Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccha-rides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and as-sociated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) sug-gest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.

Lower urinary tract dysfunction (LUTD) was associated with bladder inflammation and tissue hypoxia with oxidative stress. This study investigated the profiles of urine inflammatory and oxidative stress biomarkers in females with LUTD and to develop a urine biomarker-based decision tree model for the prediction. Urine samples were collected from 31 female patients with detrusor overactivity (DO), 45 with dysfunctional voiding (DV), and 114 with interstitial cystitis/ bladder pain syndrome (IC/BPS). The targeted analytes included 15 inflammatory cytokines and 3 oxidative stress biomarkers (8-hydroxy-2-deoxyguanosin, 8-isoprostane, and total antioxidant capacity [TAC]). Different female LUTD groups had distinct urine biomarker profiles, including IL-1β, IL-2, IL-8, IL-10, eotaxin, CXCL10, MIP-1β, RANTES, TNFα, VEGF, NGF, BDNF, 8-isoprostane, and TAC. The urine biomarker-based decision tree, using IL-8, IL-10, CXCL10, TNFα, NGF, and BDNF as nodes, demonstrated an overall accuracy rate of 85.3%. DO, DV, and IC/BPS accuracy rates were 74.2%, 73.3%, and 93.0%, respectively. Internal validation revealed similar overall accuracy rate. Random forest models supported the significance and importance of all selected nodes in this decision tree model. Urine inflammatory and oxidative stress biomarker profiles of different female LUTDs were different. This internally validated urine biomarker-based decision tree model predicted different female LUTDs with high accuracy.

Many spectroscopic diagnostics are routinely used as a technique to infer the plasma parameters from line emission spectra but their accuracy depends on the numerical model or code used for the fitting process. However, the validation of a line shape code requires some steps : comparison of the line shape code with other similar codes for some academic (simple) cases and then more complex ones, comparison of the fitting parameters obtained from the best fit of the experimental spectra with those obtained with other diagnostic techniques and/or comparison of the fitting parameters obtained by different codes to fit the same experimental data. Here we compare the profiles of the hydrogen Balmer β line in a helium plasma computed by six codes for a selected set of plasma parameters and we report on the plasma parameters inferred by each of them from the fitting to a number of experimental spectra measured in a helium corona discharge where the pressure was in the range 1- 5 bar.

Severe cancer pain significantly diminishes patients' quality of life, leading to increased reliance on caregivers. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD) with symptoms such as nausea, vomiting, drowsiness, and constipation. While controlled-release oxycodone is a viable option, its prolonged use can lead to opi-oid-induced constipation (OIC). Addressing this, a relative novel formulation - a fixed 2:1 ratio of oxycodone and naloxone in prolonged release - aims to provide analgesia while alleviating OIC. This review critically assesses the evidence on the efficacy, safety, and patient experience of ox-ycodone/naloxone prolonged release in managing severe cancer pain, emphasizing the necessity for a targeted approach in this patient population.

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.

Preclinical studies have identified glial cells as pivotal players in the genesis and maintenance of neuropathic pain after nerve injury associated with diabetes, chemotherapy, major surgeries, and virus infections. Satellite glial cells (SGCs) in the dorsal root and trigeminal ganglia of the peripheral nervous system (PNS) and astrocytes in the central nervous system (CNS) express similar molecular markers and are protective under physiological conditions. They also serve similar functions in the genesis and maintenance of neuropathic pain, downregulating some of their homeostatic functions and driving pro-inflammatory neuro-glial interactions in the PNS and CNS, i.e. “gliopathy”. However, the role of SGCs in neuropathic pain is not simply as “peripheral astrocytes”. We delineate how these peripheral and central glia participate in neuropathic pain by producing different mediators, engaging different parts of neurons, and becoming active at different stages following nerve injury. Finally, we highlight the recent findings that SGCs are enriched with proteins related to fatty acid metabolism and signaling such as Apo-E, FABP7, and LPAR1. Targeting SGCs and astrocytes may lead to novel therapeutics for the treatment of neuropathic pain.

Cardiovascular disease is the first leading cause of death in the world. Patients with cardiovascular disease may experience various problems, including physiological and psychological problems. Apart from pharmacological therapy, complementary therapy is necessary as a support to conventional medicine. This review aims to describe complementary and alternative therapies for pain and anxiety in patients with cardiovascular disease. This review utilized data from ProQuest, ScienceDirect, and PubMed with search keywords of "Complementary" AND "Nursing" AND "Pain" AND "Anxiety" AND "Coronary artery disease". Ten articles that met the inclusion criteria were analyzed. The results show that nursing actions increasingly develop along with the patient needs. One form of holistic nursing action is complementary and alternative therapy (CAT) that consists of three categories: body-based methods, mind therapies, and sensory therapies. CAT has positive impacts on patients with heart disease. It can reduce anxiety and pain, lower blood pressure, and improve the quality of life. This review also shows that CAT has a positive impact on the recovery of patients with heart disease. Proper therapeutic management should be implemented to reduce the risks of physiological and psychological problems in patients.

Our previous study found that intravesical perfusion metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel for-mulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong in-hibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and expression of tumour biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPK/mTOR signalling pathway compared with metformin alone. These findings highlighted the potential of this novel formulation as an efficient candidate for managing BC via intravesical ad-ministration.

Carboxypeptidase A4 (CPA4) has shown the potential possibility as a biomarker in the early diagnosis for certain cancers. However, no previous research has linked CPA4 to therapeutic or prognostic significance in bladder cancer. Using data from The Cancer Genome Atlas (TCGA) database, we set out to determine the full extent of the link between CPA4 and BLCA. We further analyzed the interacting proteins of CPA4 and infiltrated immune cells via TIMER2，STRING and GEPIA2 databases. The expression of CPA4 in tumor and normal tissues was compared using the TCGA+GETx database. The connection between CPA44 expression and clinicopathologic characteristics and overall survival (OS) was investigated using multivariate methods and Kaplan-Meier survival curves. The potential functions and pathways were investigated via gene set enrichment analysis. Furthermore, we analyze the associations between CPA4 expression and infiltrated immune cells with their respective gene marker sets using the ssGSEA, TIMER2, and GEPIA2 databases. Compared to matching normal tissues, human CPA4 was found to be substantially expressed. We confirmed that overexpression of CPA4 is linked with shorter OS, DSF, PFI, and increased diagnostic potential using Kaplan-Meier and ROC analysis. The expression of CPA4 is related to T-bet, IL12RB2, CTLA4, and LAG3, among which T-bet and IL12RB2 are Th1 marker genes, while CTLA4 and LAG3 are related to T cell exhaustion, which may be used to guide the application of checkpoint blockade and the adoption of T cell transfer therapy.

Down Syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, causing interstitial pneumonia, is associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient suffering from DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with Ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

Symptoms attributed to the gastrointestinal manifestations of multi-system disorders play an important role in the long-term management of these conditions. Gastrointestinal complications of a variety of connective tissue disorders have been studied and there is an increased interest in the incidence and prevalence of these symptoms. Descriptions of the occurrence of gastrointestinal complications in Marfan syndrome have appeared infrequently in the medical literature. In this review article we focus on both structural and functional gastrointestinal pathology that may occur in patients with Marfan syndrome.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by swelling in at least one joint. Owing to an overactive immune response, extra-articular manifestations are observed in certain cases, with interstitial lung disease (ILD) being the most common. Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is characterized by chronic inflammation of the interstitial space, which causes fibrosis and the scarring of lung tissue. Controlling inflammation and pulmonary fibrosis in RA-ILD is important because they are associated with high morbidity and mortality. Pirfenidone and nintedanib are specific drugs against idiopathic pulmonary fibrosis and have shown efficacy against RA-ILD in several clinical trials. Immunosuppressants and disease-modifying antirheumatic drugs (DMARDs) with antifibrotic effects have also been used to treat RA-ILD. Immunosuppressants moderate the overexpression of cytokines and immune cells to reduce pulmonary damage and slow the progression of fibrosis. DMARDs with mild antifibrotic effects target specific fibrotic pathways to regulate fibrogenic cellular activity, extracellular matrix homeostasis, and oxidative stress levels. Therefore, specific medications are required to effectively treat RA-ILD. In this review, the commonly used RA-ILD treatments are discussed based on their molecular mechanisms and clinical trial results. In addition, a computational approach is proposed to develop specific drugs for RA-ILD.

While paresthesia-based spinal cord stimulation (SCS) has been proven effective to treat chronic neuropathic pain, initial benefits may lead to the development of “Failed SCS Syndrome’ (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neu-rostimulation adapters, in patients already implanted with SCS and experienced LoE. We retro-spectively analyzed a cohort of patients who were offered new SCS programs/waveforms through an implanted adapter between 2018 and 2021. Patients were evaluated before, and at 1, 3, 6 and 12-month follow-up. Outcomes included pain intensity rating with Visual Analog Scale (VAS), pain/coverage mappings and stimulation preferences. Last follow-up evaluations (N=27) showed significant improvement in VAS (p = 0.0001), ODI (p = 0.021) and Quality of Life (p=0.023). In the 11/27 patients with LoC, SCS efficacy on pain intensity (36.89%) was accompa-nied by paresthesia coverage recovery (55.57%) and pain surface decrease (47.01%). At 12-month follow-up, 81.3% preferred to keep tonic stimulation in their waveform portfolio. SCS conver-sion using adapters appears promising as a salvage solution, with an emphasis on paresthesia recapturing enabled by spatial retargeting. In light of these results, adapters could be integrated to SCS rescue algorithms or should be considered in SCS rescue.

Low back pain is prevalent in equestrian athletes, but prevalence and associated factors are unknown in the Portuguese equestrian population. A questionnaire regarding low back pain and possible associated factors was answered by 347 respondents. Estimated 12-month prevalence was 67.1%. The probability of suffering from low back pain was higher in individuals with higher weekly riding workload, that reported equestrianism as their main occupation and that performed daily stable duties. The Roland Morris disability questionnaire was applied to the respondents that stated having experienced low back pain in the past 12 months, resulting in an average score of 5.39 ± 4.42. 63.1% of respondents stated that low back pain impaired their performance. Individuals that stated equestrianism was their main occupation showed a significant higher risk (OR = 1.759) of exhibiting a score ≥ 4, as measure of dysfunctionality. Age and high body mass index were also associated to a dysfunctional score. Further research is needed to fully understand the impacts of low back pain in Portuguese equestrian athletes.

According to the literature, patients with chronic pain and mental disorders constitute a huge, heterogeneous group. However, it is known that social and psychological processes closely affect the level and expression of chronic pain. In this paper, we present a review of the literature, define methods of identifying pain biomarkers and consider the possibility of using them to assess pain in mental disorders. Group researchers searched PubMed, Scope, and Cochrane databases for "pain biomarkers in mental disorders" between 2011 and 2021. for available databases for full-text, peer-reviewed studies and review publications using the following keywords: pain biomarkers, neuroimaging pain, pain metabolomics, pain and psychiatric disorders, pain electroencephalography (EEG), serum pain biomarkers, saliva biomarkers, and diagnosis pain. The search included full-text articles, clinical trials, randomized controlled trials, and systematic reviews. Was used part of the PRISMA method to review the literature systematically. A literature search identified 283 studies based on the initially set inclusion and exclusion criteria. In the subsequent selection stages, 11 studies were selected for analysis. There are three main areas of the possible use of biomarkers for the clinical assessment of pain in psychiatric patients, neuroimaging, changes in metabolite levels in body fluids, and changes in gene expression. As a result of the review, individual pain mediators were distinguished that may be markers of pain in psychiatric patients. Some mediators indicate the specificity of pain and are of diagnostic importance. However, despite significant advances in research, most of the described biomarkers found in clinical trials assessing the severity and frequency of pain have no practical significance in psychiatric disorders. It is possible to diagnose pain based on neuroimaging using various methods, genetic methods, body fluids: blood and urine. Of the many, body fluid biomarkers are the most advanced. Discussion: Biomarker research is a dynamically developing field. The review has proposed new ways to diagnose pain by identifying pain biomarkers. Work presented pain diagnostics in psychiatric disorders based on biomarkers from various neuroimaging methods, blood and urine analysis. The possibility of new, effective techniques gives hope for the correct diagnosis of pain, especially in patients with mental disorders, which would allow for appropriate and adequate therapeutic therapies. In clinical practice is limited to a few methods. Assessment of pain biomarkers in body fluids (serum, saliva, and urine) seems to be the most practical and promising method of clinical application. Conclusions: There are new techniques that give hope for the correct diagnosis of pain, especially in patients with mental disorders, which will allow for their proper and adequate therapy. According to the literature, patients with chronic pain and mental disorders constitute a huge, heterogeneous group. However, it is known that social and psychological processes closely affect the level and expression of chronic pain.

The objective of this study was to analyze the effects of a pulmonary telerehabilitation (TR) program in young adults with post-COVID-19 syndrome. The information of sixteen students' medical files were analyzed and allocated to one of two groups (control=CG/experimental=EG). Twelve TR sessions were performed distantly and asynchronously at the EG patients' homes during 4-weeks. The program included diaphragmatic pattern breathing and aerobic exercises. The parameters: i) vital signs (oxygen saturation "SpO2", heart rate "HR", respiratory rate "RR" and blood pressure "BP"; ii) physical capacity “Sit-to-stand test”; iii) cardiorespiratory capacity “6-Minute Walk Test”; and iv) perceived effort "Borg scale" were assessed in both groups. The statistical analyses showed a significant decrease of RR and HR (p < 0.012) accompanied by a significant increase in SpO2 (p < 0.042), physical (p < 0.012) and respiratory (p < 0.028) capacity. The perceived effort decreased significantly in both groups (CG: p < 0.006; EG p < 0.001) only for physical but not for cardiorespiratory capacity (p < 0.106). There were no statistical changes registered in BP (p > 0.05). The current study suggests that a TR program that involves breathing and aerobics exercises is feasible and effective in treating post-COVID-19 syndrome in young patients.

Gilbert's syndrome (GS) is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism. This review, based on data from peer-reviewed articles and journals spanning from 1977 to January 2024, provides a comprehensive overview of over four decades of research on GS. Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome, laying the foundation for subsequent investigations. More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase, which has significantly enhanced our understanding of the pathogenesis of GS. Furthermore, recent studies have shed light on the clinical implications of GS, including its association with non-alcoholic fatty liver disease and mortality risk, highlighting the complex interplay between genetic factors, bilirubin metabolism, and clinical outcomes. Despite its generally benign nature, thorough research is essential to fully understand the impact of GS on patients' lives. This review emphasizes the importance of ongoing research to deepen our understanding of GS and its broader implications.

The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

Throughout this paper the effects of injuries on athletes are highlighted in different aspects. Exertional compartment syndrome is a specific injury related to athletes that is thoroughly explored in this paper through an analysis of the anatomy, symptoms, diagnosis and treatments of the syndrome. Exertional compartment syndrome is an exercise-induced muscle and nerve condition that causes pain, swelling as well as disability in the affected muscles of the lower leg. This syndrome commonly develops in young athletes involved in sports with excessive running and repetitive impact such as track and field, soccer, basketball and lacrosse. Exertional compartment syndrome is commonly misdiagnosed as other less severe injuries such as shin splints, which is symptomatic of pain along the tibia bone of the lower leg caused by overuse. The misdiagnosis of exertional compartment syndrome allows the syndrome to worsen and intensify resulting in the only effective treatment to be fasciotomy, a surgical procedure to release the pressure within the compartment of the lower leg. There is no definitive protocol developed for patients after fasciotomy is performed. Athletes experiencing similar symptoms after surgery are usually treated for their symptoms rather than the syndrome as a whole, which does not have a high degree of success. The development of a definitive protocol utilizing the techniques of manual therapy, mobility stretching and corrective strength training can improve the adverse effects of exertional compartment syndrome as well as restore functionality to the athlete. Raising awareness of this syndrome in athletics will be effective in treating the athlete early on in order to avoid severe effects and invasive procedures.

Both Stevens Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are main injurious cutaneous medication reactions that mostly affect the epidermis and mucus membranes. TEN and SJS affecting nearly 1 or 2/1,000,000 people per year, and can recognized as medical crises since they may be deadly. Mucocutaneous discomfort, hemorrhagic erosions, erythema, and more or less severe epidermal separation that appear as ulcer and patches of dermic loss are their defining characteristics. The sole difference between TEN and SJS at this time is the degree of skin detachment, making them two extremes of a spectrum of severe cutaneous adverse drug reactions (cADRs). In the majority of cases, drugs are considered as the principal reason of SJS/TEN, but herpes simplex virus and Mycoplasma pneumoniae infections are also recognized causes, along with lesser number of cases in which the cause is still unknown. Among the drugs with a "high" likelihood of producing TEN/SJS are carbamazepine (CBZ), trimethoprim-sulfamethoxazole, phenytoin, aminopenicillins, allopurinol, cephalosporins, other sulfonamide antibiotics, quinolones, phenobarbital, and NSAIDs of the oxicam variety. There is strong genetic evidence for SJS and TEN in Han Chinese due to the substantial association between the human leukocyte antigen (HLA-B*1502) and SJS brought on by CBZ. The diagnosis is made mostly based on clinical symptoms and the histological study of a dermal biopsy. Pemphigus vulgaris, bullous pemphigoid, linear IgA dermatosis, paraneoplastic pemphigus, disseminated fixed bullous drug eruption, acute generalized exanthematous pustulosis (AGEP), and staphylococcal scalded skin syndrome (SSSS) are among the differential diagnoses. The management of patients with SJS/TEN is complicated by the high risk of mortality, necessitating early diagnosis, estimation of the SCORTEN prognosis, identification and discontinuation of the causative drug, specialized supportive care, and high-dose injectable Ig therapeutic interventions. The reported fatality rates for SJS are 1-5% on average and 25-35% for TEN; it can be even higher in patients who are elderly or who have a significant amount of epidermal detachment on their skin. More than 50% of TEN patients who survive the disease experience long-term consequences.

SGLT2 inhibitors act to induce glucosuria and have been shown to be efficacious in the treatment of type II diabetes mellitus but have also been shown to positively affect cardiovascular conditions and some benefitting kidney function. SGLT2i have shown to be effective in more advanced conditions but may eventually be a treatment in more general metabolic dysfunction. Metabolic syndrome is a clinical diagnosis for establishing risk for ischemic heart disease and diabetes. The prevalence of type II diabetes mellitus, heart disease, and severe vascular events steadily increased over recent decades. In addition to the established benefits of diet and exercise, SGLT2 inhibitor therapy may be able to aid in the treatment of metabolic syndrome from its proven cardiovascular and anti-hyperglycemic benefits. Pharmacologic modeling in canines is also considered, as they present with similar diagnoses and offer a model that shares many of the characteristics of humans in metabolic dysfunction.

This observational study was ordered by the Medical Practitioners’ Chamber in Warsaw. The objective of the study was to evaluate the health status of physicians in relation to their occupational duties. Professional burnout was considered relative to different features of personality. This study was initially carried out from 2005–2008, but further analysis of burnout and personality was carried out from 2017–2018. The research tools were anonymous, validated questionnaires. The sample size was based on the size of the population— the registry of the Regional Chamber of Medical Practitioners— and literature on burnout prevalence. The respondents’ work places were randomly selected from the Mazovian District register. The test on burnout was completed by 378 respondents, while 62 subjects completed a personality test. Results showed that burnout syndrome was an occupational problem for healthcare workers. Professional burnout affected as many as 42% of respondents(n = 158). It affected two age groups in particular: physicians up to 31 years old and individuals aged 41-50. Moreover, neuroticism was found to be significantly related to burnout syndrome. In conclusion, burnout syndrome is common among medical practitioners, and neuroticism may be correlated with burnout syndrome.

Meier–Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, absent or hypoplastic patellae and other skeletal anomalies. Overlapping skeletal symptoms make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical Exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T&gt;C(p.Met1Thr) and c.449+5G&gt;A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G&gt;A. An in vitro minigene assay demonstrated that variant c.449+5G&gt;A causes a complete skipping of exon 4 in ORC6 gene. The parents asked for urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Thus, this case report may help to prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS aetiology and improve the quality of genetic counselling for affected families.

Background: Chronic Back Pain due to Facet Joint Syndrome is a common and debilitating con-dition. Advances in regenerative medicine have shown that Autologous Unmodified Adipose Tissue-Derived Regenerative Cells (ADRC) provide several beneficial effects [1,2]. These regen-erative cells can differentiate into various tissues [3] and exhibit a strong anti-inflammatory po-tential. ADRCs can be obtained from a small amount of fatty tissue derived from the patient´s abdominal fat. Methods: We report long-term results of 37 patients (age 31-78 years, mean 62.5) suffering from “Facet Joint Syndrome” The pathology was confirmed by clinical, radiological examinations and fluoroscopically guided test injections. Then liposuction was performed. 50-100 cc of fat were harvested. To recover stem cells from adipose tissue, we use the CE-certified Transpose RT™ system from InGeneron GmbH. The cells were then injected under fluoroscopic control in the periarticular fat. Follow-up examinations were performed at one week 1 and 5 years. Results: Every patient reported improved VAS pain at any follow-up (1 week, 1, and 5 years) with ADRCs compared to the baseline. Conclusion: Our observational data indicate that facet joint syndrome patients treated with unmodified adipose tissue-derived regenerative cells experience improved quality of life in the long term.

We describe a recently developed approach to quantify welfare loss in animals, the Cumulative Pain metric. It combines the two most relevant dimensions of negative affective experiences: intensity and duration. The metric enables estimating the time individuals spend in negative affective states of a physical or psychological nature (operationally referred to simply as ‘pain’) of different intensities as the result of one or more challenges (e.g., diseases, injuries, deprivations). A new notation protocol (the Pain-Track) is used in which the duration of the experience is represented along the horizontal axis and intensity is represented by four categories in the vertical axis. Pain experiences are partitioned into temporal segments, where hypotheses for the experienced duration and intensity are proposed based on existing welfare indicators (e.g., neurophysiological, behavioral, anatomical, evolutionary). This structure forces transparency about assumptions and uncertainties, highlights knowledge gaps, and enables estimates to be continuously adjusted. Because the Cumulative Pain metric is based on parameters with a broadly common biological meaning, it provides the much needed interoperability among assessments of animal welfare. It enables comparing the impact of practices and living conditions, policies and interventions, and the calculation of welfare footprints of animal-sourced products using a universal measurement unit.

Malnutrition and dental caries in early childhood remain persistent and intertwined global health challenges, particularly for indigenous and geographically-remote populations. To examine the prevalence and associations between early childhood dental caries, parent-reported mouth pain and malnutrition in the Amazonian region of Ecuador, we conducted a cross-sectional study of the oral health and nutrition status of 1,407 children from birth through age 6 in the “Alli Kiru” program (2011-2013). We used multivariate regression analysis to examine relationships between severe caries, parent-reported mouth pain measures, and nutritional status. The prevalence of dental caries was 65.4%, with 44.7% of children having deep or severe caries, and 33.8% reporting mouth pain. The number of decayed, missing and filled teeth dmft) increased dramatically with age. Malnutrition was prevalent, with 35.9% of children stunted, 1.1% wasted, 7.4% underweight, and 6.8% overweight. As mouth pain increased in frequency, odds for severe caries increased. For each unit increase in mouth pain frequency interfering with sleeping, children had increased odds for underweight (AOR: 1.27; 95% CI: 1.02 – 1.54) and decreased odds for overweight (AOR: 0.76; 95% CI: 0.58 – 0.97). This relationship was most pronounced among 3-6 year-olds. Early childhood caries, mouth pain and malnutrition were prevalent in this sample of young children. Parent-reported mouth pain was associated with severe caries, and mouth pain interfering with sleeping was predictive of poor nutritional status. We demonstrate the utility of a parsimonious parent-reported measure of mouth pain to predict young children’s risk for severe early childhood caries and malnutrition, which has implications for community health interventions.

Fragile X syndrome (FXS) is a genetic disorder caused by a mutation in the fragile X messenger ribonucleoprotein 1 (FMR1) gene and known to be a leading cause of inherited intellectual disability globally. It results in a range of intellectual, developmental, and behavioral problems. Fragile X premutation associated conditions (FXPAC), also caused by a smaller CGG expansion (55 to 200 CGG repeats) in the FMR1 gene, is linked to other conditions that increase morbidity and mortality for affected persons. Limited research has been conducted on the burden, characteristics, diagnosis, and management of these conditions in Africa. This comprehensive review provides an overview of the current literature on FXS and FXPAC in Africa, epidemiology, clinical features and challenges faced, such as discrimination against affected persons, limited awareness and research, poor access to resources and genetic services and treatment. It further provides an in-depth analysis of the existing worldwide data for the diagnosis and treatment of these disorders. This review will improve understanding of FXS and FXPAC in Africa by incorporating existing knowledge, identifying research gaps, and potential topics for future research to enhance the well-being of individuals and families affected by FXS and FXPAC in the region.

： Anti-MDA5 antibody bearing (anti-MDA5+)-dermatomyositis (DM) or polymyositis (PM) is notorious for causing rapidly progressive interstitial lung disease (RPILD) &amp;/or cancers with high mortality rate. However, anti-MDA5 antibodies (Abs) are also found in other connective tissue diseases and their link with RPILD especially with regards to the mortality rate are unknown. We retrospectively recruited 71 patients bearing anti-MDA5-Abs in serum, stratified them in terms of a presence or absence of RPILD, and evaluated their clinical features, laboratory findings, associated myositis antibodies, concurrent connective tissue disease (CTD) as well as newly developed malignancies. Thirty-nine (55%) patients presented with DM/PM but 32 (45%) didn’t. Twenty-two of the former and 11 of the latter developed RPILD eventually, accounting for a total of 46% of all MDA5 bearing patients. On the other hand, 15 of all 71 (21.1%) patients had cancers. Among 32 patients who didn’t have DM/PM, 27 (38.0% of all 71) had other CTDs, indicating that only 5 (7.0% of 71) patients did not have CTDs. Senility (odds ratio [OR]=1.816, P=0.032), presence of anti-Ro-52 antibody (OR=1.676, P=0.018), elevated C-reactive protein (CRP, OR= 4.354, P&lt;0.001) and carcinoembryonic antigen (CEA, OR=2.625, P=0.005) posed risks for RPILD. High lactose dehydrogenase (LDH, p=0.009), CRP (p=0.001), CEA (p=0.001), ferritin (p ≤ 0.001) and low albumin (p ≤ 0.001) were significantly associated with mortality. Anti-SAE antibodies were negatively correlated with RPILD as analyzed by univariate (OR=0.245, P=0.017) and multivariate (OR= 0.058, P=0.036) regressions, indicating that they may be a protective factor from RPILD (OR= 0.543, P=0.008) or fatality (OR= 0.707, P=0.012), which was also demonstrated in subgroup analyses. In contrast to various risk factors for RPILD or mortality, anti-SAE antibodies might be conversely a protective factor in anti-MDA5+ patients.

Many large-scale studies revealed that exogenous erythropoietin, erythropoie-sis-stimulating agents, have no renoprotective effects. We investigated the effects of en-dogenous erythropoietin on renal function in ischemic reperfusion injury (IRI) of kidney using prolyl hydroxylase domaine (PHD) inhibitor, Roxadustat (ROX). 4 hr hypoxia (7% O2) and 4 hr treatment by ROX prior to IRI did not improve renal function. In contrast, 24-72 hr pre-treatment by ROX largely improved the decline of renal function by IRI. Hy-poxia and 4 hr ROX increased interstitial cells-derived Epo production by 75 and 6-fold, respectively, before IRI and worked as exogenous Epo. 24-72 hr ROX treatment increased Epo production during IRI by 9-fold. Immunohistochemistry revealed that 24 hr ROX caused Epo production in proximal and distal tubules and worked as endogenous Epo. Our data show that 24-72 hr ROX-induced tubular endogenous Epo production results in renoprotection but peritubular exogenous Epo production by interstitial cells-derived in-duced by hypoxia and 4 hr ROX did not. Stimulation of tubular but not peritubular Epo production may link to renoprotection.

To understand lung damage caused by COVID-19, we deduced two-phase lung damage mechanisms. After the lungs are infected with SARS-CoV-2 virus, the affected lung tissue swells and surface properties of pulmonary capillaries change, resulting in an increased flow resistance of affected capillaries. If a sufficient number of capillaries are affected by the infection, the swelling and increased cell wall adhesion collectively raise pulmonary vascular resistance. The increased vascular resistance further increases the dwell times of WBCs in affected capillaries and nearly capillaries. When pulmonary pressure is sufficiently higher, WBCs are forced to squeeze into interstitial spaces or alveolar spaces when local pressures are higher than what the capillaries can withstand. When more and more WBCs are dynamically retained, the flow resistance of more capillaries rises, pulmonary vascular resistance rises, and pulmonary pressure rises. The rise in the pulmonary pressure in turn results in elevated capillary pressures. When capillary pressures around the alveoli are sufficiently high, they cause interstitial pressures to change from normally negative values to positive values. The positive pressures cause fluid leakage to the alveolar space and thus degrade lung function. Tissue swelling, and occupation of WBCs in interstitial spaces and alveolar spaces further reduce compressible volume, and thus cause further rise in the pulmonary vascular resistance and pulmonary pressure. When the pulmonary pressure has reached a critical point as in the second phase, the blood breaks capillary walls and squeezes through interstitial spaces to reach alveolar spaces, resulting in irreversible lung damages. The available free volume in the thorax cage, organ usable capacities, temperature and humid are expected to have great impacts on degree of lung damages. The free volume in the thorax cage, lung usable surplus capacity, and other organ usable capacities determine the arrival time of last-phase irreversible damage. The mechanisms imply that the top priority for protecting lungs is maintaining pulmonary micro-circulation and preserving organ functions in the entire disease course while controlling viral reproduction should be stressed in the earliest time possible. The mechanisms also explain leukecytes are recruited and migrated into inflamed tissues by increasing their dwell times caused by increased local flow resistance.

This study aimed to investigate the effect of adding Mirror Visual Feedback Therapy (MFT) after Dry Needling (DDN) on sensitivity and motor performance in patients diagnosed with Post-Needling pain from Myofascial Trigger Points (MTrPs) in lateral elbow pain patients. A randomized, controlled, two-arm pilot trial following Consolidated Standards of Reporting Trials (CONSORT) was conducted at the European University of Madrid between February 1, 2023, and June 2, 2023. A total of 49 patients (F=23, M=26) were randomly assigned to the Experimental Group Deep Dry Needling, Ischemic Compression, Cold Spray, Stretching, and Mirror Therapy (n=25), and the others receiving the same interventions without Mirror Therapy (n=24). Pre- and post-treatment assessments encompassed Post-needling pain (VAS), pressure pain threshold (PPT), two-point discrimination threshold (TPDT), and maximum hand grip strength (MHGS). Post-needling pain intensity in the EG showed statistically significant reductions (MD = 0.400, SEM = 0.271, W = 137.00, p = 0.047) following the addition of MT to the DDN protocol. Similarly, PPT exhibited significant improvements (MD = 0.148 Kg/cm2, SEM = 0.271, W = 262.00, p < 0.001). However, TPDT and MHGS did not show significant differences between initial and post-treatment measurements. The addition of MFT to DDN for MTrPS in lateral elbow pain reduced Post-needling pain and influenced on sensory perception in lateral elbow pain patients with Myofascial Trigger Points. Despite observed clinical effects not reaching statistical significance, these findings offer valuable insights for future research considerations.

Following spinal cord injury (SCI), pathological reflexes develop that result in altered bladder function and sphincter dis-coordination, with accompanying changes in the detrusor. Bladder chemodenervation is known to ablate the pathological reflexes, but the resultant effects on the bladder tissue are poorly defined. In a rodent model of contusion SCI, we examined the effect of early bladder chemodenervation with botulinum toxin A (BoNT-A) on bladder histopathology and collagen deposition. Adult female Long Evans rats were given a severe contusion SCI at spi-nal level T9. The SCI rats immediately underwent open laparotomy and received detrusor injec-tions of either BoNT-A (10 U/animal) or saline. At 8 weeks post injury, the bladders were col-lected, weighed, and examined histologically. BoNT-A injected bladders of SCI rats (SCI-BoNT-A) weighed significantly less than saline injected bladders of SCI rats (SCI-saline) (241 ± 25 mg vs. 183 ± 42 mg; p<0.05). Histological analyses showed that SCI resulted in significantly thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from uninjured animals (339 ± 89.0 m vs. 193 ± 47.9 m; p<0.0001). SCI-BoNT-A animals had significantly thinner bladder walls compared to SCI-saline animals (202 ± 55.4 m vs. 339 ± 89.0 m; p<0.0001). SCI-BoNT-A animals had collagen organization in the bladder walls similar to that of uninjured animals. Detrusor chemodenervation soon after SCI appears to preserve bladder tissue integrity, by reducing the development of detrusor fibrosis and hypertrophy associated with SCI.

Comparing to males, females require much more morphine to produce comparable levels of analgesia, suggesting a difference in the endogenous hyperalgesia and analgesia modulation between sexes. Aside from hormones, emerging evidence suggests sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and American College of Gastroenterology (ACG), up to 25 % of the population having visceral pain at any one time, and in the United States 10-15 percent of adults suffering from irritable bowel syndrome (IBS). Here we analyzed literatures on clinical reports of sex differences in visceral pain focusing on IBS, other form of bowel dysfunction and comorbidities, and summarized animal models that provided means to investigate the underlying molecular mechanisms in sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems all contribute to sex-dependent nociception and nociplasticity in the painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI), and other patient-reported outcomes (PROs), such as the visual analog scale (VAS) for symptoms and EULAR sicca score (ESS), are used to assess the disease activity of primary Sjögren’s syndrome (pSS). Recently, Clinical ESSDAI (ClinESSDAI) and Clinical Trials ESSDAI (ClinTrialsESSDAI) were developed for objective clinical disease activity indexes. However, the relationship of ClinESSDAI and ClinTrialsESSDAI with PROs as well as that between ESSPRI and other PROs and the objective parameters of glandular function in pSS have not been established. Herein, we investigated the correlation of ESSPRI and other PROs with the objective parameters of glandular function and the relationship of PROs with ClinESSDAI and ClinTrialsESSDAI in 66 patients with pSS. Correlations were calculated with Spearman’s correlation coefficient. ClinTrialsESSDAI was correlated with ESSPRI, dryness (ESSPRI-Dryness), fatigue, and pain domains of ESSPRI, VAS for oral dryness (oral-VAS), and patient’s global assessment. Although ESSPRI did not correlate with the objective parameters of glandular function, ESSPRI-Dryness, ESS, and oral- and ocular-VAS did. These results suggest that ESSPRI-Dryness, ESS, and VAS for symptoms, but not ESSPRI, reflect the glandular dysfunction and that ClinTrialsESSDAI correlates with PROs for dryness in pSS.

Treacher Collins syndrome (TCS) is a rare congenital disorder characterized by craniofacial abnormalities due to underdeveloped facial bones. In addition to physical deformities, TCS also presents with several neurological disorders resulting from facial defects and brain malformations. This paper reviews the neurological manifestations of TCS with a focus on facial nerve paralysis, neurodevelopmental delay, intellectual disability, and autism spectrum disorder. Facial nerve hypoplasia leads to an inability to control facial muscles and expressions. Neurodevelopmental delays in motor function and language acquisition are commonly reported in infants with TCS due to hearing loss, facial impairments, poor nutrition, infections, and structural brain changes. Intellectual disability with below average IQ is also more prevalent in TCS, affecting about one third of patients. Brain imaging reveals abnormalities like white matter hypoplasia, cortical atrophy, and reduced grey matter volume which likely contribute to cognitive deficits. Additionally, the rate of autism spectrum disorder is significantly higher in TCS compared to the general population. The reasons are unclear but may involve hearing loss, facial dysmorphisms, and socio-emotional processing centers in the brain. Management is multidisciplinary, focusing on early interventions like speech, physical, feeding, and behavioral therapy to maximize developmental and functional outcomes. Further research on the neurological pathophysiology of TCS is needed to better elucidate the mechanisms linking craniofacial defects with adverse neurodevelopmental consequences.

Prediction and early detection of atrial fibrillation (AF) remain a permanent challenge in everyday practice. Timely identification of an increased risk for AF episodes (which are frequently asymptomatic) is essential in the primary and secondary prevention of cardioembolic events. One of the noninvasive modalities of AF prediction is represented by the electrocardiographic P-wave analysis. This includes the study and diagnosis of interatrial conduction block (Bachmann`s bundle block). Bayés’ Syndrome (named after its first descriptor) denotes the association between interatrial conduction defect and supraventricular arrhythmias (mainly AF) predisposing to cardioembolic events. Our short review presents an update of the most important data concerning this syndrome: brief history, main ECG features, pathophysiological background and clinical implications.

Aims: Clinical evidence indicates that innate immune cells may contribute to the onset and outcome of acute coronary syndrome (ACS). Our prospective study aimed at analysing neutrophil phenotypes in ACS and their role in predicting 1-year major cardiovascular events. Methods: Blood neutrophil phenotypes were analysed by flow cytometry. Differential blood cell count and plasma levels of soluble markers were recorded at admission and at 6-month follow-up. Results: 108 patients categorized in chronic stable coronary artery disease (n=37), unstable angina (UA) (n=19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n=25), and ST-Elevation Myocardial Infarction (STEMI) (n=27) were included. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR) than stable and UA patients (P<0.0001), which normalized at 6-month after MI. STEMI patients were characterized by elevated percentages of band cells in low-density neutrophils (P=0.007) and in high-density neutrophils (P=0.019) compared to the other patients. Multivariable logistic regression analysis revealed that plasma levels of total MPO was associated with STEMI when compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P<0.0001), UA (1.47; 1.146-1.886; P=0.002), and NSTEMI (1.213; 1.1-1.134; P=0.0001) patients, while increased neutrophil SSC signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; P=0.045). Based on multivariable Cox regression analysis, elevated plasma levels of PCSK9 and low-density neutrophil percentage predicted 1-year outcome independently of cardiovascular risk factors (c-index: 0.915; IQR: 0.908-0.929). Conclusions: Changes in neutrophil phenotype are concomitant to ACS. These changes may differ between STEMI and NSTEMI. They may also contribute to ACS risk and patient outcome.

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wild type cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.

Insulin resistance is a prominent pathophysiologic syndrome in a plethora of metabolic disorders including obesity, prediabetes, type 2 Diabetes Mellitus (Ten et al., 2007), impaired glucose tolerance, dyslipidemia, polycystic ovary syndrome and hypercoagulability (Smith & LeRoith, 2004). It is strongly associated with obstructive sleep apnea, hypoventilation syndrome, pancreatitis, nonalcoholic fatty liver disease, steatohepatitis, cirrhosis, gall bladder disease, multiple cancers (breasts, uterus, cervix prostate, kidney, colon, esophagus, pancreas and liver), stroke, cataracts, coronary heart disease, and hypertension. It is also associated with causation of abnormal menses, infertility, polycystic ovary syndrome, osteoarthritis, phlebitis and other venous diseases. Insulin resistance is thought to be caused by intrinsic and extrinsic factors that contribute to its development. Once present, insulin resistance affects the metabolism, behavior, physical appearance and has lasting effects. This paper will review the latest evidence in development of insulin resistance, its pathogenesis and manifestation and its relation to other conditions. The final aim is to raise awareness of its role on diet, metabolic, genetics and microbiome.

Neuropathic pain is caused by a lesion or disease of the somatosensory system and is one of the most incapacitating pain types, representing a significant non met medical need. Due to the increase in research in the field and since innovative therapeutic strategies are required, namely in intractable neuropathic pain, neurostimulation has been used. Within this approaches, transcranial magnetic stimulation (TMS) that uses a transient magnetic field to produce electrical currents over the cortex emerges in the literature. Since this is an area in expansion and due to the putative role of TMS, we performed a bibliometric analysis in Scopus with the primary objective of identify the scientific production related to the use of TMS to manage neuropathic pain. The research had no restrictions and the analysis focused on the characteristics of the literature retrieved, scientific collaboration and main research topics from inception to July 6, 2023. A total of 474 articles were collected. A biggest co-occurrence between the terms “neuropathic pain” and “transcranial magnetic stimulation” was obtained. The journal “Clinical Neurophysiology” leads the Top 5 most productive sources. The United States is the most productive country with 50% of the documents being “review articles” followed by France with 56% of the documents being “original articles”. Lefaucheur, JP and Saitoh, Y are the two most influents authors. The most frequent type of documents was “original article”. This study allows to perform a general overview in the field of TMS application for neuropathic pain and is useful to establish future directions of research in this field.

An imbalance in any metabolic system can be traced to its homeostasis. When homeostatic environment is not attainable then there will be a response from the body. A new shift has emerged, “the negative feedback effect of high fructose consumption;” more pain than gain. The human metabolic system daily combat fructose sugar metabolism which emanates from high consumption. This inadvently lead to a chronological series of complications arising from the feedback. These feedbacks play pivotal roles in skeletal muscle damage and other body frameworks, it also fosters toxic advanced glycation end products (AGEs), factors that impose and inflict damaging effects to the body`s energy currency and serious threat to health. These damages are missed or overlooked because of early nonspecific physiological symptoms. High level of fructose has both long- and short-term effects on human metabolic processes. These effects which are majorly through the production of reactive oxygen species (ROS) and other free radicals, are felt in the disruption of biomolecules such as causing DNA mutation, lipid peroxidation etc. these effects in turn lead to various diseases such as cancer, diabetes, atherosclerosis, and other health issues. In this review, we will focus on the damaging effects this sugar has on human health and the present solutions being applied. We will also look at the next step in combatting and controlling these negative feedbacks.

The traditional standards employed for pain assessment have many limitations. One such limitation is reliability because of inter-observer variability. Therefore, there have been many approaches to automate the task of pain recognition. Recently, deep-learning methods have appeared to solve many challenges, such as feature selection and cases with a small number of data sets. This study provides a systematic review of pain-recognition systems that are based on deep-learning models for the last two years only. Furthermore, it presents the major deep-learning methods that were used in review papers. Finally, it provides a discussion of the challenges and open issues.

Due to the proliferation of genetic testing, pathogenic germline variants predisposing to hereditary hematological malignancy syndrome (HHMS) have been identified in an increasing number of genes. Consequently, the field of HHMS is gaining recognition among clinicians and scientists worldwide. Patients with germline genetic abnormalities often have poor outcomes and are candidates for allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT using blood from a related donor should be carefully considered because of the risk that the patient may inherit a pathogenic variant. At present, we now face the challenge of incorporating these advances into clinical practice for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and optimizing the management and surveillance of patients and asymptomatic carriers, with the limitation that evidence-based guidelines are often inadequate. The 2016 revision of the WHO classification added a new section on myeloid malignant neoplasms, including MDS and AML with germline predisposition. The main syndromes can be classified into three groups. Those without pre-existing disease or organ dysfunction; DDX41, TP53, CEBPA, those with pre-existing platelet disorders; ANKRD26, ETV6, RUNX1, and those with other organ dysfunctions; SAMD9/SAMD9L, GATA2, and inherited bone marrow failure syndromes. In this review, we will outline the role of the genes involved in HHMS in order to clarify our understanding of HHMS.

Introduction: Obstructive Sleep Apnea (OSA) is a respiratory condition identified by the partial or complete obstruction of the upper air passages during sleep. These episodes can lead to complications in neurobehavioral and cognitive domains and cardiovascular issues, especially in children. The involvement of OSA in ocular health during adulthood has been reported, but it remains a topic of debate in pediatric cases. Objective: This review aims to analyze the correlation between OSAS and ocular health in children. Specifically, it investigates the effects of OSA on ocular structures and conditions and explores potential improvements through treatment. Subjects and Methods: The research employed three search engines: PUBMED/MEDLINE, SCOPUS, and WebOfScience. After initial identification, 120 irrelevant articles were excluded. Of these, 10 pertained to the adult population, and 110 focused on the pediatric population. Following a careful selection process and the application of enrollment criteria, six relevant articles were included, all in English, focusing on the effects of OSA on children's eyes. Among these, three studies explored correlations with choroidal alterations, while three investigated retinal and optic nerve changes. Two studies analyzed post-otorhinolaryngological intervention ocular changes. Results: OSA leads to increased intraocular pressure and reduced optic nerve thickness in adults, but treatment alleviates this condition. An immediate correlation between OSA and optic nerve thickness in children does not readily emerge, although age appears to play a role. Pediatric patients with OSA exhibit corneal anomalies and an increase in optic nerve thickness, possibly due to intermittent hypoxia. Studies indicate that OSA can influence retinal vascular density in children, with an increase observed after treatment and reduced choroidal thickness in cases of adenotonsillar hypertrophy. Conclusion: This literature review has highlighted how OSA in children can significantly impact ocular health, with observed alterations in the optic nerve, choroid, retina, and cornea. While the direct correlation with the optic nerve may not always be evident, OSA can elevate intraocular pressure and lead to structural changes. However, treatment appears to bring about improvements. The necessity for regular monitoring to detect potential adverse effects underscores the importance of promptly addressing childhood OSA.

Abstract: Background and Objectives: A growing number of epidemiologic studies have found that diabetes mellitus may increase cancer risk and is implicated in numerous other metabolic and inflammatory disorders. The increase in pro-inflammatory cytokines plays a major role in insulin resistance and leads to hypoalbuminemia, and micro- and macrovascular diabetes complications, including kidney disease and anemia. This study aimed to investigate the utility of CEA, CRP, serum albumin level, hemoglobin, and LDH as biomarkers for cancer risk and the biological implications of diabetes on the evolution and prognosis of oncological patients. Material and methods: We conducted a retrospective, longitudinal, observational study, on a total group of 434 patients, 217 diagnosed with a form of cancer and with type 2 diabetes as a comorbidity, and the other 217 – control group, without diabetes. These patients were admitted to the oncology clinic. In subgroups, the same number of patients was considered, depending on the location of the oncological pathology. Anemia, hypoalbuminemia, elevated lactate dehydrogenase, glycated hemoglobin, and C-reactive protein levels are more pronounced in subjects with type 2 diabetes and cancer. Conclusions: The presence of diabetes negatively affects the clinical and biological prognosis of cancer patients.

Embryologically, the left brachiocephalic vein (LBV) originates as an anastomotic channel between the right and left anterior cardinal veins 1 . This positions the LBV between the manubrium sterni anteriorly and the innominate artery posteriorly 2 . This pattern of adjacency of the aorta to the LBV is unique to mammals and results from a quirk of evolution 3 . With age, the ascending aorta unfolds, elongates and dilates 4 . Simultaneously, there is a change in the thoracic geometry that reduces the thoracic volume primarily from disc height loss and kyphosis 5 . These transitions progressively compress the LBV. Normally this compression is circumvented via collateral pathways and "Blood finds a way" 6 . However, traversing these circuitous pathways comes at a cost and can result in delayed transit times and venous congestion. While it is possible that compression of the LBV in the setting of adequate collateral channels may fail to provoke any pathologic sequelae, we propose a phenomenon in which such compression in the setting of inadequate collateral circulation may lead to a state of pathologic venous congestion. This anatomic anomaly and its associated clinical features, if identified, can offer a new avenue for treatment options for some of the hitherto unexplained neurologic disorders.

(1) Background: Metabolic syndrome is a strong predictor of cardiovascular disease thus the objective of the study was to verify the prevalence of metabolic syndrome in farmers, as well as to verify the association with sociodemographic, work and lifestyle factors. (2) Methods: Cross-sectional, observational study, carried out with 790 individuals. For the diagnosis of metabolic syndrome, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) criteria were used. Pearson's chi-square test and binary logistic regression were used to verify factors associated with metabolic syndrome (3) Results: The prevalence of MS according to the IDF criteria was 16.3% overall, with 9.7% of women (95% CI: 6.66–16.16) and 6.6% of men (95% CI: 5.17–11.97). According to the NCEP/ATP III criterion, it was 12.3% overall, with 7.5% corresponding to women (95% CI: 6.62 – 13.13) and 4.8% to men (95% CI: 3.5 – 8.70). With regard to the conditions that make up metabolic syndrome, it was found that high density lipoprotein, high blood pressure and high waist circumference were the most prevalent. (4) Conclusions: The prevalence of metabolic syndrome is considerable in the population when compared to other regions, both rural and urban, in Brazil.

Repeated desaturation of oxyhemoglobin, micro-arousals, which are typical in obstructive sleep apnea syndrome (OSAS), have negative effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction) cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), neuropsychiatric complications and a wide range of malignancies. This in turn has a multilateral effect on familial, occupational and social life, as well as increasing the risk of road traffic accidents or accidents at workplace. Awareness, timely screening and prevention of complications play an important role in the diagnosis and treatment of comorbid conditions. This review focuses on comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

Takotsubo syndrome (TTS), recognized as stress’s cardiomyopathy, or better as left ventricular apical balloon syndrome in the recent years, is a rare pathology, described for the first time by Japanese researchers in 1990. TTS is characterized by an interindividual heterogeneity in onset and progression, and by the strong predominance in postmenopausal women. The clear causes of these TTS features are uncertain, given the reduced understanding of this intriguing syndrome until now. However, the increasing frequency of TTS cases in the last years, and particularly correlated to SARS-CoV-2 pandemic, leads us to imperative necessity both of a complete knowledge of TTS pathophysiology for identifying biomarkers facilitating its management, and targets for specific and effective treatments. The suspect of a genetic basis in TTS pathogenesis has been evidenced. Accordingly, familial form of TTS has been described. But a systematic and comprehensive characterization of the genetic or epigenetic factors significantly associated with TTS is lacking. Thus, we, here, conducted a systematic review of literature before June 2021, to contribute to identify potential genetic and epigenetic factors associated with TTS. Interesting data were evidenced, but of reduced number and with diverse limitations. Consequently, we concluded further work is needed to address the gaps discussed, and probably a clear evidence may arrive using multi-omics investigations.

To reduce the risk factors for mortality, the paper has focused on the assessment of the socioeconomic, clinical, physical, biophysiological, and biochemical characteristics of Down's syndrome which can be affected by the type of nutrition system, toxicity, and ecological footprint. Patients were males with trisomy 21 diagnosed by karyotype test and assessed by clinical examinations. Samples were collected from different biofluids. The physicochemical analyses of the biomatrix samples were performed and these properties had compared to findings of healthy males and age-matched controls. Duraphat application was proved effective for their oral treatment and saliva was the optimum biomarker for detecting malnutrition. Patients were hypersensitive to Cu while the Mn content in blood and hair was considered an expression to the degree of epileptic condition and chronic seizure development. The ecological footprint was 5.6 gha and carbon footprint was recognised in food poverty habits. These can be reduced by eating more plant-based proteins and fibre-rich foods with low saturated fats and sodium. The findings provide an up-to-date reference for expected developmental outcomes in children with DS in terms of biophysicochemistry. The genetically sensitive intervention is affected by heredity factor and sensitivity to toxics. Down's syndrome is encouraged to live green-hipster life.

Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.

This study aims to provide an updated overview of the systematic evaluation and management of Post-Traumatic trigeminal neuropathic pain (PTTN) resulting from dental procedures or trauma. PTTN arises following an injury to the trigeminal nerve, which is responsible for sensory and motor functions in the maxillofacial region. The etiology encompasses various dental procedures and craniofacial trauma, leading to a spectrum of symptoms, from tingling to severe pain. Diagnostic challenges stem from the absence of standardized criteria and the overlap with focal neuralgia, necessitating comprehensive evaluation. Misdiagnosis can result in prolonged suffering and unnecessary procedures. Successful management hinges on prompt diagnosis and interdisciplinary collaboration, with early intervention crucial in mitigating chronicity. While nerve recovery post-trauma is challenging, preventive measures through accurate evaluation and treatment are paramount.  Management for PTTN includes non-invasive and surgical interventions. Non-invasive intervention includes systematic and local pharmacological management. This review enhances uniformity in PTTN evaluation and treatment approaches despite standardized study limitations.

Background: Musculoskeletal pain is a non-negligible multifaceted condition affecting more than 30% of the global population. Superficial heat therapy (HT) through increasing tissues temperatures plays a role in increasing local metabolism and function and relieving pain. Knee pain and sports represent two relevant fields of superficial HT application. Methods: In the present paper a panel of experts performed a narrative review of the literature regarding the role of superficial HT in the management of knee pain and sport activities. Results: According to the reviewed literature, HT represents a therapeutic option in the management of musculoskeletal pain due to three main effects: pain relief, promotion of healing and return to normal function and activity. Moreover, HT plays a role in sport activities both before and after exercise. Before performing sports, HT helps in preparing muscles for performance. After performing sports, it is capable to promote recovery and healing pathways. Combining and sequencing superficial heat and cold therapy represent an interesting topic of study. Overall, application of heat wraps for superficial HT can be considered safe. Conclusions: Despite being an ancient method, HT shows to be a potentially beneficial and safe option in the management of several conditions including KP and sports. The key in the application of superficial HT is a multimodal and multidisciplinary approach.

Background. The purpose of the study was to evaluate the intensity and frequency of low back pain (LBP) in people with multiple sclerosis (PwMS) and the patient's knowledge of physiotherapeutic methods of combating. Methods. In this study, patients with confirmed multiple sclerosis were selected. The study was carried out using an original survey questionnaire and a numerical pain intensity scale (Visual Analogue Scale). PwMS were divided into 3 age groups: 18-30 years, 31-50 years, and over 50 years. Results. Ninety PwMS (68 women and 22 men) aged 18 to 60 years were included in the study. The mean duration of the disease was 9.5±4.9 years, and the mean EDSS was 3.5±1.6. Most of the patients had a relapse-remitting form. 68.9% of PwMS felt lower back pain (n = 62). The relationship tested was statistically significant (p=0.0000012), and the strength of the relationship was high (rc=0.695). The average level of low back pain among PwMS was 4.7 out of 10 on the VAS scale. The prevalence of LBP was higher in female patients (p<0.001), with a secondary progressive form (p<0.001) and with a longer duration of the disease (p=0.023). The most widely used methods of LBP therapy were kinesitherapy and manual therapy. Conclusions. LBP is common in multiple sclerosis. A female sex, a secondary progressive form of MS, and a longer duration of the disease increased the risk of LBP. It is important to implement properly planned physiotherapy activities and educate patients on how to combat LBP.

To systematically assess the effect size of different methods for patients with low back pain. PubMed, Cochrane Library, Web of Science, and Google Scholar. databases were searched in January 2023. This study has been developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The key search terms were: “Low back pain”, “Back pain”, “SF-36”, “VAS”, “VASP”, “Roland-Morris”, “Oswestry Disability Index”, and “conservative treatment”. The risk of bias was determined for each randomized trial using the Cochrane Risk of Bias Tool, and the methodological index for non-randomized studies (MINORS). The outcomes included SF-36 Mental, SF-36 Physical, VAS, Roland-Morris, and Oswestry Disability Index. R 4.0.5 software was used, and standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated for continuous outcomes, random model. Twenty-five studies were included. Depending on the outcome being measured, the effect size of different methods in treating low back pain varies from small to large as follows: SF-36 Mental (SMD = 0.39, p &lt; 0.0001), SF-36 Physical (SMD = 0.55, p &lt; 0.0001), VAS (SMD = -0.84, p &lt; 0.0001), Roland-Morris (SMD = -0.45, p &lt; 0.0001), and Oswestry Disability Index (SMD = -0.61, p &lt; 0.0001). Our meta-analysis indicates the positive effects of applying different methods in the treatment of low back pain. PROSPERO registration number: CRD42022371282

Pancreatic neuroendocrine tumor (P-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional P-NETs, typically when liver metastases occur. NETs diagnosis is frequently late, along with symptoms related to hormone hypersecretion. We described the case of a patient with a low-grade non-functional P-NET, but with a typical clinical presentation of a carcinoid syndrome; moreover, we reviewed the literature regarding this topic. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hypervascular mass; then a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum Chromogranin A and urinary 5-HIAA measurements resulted negative. Given the small size of the lesion (8 mm), we preferred to perform an endoscopic ultrasonography (EUS) with fine-needle biopsy (EUS-FNB), allowing the diagnosis of low-grade (G1) non-functional P-NET (NF-P-NET). Surgery was waived, while a follow-up strategy was chosen. Early recognition of P-NETs, although rare, is necessary to improve patient’s survival. EUS-FNB should be the protocol of choice for an early characterization of these tumors.

The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether administration of noxious and non-noxious electrical stimuli synchronized with the cardiac cycle resets BRS, reestablishing pain inhibition. 30 pain-free normotensives controls (NC) and 32 normotensives fibromyalgia (FM) patients received two, ≈8 minute-epochs of cardiac-gated, peripheral electrical stimuli. Non-painful and painful electrical stimuli were synchronized to the cardiac cycle as the neuromodulation experimental protocol (EP) with 2 control conditions (CC1, CC2). BRS, heart-rate-variability (HRV), pain threshold and tolerance, and clinical pain intensity were assessed.Reduced BRS in FM at baseline increased by 41% during two, ≈8 minute-epochs of stimulation. Thresholds in FM increased significantly during the experimental protocol (all Ps<0.001) as did HRV. FM levels of clinical pain significantly decreased by 35.52% during the experimental protocol but not during control stimulations (P<0.001). Baroreceptor training may reduce FM pain by BRS-mediated effects on intrinsic pain regulatory systems and autonomic pain modulation. These processes seem to be linked by classical and operant conditioning.

Nerve hydrodissection (HD), a technique used when treating nerve entrapments, involves using an anesthetic or solution such as saline or 5% dextrose solution to separate the nerve from the surrounding tissue, fascia, or adjacent structures. This technique aims to treat neuropathic pain, or pain caused by the nerve. Ultrasound-guided HD of peripheral nerves has gained significant attention in the medical profession and pain management fields in recent years. This is due to a number of high impact publications of randomized control trials demonstrating the efficacy and safety of this technique for the treatment of carpal tunnel syndrome. Even the 20th edition of Harrison’s Principles of Internal Medicine textbook lists injection of 5% dextrose as an alternative local treatment that does not have the side effects of corticosteroids. At present, there is no review of the current literature on this technique. This manuscript will summarize and discuss the following: 1) the different approaches to doing ultrasound-guided HD of nervous structures, 2) its usages in different clinical situations, 3) its clinical pearls, 4) the solution used, and 5) the postulated mechanisms of action.

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

Abstract: This study evaluates the effect of paravertebral spinal injection (PSI), utilizing both subjective and objective assessments in chronic low back pain (LBP) associated with facet joint arthrosis over a one-month duration. Subjective questionnaires included the Visual Analogue Scale (VAS) for pain, Oswestry Disability Index, Health Survey SF-12, and the short Falls Efficacy Scale International (FES-I). Objective assessments included in-clinic gait and timed-up-and-go (TUG) tests using wearable sensors, as well as 48-hour daily physical activity (DPA) monitored using a chest-worn tri-axial accelerometer. Subjective and objective measures were performed prior to treatment, immediately after the treatment, and one-month afterthe treatment. Eight LBP patients were recruited for this study (mean age = 54±13 years, body mass index = 31.41±6.52 kg/m2, 50% males). Results show significant decrease in pain (~55%, p<0.05) and disability (Oswestry scores, ~21%, p<0.05). In-clinic gait and TUG were also significantly improved (~16% and ~18% faster walking and shorter TUG, p<0.05); however, DPA (including percentage of physical activities (walking and standing) and the number of steps) showed no significant change after PSI (p>0.25; effect size≤0.44). We hypothesize that DPA may continue to be truncated by conditioned fear-avoidance, a psychological state that may prevent increase in daily physical activity to avoid pain.

Background: Previous data indicate a role of IL-1 and IL-1RA imbalance in bladder carcinoma (BC) and inhibition of IL-1 signaling might be considered a treatment option. Objective: To assess expression patterns and the prognostic role of IL-1ß and IL-1RA in invasive BC and to evaluate their interaction with AKT signaling and proliferation. Design, Setting, and Participants: The study included two independent cohorts of n=92 and n=102 patients who underwent radical cystectomy for BC. Specimen from BC and benign urothelium (n=22 and n=39) were processed to a tissue microarray and immunohistochemically stained for IL-1ß, IL-1RA, AKT and Ki-67. Expression scores were correlated to clinical variables and Ki-67 and AKT expression. Outcome measurements and statistical analysis: Association with outcome was assessed using Wilcoxon Kruskal-Wallis tests, Chi-square tests or linear regression, dependent on the variable’s category. Kaplan–Meier and Cox proportional hazard analyses were used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Results: Both, IL-1ß and IL-1RA were significantly overexpressed in invasive BC compared to benign urothelium in both cohorts (p&lt;0.005). IL-1ß was associated with vascular invasion (210 vs. 183, p&lt;0.02), lymphatic invasion (210 vs. 180, &lt;0.05) and G3 cancer (192 vs. 188, &lt;0.04). Survival analysis revealed favorable RFS, CSS, and OS in case of high IL-1ß expression (p&lt;0.02, &lt;0.03 and &lt;0.006, respectively). Multivariate analyses revealed an independent impact of (low) IL1ß expression on RFS, CSS and OS. IL-1ß and IL-1ß/IL-1RA ratio were positively correlated to AKT expression (p&lt;0.05 and &lt;0.01, respectively). Additionally, high expression of Ki-67 (&gt;15%) correlated with higher levels of IL-1β (p=0.01). Conclusions: Overexpression of IL-1ß and IL-1RA is frequently found in BC, with a prognostic significance observed for IL-1ß protein expression. The observed link between the IL-1ß / IL-1RA axis and AKT signaling may indicate possible autophagy activation processes beside the known tumor-promoting effects of AKT.

Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years¹. Due to high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. There is, therefore, a critical need to develop innovative molecular and cellular tools to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.

Resistance of tumor cells to anticancer drugs is a major obstacle in tumor therapy. In this study, we investigated the mechanism of cordycepin-mediated resensitization to cisplatin inT24R2, a derived T24 cell line. Treatment with cordycepin or cisplatin (2 g/ml) alone could not induce cell death of T24R2, but combination treatment of these drugs significantly induced apoptosis of the cells through mitochondrial pathway including depolarization of mitochondrial membrane, decrease of anti-apoptotic proteins, Bcl-2, Bcl-xL, and Mcl-1, and increase of pro-apoptotic proteins, Bak and Bax. . High expression of MDR1 was the cause of cisplatin resistance in T24R2, and cordycepin significantly reduced MDR1 expression through inhibition of MDR1 promoter activity. MDR1 promoter activity was dependent on a transcription factor, Ets-1, in T24R2 cells. Although there is a correlation between MDR1 and Ets-1 expression in bladder cancer patients, active Ets-1, Thr-38 phosphorylated form (pThr-38), was critical to induce MDR1 expression. Cordycepin decreased pThr-38 Ets-1 level through inhibition of AKT, which reduced MDR1 transcription and induced the resensitization of T24R2 to cisplatin. The results suggest that cordycepin effectively resensitizes cisplatin-resistant bladder cancer cells to cisplatin, thus serving as a potential strategy for treatment of anti-cancer drug resistant patients.

Cyclin E2, a member of the cyclin family, is a key cell cycle-related protein. This protein plays essential roles in cancer progression, and as such, an inhibitor of cyclin E2 has been approved to treat several types of cancers. Even so, mechanisms underlying how to regulate cyclin E2 expression in cancer remain largely unknown. The current study found that miR-3687 is up-regulated in clinical bladder cancer (BC) tumor tissues, TCGA database and human BC cell lines. Inhibition of miR-3687 expression significantly reduces human BC cell proliferation in vitro and tumor growth in vivo, which are concurrently with the induction of G0/G1 cell cycle arrest and downregulation of cyclin E2 protein expression. Interestingly, overexpression of cyclin E2 reversed the inhibition of BC proliferation induced by miR-3687. Mechanistic studies suggest that miR-3687 could bind to the 3'-UTR of foxp1 mRNA, downregulates FOXP1 protein expression, and in turn promotes the transcription of cyclin E2, thereby promoting the growth of BC cells. Collectively, the current study not only establishes a novel regulatory axis of miR-3687/FOXP1 in regard to regulation of cyclin E2 expression in BC cells, but also provides strong suggestive evidence that miR-3687 and FOXP1 may be potentially promising targets in therapeutic strategies of human BC.

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

Abstract: Background: Adolescents frequently self-report pain, according to epidemiological research. The knee is one of the sites where the pain is most common. One of the main factors contributing to the number of years people spend disabled and having substantial personal, societal, and economic burdens globally is musculoskeletal disorders. Insidious, slowly building onset that neither the adolescent nor the parent is aware of [5]. Patellofemoral Pain (PFP) is a clinical knee pain commonly affecting adolescents. In the present study, the authors aimed to estimate the frequency of knee pain in Saudi adolescents. Methods: This cross-sectional survey carried out from June to November 2022 included 676 adolescents, ages 10 to 18. The data are presented as frequencies and percentages for categorical variables. Analysis of variance (ANOVA) was used to compare means between groups, while the chi-square test was used for the comparison of categorical variables. Statistical significance was set at p < 0.05. Results: Adolescents were invited to take part in the study; 57.5% were female and 42.5% were male, and 68.8% were aged between 15 and 18. The prevalence of knee pain was considerably high among females (26%), while it was 19.2% among males. Moreover, age was a significant predictor for knee pain, and BMI was as well. We also found a significant difference between BMI classification and stiffness of the knee (p = 0.008). There is a difference between adolescents who do physical activities in leisure and difficulty bending (p = 0.03). Conclusion: Our study noted a high rate of knee pain among adolescents, so we need to raise awareness about risk factors. Adolescent knee pain can be prevented with conservative methods and some minor lifestyle/activity modifications.

Pulmonary fibrosis is a chronic, progressive, and irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (EM) due to a persistently activated wound-repair response. The aberrant activation of myofibroblasts in the alveolar environment by Transforming Growth Factor beta (TGF-β) and other signaling molecules is considered a key event in the development and progression of fibrosis. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in extracellular matrix deposition. CTHRC1 is transcriptionally regulated by TGF-β and inhibits both TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 is vital in regulating tissue remodeling during wound repair. In this review, we will highlight recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, rheumatoid arthritis-interstitial lung disease, systemic sclerosis, and post-COVID lung fibrosis. Notably, the expression of CTHRC1 is responsive to antifibrotic drugs such as pirfenidone indicating its potential as a therapeutic target. Collectively, these findings suggest that CTHRC1 may present new opportunities for the diagnosis, stratification, and treatment of patients with lung fibrosis.

Pain is a multifaceted multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central-stimulation (tDCS) and peripheral-stimulation (TENS) in pain-inhibition during a cognitive-task in healthy volunteers and to observe potential neuro-cognitive improvements. Healthy eighty volunteers went through a complete experimental protocol comprising pain-induction (CPT), administration of tDCS/TENS, EEG-data acquisition, and cognitive assessments. The protocol for this study is categorized into 04-groups: G1(Control), G2(TENS), G3(Anodal-tDCS), and G4(Cathodal-tDCS). Paired t-tests (p

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

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

The definition of patients with Special Needs (SN) is used in the literature to refer to individuals with mental and physical disorders for whom the usual perioperative pathways are not applicable due to lack of cooperation, regardless of age. Studies in the literature recognize the appropriateness of general anesthesia for performing day surgery dental care in this type of patient. The present retrospective, single-center, observational study involved 41 uncooperative patients aged between 3 and 17 undergoing dental surgery under general anesthesia. The main objective was to assess the possible incidence of difficult airway management, understood as difficulty ventilating and/or intubating the patient. A secondary objective was to highlight the influence of general anesthesia on patient outcomes by testing the incidence of perioperative complications. Tracheal intubation was successfully completed in all of the patients considered, and in no case did the patient have to be woken up because of difficulty in airway management. No perioperative complications attributable to anesthesia were found in any patients. From the present experience, it can be concluded that general anesthesia is a suitable option for performing dental care in pediatric subjects with special needs, and that although the peculiar peri-operative management of these patients might increase the risk of possible anesthesia-related side effects, no complications have been encountered in any case.

A recent study published in Nature Medicine (Mautner et al., Nat Med 2023 Nov 2. doi: 10.1038/s41591-023-02632-w. Epub ahead of print) reported findings regarding a four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients, aimed at comparing the therapeutic effectiveness of orthobiologic interventions against corticosteroid injections for the treatment of knee osteoarthritis (OA). The study concluded that, one-year post-treatment, all orthobiologic therapies examined were equivalent in effectiveness to each other and to corticosteroid injections. While we commend the scope and methodological rigor of the trial, the publication could be enhanced by a more comprehensive presentation of data to support the conclusions drawn. Particularly, the omission of baseline data for primary outcomes, the missing context to evaluate absolute values, the lack of discussion regarding interindividual variability, and the unexpectedly favorable results for corticosteroids that contrast the established literature, are areas that merit additional examination and insight. Here we aim to highlight these points for consideration, and advocate for the release of supplementary data to facilitate a comprehensive understanding and utilization of this rich dataset.

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 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.

Low back pain (LBP) is a pandemic and costly musculoskeletal condition in the United States. Patients with LBP may endure surgery, injections, and expensive visits to emergency departments. Some suggest that using physical therapy or chiropractic in the earlier stage of LBP reduces the utilization of expensive health services and lowers the treatment costs. Nevertheless, there is no consistent evidence to declare which one of these methods is a cost-effective treatment within a short (less than a year) period of time. The purpose of this study was to investigate the cost-effectiveness of chiropractic versus physical therapy in the United States. A decision tree analytic model was used for estimating the economic outcomes. The findings showed that in the chiropractic group, the total average cost was $48.56 lower than the physical therapy group, and daily adjusted life years (DALY) was 0.0043 higher than the physical therapy group. Chiropractic care was shown to be a cost-effective alternative compared with physical therapy for adults with at least three weeks of low back pain over six months.

Gardasil 4, a human papilloma virus vaccine, has been shown to protect against various cancers, including cervical cancer. Common side effects include injection site pain, fever, headaches, and muscle aches. In some individuals, the severe side effect of postural orthostatic tachycardia syndrome (POTS) has been reported. POTS is characterized by the abnormal response of lightheadedness, blurry vision, and dizziness while transitioning to an upright posture. POTS predominately affects women, with more than eighty-five (85) percent of POTS patients being female. POTS on average, takes five years and eleven months to receive the diagnosis. Additionally, ​A strong association between POTS and Ehlers Danlos Syndrome Type III (EDS) exists. Eighty (80) percent of patients with EDS have POTS. This severe side effect dictates that providers need to be aware of this strong association of HPV vaccinations and POTS. ​In this report we will present a case of a young women with a past medical history significant for EDS type III who was diagnosed with POTS after receiving Gardasil 4 vaccination. This case demonstrates the need for physicians to be aware of the association of POTS with EDS type III and HPV vaccination. Physician awareness of the associations, signs and symptoms of POTS and earlier testing at the first presentation of signs and symptoms will limit the negative impact on patient’s quality of life.

Neuropathic pain (NP) affects about the 8% of the general population. Current analgesic therapies have limited efficacy, making NP one of the most difficult to treat pain conditions. Evidence indicates that excessive oxidative stress can contribute to the onset of chronic NP and several natural antioxidant compounds have showed promising efficacy in NP models. Thus, the aim of the present study was to investigate the pain-relieving activity of honokiol (HNK)-rich standardized extract of Magnolia officinalis Rehder &amp; E. Wilson bark (MOE), well known for its antioxidant and anti-inflammatory properties, in the spared nerve injury (SNI) model. The molecular mechanisms were investigated in spinal cord samples from SNI mice and in LPS-stimulated BV2. MOE and HNK showed antioxidant activity. MOE (30 mg/kg p.o.), produced an antiallodynic effect in the absence of locomotor impairment. MOE treatment reduced spinal p-p38, p-JNK1, iNOS, p-p65, IL-1ß and Nrf2 overexpression, increased IL-10 and MBP levels and attenuated the Notch signaling pathway by reducing Jagged1 and NEXT. All these effects were prevented by the CB1 antagonist AM251. HNK reduced the proinflammatory state of LPS-stimulated BV2 cells and reduced Jagged1 overexpression. MOE and HNK, by modulating oxidative and proinflammatory responses, might represent interesting candidates for NP management.

Objective: To explore the efficacy and safety of breathing exercises for pain management in cancer survivors. Design: A systematic review. Data sources: Thirteen databases, including PubMed, EMBase, CENTRAL, Medline, CINAHL, JBI, Science Direct, Scopus, SocINDEX, Web of Science, PsycINFO, CNKI, and Wan Fang, were searched from inception to May 24, 2021. Review/analysis methods: Studies that focused on the efficacy of breathing exercises for pain management in cancer survivors were included. Cochrane tools were used for the quality appraisal of the included studies. Due to the heterogeneity of the studies, descriptive data analysis was used to summarize the results. Results: A total of 10 studies were included in this systematic review. Slow pursed lip breathing showed benefits for post-surgical pain. Contradictory findings were identified in the Enhanced Recovery After Surgery breathing exercise for post-surgical pain. Slow deep breathing and Hey-Hu regular breathing techniques were effective for pain management in pediatric cancer patients. The Active Cycle of Breathing Technique and five-minute mindful breathing did not have any statistically significant effects on pain relief. Quality of life was measured in three studies, with some improvement. Only one study addressed adverse events and reported that no adverse events associated with the breathing exercises occurred during the study. Conclusion: This review found some evidence of positive effects of breathing exercises for pain relief in cancer survivors. However, the unsatisfactory methodological quality of the studies prevents its generalizability. More large-scale studies are needed to assess the efficacy and safety of breathing exercises for pain relief in cancer survivors.

Pain is an unpleasant emotional and sensory experience. For many years orthodontists have been looking for an effective method of reducing this feeling of discomfort. In recent years, low-level laser therapy (LLLT) has taken hold in the orthodontic field. Among the countless advantages it can modulate the painful feeling. The aim of this research is to identify the use of photobiomodulation in subjects undergoing fixed orthodontic treatment, to reduce the pain and discomfort that it causes. The research was conducted from the Web of Science, Pubmed and Scopus databases. Only 14 of all articles met the inclusion and exclusion criteria and were therefore used to conduct the research. The different studies compared, in most cases, patients whose mouth was divided into a part treated with laser therapy and a placebo part. The results show a statistically significant difference in perceived pain between the irradiated arch and the non-irradiated arch. Three authors didn’t find statistically significant results in favour of low-laser therapy, but it is important to remember that they used different parameters. To obtain generally valid studies, with consistent and reproducible results, it is necessary to standardize the different parameters used that are independent by operator performing the procedure.

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different between the cohorts, but specific clinical features varied between the cohorts. Overall severity from first to last visit increased in the younger cohort but not in the older cohort. While some specific clinical features in the older cohort were stable from the first to the last visit, others showed improvement or worsening. These data do not support the hypothesis that mild MECP2 variants or less overall severity leads to increased longevity in RTT but demonstrate that clinical features change with increasing age in adults with RTT. Additional work is needed to understand disease progression in adults with RTT.

. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation (p-Tau) and intracellular p-Tau aggregates known as neurofibrillary tangles (NFTs). This is particularly evident in individuals with Down syndrome (DS), who develop Alzheimer’s disease-like (AD) neuropathology early in life with almost complete penetrance, associated with the development of dementia symptoms in their 40s or 50s. Our previous findings have shown that certain forms of p-Tau are present already in childhood in individuals with DS in neuron-derived exosomes, suggesting an early phosphorylation profile in this population that could influence the development of AD pathology. Misfolded p-Tau isoforms are known to be seeding competent and may be responsible for spreading AD pathology in different regions of the brain. This review is focused on the accumulation of p-Tau in the brain of individuals with DS and potential consequences for brain function.

Introduction: Nephrotic syndrome (NS) remains the most frequent mode of presentation of glo-merular diseases in children; in addition, the NS is primitive, i.e., idiopathic in 90% of cases with an average age of onset between 2 and 10 years. The objective of our study was to describe the char-acteristics and outcome of NS in children from 3 major hospitals from one of the poorest countries worldwide (Chad). Patients and Methods: Observational, cross-sectional, descriptive and multicenter study which took place over a period of 36 months (January 1,2019-December 31,2021) carried out in 3 hospitals in N’Djamena (Chad). All children aged 1-15 years presenting with NS were included. Results: Out of 16,776 children hospitalized or followed-up in outpatient clinics, 24 cases of NS were identified, giving a prevalence of 0.14%. The median age at presentation was 6.16(1-10) years. Nineteen children were male (sex ratio 3.8). There were 8 impure NS (33.3%). Edema was present in all patients, oliguria in 29.16%(n=7), and arterial hypertension in 20.83%(n=5) of cases. Mean proteinuria, albuminemia and total proteins were 2.86g/L, 19.13g/L and 30.41g/L respectively. Median serum creatinine was 87.3 µmol/L(75-1375µmol/L); three patients had acute renal failure on admission. Four patients had secondary NS. All patients (n=20) with idiopathic NS had received corticosteroid therapy; steroid-sensitivity was found in 90% of patients. Those who were not ster-oid-sensitive or relapsed underwent kidney biopsy (n=7); the most represented histological lesion was focal segmental glomerulosclerosis (FSGS; n=4), followed by minimal change disease (n=2), and membranoproliferative glomerulonephritis (n=1). The median length of hospitalization stay was 10.67 (5-27) days. None of the patients with idiopathic NS died. At last follow-up sixteen patients (80%) achieved long-term complete remission with normal renal function; however, 4 had subse-quent relapses. 16 patients. One patient with secondary NS died. Conclusion: In Chad childhood idiopathic nephrotic syndrome involves mostly young male; steroid sensitivity is as high as 95% and in the long-term 80% of the patients are in remission with normal renal function.

The metabolic syndrome, first introduced by Hermann Haller in 1975, was sometimes also known as insulin resistance syndrome, syndrome X, and plurimetabolic syndrome. In 1989 it was rechristened by Kaplan as "Deadly Quartet" based on a consolidation of central obesity, impaired glucose tolerance, dyslipidemia, and systemic hypertension. Metabolic syndrome is positively associated with a pro-inflammatory and pro-thrombotic state, attributed to increased pro-thrombotic and inflammatory markers activity. Moreover, Metabolic syndrome is frequently associated with increased atherosclerotic cardiovascular disease, impaired glucose tolerance, hyperuricemia, obstructive sleep apnea, and chronic kidney disease. Despite concerted endeavors worldwide, the complexity of the pathophysiology of metabolic syndrome is still not clearly understood. Currently, therapeutic possibilities are confined to individual therapy of hyperglycemia, hypertension, hypertriglyceridemia, hyperuricemia, regular physical exercise, and a restricted diet.

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in-utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine disrupting chemical exposure, and the influence of lifestyle factors such as poor quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.

Lynch syndrome (LS) is an autosomal dominant genetic condition caused by mutations in the DNA mismatch repair (MMR) genes in the germline. Colorectal cancer and/or LS-associated cancer are more likely in people who carry pathogenic mutations in these genes. Cancers of the endometrium, small intestine, stomach, pancreas, and biliary tract, ovarian, brain, upper urinary tract, and skin are among the cancer types linked to LS. The criteria for a clinical diagnosis of LS, as well as the processes for genetic testing to identify carriers of pathogenetic mutations in MMR genes, have been known for a long time. The precise description of the pathogenicity associated with MMR genetic variants is critical in the mutation detection analysis, especially in order to enroll mutation carriers in endoscopic surveillance programs that are more suited to them. As a result, this may aid in the improvement of LS-related cancer prevention efforts. In this review, we discuss recent advances in the molecular genetics of LS.

To assess cognitive impairment and affective symptoms and their association with damage to normal-appearing white matter (NAWM) in patients with clinically isolated syndrome (CIS), we compared neuropsychological test scores between patients with CIS and healthy controls, and examined correlations between these and proton magnetic resonance spectroscopy (1H-MRS) outcomes in patients with CIS. Forty patients with CIS and 40 healthy participants were tested with the set of neuropsychological tests, the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Single-voxel 1H-MRS was performed on frontal and parietal NAWM of patients with CIS to assess ratios of N-acetyl-aspartate (NAA) to creatine (Cr), myo-inositol (mI), and choline (Cho), as well as mI/Cr and Cho/Cr ratios. Patients with CIS had lower cognitive performance, higher scores for the BDI and anxiety subscale of HADS than healthy controls. There were significant correlations between the following neuropsychological tests and metabolic ratios in the frontal NAWM: Stroop Color-Word Test and Cho/Cr, Symbol Digit Modalities Test and mI/Cr as well as NAA/mI, Go/no-go reaction time and NAA/Cho as well as NAA/mI, Californian Verbal Learning Test and NAA/Cr. BDI scores were related to frontal NAA/mI and parietal NAA/Cr and Cho/Cr ratios, whereas HADS-depression scores were associated with frontal NAA/Cr and NAA/mI, and parietal NAA/Cr and Cho/Cr ratios. HADS-anxiety correlated with parietal NAA/Cr ratio. This study suggests that neurochemical changes in the NAWM assessed with single-voxel 1H-MRS are associated with cognitive performance and affective symptoms in patients with CIS.

The risk factors associated with COVID-19 related severity, morbidity, and mortality, i.e., obesity (often associated with NAFLD), hyperglycemia, hypertension and dyslipidemia all cluster together as metabolic syndrome (MetS). Instead of studying association of these risk factors with COVID-19, it makes sense studying the association between MetS on one hand and COVID-19 on the other. This study explores a molecular basis underpinning the above association. Severity of COVID-19 patients with MetS could be due to functional alterations of host proteins due to their interactions with viral proteins. We collected data from Enrichr (https://amp.pharm.mssm.edu/Enrichr/), DisGeNET (https://www.disgenet.org/) and others and carried out enrichment analysis using Enrichr. Various biological processes and pathways associated with viral protein interacting partners are known to involve in metabolic diseases. The molecular pathways underlying insulin resistance, insulin signaling and insulin secretion are not only involved in diabetes but also in CVD and obesity (associated with non-alcoholic fatty liver disease; NAFLD). Lipid metabolism/lipogenesis, fatty acid oxidation and inflammation are associated with MetS. Viral interacting host proteins are associated and enriched with terms like hyperglycemia, coronary artery disease, hypertensive disease related to CVD and liver diseases in DisGeNET. Association of viral interacting proteins with disease-relevant biological processes, pathways and disease-related terms suggests that altered host protein function following interaction with viral proteins might contribute to frequent occurrence and/or severity of COVID-19 in subjects with MetS. Such analysis not only provides a molecular basis of comorbidity but also incriminates host proteins in viral replication, growth and identifies possible drug targets for intervention.

1) This study describes the good evolution of a 6-year-old girl genetically diagnosed with Rett syndrome (RTT), after having been treated with IGF-1, MT (MT), blackcurrant extracts (BC), and rehabilitation during 6 months. 2) The patient stopped her normal development from the first year of age. The patient showed low weight and height and met the main criteria for typical RTT. Curiously, there was pubic hair (Tanner II), very high plasma testosterone, despite low gonadotropins. No adrenal enzymatic deficits existed, and ultrasound abdominal studies were normal. Treatment consisted in IGF-1 (0.04 mg/kg/day, 5/week, sc) during 3-months and then 15-days resting, MT (50 mg/day, orally, uninterruptedly) and neurorehabilitation. The new blood tests were absolutely normal and the pubic hair disappeared. Then, a new treatment with IGF-1, MT, and BC started for another 3 months. After it, pubic Tanner stage increased to III, without a known cause. 3) The treatment followed led to clear improvements in most of the initial impairments, perhaps because of the effect of IGF-I, the antioxidant effects of MT and BC, and the increase in cyclic-glycine-proline (cGP) after BC administration. 4) A continuous treatment with IGF-1, MT and BC may recover most of the neurologic disabilities that occur in RTT.

Sinulariolide, a natural product extracted from cultured-type soft coral Sinularia flexibilis, possesses bioactivity against the movement of several types of cancer cell. However, the molecular pathway of its effects on human bladder cancer remain poorly understood. Using a human bladder cancer cell line as an in vitro model, this study investigated the underlying mechanism of sinulariolide against cell migration/invasion in TSGH-8301 cells. We found that sinulariolide inhibited TSGH-8301 cell migration/invasion, and the effect was concentration-dependent. Furthermore, the protein expressions of matrix metalloproteinases (MMPs) MMP-2 and MMP-9, as well as urokinase, were significantly decreased after 24-h sinulariolide treatment. Meanwhile, the increased expressions of tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 were in parallel with an increased concentration of sinulariolide. Finally, the expressions of several key phosphorylated proteins in the mTOR signaling pathway were also downregulated by sinulariolide treatment. Our results demonstrated that sinulariolide has significant effects against TSGH-8301 cell migration/invasion, and its effects were associated with decreased levels of MMP-2/-9 and urokinase expression, as well as increased TIMP-1/TIMP-2 expression. The inhibitory effects were mediated by reducing phosphorylation proteins of the PI3K, AKT and mTOR signaling pathway. The findings suggested that sinulariolide is a good candidate for advanced investigation with the aim of developing a new drug for the treatment of human bladder cancer.

The term "Osmotic Demyelination Syndrome" (ODS) is synonymous with central pontine myelinolysis (CPM), denoting a condition characterized by brain damage, particularly affecting the white matter tracts of the pontine region. This damage arises due to rapid correction of metabolic imbalances, primarily cases of hyponatremia. Noteworthy triggers encompass severe burns, liver transplantations, anorexia nervosa, hyperemesis gravidarum, and hyperglycaemia, all linked to the development of CPM. Clinical manifestations encompass a spectrum of signs and symptoms, including dysphagia, dysarthria, spastic quadriparesis, pseudobulbar paralysis, ataxia, lethargy, tremors, disorientation, catatonia, and, in severe instances, locked-in syndrome and coma. A recent case involving a 45-year-old woman illustrates these complexities. Upon admission to the Medicine Intensive Care Unit, she presented with symptoms indicative of diminished responsiveness and bilateral weakness in upper and lower limbs. Of significance, the patient had a pre-existing medical history of hyperthyroidism. Extensive diagnostic investigations were undertaken, revealing compelling evidence of profound hyponatremia through blood analyses. Furthermore, magnetic resonance imaging (MRI) was performed, unveiling conspicuous areas of abnormal hyperintensity located in the central pons, intriguingly accompanied by spared peripheral regions. These radiological findings align with the characteristic pattern associated with osmotic demyelination syndrome, illuminating the underlying pathology.

A patient in her early 20s presented with constant and progressive lower abdominal and back pain, mainly on the right side of the abdomen, purulent vaginal discharge and pyrexia. Radio-logical assessment revealed a possible tuboovarian abscess and incidental diagnosis of ipsilateral renal agenesis. The patient was treated for pelvic inflammatory disease (PID), however after antibiotic administration and since the symptoms were not resolving, an abdominal MRI was requested which revealed a uterus didelphys with two cervices, an obstructed haemivagina and evidence of haematocolpos. The diagnosis of OHVIRA syndrome was confirmed and the patient underwent an excision of the vaginal septum, drainage of the haematopyocolpos and laparoscopic drainage of the tuboovarian abscess. She achieved a good recovery.

The term STODS (Surgical Temporary Ocular Discomfort Syndrome) has been coined to describe the ocular surface perturbations induced by surgery. As one of the most important refractive elements of the eye, Guided Ocular Surface and Lid Disease (GOLD) optimization is fundamental to success in achieving refractive outcomes and mitigating STODS. Effective GOLD optimization and the prevention/treatment of STODS, requires an understanding of the molecular, cellular and anatomic factors that influence ocular surface microenviroment and the associated perturbations induced by surgical intervention. By reviewing the current understanding of STODS etiologies, we will attempt to outline a rationale for a tailored GOLD optimization depending on the ocular surgical insult. With a bench to bedside approach, we will highlight clinical examples of effective GOLD perioperative optimization can mitigate STODS deleterious effect on preoperative imaging and postoperative healing.

Fragile X syndrome (FXS) is a neurodevelopmental disorder associated with a wide range of cognitive, behavioral and medical problems. It arises from the silencing of the fragile X mental retardation 1 (FMR1) gene, and consequently, in the absence of its encoded protein, FMRP (Fragile X Mental Retardation Protein). FMRP is a ubiquitously expressed and multifunctional RNA-binding protein, primarily considered as a translational regulator. Pre-clinical studies of the past two decades have therefore focus on this function to relate FMRP’s absence to the molecular mechanisms underlying FXS physiopathology. Based on these data, successful pharmacological strategies were developed to rescue fragile X phenotype in animal models. Unfortunately, these results did not translate into human, as clinical trials using same therapeutic approaches did not reach the expected outcomes. These failures highlight the need to put into perspectives the different functions of FMRP in order to get a more comprehensive understanding of FXS pathophysiology. In this review, FMRP’s involvement on noteworthy molecular mechanisms are pointed out; ultimately contributing to various biochemicals alterations composing the fragile X phenotype.

There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjӧgren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS, although TGFβ family members seems to have ambiguous effects on the function of pSS salivary glands. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.

Hydrotherapy, including the use of therapeutic showers and bathtubs, has been studied for its potential benefits in labor pain management. Previous research has indicated that hydrotherapy can alleviate pain, but comparative studies between therapeutic showers and bathtubs are scarce. Objective: This study aims to compare the effects of therapeutic showers and bathtubs on pain perception, labor duration, use of epi-dural analgesia, and maternal and neonatal outcomes during labor. Methods: A total of 124 pregnant women were included in this study. Participants were divided into two groups: those who used a thera-peutic shower and those who used a bathtub during labor. Pain levels were measured using a visual analog scale (VAS). Labor duration, use of epidural analgesia, types of delivery, maternal outcomes (postpartum hemorrhage, perineal status, maternal hypotension, fever, and breastfeeding), and neonatal outcomes (APGAR scores, fetal heart rate, complications, and neonatal unit admissions) were recorded and analyzed. Results: Both the therapeutic shower and the bathtub effectively reduced pain perception, with the bathtub showing a greater reduction in VAS scores. The therapeutic shower group experienced a signifi-cantly shorter labor duration compared to the bathtub group. The majority of participants in both groups did not require epidural analgesia, with no significant differences between the groups. There were no sig-nificant differences in the types of delivery. Maternal outcomes indicated a lower incidence of perineal tears and episiotomies in the therapeutic shower group. Neonatal outcomes, including APGAR scores and fetal heart rate, were similar between the groups, with no significant differences in complications or neo-natal unit admissions. Conclusions: Both therapeutic showers and bathtubs are effective for pain relief during labor, with the bathtub showing a higher reduction in pain intensity. The therapeutic shower is as-sociated with a shorter labor duration and a lower incidence of perineal tears and episiotomies. Both meth-ods are safe for neonatal well-being, making hydrotherapy a viable non-pharmacological option for pain management in labor. However, the therapeutic shower may offer additional benefits in terms of labor du-ration and maternal outcomes.

The prevalence of back pain (BP) among children and adolescents has increased over recent years. Some authors advocate promoting back-health education in the school setting. It is therefore important to adopt a uniform suite of assessment instruments to measure the various constructs. The present study aimed to perform a cultural adaptation of a validated measurement instrument (BackPEI), beginning with a translation and cultural adaptation phase, followed by a second phase to test reliability using a test-retest design. The translation and cross-cultural adaptation were performed based on the guidelines. Reliability was tested by applying the questionnaire to 224 secondary school students, at two different times with a 7-day interval between the tests. In general, the Spanish version presented adequate agreement for questions 1–20, with only question 9 achieving a low Kappa range of .312 [-.152- .189]. The question about pain intensity did not show differences between the averages for the test (4.72 ± 2.33) and re-test (4.58 ± 2.37) (p = .333), and the responses for these two tests were highly correlated (ICC= .951 [.928- .966]; p= .0001). Psychometric testing indicated that the Spanish version of the BackPEI is well-adapted and reliable, based on the test-retest design, providing similar results to the original Brazilian version.

The clinical practice implies a research translation that helps the use of scientific data and thera-peutic evidence for patient benefits. This review critically summarizes the potential impact of cannabinoids in concomitance with other drugs in the following chronic diseases as Epilepsy, Au-tism Spectrum Disorders (ASD), Oncology, Multiple Sclerosis, and Chronic Pain. The potential in-teractions can change the predicted clinical outcomes of therapeutic protocols and need to be evaluated. Some of the effects would be additive, synergistic or antagonistic, but can also enroll changes in absorption, distribution, metabolism, particularly via cytochrome P450 (CYP) isoen-zymes (e.g CYP2C9 and CYP3A4) and excretion. For instance, the combination of canna-bis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases plasma concentration of Δ-9-tetrahydrocannabinol (THC) and CBD (CBD). Opposable, rifampic-in, a CYP3A4 inducer, stands out for the approximately 20-40% reduction in plasma THC levels and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Indeed, pharmacokinetic interactions have been also reported with antiseizure drugs. Moreover, pharmacodynamic interactions between cannabinoids and drugs with sympathomimetic effects (eg tachycardia, hypertension), central nervous system depressants (eg drowsiness, ataxia), and anticholinergics (eg tachycardia and drowsiness) are also expected. Even though pending further studies, there is currently clinical evidence supporting drug interaction with cannabinoids, demanding doctors evaluate the risk of drug combinations with cannabinoids. The tables herein provided were designed to facilitate the identification of bi-orelevant interactions that may compromise therapeutic efficacy and toxicity.

Osteoarthritis (OA) is the most common cause of pain and disability in adults. Dietary supplements such as undenatured type II collagen (UC-II) have shown to have some benefits in OA treatment. This study aimed to assess changes in pain levels among knee OA patients treated with UC-II for 6 months. Patients with knee OA of any grade were given a daily 40 mg dose of UC-II (CondroArtil®) as a dietary supplement for 6 months. Pain levels were measured using the visual analog scale (VAS) before starting UC-II 6 months thereafter. A total of 100 patients (62/38: male/female) with a mean age of 46.3 ± 13.8 years participated in the study. Most patients (60%) had mild to moderate OA (grade I or II). The UC-II supplementation was shown to significantly reduce pain levels (p<0.001) with a negative correlation between pain reduction and age (p=0.006) and BMI (p=0.049). The OA severity also affected pain reduction (p=0.011), with grade II OA experiencing higher pain levels. Previous physical therapy and food supplements had a significant impact on pain reduction (p=0.017 and p=0.012, respectively). The study suggests that UC-II is an effective treatment for reducing pain in patients with knee OA.

This research used an experimental study design in which 60 subjects were randomly assigned to either an experimental (image e-book guidance) group or a control (text guidance) group after meeting the admission conditions and agreeing to participate in the study. It was proven that providing image e-book guidance before surgery significantly changed the behavior of patients and promoted relief of urinary catheter discomfort through self-efficacy to reduce urinary catheter pain after surgery. It was found that providing image e-book guidance can shorten the time for health education and provide patients with repeated medical education and familiarity with health guidance, which can help to address the important clinical service demand issue and the shortage of nursing staff.

Introduction People are presenting with chronic musculoskeletal pain at a younger age, and many fulfil criteria for fibromyalgia. We have recently shown a strong association between fibromyalgia symptoms and autistic traits in a self-selected community population, with the relationship mediated in part by the presence of hypermobility. Many respondents also described food sensitivities and intolerances. This study explores relationships between food issues and fibromyalgia symptoms in this population Methods The study used a nonexperimental, correlational design with data collected from a volunteer sample of 442 adults (aged 18-60) who completed online self-report questionnaires assessing each of fibromyalgia symptoms (ACR criteria), autistic traits (RAADS score) and hypermobility (Beighton’s test). Subjects were also asked to record any food sensitivities, allergies, or intolerances, along with their consequences. Correlation analyses and linear regressions were used to test the relationships between these features and each of fibromyalgia, autistic traits and hypermobility. Data was analysed using parametric and non-parametric techniques to assess the strength and significance of relationships, causes of variance and the potential mediating effect of food-related symptoms in the correlation between fibromyalgia features and autistic traits Results Our self-selected community population had a mean age of 24 years and was 77% female. The prevalence of fibromyalgia, autistic traits and hypermobility was 40%, 65% and 44% respectively. Half of all subjects reported food sensitivity and 31% reported food intolerance. The incidence of food-related symptoms was higher among subjects who met criteria for fibromyalgia than those who reported autistic traits or hypermobility. Food sensitivity and food intolerance were both more significantly associated with fibromyalgia (r=0.24, p>0.001 and r=0.38, p>0.001) than with autistic traits (r=0.15, p>0.01 and r=0.17, p>0.01). Discussion This is the first community study to provide evidence for a direct association between features of fibromyalgia and reported food intolerance and sensitivity. Although self-selected, the findings in our predominantly young population suggest that gluten and lactose consumption may be associated with higher levels of musculoskeletal pain. Avoidance of these foodstuffs was commonly reported to reduce symptoms. Dietary adjustment may merit further investigation as a therapeutic modality for some patients with fibromyalgia.