methodology was designed and published in PROSPERO (CRD42022347308) to report meta-epidemiology analyses using databases including PubMed, Web of Science, ScienceDirect, EMBASE, The Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials and MEDLINE for studies published between the 1^st of January 1980 - 31^st December 2022. A random-effects model was used to estimate the pooled proportion of multimorbidity in adults. Forest plots, pooled odds ratios and statistical heterogeneity metrics were used to assess the association between multimorbidity and investigated factors. Funnel plots and Egger’s regression were used to detect and correct for publication bias. Our findings identified women to be 0.32 times more likely to have multimorbidity in comparison to males. In regard to ethnicity, white people were 0.47 times less likely to develop comorbidities than black people. People who identified as a drinker or unmarried were more likely to develop comorbidities than those who are non-drinkers or married, respectively. Regardless of smoking status, people were equally likely to have comorbidity. In terms of environmental influences, people in rural areas were found to be 0.2 times less likely to have comorbidity in comparison to those living in urban areas. Interestingly, people with a higher education level were 0.57 times more likely to develop comorbidities than those with only a high school education. It is evident that multimorbidity has a significant burden globally and impacts the provision of care necessitated across populations given its association with several social determinants of health. Robust research and healthcare policies are required to better manage multimorbidity in patients. An example of such intervention includes employing prevention programs to reduce risk and incidence of multimorbidity within at-risk populations.

Body composition measurement plays an important auxiliary role in the nutritional assessment of diseases, nutritional diagnosis and the evaluation of the effect of nutritional therapy. There are many techniques and methods available for the measurement of body composition. Bioelectrical impedance analysis (BIA ) of body composition has been widely used and explored in many diseases in the past 30 years. Its main advantages are its non-invasiveness, non-radiation, economy, convenience and feasibility. With the development of bioelectrical impedance technology, bioelectrical impedance analysis has gradually developed from single-frequency BIA (SF-BIA) to dual-frequency BIA (DF-BIA). now devices are available that measure at multiple fixed frequencies (multi-frequency BIA, MF-BIA) and over a range of frequencies (bioimpedance spectroscopy, BIS). The clinical significance of nutrition management in chronic kidney disease has gradually become prominent. Bioelectrical impedance analysis of body composition is favored by nephrologists and nutritionists as an auxiliary method for nutrition diagnosis, treatment and monitoring. In the past 20 years, there have been many studies on body composition measurement by bioelectrical impedance analysis in the nutritional management of CKD patients. This article will summarize the recent research results of BIA of body composition method in the nutrition management of CKD patients in pre-dialysis, hemodialysis, peritoneal dialysis and kidney transplantation, in order to provide reference for the application and research of BIA method in the nutrition management of chronic kidney disease in the future.

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

Long Covid is a heterogeneous clinical condition in which Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and brain fog stand out among the different clinical symptoms and syndromes. The cerebral metabolic alterations and neuroendocrine disorders seem to constitute an important part of Long Covid. Given the substantial lack of drugs and effective therapeutic strategies, hypothalamic phospholipid liposomes which have been on the market for several years as adjuvant therapy of cerebral metabolic alterations resulting from neuroendocrine disorders, can be taken into consideration in an overall therapeutic strategy that aims to control the Long Covid associated symptoms and syndromes. Their pharmacological mechanisms and clinical effects strongly support their usefulness in Long Covid. Our initial clinical experience corroborates this rationale. Further research is imperative in order to obtain robust clinical evidence.

Objective: This study aimed to examine the relationship between health structure disparities and hospitalizations and deaths among the pediatric population in different regions. Method: The study employed an ecological time series design, utilizing population-based secondary data ob-tained from DATASUS, from the Brazilian Ministry of Health. The data included in this study encompassed the population aged zero to 19 years, health establishments, physicians working in health establishments, hospitalizations, and deaths related to Morbidities listed in the Interna-tional Classification of Diseases. The focus was explicitly on individuals diagnosed with Cere-bral Palsy and other paralytic syndromes. The data for this study were gathered from January 2018 to December 2021. TABNET was used for data collection, and Excel for tabulation and anal-ysis. Results: Analysis of health structure data across regions revealed notable disparities, par-ticularly in the North and Northeast regions, compared to other regions. These discrepancies prompted a decision to conduct a comparative assessment between these regions and the rest of the country. Conclusion: In the North region, a significant 50% difference in hospitalizations based on residence versus a place of care was observed for individuals with Cerebral Palsy and other paralytic syndromes, indicating the necessity for relocation to access appropriate medical treatment.

Pediatric chronic pain is an important public health issue given its notable impact on numerous domains of living. Pediatric chronic pain is also often comorbid with emotional, developmental, or behavioral conditions which can lead to more severe negative outcomes and an even greater reduction in positive outcomes compared to those without comorbidities. Flourishing is a positive outcome that chronic pain status has been shown to impact. We explored flourishing in children aged 6-17 years living with chronic pain as well as those with chronic pain and comorbidities using data from the 2018/2019 National Survey of Child Health. There were significant associa-tions between chronic pain condition status and all demographic variables (sex, age, race/ethnicity, poverty level, parental education, health insurance status). Results of hierarchical logistic regression found that chronic pain condition status significantly predicted flourishing. Children with chronic pain were 2.33 times less likely to flourish, and children with chronic pain plus an emotional, developmental, or behavioral comorbidity were 13 times less likely to flourish than typical peers. Given their significantly lower likelihood of flourishing, there is an urgent need for interventions targeted at children experiencing chronic pain and mental health comor-bidities.

Chronic kidney disease (CKD) is a progressive condition of kidney dysfunction due to diverse causes of injury. In healthy kidneys, protein-bound uremic toxins (PBUTs) are cleared from the systemic circulation by proximal tubule cells through the concerted action of plasma membrane transporters that facilitate their urinary excretion, but the endogenous metabolites are hardly removed with kidney dysfunction and may contribute to CKD progression. Accumulating evidence suggests that senescence of kidney tubule cells influences kidney fibrosis, the common endpoint for CKD with an excessive accumulation of extracellular matrix (ECM). Senescence is a special state of cells characterized by permanent cell cycle arrest and limitation of proliferation, which promotes fibrosis by releasing senescence-associated secretory phenotype (SASP) factors. The accumulation of PBUTs in CKD causes oxidative stress and increases the production of inflammatory (SASP) factors that could trigger fibrosis. Recent studies provide some clues that PBUTs may also promote senescence in kidney tubular cells. This review provides an overview on how senescence contributes to CKD and the involvement of PBUTs in this process, and how kidney senescence can be studied, Finally, some suggestions for future therapeutic options for CKD while targeting senescence are given.

Uncontrolled chronic inflammation results in cardiovascular disease and early death. In this review, we studied the impact of rheumatoid arthritis on the cardiovascular system, including the early and accelerated development of atherosclerosis, and its clinical manifestations, focusing on the inflammatory mechanisms leading to arterial wall damage, rapid atherosclerotic plaque formation, and thrombosis. Furthermore, the influence of medications used to treat rheumatoid arthritis on the cardiovascular system. The influence of chronic inflammation and medicaments on traditional cardiovascular risk factors is not the main subject of this review. We found that uncontrolled chronic inflammation and some medications directly impact all stages of atherosclerosis. In conclusion, reducing inflammation and maintaining long-term remission in rheumatoid arthritis may pre-vent early atherosclerosis. We believe that this review will encourage a better interdisciplinary approach for these patients and further research in this field.

There is an increasing interest in biomarkers of nitric oxide dysregulation and oxidative stress to guide management and identify new therapeutic targets in patients with chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis of the association between circulating metabolites within the arginine (arginine, citrulline, ornithine, asymmetric, ADMA, and symmetric, SDMA dimethylarginine), transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6, and vitamin B12) metabolic pathways and COPD. We searched electronic databases from inception to 30 June 2023 and assessed the risk of bias and the certainty of evidence. In 21 eligible studies, compared to healthy controls, patients with stable COPD had significantly lower methionine (standardized mean difference, SMD=-0.50, 95% CI -0.95 to -0.05, p=0.029) and folic acid (SMD=-0.37, 95% CI -0.65 to -0.09, p=0.009), and higher homocysteine (SMD=0.78, 95% CI 0.48 to 1.07, p˂0.001) and cysteine concentrations (SMD=0.34, 95% CI 0.02 to 0.66, p=0.038). Additionally, COPD was associated with significantly higher ADMA (SMD=1.27, 95% CI 0.08 to 2.46, p=0.037), SDMA (SMD=3.94, 95% CI 0.79 to 7.08, p=0.014), and ornithine concentrations (SMD=0.67, 95% CI 0.13 to 1.22, p=0.015). In subgroup analysis, the SMD of homocysteine was significantly associated with the biological matrix assessed and the forced expiratory volume in the first second to forced vital capacity ratio, but not with age, study location, or analytical method used. Our study suggests the presence of significant alterations in metabolites within the arginine, transsulfuration, and folic acid pathways which can be useful for assessing nitric oxide dysregulation and oxidative stress and identifying novel treatment targets in COPD. (PROSPERO registration number: CRD42023448036)

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

Feline immunodeficiency virus (FIV) is a lentivirus in the family Retroviridae that infects domestic cats resulting in an immunodeficiency disease featuring a progressive and profound decline in multiple sets of peripheral lymphocytes. Despite compelling evidence of FIV-associated immunopathology, there are conflicting data concerning the clinical effects of FIV infection on host morbidity and mortality. To explore FIV-associated immunopathogenesis and clinical disease, we experimentally inoculated a cohort of 4 specific pathogen free kittens with a biological isolate of FIV clade C and continuously monitored these animals along with 2 uninfected control animals for more than 13 years, from the time of inoculation to the humane euthanasia endpoint. Here we report the results obtained during the late asymptomatic and terminal phases of FIV infection in this group of experimentally FIV-infected cats.

Oxidative stress (OS) is reported in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyzes the dismutation of superoxide anion with a protective role on endothelial cells. In chronic kidney diseases (CKD), OS and thyroid dysfunction (low T3 syndrome) are fre-quently present, but their relationship has not been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into: “acute hemodialytic pa-tients” (AH, 1-3 months of treatment) and “chronic hemodialytic patients” (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and the relation-ships with thyroid hormones. Two basal samples (“basal 1”, 3 days after the last dialysis and “basal 2”, 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs AH in all determinations. Moreover, they pre-sented lower TAC values. Dividing CH patients into two subgroups according to fT3 levels (nor-mal or low) we found significantly lower ec-SOD values in the group with low fT3 at basal, 5 and 10 min samples. Finally, a significant correlation was observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low T3 syndrome in CKD, suggest that low fT3 concentrations can influence ec-SOD activity and therefore contribute to possible endothelial oxi-dative damage in such a situation.

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

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide (NADPH) oxidase enzyme complex. This review aimed to provide a comprehensive approach to the pathogens associated with chronic granulomatous disease (CGD) and its management. The topics covered included common pathogens infecting CGD patients, granulomas, and CGD-related infectious diseases, including invasive aspergillosis, Mulch pneumonitis, and liver abscesses. In addition, we also covered the differential diagnosis of CGD and its management. Patients with CGD, often children, have recurrent life-threatening infections and may develop infectious or inflammatory complications. The most common microorganisms observed in the patients with CGD are Staphylococcus aureus, Aspergillus spp, Candida spp, Nocardia spp, Burkholderia spp, Serratia spp, and Salmonella spp. Triple-dose antimicrobial prophylaxis with empiric regimens is recommended. Therefore, therapeutics against this disease must be optimised, considering the lack of curative therapies and the long-term side effects of prophylactic regimens. Consequently, allogeneic haematopoietic stem cell transplantation from a human leukocyte antigen-identical donor has been proven to cure CGD.

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising >2,000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this pa-per presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid, and is expected to continue to evolve with further development.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and debilitating disease with a significant global prevalence of over 65 million individuals. It affects various systems, including the immune, neurological, gastrointestinal, and circulatory systems. Studies have shown abnormalities in immune cell types, increased inflammatory cytokines, and brain abnormalities. Further research is needed to identify consistent biomarkers and develop targeted therapies. A multidisciplinary approach is essential for diagnosing, treating, and managing this complex disease. The current study aims at employing explainable artificial intelligence (XAI) and machine learning (ML) techniques to identify discriminative metabolites for ME/CFS. Material and Methods: The present study used a metabolomics dataset of CFS patients and healthy controls, including 26 healthy controls and 26 ME/CFS patients aged 22-72. The dataset encapsulated 768 metabolites, classified into nine metabolic super-pathways: amino acids, carbohydrates, cofactors, vitamins, energy, lipids, nucleotides, peptides, and xenobiotics. Random forest-based feature selection and Bayesian Approach based-hyperparameter optimization were implemented on the target data. Four different ML algorithms [Gaussian Naive Bayes (GNB), Gradient Boosting Classifier (GBC), Logistic regression (LR) and Random Forest Classifier (RFC)] were used to classify individuals as ME/CFS patients and healthy individuals. XAI approaches were applied to clinically explain the prediction decisions of the optimum model. Performance evaluation was performed using the indices of accuracy, precision, recall, F1 score, Brier score, and AUC. Results: The metabolomics of C-glycosyltryptophan, oleoylcholine, cortisone, and 3-hydroxydecanoate were determined to be crucial for ME/CFS diagnosis. The RFC learning model outperformed GNB, GBC, and LR in ME/CFS prediction using the 1000 iteration bootstrapping method, achieving 98% accuracy, precision, recall, F1 score, 0.01 Brier score, and 99% AUC. Conclusion: RFC model proposed in this study correctly classified and evaluated ME/CFS patients through the selected biomarker candidate metabolites. The methodology combining ML and XAI can provide a clear interpretation of risk estimation for ME/CFS, helping physicians intuitively understand the impact of key metabolomics features in the model.

Diabetes and mental disorders have been recognized as two significant public health concerns globally. Recent research indicates that there is a bidirectional relationship between these two conditions, with each influencing the other's course and outcomes. Nutrition plays an essential role in the prevention and treatment of both mental disorders and diabetes. A comprehensive review of existing literature was conducted to examine the impact of anxiety and depression on the development of diabetes and the influence of diabetes on the occurrence of mental health disorders such as anxiety and depression. Additionally, the effects of nutrition on the prevention and management of mental disorders, diabetes, and related complications in at risk individuals were assessed. Our findings show that mental disorders, such as depression and anxiety increase the risk of developing type 2 diabetes and are associated with poorer glycemic control, increased diabetes-related complications, and higher mortality rates. Conversely, diabetes is also linked with an increased risk of developing mental health disorders, including depression, anxiety, and cognitive decline. The biological, psychological, and social factors that contribute to the comorbidity between these two conditions are complex and multifaceted. Therefore, an integrated approach to the management of both conditions is critical for improving patient outcomes and reducing the overall burden of disease. Nutritional interventions should be utilized to reduce the risk of diabetes in patients with anxiety and depression as well as enhance mental health in patients with diabetes.

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

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

Abstract Sickle cell anaemia (SCD) is a life-threatening haematological disorder which is predominant in sub-Saharan Africa and is triggered by a genetic mutation of the β-chain haemoglobin gene resulting in the substitution of glutamic acid with valine. This mutation leads to the production of an abnormal haemoglobin molecule called haemoglobin S (HbS). When deoxygenated, haemoglobin S (HbS) polymerizes and results in a sickle-shaped red blood cell which is rigid and has a significantly shortened life span. Various reports have shown a strong link between oxidative stress, inflammation, the immune response, and the pathogenesis of sickle cell disease. The consequence of these processes lead to the development of vasculopathy (disease of the blood vessels) and several other complications. The role of the immune system, particularly the innate immune system, in the pathogenesis of SCD has become increasingly clear in recent years of research, However, little is known about the roles of the adaptive immune system in this disease. This review examines the interaction between the immune system, inflammation, oxidative stress, blood transfusion, and their effects on the pathogenesis of sickle cell anaemia

A cell filtration platform that affords accurate size separation and minimizes fouling was developed. The platform features an ultra-thin porous membrane (UPM) filter, a pumping head for backflushing (PHB), and cell size measurement (CSM) software. The UPM chip is an ultrathin free-standing membrane with a large window area of 0.68 mm2, a pore diameter of 5 to 9 μm, and a thickness of less than 0.9 μm. The PHB prevents filter fouling. The CSM software analyzes the size distributions of the supernatants and subnatants of isolated cells and presents the data visually. The D99 particle size of cells of the chronic myeloid leukemia (CML) line K562 decreased from 22.2 to 17.5 μm after passage through a 5-μm filter. K562 cells could be separated by careful selection of the pore size; the recovery rate attained 91.3%. The method was compared to conventional blocking models by evaluating the mean square errors (MSEs) between the measured and calculated filtering volumes. The filtering rate was fitted by a linear regression model with a significance that exceeded 0.99 based on the R2 value. The platform can be used to separate various soft biomaterials and affords excellent stability during filtration.

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

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

The aim of the present study was to investigate whether chronic undernutrition modifies the response to rostafuroxin in juvenile rats. Chronic undernutrition was induced in male rats using a multideficient diet known as Regional Basic Diet (RBD), mimicking alimentary habits in impoverished regions worldwide. Animals were given RBD – or a control/CTRL normal diet for rodents – from weaning to 90 days, and rostafuroxin (1 mg/kg body mass) or vehicle were orally administered during the last 30 days. Undernourished rats became hypertensive at 55–60 days of age (tail-cuff recording). During the last two days, the rats were hosted in metabolic cages to measure food/energy, water, Na⁺ ingestion, and urinary volume. Blood and kidneys were collected after euthanasia. Rostafuroxin increased food/energy and Na⁺ intake in CTRL and RBD rats but had opposite effects on Na⁺ balance (intake minus urinary excretion): negative in CTRL and positive in RBD. The drug normalized the decreased plasma Na⁺ concentration found in RBD rats, increased urinary volume in RBD but not in CTRL, and decreased and increased urinary Na⁺ concentration in the RBD and CTRL groups, respectively. Rostafuroxin decreased the ouabain-sensitive (Na⁺+K⁺)ATPase and increased the ouabain-resistant, furosemide-sensitive Na⁺-ATPase from proximal tubule cells in both groups, and normalized the systolic blood pressure in RBD without effect in CTRL rats. We conclude that chronic undernutrition modifies the response of blood pressure, caloric metabolism, Na⁺ distribution in liquid compartments, mobilization of Na⁺ from non-osmotic compartments, Na⁺ and water balance, and activity of renal Na⁺-transporting ATPases to rostafuroxin.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in activities of daily living. Fractures in the elderly people are associated with bone fragility, which is influenced by diabetes and chronic kidney disease. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in ADL. Fractures in the elderly people are associated with bone fragility. Diabetes and chronic kidney disease are associated with bone fragility. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

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

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment modality, frequently applied in patients suffering from haematological malignancies. In the last two decades, there have been multiple randomised controlled trials (RCTs), review articles, and meta-analyses addressing the efficacy of rabbit anti-thymocyte globulin (r-ATG) as a graft-versus-host disease (GvHD) prophylaxis. Nevertheless, only a few aimed to compare the effectiveness of different r-ATG formulations. We performed a systematic literature review of articles published since 2017 to this day utilising PubMed, Scopus, Cochrane, and MEDLINE, with the main endpoints being prophylaxis of acute GvHD (aGvHD) and chronic GvHD (cGvHD). We subjected to scrutiny a total of 5 studies, of which 4 compared the differences between Thymoglobulin (ATG-T) and Grafalon (ATG-G), and 1 discussed the impact of ATG-T dose. Overall cGvHD, aGvHD grades II-IV, TRM, OS, NRM, LFS, relapse, overall infections, and EBV reactivation do not seem to be affected by the type of utilised rATG. However, data on aGvHD grades III-IV, GRFS, moderate-severe cGvHD, and CMV reactivation is conflicting. Through our research, we sought to summarise the most recent findings concerning r-ATGs in allo-HCT, and provide insight into the differences between the targets and origin of various ATG formulations.

Keywords: chronic lymphocytic leukemia; older patient, Bruton tyrosine kinase, BCL2, cost-effectiveness Bruton tyrosine kinase inhibitors (BTKi) and the BCL2 inhibitor venetoclax, with or without the anti CD20 monoclonal antibody Obinutuzumab, represent the preferred options for the first-line therapy of CLL because they are more effective and may improve quality of life. However, pa-tient’s inclusion criteria were heterogeneous across trials designed for older patients and the identification of CLL-specific parameters identifying unfit patients at risk of developing drug-specific adverse events are required to guide treatment choice. Due to inclusion/exclusion criteria in trials, higher discontinuation rates with BTKi were reported in real-world studies and registry analyses provided useful information on factors predicting for earlier discontinuation in a real-world setting. Though targeted agents were shown to be cost-effective treatments in high-income countries, the out-of-pocket expenses may limit accessibility to these drugs and the overall expenditure for new drugs in CLL is projected to increase substantially posing an issue for sustainability. This being said, the choice of a finite duration treatment based on venetoclax containing regimens or treatment until progression with BTKi is today possible in high- income countries and the therapy choice drivers are represented by coexisting medical conditions rather than age, by patient expectations, logistics and sustainability.

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

Long coronavirus disease 2019 (COVID-19) may occur after experiencing acute COVID-19 infec-tion with many effects on patients´ kidneys. This study aimed to evaluate the clinical and labora-tory aspects of kidney function in individuals with long COVID in the Amazon region of Brazil. This cross-sectional study selected participants from a ‘long COVID’ clinical care program. Clini-cal data and baseline demographics were obtained, and blood samples were collected to quantify kidney-related markers. Patients were evaluated after COVID-19 infection at several time points as follows: 0–3 months, 3–6 months, 6–12 months, and 12 months. Altogether, 246 patients were selected for this study, and only 79 were hospitalised (9 in the intensive care unit because of COVID-19. Of the patients, 38 were diagnosed with hypertension after COVID-19, 52 cases had to have their medications adjusted, and 83 patients presented with kidney function decline. The older age group and individuals with glycaemic alterations presented with a higher risk of devel-oping kidney dysfunction. Therefore, health professionals should monitor long-term kidney mark-ers in long COVID.

Glitter particles are considered a model of microplastics, which are used in a wide range of products. In this study, we evaluated the toxicity of green and white glitter dispersions on the embryonic development of the sea urchins Echinometra lucunte, Arbacia lixula, and the mussel Perna perna. The Toxicity Identification and Evaluation (TIE) approach was used to identify possible chemicals related to toxicity. Glitter dispersions were prepared using 0.05% ethanol. The tested dispersions ranged from 50 to 500 mg/L. The white glitter was composed of a vinyl chloride-methyl acrylate copolymer. The effective concentrations of green glitter to 50% embryos (EC50) were 246.1 (235.8 – 256.4) mg/L to A. lixula, 23.0 (20.2 - 25.8) mg/L to P. perna and 105.9 (61.2 - 150.2) mg/L, whereas the EC50 of white glitter to E. lucunter was 272.2 (261.5 – 282.9) mg/L. The EC50 for P. perna could not be calculated; however, the lowest effect concentration was 10 mg/L. The filtered suspension of green glitter had Ag levels exceeding the legal standards for marine waters. TIE showed that metals, volatiles, and oxidant compounds contribute to toxicity. The results showed that glitter may adversely affect marine organisms; however further studies are necessary to determine its environmental risks.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide (NADPH) oxidase enzyme complex. This review aimed to provide a comprehensive approach to the pathogens associated with chronic granulomatous disease (CGD) and its management. The topics covered included common pathogens infecting CGD patients, granulomas, and CGD-related infectious diseases, including invasive aspergillosis, Mulch pneumonitis, and liver abscesses. In addition, we also covered the differential diagnosis of CGD and its management. Patients with CGD, often children, have recurrent life-threatening infections and may develop infectious or inflammatory complications. The most common microorganisms observed in the patients with CGD are Staphylococcus aureus, Aspergillus spp, Candida spp, Nocardia spp, Burkholderia spp, Serratia spp, and Salmonella spp. Triple-dose antimicrobial prophylaxis with empiric regimens is recommended. Therefore, therapeutics against this disease must be optimised, considering the lack of curative therapies and the long-term side effects of prophylactic regimens. Consequently, allogeneic haematopoietic stem cell transplantation from a human leukocyte antigen-identical donor has been proven to cure CGD.

Living with a chronic disease involves a variety of daily life limitations that severely affect people in their daily life. Identifying and promoting self-management strategies may improve health outcomes and increase patients’ autonomy. The purpose of the present study was to explore the perceived limitations and self-management strategies of elder patients suffering from chronic diseases. An inductive content analysis was applied, with a purposive sampling of 21 patients living with chronic conditions. Data was collected through semi-structured interviews. Two main-categories were emerged from content analysis, namely “Limitations of daily life” and “Disease Management”. Physical restrictions and negative feelings were referred to as daily burdens, while scheduling and self-care, supporting environment and technology were related to disease management. Information, training and provision of digital literacy may increase patients' self-efficacy in managing their chronic condition.

Asthma is the most prevalent cause of chronic respiratory diseases. Herein, we evaluate asthma burden in Mexico based on results from the Global Burden of Disease (GBD 2019) study 2019. Using data from the GBD 2019, we estimated asthma prevalence, incidence, mortality, and disability-adjusted lived years (DALYs) counts and crude and age-standardized rates per 100,000 people with a 95% uncertainty interval (UI) by sex and age at the national and subnational levels in Mexico from 1990 to 2019. At the national level, asthma affected 3.35 million (95% UI, 2.59-4.37) people, with 606.0 thousand (433.0-811.1) new incident cases and 1,655 (3-1,931) deaths during 2019. Asthma caused a slightly higher burden in females and affected mainly age groups between 1 and 14 years of age. The burden of asthma gradually decreased from 1990 to 2010. However, during the last decade (2010-2019), prevalence increased by 8.2%, as did incidence by 11.3%, whereas mortality and DALYs decreased by 23.3 and 1.6%, respectively. Finally, the burden of asthma displayed a heterogeneous pattern of disease at the subnational level. In conclusion, asthma causes a significant health loss in Mexico that differentially affects the population distributed among the states of the country, thus causing health disparities that should be addressed to provide sustainable asthma diagnosis and control to reduce its burden, especially at early stages of life.

Background and Objectives: Elders’ needs are rarely examined beforehand, and thus, although technology-based tools can enhance self-management, acceptability rates are still low. This study aimed to examine and compare self-reported needs, priorities, and preferences of elders with heart failure (HF), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD) toward technology use to enhance self-management. Materials and Methods: A convenience sample of 473 participants over 60s (60.5% females), diagnosed with HF (N=156), DM (N=164), or COPD (N=153) was recruited. They were administered a questionnaire about the usefulness of technology in general and in specific areas of disease management. Results: Most participants (84.7%) admitted that technology is needed for better disease management. This was equally recognized across the three groups both for the overall and specific areas of disease management (in order of priority: ‘Information’, ‘Communication with Physicians &amp; Caregivers’, and ‘Quality of Life &amp; Wellbeing’). Sociodemographic differences were found. Cell phones and PCs were the devices of preference. The four common features prioritized by all three groups were related to ‘information about disease management’ (i.e., monitoring symptoms, reminders for medication intake, management and prevention of complications), whereas the fifth one was related to ‘communication with physicians and caregivers (i.e., in case of abnormal or critical signs). The top disease-specific feature was also monitoring systems (of respiratory rate or blood sugar or blood pressure, oxygen), whereas other disease-specific features followed (i.e., maintaining normal weight for HF patients, adjusting insulin dose for DM patients, and training on breathing exercises for COPD patients). Conclusions: Elders in these three samples seem receptive to technology in disease management. mHealth tools, incorporating both common and disease-specific features and addressing different chronic patients, and being personalized at the same time, could be cost-saving and useful adjuncts in routine clinical care to improve self-management.

Background: Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a rare disease entity characterized by the emergence of an extramedullary tumour which may be antecedent, coexisting or manifest secondarily to an ongoing malignancy of lymphoid origin. Owing to its low prevalence, scientific reports addressing this matter comprise mainly retrospective studies with a limited number of participants, rather low-quality research and only few case reports. Despite MS’s rarity, the need for enhancing diagnostic tools and refinement of therapeutic regimens is broadly recognised among physicians. Case summary: In this case series, we present the clinical histories of two patients diagnosed with MS. The former (Case 1) exhibited MS of the sternum alongside chronic myeloid leukemia (CML), while in case of the latter (Case 2) MS was the initial manifestation of a current acute myeloid leukemia (AML). Regardless of treatment institution comprising chemotherapy (CHTH) and radiotherapy (RT), the patient afflicted by CML did eventually pass due to cardiorespiratory insufficiency secondary to an infection, whereas the second one is in clinical remission up to this date, that is 16 months since MS had been diagnosed. Furthermore, a comprehensive analysis of previously reported cases was conducted which involves MS in patients with AML and CML. Conclusion: The objective of this report is to emphasize the heterogeneity among the clinical manifestations of MS, to underline the relevance of histopathological and molecular diagnostic tools in opting for the appropriate therapy and that, in spite of it occurring rather uncommonly, physicians should think of MS in presence of pathological masses in patients under risk of hematological malignancies.

Background: Cell-free plasma DNA (cfDNA) is composed of circulating extracellular DNA originating from apoptosis or cell necrosis. It is generally present in healthy individuals, but its levels increase in different clinical conditions, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. Caspase-3 plays a central role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis of chronic kidney disease (CKD). Methods: We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating the modification of their concentrations according to CKD stage. We also analyzed the correlation between cfDNA and caspase-3 levels in CKD patients and the correlation between cfDNA and caspase-3 levels and creatinine and urea. Results: CfDNA and caspase-3 levels were higher in CKD patients compared to healthy subjects, in particular in patients with advanced renal disease. A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea was also observed. Conclusion: Patients with chronic kidney disease present higher levels of cfDNA and caspase-3 levels compared with healthy subjects. The worsening of renal damage and the increase in uremic toxin concentration are associated to higher levels of cfDNA and caspase-3 levels, thus reflecting a central role of apoptosis in the pathogenesis of CKD.

Early stable deep molecular response (DMR) of nilotinib is associated with goal of treatment-free remission (TFR) for patients with chronic-phase chronic myeloid leukemia (CML-CP). It is significant to early distinguish patients who can obtain DMR and fit for TFR. We performed a multicenter study to explore early cumulative MR4.5 rate by 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. From 29 institutes, 106 ND-CML-CP patients received nilotinib (300mg BID). The cumulative MR4.5 rate of nilotinib by 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates of nilotinib by 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with ultra-early molecular response (u-EMR) at 6 weeks were not significantly different to obtain DMR or MMR by 24 months compared to those without u-EMR (P=0.7584, P=0.9543, respectively). Our study demonstrated that treatment with nilotinib in patients with ND-CML-CP contributed to obtain high early MR4.5.

Breath volatile organic compound analysis is a non-invasive tool for assessing health status; the compositional profile of these compounds in the breath of patients with chronic kidney disease is believed to change with decreasing renal function. We aimed to identify breath volatile organic compounds for recognizing patients with chronic kidney disease. Using thermal desorption-gas chromatography-mass spectrometry, untargeted analysis of breath markers was performed using breath samples of healthy controls (n=18) versus non-dialysis (n=21) and hemodialysis (n=12) patients with chronic kidney disease in this cross-sectional study. A total of 303 volatile organic compounds alongside 12 clinical variables were used to determine the breath volatile organic compound profile. Metabolomic analysis revealed that age, systolic blood pressure, and fifty-eight breath volatile organic compounds differed significantly between the chronic kidney disease group (non-dialysis + hemodialysis) and healthy controls. Thirty-six volatile organic compounds and two clinical variables that showed significant associations with chronic kidney disease in the univariate analysis were further analyzed. Different spectras of breath volatile organic compounds between the control and chronic kidney disease groups were obtained. Multivariate model incorporating age, 2-methyl-pentane, and cyclohexanone showed high performance (accuracy, 86%) in identifying patients with chronic kidney disease, with odds ratios (95% confidence interval) P-values of 0.18 (0.07-2.49) 0.013; 2.10 (0.94-2.24) 0.025; and 2.31 (0.88–2.64) 0.008, respectively. Hence, renal dysfunction-associated characteristic profiles of breath volatile organic substances can be used as non-invasive markers to screen for chronic kidney disease.

(1) Background: Inflammatory bowel diseases (IBD) involve complex interactions between genetic factors, aberrant immune activation, and gut microbial dysbiosis. While metabolomic studies have focused on feces and serum, fewer investigations have examined the intestinal mucosa despite its crucial role in metabolite absorption and transport. The current study aimed to identify novel mucosal metabolic pathways that are altered during chronic colitis and to determine microbial contributions to such changes. (2) Methods: The chronic Dextran sulfate sodium (DSS) colitis was induced for five weeks in 7-9-week-old wild-type C57BL/6J male mice followed by microbial profiling with targeted 16srRNA sequencing service. Mucosal metabolite measurements were performed by Metabolon (Morrisville, NC). The data were analyzed using the bioinformatic tools Pathview, MetOrigin, and Metaboanalyst. (3) Results: Our novel findings demonstrated increases in several host- and mi-crobe-derived purine, pyrimidine, endocannabinoid, and ceramide metabolites in colitis. Origin analysis revealed microbial-related tryptophan metabolites kynurenine, anthranilate, 5-hydroxyindoleacetate, and C-glycosyltryptophan were significantly increased in colon mucosa during chronic inflammation and strongly correlated with disease activity. (4) Conclusions: These findings offer new insights into the pathophysiology of IBD and provide novel potential targets for microbial-based therapeutics.

Background: This study analyzes sex-based differences in renal structure and response to the Angiotensin-Converting Enzyme (ACE) inhibitor enalapril in a mouse model of atherosclerosis. Methods: ApoE-/- mice (8 weeks old) received enalapril (5 mg/kg/day, subcutaneous) or PBS as a control for an additional 14 weeks. Each group consisted of six males and six females. Results: Females exhibited elevated LDL-cholesterol levels, while males presented higher creatinine levels and proteinuria. Enalapril effectively reduced blood pressure in both groups, but proteinuria decreased significantly only in females. Plaque size analysis and assessment of kidney inflammation revealed no significant sex-based differences. However, males displayed more severe glomerular injury, with increased mesangial expansion, mesangiolysis, glomerular foam cells and activated parietal epithelial cells (PECs). Enalapril mitigated mesangial expansion, glomerular inflammation (particularly in females), and the hypertrophy of PECs in males. Conclusion: This study demonstrates sex-based differences in the response to enalapril in a mouse model of atherosclerosis. Males exhibited more severe glomerular injury, while enalapril provided renal protection, particularly in females. These findings suggest potential sex-specific considerations for ACE inhibitor therapy in chronic kidney disease and atherosclerosis cardiovascular disease. Further research is needed to elucidate the underlying mechanism behind these observations.

Background: Chronic non-specific low back pain (CNSLBP) is defined as back pain that lasts longer than 12 weeks. Objectives: To investigate the efficacy of manual therapy (MT) program combined with Capacitive and Resistive Electric Transfer (TECAR) therapy in individuals with CNSLBP. Method: Sixty adults with CNSLBP were randomly equally divided into three groups. The first group followed an MT protocol in the lumbar region (MT group), the second group followed the same MT protocol combined with TECAR therapy (MT + TECAR group) using a conventional capacitive electrode as well as a special resistive electrode bracelet and the third group (Control group) received no treatment. Both intervention programs included six treatments over two weeks. Pain in the last 24 hours with the Numeric Pain Rating Scale (NPRS), functional ability with the Roland-Morris Disability Questionnaire (RMDQ), Pressure Pain Threshold (PPT) in the lumbar region with pressure algometry, and mobility of the lumbo-pelvic region through fingertip-to-floor distance (FFD) test were evaluated before and after the intervention period with a one-month follow-up. Analysis of variance with repeated measures was applied. Results: In the NPRS score, both intervention groups showed statistically significant differences compared to the control group both in the second week as well as in the one-month follow-up (p < .001). Between-groups differences were also noticed between the two intervention groups in the second week (p < .05). Differences in the RMDQ score in the second week and on the one-month follow-up were detected between the intervention groups and the control group (p < .001), while differences between the two intervention groups were only detected in the one-month follow-up (p < .001). Regarding the PPT values, differences were found mainly between the MT + TECAR and the control group and between the MT + TECAR and the MT group (p < .05), with the MT + TECAR group in most cases showing the greatest improvement compared to the other two groups, which remained statistically significant in the one-month follow-up (p < .05). Finally, both intervention groups improved the mobility of the lumbo-pelvic region in both time points compared to the control group without, however, statistically significant differences between them (p> .05). Conclusion: The application of an MT protocol with TECAR therapy appeared more effective than conventional MT as well as compared to the control group in reducing pain and disability and improving PPT in individuals with CNSLBP. No further improvement was noted in mobility of the lumbo-pelvic region by adding TECAR to the MT intervention.

Coronary revascularization is one of the most studied treatment modalities in cardiology, however, there is no consensus among experts about its indications in patients with stable coronary artery disease (SCAD). Contemporary data regarding the role of revascularization in SCAD are in clear conflict with the current European guidelines. This article discusses the main statements of the most significant American and European Guidelines on myocardial revascularization of the last decade, and also analyzes the appropriateness of revascularization to improve the prognosis and symptoms in CCS in the light of new research data, primarily the ISCHEMIA study (NCT01471522) and ACC/AHA 2021 Revascularization Guidelines based on them. Data on the revascularization in CCS obtained after the completion of ISCHEMIA (including the interim analysis of ISCHEMIA-EXTEND) and their potential significance are discussed. The results of ISCHEMIA sub-analyses in the most important ‘controversial’ subgroups (3-vessel disease, proximal left anterior descending artery (LAD) disease, strongly positive stress test, etc.) are reviewed, as well as the results of the ISCHEMIA-CKD substudy in patients with severe chronic kidney disease (CKD).

A relatively loud sound is audible when a vibrator is attached to the aural cartilage. This form of conduction is referred to as cartilage conduction (CC). In Japan, a new type of hearing aid has been developed using CC and is available in clinical practice since 2017. A clinical study conducted prior to its launch demonstrated its benefits, particularly in patients with aural atresia who were unable to use air-conduction hearing aids. Several studies have been published on the benefits of CC hearing aids since their introduction in clinical practice. Most of the patients included in these studies had canal stenosis or aural atresia, and the purchase rates of CC hearing aids in these patients were relatively high. However, the number of patients with open ears was small, with overall poor results in the trials, with the exception in patients with continuous otorrhea. CC hearing aids are considered a good option for compensating hearing loss in ears with canal stenosis or atresia in both bilateral and unilateral cases. However, CC hearing aids are not currently considered the first choice for patients with an open ear,.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are 4 main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans by undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

Ehlers–Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Among the different types, the hypermobile EDS (hEDS) is the most frequent, and includes generalized joint hypermobility as the major diagnostic criterion. Joint hypermobility in hEDS is often associated with pain that not always allow the use of effective pain-reducing treatments. Patients with hEDS always talk about pain using a lot of descriptions. Eighty-nine patients with diagnosis of hEDS were recruited and evaluated. They were asked to write down what grief was to them. The texts were analyzed through LIWC. Correlational analyses were conducted between pain perception and language. A comparison of high/low pain perception and quality of metaphors was carried out. The results showed, depending on the level of pain perception, different language quality is evidenced. The greater the pain the lesser the positive effects and the greater the negative effects and dehumanizing metaphors. Moreover, greater pain seems to be related to a verbal experience of greater isolation and less self-care. In conclusion, the use of metaphors is a useful tool for exploring illness experience and may help clinicians in the rehabilitation program.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and is the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described, a clinical isolate infection model, utilizing isolates obtained from patients with CF, an incomplete antibiotic clearance model, leading to bacterial bounce-back and the establishment of chronic infection, and an adapted water bottle chronic infection model. These models circumvent the requirement for surgical procedure and importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections.

Background: Chronic, non-cancer pain represents a serious public health and economic issue affecting approximately 20% of the global population. Chronic pain can affect many aspects of patient’s lives, including mental health, employment, and relationships. Current medical management is largely focussed on investigating and managing acute pain. Patients and clinicians are now increasingly aware of the potential benefits of combined treatments or complex interventions in alleviating chronic pain. These approaches include both physical interventions, such as exercise or yoga, as well as psychological support including cognitive behavioural therapy (CBT) and talking therapies. Methods: This study used network meta-analyses to explore the prevalence of complex interventions in pain management, and the effects of these interventions on quality of life, using outcome measures including intensity of chronic pain, assessment of functional disability and participant’s psychological state. Results: Psychological interventions were associated with improvements in pain intensity and depression. Exercise and manipulation technique-based treatments provided a statistically significant reduction in pain intensity. This effect was enhanced when exercise and CBT were combined. Mensendieck somatocognitive therapy (MSCT) plus standard gynaecological treatment (STGT) treatments appeared to have a better effect on chronic pain than multimodal exercise plus CBT treatment. Combined MSCT and STGT treatment, and multimodal exercise plus CBT treatments, reduced pain intensity, whilst MSCT+STGT treatments had a slightly better effect than exercise plus CBT treatment.Conclusions: Complex interventions have become more popular with patients as the risks associated with other interventions including surgery and pharmacological management have become better understood. These interventions can have a significant positive effect both on the physical and psychological health of patients. The analysis presented in this study suggests that further work is warranted in this area and that additional studies are required, both in more geographically diverse locations, and with larger cohorts.

Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) share similarities regarding their epidemiology, symptomatology and craniospinal physiology. Indeed, the cardinal feature of CFS, fatigue, is also a major factor in the symptomatology of the majority of MS patients. Recently, we have found that there is a significant reduction in the craniospinal compliance in MS which affects both the stiffness of the walls of the spinal canal and the walls of the cerebral venous system. This change in compliance brings about an alteration in the effectiveness of the pulse wave dampening in the craniospinal system. The result is an impedance mismatch between the cortical veins and their draining sinuses, leading to dilatation of these upstream veins. We deduce this dilatation can only be brought about by an increase in the pressure gradient between the vein lumen and the subarachnoid space (i.e. the transmural pressure gradient). We hypothesise that given the similarities between MS and CFS, a similar mechanism underlies the physiology of CFS. We present two case studies to highlight the expected findings in CFS patients if this hypothesis were proven to be correct.

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

Although relatively rare, affecting 8% of the general population, autoimmune disorders are causative linked with chronic diseases and morbidity. Control of the course of the disease is closely dependent on the ability to monitor its onset as well as response to treatment. In the present report, we review the progress in the development of biosensor-based approaches and related tools for the Point-of-Care diagnosis and monitoring of biomarkers related to several autoimmune diseases, such as Myasthenia Gravis, Rheumatoid Arthritis, Multiple Sclerosis, Systemic Erythematosus Lupus, Crohn’s Disease, Diabetes Mellitus, Behcet’s disease, Psoriasis and Celiac Disease. Various biosensing technologies are discussed, including electrochemical, optical and mechanical ones, along with the use of advanced nanomaterials and immobilization techniques for the biorecognition elements. The need for innovative devices with unique features of rapid, low-cost, real-time detection is considered in the context of preventing permanent organ and tissue damage from chronic autoimmune diseases.

Studies have shown increased nontuberculous mycobacterial pulmonary disease (NTM) incidence with inhaled corticosteroid (ICS) use in patients with chronic respiratory diseases; however, this association in chronic obstructive pulmonary disease (COPD) remains insufficiently studied. Using a nationwide population-based database of the Korean National Health Insurance Service, newly diagnosed COPD patients (20052018) treated with inhaled bronchodilators were selected. An NTM case was defined by the presence of the first diagnostic code following inhaled bronchodilator use. Results indicated that ICS users did not have an increased risk of NTM disease compared to non-ICS users (hazard ratio [HR], 1.121; 95% confidence interval [CI], 0.9501.323; p = 0.1755). The highest quartile of the cumulative ICS dose was associated with the development of NTM (1.200, 0.9501.323, p = 0.0497). Medium (1.229, 1.0081.499, p = 0.0410) and high daily doses of ICS (1.637, 1.2412.160, p = 0.0005) were associated with an increased risk of NTM disease. There was no difference in the risk of NTM according to ICS type. ICS use may not increase the risk of developing NTM disease in patients with COPD. However, physicians should weigh the potential benefits and risks of ICS, especially when using high doses and prolonged durations.

Chronic hepatitis B (CHB) infection and the Hepatitis B virus X protein (HBx) are major risk factors associated with hepatocellular carcinoma (HCC). In CHB infection, HBx induces mitochondrial dysfunction, exhaustion and impaired function in hepatocytes. Restoring hepatocyte health along with reduction in virus replication could be an ideal treatment for CHB. Thiourea derivatives are well known for their antiviral property though their effect on mitochondrial and/ or hepatocyte health remains obscure. This study focus on the repurposing of thiourea derivatives (DSA-00, DSA-02, and DSA-09) on hepatocyte replenishment. HepG2.2.15 cells were treated with thiourea derivatives, alongside Entecavir (ETV). The proteomics analysis showed both DSA-00 and ETV were enriched with proteins associated with antiviral responses. In addition, DSA-00 additionally showed increase in proteins linked to mitochondrial response. Whereas DSA-02 exhibited association with innate immune system and citric acid cycle and DSA-09 displayed pathways similar to DSA-00 and ETV. Treated groups exhibited enhanced bio-energetic and antiviral response as compared to the untreated group. FACS analysis revealed the restoration of exhausted hepatocytes by thiourea derivatives through targeting mitochondria. Our findings suggest that thiourea derivatives hold potential as a novel therapeutic agent that seems to restore mitochondrial health along with anti-viral response in CHB.

Chronic non-cancer pain is a highly debilitating condition affecting approximately 20% of the global population. Chronic pain may lead to significant physical disability, emotional distress, social isolation and financial burden. Whilst^. pharmacological therapies remain the cornerstone of pain management in non-cancerous chronic pain, factors including the current opioid epidemic have led to non-pharmacological techniques becoming a more attractive proposition. We explored the prevalence of medical device use and their treatment efficacy in non-cancer pain management. A systematic methodology was developed, peer reviewed and published in PROSPERO (CRD42021235384). Key words of medical device, pain management devices, chronic pain, lower back pain, back pain, leg pain and chronic pelvic pain using Science direct, PubMed, Web of Science, PROSPERO, MEDLINE, EMBASE, PorQuest and ClinicalTrials.gov. All clinical trials, epidemiology and mixed methods studies that reported the use of medical devices for non-cancer chronic pain management published between the 1^st of January 1990 and the 30^th of April 2022 were included. 13 studies were included in systematic review, of these 6 were used in the meta-analysis with 173 participants. Our meta-analysis for pain reduction in each study showed that transcutaneous electrical nerve stimulation combined with instrument-assisted soft tissue mobilization treatment and pulsed electromagnetic therapy produced significant treatment on chronic lower back pain patients. Pooled evidence revealed the use of medical device related interventions resulted in 0.7 degree of pain reduction under a 0-10 scale. Significant improvement in disability scores, with a 7.44 degree reduction in disability level compared to a placebo using a 50 score range was also seen. The application of medical devices in patients with chronic pain has gained popularity due to increasingly cost effective techniques, minimally invasiveness and greater awareness of risks associated with pharmacological management. Our analysis has shown that the optimal use of medical devices in a sustainable manner requires further extensive research, needing larger cohort studies with greater gender parity, in a more diverse range of geographical locations.

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

Background: Portable oxygen concentrators (POCs) have shown efficacy in delivering adequate oxygen for various patient scenarios; however, there is a lack of research on POCs’ efficacy across different respiratory rates specifically among COPD patients. Methods: This bench study was conducted using the IngMar Medical Active Servo Lung 5000 attached to flexible tubing, which simulated an adult patient’s nares. An oxygen analyzer (Maxtec Handi+) was connected to the tubing 6 inches below the nares to estimate the inspired oxygen concentration at the adult trachea. A standard nasal cannula was placed in the simulated patient nares, which was also attached to each POC. The IngMar Lung was programmed to simulate a COPD patient at the following respiratory rates: 15, 20, 30, and 40 breaths/min. POC devices were then compared to an oxygen wall outlet and a standard oxygen concentrator (non-portable CAIRE device). The POCs included the CAIRE FreeStyle Comfort (with Autosat), CAIRE FreeStyle Comfort (without Autosat), Inogen G4, Inogen G5, Phillips SimplyGo Mini, GCE Zen-O lite, Drive Medical iGo2, and Kingon POCs. Descriptive statistics and ANOVAs were computed to determine statistically significant differences between POCS and control devices (wall oxygen and standalone oxygen concentrator). Results: Across most respiratory rate scenarios, the wall oxygen and standalone oxygen concentrator (control group) resulted higher oxygen measurements compared to the POCs. Among the POCs on setting 2, the highest oxygen measurement for 15, 30, and 40 breaths/min was the CAIRE FreeStyle Comfort with AutoSat on sensitivity 5 (24.43%, 24.81%, and 25.0%, respectively). On setting 2, the 20 breaths/min highest oxygen measurement was the Inogen G4 (24.43%). For setting 5, the highest oxygen measurement for 15 breaths/min and 40 breaths/min was the CAIRE FreeStyle Comfort without AutoSat (31.56% and 26.13%, respectively), while the highest oxygen measurement for 20 breaths/min was the Inogen G5 (30.26%), and the highest oxygen measurement for 30 breaths/min was the CAIRE FreeStyle Comfort with AutoSat on sensitivity level 5 (27.89%). Conclusions: The oxygen administered through the wall and the standalone CAIRE oxygen concentrator all delivered higher oxygen levels compared to the POCs (with the exception of the 40 breaths/min scenario on setting 2). However, among the POCs, the CAIRE Freestyle Comfort with AutoSat, CAIRE Freestyle Comfort without AutoSat, and the Inogen G4 all performed the best among the various breathing rate scenarios.

Ibrutinib, a first-in-class Bruton’s Tyrosine Kinase inhibitor (BTKi), is a commonly deployed therapeutic option for previously untreated, and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia (CLL). The use of ibrutinib is, however, partially limited by significant off-target side effects. Zanubrutinib (zanu) is a second-generation BTKi with enhanced target selectivity and occupancy of the kinase binding site. The SEQUOIA study showed that zanu significantly prolonged progression-free survival (PFS) when compared to bendamustine–rituximab (BR) in treatment-naive CLL patients with an acceptable safety profile. More recently, data from the phase III ALPINE trial which directly compared zanu with ibrutinib has demonstrated that zanu’s advantages are both an improved safety profile and enhanced clinical efficacy. Based on the results of the SEQUOIA and ALPINE pivotal trials the Food and Drug Administration (FDA) and European Medicines Agency (EMA) licensed zanu for the treatment of patients with CLL or small lymphocytic lymphoma (SLL) in January 2023. The updated (v2.2023) National Comprehensive Cancer Network (NCCN) guidelines and newly released German CLL algorithm, suggest that zanu may replace first-generation BTKi as one of the preferred therapeutic options for patients with CLL/SLL due to its increased selectivity for the kinase binding site, improved therapeutic efficacy, and favorable toxicity profile.

IHepatitis C virus (HCV) has a high genetic diversity, with seven genotypes with 86 subtypes. This genetic variability confers persistence in the infection and escape of the immune system with evolution to cirrhosis and cancer. Environmental factors can contribute to different disease progression, being essential to assess the viral genotype in the infection and discuss the environmental particularities of Eastern Amazon, and the frequencies of Liver fibrosis between different HCV genotypes in patients living in a region of the Brazilian Eastern Brazilian Amazon. Consists in an observational cross-sectional study. Sociodemographic and clinical data of 76 individuals diagnosed with Hepatitis C between 2019 and 2020 in public health services were selected. Data collected was tabulated in Microsoft Excel 2010TM spreadsheets and analysed in GraphPad Prism 5.0TM. Liver fibrosis was associated with genetic subtypes. Subtype 1b was predominant (42.1%), followed by 1a (13%) and 3a (1.3%). 69.7% of participants had chronic hepatitis, with mild fibrosis (F1/F2) being the most prevalent (38.1%). Severe fibrosis was detected in 75% of individuals infected with the subtype 1b, that is associated with more severe disease. We suggest further studies, to assess other communities in the region, as well as the monitoring of these patients with Liver Elastography to determine the disease evolution and its better management.

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