For decades, neurologic and other extra glandular manifestations have been described in Sjögren’s syndrome (SS). More recently, neuropathic, psychological and cognitive alterations are being considered part of the disease. The lacrimal glands (LG), the ocular surface (OS), salivary glands (SG) and the central nervous system (CNS) are integrated to modulate the autonomic functions and, not just those organs, but also the hippocampus, which is linked to the autonomic nervous system, and modulate behavior responses appears to be compromised in the SS. Recent studies confirm that the tryptophan/kynurenine pathway (TKP) can be stimulated by interferon-γ (IFN-γ) and other cytokines, activating the indoleamine-pyrrole 2,3-dioxygenase (IDO) in SS. This pathway interferes on serotonergic and glutamatergic neurotransmission, mostly in the hippocampus, and other structures of the CNS. Although not demonstrated, it is plausible that this constant interference induces clinical signs of SS, and contributes to the discrepancy between symptoms and signs, towards manifestations of hyperalgesia and depression in patients with SS. Therapeutic strategies are being reexamined and new options designed and tested to regulate the involved steps of the TKP. In the future, the application of this concept may offer a clue to the mosaic of manifestations of SS.

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

Kynurenine or tryptophan catabolite (TRYCAT) pathway contributes to the pathophysiology of major depression disorder (MDD) and major depressive episodes (MDE) in bipolar disorder and suicidal behaviors. The consequences of the overactivation of this pathway large reduced tryptophan (TRP) levels in peripheral blood and the CNS and increased levels of neurotoxic TRYCATs including kynurenine (KYN), 3-hydroxy kynurenine (3HK), quinolinic acid (QA), xanthurenic acid (XA), and picolinic acid (PA). However, other TRYCATs are protective, such as kynurenic acid (KA) and anthranilic acid (AA). Inflammation and cell-mediated immune activation along with oxidative and nitrosative stress (O&NS) may stimulate the first and rate-limiting enzyme of this pathway, namely indoleamine-2,3-dioxygenase (IDO). Therefore, during depression, balancing neuroprotective versus neurotoxic TRYCATs and balancing activation of the immune response system (IRS) versus the compensatory immune response system is crucial for achieving better treatment outcomes. Furthermore, targeting the causes of TRYCAT pathway activation (immune activation and O&NS) is probably the most effective strategy to treat depression. In the present review, we aim to provide a comprehensive explanation of the impact of TRYCATs in terms of pathophysiology and treatment of MDD and MDE.

Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently growing number of preclinical studies has revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among other. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)-kynurenine (KYN) metabolic system, which observably contributes to development of pathological conditions including neurological and psychiatric disorders. This narrative review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases, and psychiatric disorders. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants, and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses, and chronic diseases. KYN, kynurenic acid, xanthurenic acid, and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2, 3-oxygenases, and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines, and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia, and autism spectrum disorder.

Background: Abdominal migraine (AM) is a clinical diagnosis specified by Rome IV and ICHD III as a functional gastrointestinal disease (FGID) and a migraine associated syndrome, respectively. AM is undiagnosed and undertreated, and thus far the FDA has not approved any drug for AM treatment. We and others showed that changes in the kynurenine (KYN) pathway of tryptophan (TRP) metabolism played an important role in the pathogenesis and treatment of FIGDs. Changes in the KYN pathway were shown in migraine. Findings: Abdominal migraine reflects impairments in communication within the gut-brain axis. Treatment approaches have not been sufficiently documented and are based on experience of physicians, presenting personal rather than evidence-based practice and including efficacy of some drugs used in adult migraine. Non-pharmacological treatment of AM is aimed preventing or ameliorating AM triggers. Modulations within the KYN pathway of TRP metabolism induced by changes in TRP content in the diet, may ameliorate FGIDs and support their pharmacological treatment. Pharmacological manipulations of brain KYNs in animals have brought promising results for clinical applications. Conclusions: In conclusion, controlled placebo-based clinical trials with dietary manipulation to adjust the amount of the product of the KYN pathway of TRP metabolism are justified in children and adolescents with AM. Further preclinical studies are needed to establish details of these trials.

Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of the KP alteration observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota to the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in Primary Sjogren’s syndrome (pSS). The aim of this research was to assess the imbalance of subsets within CD8+ cells in peripheral blood. We examined blood samples from 34 patients with pSS and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA, and CD45. For immunophenotyping of ‘polarized’ CD8+ T cell subsets we used the following monoclonal antibodies:CXCR5, CCR6,CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of 'naïve' CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, Rheumatoid factor, the Schirmer test, and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS.

Abstract Background The advent of monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a e challenge. Objective This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. Methods We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Results Our search included 55 pertinent studies conducted between 2019 and 2023. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, disability), high responder rates, and optimal safety and tolerability profiles. Conclusion Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an unprecedented finding in clinical neurology.

Tryptophan is an essential nutrient required to produce niacin (vitamin B3), which is needed for energy metabolism and DNA production. Alterations in tryptophan metabolism could have significant effects on aging and musculoskeletal health. The kynurenine pathway, the main catabolic route of tryptophan, is modulated by inflammatory factors, which are increased in older persons, a process known as inflammaging. Osteoporosis, sarcopenia, osteosarcopenia and frailty have also been linked with chronic increased levels of inflammatory factors. Due to the disruption of the kynurenine pathway by chronic inflammation and/or changes in the gut microbiota, serum levels of toxic kynurenines are increased and have been associated with osteoporosis, sarcopenia and frailty. In contrast, anabolic end products of this pathway, such as picolinic acid, have demonstrated a beneficial effect on bone and muscle. In addition, recent studies have shown that physical activity can modulate this pathway by promoting the secretion of anabolic kynurenines. According to the evidence collected, kynurenines could have a promising role as biomarkers for osteoporosis sarcopenia, osteosarcopenia and frailty in older persons. In addition, some of these metabolites could become important targets for developing new pharmacological treatments for these conditions.

The tryptophan catabolite (TRYCAT) pathway is implicated in the pathophysiology of schizophrenia (SCZ) since the rate-limiting enzyme indoleamine-dioxygenase (IDO) may be induced by inflammatory and oxidative stress mediators. This systematic review searched PubMed, Web of Science, and Google Scholar for papers published from inception until August 2021 and meta-analyzed the association between SCZ and TRYCATs in the central nervous system (CNS) and peripheral blood. We included 61 studies comprising 2813 patients and 2948 healthy controls. In the CNS we found a significant (p<0.001) increase in the kynurenine/tryptophan (KYN/TRP) (standardized mean difference, SMD=0.769, 95% confidence interval, CI: 0.456; 1.082) and kynurenic acid (KA)/KYN+TRP (SMD=0.697, CI:0.478-0.917) ratios, KA (SMD=0.646, CI: 0.422; 0.909) and KYN (SMD=1.238; CI: 0.590; 1.886), while the 3OH-kynurenine (3HK) + KYN-3-monooxygenase (KMO)/KYN ratio was significantly reduced (SMD=-1.089, CI: -1.682; -0.496). There were significant differences between KYN/TRP, (KYN+KA)/TRP, (3HK+KMO)/KYN, KA, and KYN levels among the CNS and peripheral blood, and among serum and plasma KYN. The only useful peripheral marker of CNS TRYCATs findings was the increased KYN/TRP ratio in serum (SMD=0.211, CI: 0.056; 0.366, p=0.007), but not in plasma. There was no significant increase in a neurotoxic composite score based on KYN, 3HK, and picolinic, xanthurenic, and quinolinic acid. SCZ is accompanied by increased IDO activity in the CNS and serum, and reduced KMO activity and a shift towards KA production in the CNS. This CNS TRYCATs profile indicates neuroprotective, negative immunoregulatory and anti-inflammatory effects. Peripheral blood levels of TRYCATs are dissociated from CNS findings except for a modest increase in serum IDO activity.

Memory and emotion are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD), which has been linked to serotonin (5-HT) metabolism disruptions. In fact, over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) meta-bolic pathway, producing a variety of bioactive molecules. The aadat (kat2) gene encodes mito-chondrial kynurenine aminotransferase (KAT) isotype 2, responsible for kynurenic acid (KYNA) production. Little is known about its role in behavior. In CRISPR/Cas9-induced aadat knockout (kat2−/−) mice, we examined the effects on emotion, memory, motor function, Trp and its metabolite levels, enzyme activities in the plasma and the urine of 8-week-old males compared to wild-type mice. Transgenic mice showed more depressive-like behaviors in the forced swim test, but not in the tail suspension, anxiety, or memory tests. They also had fewer center field and corner entries, shorter walking distances, and fewer jumping counts in the open field test. Plasma metabolite levels are generally consistent with those of urine: KYN, antioxidant KYNs, 5-hydroxyindolacetic acid, and indole-3-acetic acid levels are lower; enzyme activities in KATs, kynureninase, and monoamine oxidase/aldehyde dehydrogenase are lower, but kynurenine 3-monooxygenase is higher; and ox-idative stress and excitotoxicity indices are higher. Transgenic mice show depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits, coupled with a decrease in KYNA, a shift of Trp metabolism toward the KYN-3-HK pathway, and a partial decrease in the gut microbial Trp-indole pathway metabolite. This is the first evidence that deleting the aadat gene causes depression-like behaviors that are unique to despair experience, which appears to be linked to excitatory neurotoxic and oxidative stresses. This may lead to the development of a double-hit preclinical model in experience-based depression, better understanding of these complex condi-tions, and more effective therapeutic strategies by elucidating the relationship between Trp me-tabolism and PTSD pathogenesis.

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.

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

Background: The laryngeal mask airway Vision Mask (LMA VM) is a supraglottic airway device (SAD) with vision guidance system. The ideal head and neck position for direct laryngoscopy is known, but the ideal position for placing a LMA is not. The objective of this study is to evaluate and compare the optimal position for placement of a video laryngeal mask airway. Methods: This was a prospective observational, transversal and analytical study of 72 consecutive patients. In the same patient, laryngeal vision was first assessed with the head and neck in the sniffing position and then with the head in the neutral position. Procedures were filmed and performed by the same investigator. Assessment of the laryngeal view was performed using two classifications: modified Cormack-Lehane classification and Brimacombe classification. Device placement was considered adequate when the Cormack-Lehane rating was scored from 1 to 2 and the Brimacombe rating was from 2 to 4. Results: 72 patients were included in this study. In the assessment of the glottis using the Cormack Lehane classification for fiberoptic view, laryngeal visibility was adequate in 64 (88.89%) patients in the neutral position and in 65 (90,28%) patients in the sniffing position (p>0,05). In the fiberoptic view of the glottis, assessed using the Brimacombe classification, laryngeal visibility was adequate in 68 (93%) patients in the neutral position and in 69 (95%) patients in the sniffing position, (p>0,05). There was no statistically significant difference in the rate of success between the sniffing position (70 patients, 97.22% success rate) and the neutral position (67 patients, 93.06% success rate) during the first insertion attempt. Two patients required a second attempt in the sniffing position, while five patients required a second attempt in the neutral position. Conclusion: An adequate sniffing position did not result in a better glottic view than neutral position, and the number and type of additional maneuvers were equal in both positions.

Iron is an essential nutrient for humans and microbes, such as bacteria. Iron deficiency occurs commonly in critically ill patients, but iron replacement therapy is not considered during the acute phase of critical illness, since it increases iron availability for invading microbes and oxidative stress. However, persistent iron deficiency in the recovery phase is harmful with potential adverse outcomes such as cognitive dysfunction, fatigue and cardiopulmonary dysfunction. Therefore, it is important to treat iron deficiency timely and efficiently. This article reviews current knowledge about iron-related biomarkers in critically ill patients and provides possible criteria to guide decision-making for iron supplementation in the recovery phase of critical illness.

A ganglion cyst is a benign fluid-filled sac that typically appears on the dorsal aspect of the wrist, arising idiopathically near the joint capsule or tendon sheath. Diagnosis is primarily clinical, with MRI and ultrasound serving as confirmation tools. Treatment options range from immobilization, aspiration, hydrossection, steroid or hyaluronidase injection, to surgical intervention. Although relatively uncommon, Dorsal Ganglion Cysts (DGC) can lead to Dorsal Wrist Impingement (DWI) syndrome. This syndrome results from the thickening of the wrist capsule due to overuse, injury, or repetitive activities. This thickening can lead to the compression of the extensor carpi radialis brevis (ECRB) tendon during wrist extension and produce tenderness around the lunate. In some refractory cases, MRI findings may show recurrent ganglion cysts, while in others, they may appear "normal." Consequently, the diagnosis remains clinical, and imaging is primarily employed to rule out secondary causes. Management strategies encompass rest, immobilization, occupational therapy, non-steroidal anti-inflammatory drugs (NSAIDs), cortisone injections, and, in certain instances, surgical intervention. Despite the clinical significance of these conditions, limited studies have explored their interrelationship. In this context, we present a rare case involving a 23-year-old female with recurrent DGC accompanied by DWI syndrome. Initially, the patient reported idiopathic left dorsal wrist pain localized around the tendon sheath. Her initial X-ray did not reveal any abnormalities, but MRI identified two ganglion cysts. A series of treatments were initiated, including left tendon sheath hydrossection, corticosteroid injections into the left wrist, and the excision of ganglion cysts from the left wrist. Furthermore, occupational therapy, oral Meloxicam, and Voltaren gel treatments were integrated into the management plan. Subsequent imaging confirmed the resolution of the cysts and an overall enhancement in the range of motion and wrist strength. However, the patient experienced only minimal pain relief, and pain was still elicited during end-range wrist extension and upon dorsal wrist palpation. An electromyography (EMG) test ordered to rule out neuropathic causes did not yield any conclusive results. Nonetheless, a repeat X-ray revealed mild soft tissue swelling on the dorsal side of the wrist, and a follow-up MRI detected ganglion cysts on the dorsal aspect of the lunate and the ECRB tendons. These findings indicated a re-accumulation of dorsal ganglion cysts with a concurrent dorsal impingement syndrome component. Consequently, the patient was referred to an orthopedic surgeon for evaluation and potential revision surgery. This unique case underscores the possibility of developing DWI Syndrome after the removal of a DGC. The diagnosis of this syndrome can be elusive, particularly when X-rays, MRIs, and EMGs yield negative results. Trauma, such as repeated hand surgery or recurrent ganglion cysts, may exacerbate wrist pain despite improvements in range of motion and strength. Special consideration should be given to patients who undergo surgical cyst excisions, as this procedure heightens the risk of recurrence and can irritate the tendon sheath. Collaborative efforts between Physical Medicine and Rehabilitation (PM&amp;R), Occupational Therapy (OT), and surgical teams may play a pivotal role in managing pain associated with these conditions. We propose that future research endeavors should focus on establishing guidelines for the management of this unique condition.

In this non-exhaustive review, we discuss the importance of invariant vectors in atomic physics, such as the Laplace-Runge-Lenz vector, the Redmond vector in the presence of an electric field, the Landau-Avron-Sivardière vector when the system is subject to a magnetic field, and the supergeneralized Runge-Lenz vector for the two-center problem. Application to Stark and Zeeman effects are outlined. The existence of constants of motion in the charge-dyon system is also briefly mentioned.

This study investigates job satisfaction, burnout, and well-being among first-generation migrant physicians in anesthesia and intensive care medicine in Germany, comparing them to their native German counterparts. Utilizing a cross-sectional survey design, the study collected data from 513 physicians, 110 of whom identified as having a migration background. Job satisfaction was measured using the German version of the Warr-Cook-Wall (WCW) Job Satisfaction Scale, burnout was assessed with the Copenhagen Burnout Inventory (CBI), and well-being was evaluated using the WHO-5 Well-Being Index. The job satisfaction ratings revealed no significant differences between migrant and German physicians in most dimensions, including physical workload, freedom to choose work methods, satisfaction with colleagues, responsibility, income, skill utilization, and variety in work tasks. However, migrant physicians reported significantly higher satisfaction with recognition received for their work and lower dissatisfaction with working hours. Burnout assessments showed that migrant physicians experienced higher psychological strain, perceiving every work hour as more exhausting and having significantly less energy for family and friends. Notably, migrant physicians reported higher difficulty and frustration in working with patients. Well-being ratings indicated that migrant physicians felt less energetic and active but found their daily life more filled with interesting activities. The findings underscore the unique challenges faced by migrant physicians, particularly in terms of recognition and patient-related burnout. These results highlight the need for targeted interventions to support migrant physicians, including cultural competence training and flexible working hours to enhance their job satisfaction and overall well-being. Addressing these issues is crucial for maintaining the quality of patient care and the occupational health of migrant physicians in Germany.

Myofascial pain is the most common cause of chronic pain in the masticatory region and can be assessed through clinical analysis and muscle palpation. Generally, it appears with headache and orofacial pain associated with sensitive points (trigger points) due to the excessive contraction of the masticatory muscle fibres. The study aims to evaluate how a correct treatment of myofascial pain can improve the life quality of the affected patients. In this case series, 300 patients with myofascial pain were divided into two groups: 150 with intra- and extra-articular disorder and 150 with the only extra-articular disorder. Each group included 75 males and 75 females. All the patients were treated with gnathological therapy through passive aligners and biofeedback exercises for 4 months. They underwent pain assessment (through a visual analogue scale and muscular palpation test) before, during and after the treatment, and nuclear magnetic resonance of the temporomandibular joint before and after the gnathological treatment. The treatment considerably reduced the pain in all patients, without drugs, in 4 months, according to the visual analogue scales and the palpation test. The temporomandibular magnetic resonance in each patient was similar before and after the gnathological treatment. The improvement in pain did not depend on a change in the relationship between the articular condyle and the disc.

The microbiota–gut–brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota–gut–brain axis, offering hope for improved management of this challenging condition.

The development of anti-pain technologies in the complex treatment of pain syndromes is one of the most urgent tasks of modern medicine. We have undertaken a placebo-controlled experimental study of the therapeutic potential of low-intensity laser radiation when applied to acupuncture points, which are directly related to the autonomic nervous system. The adaptation effect of puncture photobiomodulation on the induction of stress-mediated autonomic reactions, oxidative metabolism and microcirculation in animals during the acute phase of pain stress was revealed. The data obtained are of interest for use in the complex rehabilitation of patients with pain syndrome.

This study aimed to determine the specific characteristics of extraglandular manifestations especially cutaneous involvement in patients with primary sjögren’s syndrome(pSS), focusing on the different clinical and histologic types of SS-associated vasculitis. A retrospective study was conducted and 402 patients (378 women and 24 men) with pSS were analyzed. Patients were categorized into three subgroups based on serological tests. These; 1) quadruple seropositive (positive for anti-Sjögren’s-syndrome-related antigen A antibodies (anti-SSA; anti-Ro) and anti-Sjögren’s-syndrome-related antigen B antibodies (anti-SSB; anti-La), rheumatoid factor (RF), and antinuclear antibody (ANA)), 2) double seropositive (positive for ANA and anti-SSA/Ro antibodies), 3) quadruple seronegative (negative for ANA, RF, anti-SSA/Ro and anti-SSB/La antibodies). The number of quadruple seropositive patients was 72 (18.6%), double seropositive 174 (43.2%), and quadruple seronegative was 85 (21.1%). The diagnosis age of quadruple seropositive pSS was 42.4±10.8, significantly younger than patients with double seropositive and quadruple seronegative pSS (p = 0.021, p=0.112). In terms of organ involvement, salivary gland enlargement, arthralgias, arthritis, Raynaud's phenomenon, lymphadenopathy, vasculitis-purpura, interstitial lung disease, neurological involvement, autoimmune thyroiditis, renal interstitial disease, anemia, leukopenia, hypergammaglobulinaemia and hypocomplementaemia were more common in quadruple seropositive pSS compared to quadruple seronegative (p

The restrictions imposed by the Covid-19 pandemic left many older adults isolated and confined. Under active aging theory, self-management is crucial for well-being among older adults coping with aging. The current study examines how (a) initial self-management, and (b) changes in self-management due to independent physical training, affect psychological outcomes in a sample of care home residents following outbreak of the pandemic. 64 older adults (53 females, 11 males), mean age is 82.23, reported on their self-management abilities, then embarked on six months of training in chair exercises (one session per week). The training exercises were halted after 22 sessions due to the pandemic, but some residents continued to practice independently. Eight weeks after the outbreak of the pandemic, residents who had continued to practice at least once per week (n = 35) and those who had not continued to practice (n = 29) were questioned again about their self-management, and about five psychological outcomes: anxiety, traumatic stress, satis-faction, general mood, and post-traumatic growth (PTG). Self-management improved among older adults who independently practiced the exercises, and declined among those who did not. Pre-pandemic self-management significantly predicted post-outbreak traumatic stress symptoms, anxiety, general mood, and satisfaction with life, but not PTG. However, the difference in self-management between the pre-pandemic and post-outbreak measures was associated with PTG, and made a unique contribution to prediction of the other effects. Self-management abilities among older adults can be seen as a protective factor against adverse psychological outcomes at times of trauma. Further, the improvement in self-management among older adults who independently practiced physical excises made a unique contribution beyond initial self-management abilities.

This paper questions the potential shift of reproduction towards assisted reproductive technologies due to benefits provided by genetic manipulation of embryos. In order to examine the viability of such a shift and its implications from a regulatory perspective, we relied on two panels of experts from Israel and Spain, using the Delphi method and a series of in-depth interviews. We anticipate, at a first stage, a continuous-steady growth in the use of IVF, supplemented by preimplantation genetic diagnosis and the introduction of CRISPR/Cas. At a second stage, attracting a growing share of fertile people would require developments in genomics. While it is unclear whether these developments will fully materialize, they could be replaced by technoscientific imaginaries generating perceived benefits. We conclude that the regulation of reproductive genetics is becoming more critical and complex. The aim should be to ensure good practices and equity, while providing more information to the public. A broad and inclusive societal debate may overcome the difficulty of drawing a clear line between medical uses and non-medical uses of genetic selection and engineering and may contribute to finding the right balance between allowing autonomous decisions of patients and protecting the public interest.

Urethral pain syndrome (UPS) is still a pathology in which the diagnosis is formulated as a "diagnosis of exclusion". The exact pathogenetic mechanisms are not yet fully understood and clear recommendations for the prevention and treatment of UPS are absent. The goal of the study was to assess the condition of the tissues in the female urethra in UPS, by using transvaginal ultrasound (TVUS) and cross-polarization optical tomography (CP OCT). TVUS showed an expansion in the diameter of the internal lumen of the urethra, especially in the proximal region compared with the norm. Compression elastography revealed areas with increased stiffness (presence of fibrosis) in urethral and surrounding tissues. When studied with CP OCT it was shown that with UPS, the structure of the tissues in most cases was changed: trophic alterations in the epithelium (hypertrophy or atrophy) and fibrosis of underlying connective tissue were observed. The proximal fragment of the urethra with UPS underwent changes identical to those of the bladder neck. This paper showed that the introduction of new technology — CP OCT — in conjunction with TVUS will allow verification of structural changes in tissues of the lower urinary tract at the level of their architectonics and will help doctors understand better the basics of the UPS pathogenesis.

Background: To assess the prevalence of Hypertension (HTN) in Burning Mouth Syndrome (BMS) patients and to investigate its relationship with sociodemographic factors, pain and the psychological profile. Methods: A case-control study was conducted by enrolling 242 BMS patients and 242 controls matched for age and gender. Sociodemographic and clinical characteristics were recorded, and all the participants completed the numeric rating scale (NRS), the short-form of the McGill pain questionnaire (SF-MPQ), the Hamilton rating scale for anxiety and depression (HAM-A, HAM-D), the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS). Results: The BMS patients presented a statistically significant higher prevalence of HTN compared to the controls (55% versus 33.5%; p-value: &lt;.001**) and higher median scores of the NRS, SF-MPQ, HAM-A, HAM-D, PSQI and ESS (p &lt; .001**). Multivariate regression analysis in the BMS patients indicated positive correlations between HTN and age, systemic diseases, drug consumption and anxiety (p-value: &lt;.001**) and these predictors were responsible for 11.3% of the HTN variance in the BMS patients, when considered together. Conclusions: The prevalence of HTN was significantly higher in the BMS patients, since ageing, the presence of comorbidities, drug consumption and anxiety were potential predictors. Further studies are needed to better investigate the relationship between BMS and HTN.

Tryptophan, an essential amino acid in mammals obtained from the diet, is influenced by maternal diet, which impacts early life and development of offspring. This is studied under the Developmental Origins of Diseases and Health (DOHaD) concept, so factors from conception to early childhood affect health and disease susceptibility. Tryptophan is metabolized mainly through two pathways: serotonin (5-HT) and kynurenine. The kynurenine pathway, active in the brain, gut, liver, and placenta, breaks down over 95% of tryptophan and plays roles in inflammation, neurotransmission, immune responses, and immune modulation during pregnancy. The serotonin pathway uses up to 5% of Tryptophan, mainly in the gut, adipose tissues, pancreatic cells, and central nervous system, and regulates responses to environmental changes, including sleep, cognition, and feeding behavior. Key enzymes in these pathways include Trp-2,3-dioxygenase (TDO), indoleamine-2,3-dioxygenase (IDO) type1 (IDO1), and type 2 (IDO2) (kynurenine pathway), and tryptophan hydroxylase type 1 (TPH1) and type 2 (TPH2), serotonin pathway. The fetus-placental unit manages tryptophan metabolism. Serotonin and kynurenine are crucial for placental health and fetal development. Serotonin adjusts placental blood volume and aids neurodevelopment. Kynurenine metabolites protect the fetus from maternal immunity and offer initial neuroprotection. At birth, infants switch from placental nutrients to breast milk, rich in tryptophan and protective bioactive molecules. Tryptophan, solely from breast milk, is crucial for infants. Its levels are high in newborns (first three weeks, 2-4 times higher than in adults), gradually declining to adult levels by the fourth week. The highlights the importance of tryptophan for the serotonin and kynurenine pathways in fetuses, newborns and babies applied to the DOHaD concept.

Background: Chronic post-surgical pain is a condition persisting at least three months after surgery. It is estimated that 25-60% of patients who underwent breast cancer removal surgery suffer from post-mastectomy pain syndrome and occurred anxiety, depression, sleep disturbance and catastrophizing. Physical activity can reduce the risk of chronic diseases and has a good impact on mood and cognitive function. Aim of this study was to evaluate the effects of physical activity on the intensity of pain, depression and anxiety in women underwent mastectomy for breast cancer removal. Methods: A prospective observational unicentric cohort study was performed. Patients were female underwent unilateral or bilateral mastectomy. Numerical Rating Scale (NRS), was used to assess pain intensity, Beck’s Depression Inventory (BDI) for depression and Generalized Anxiety Disorders-7 (GAD-7), for anxiety evaluation. Physical activity was assessed by International Physical activity questionnaire (IPAQ). Interleukin (IL)-17, IL-1β, cortisol, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) were also evaluated in the blood of patients. All the evaluation was assessed 3 and 6 months after the surgery. Results: Adequate physical activity reduced intensity of pain, depression and anxiety symptoms in women affected by post-mastectomy pain syndrome. Moreover, adequate active women, showed a reduction of biomarkers of inflammation, cortisol, ACTH and an increase of BDNF. Conclusions: Our results suggest that physical activity can improve quality of life, reducing intensity of pain, inflammatory markers and it can be useful in the reduction of associated anxiety and depression.

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

Carotenoids are common and diverse organic compounds with various functional roles in ani-mals. Except for certain aphids, mites, and gall midges, all animals acquire necessary carotenoids only through their diet. The House fly (Musca domestica) is a cosmopolitan pest insect that populates diverse habitats. Its larvae feed on organic substrates that may vary in carotenoid composition according to their specific content. We hypothesized that the carotenoid composition in the adult House fly’s body would reflect its composition in the larval feed. We reared house fly larvae on substrates that differed in carotenoid composition and characterized the carotenoid composition of the emerging adults. Our results indicate that the carotenoid composition of adult House flies is related to the carotenoid composition in its natal substrate, but does not directly reflect it. We suggest that these findings may be developed to identify sources of House fly in-festations. We also recommend that care should be taken when considering the rearing substrates of House fly larvae used for animal feed.

A class of models for non-Gaussian spatial random fields is explored for spatial field reconstruction in environmental and sensor network monitoring. The family of models explored utilises a class of transformation functions known as the Tukey g-and-h transformations to create a family of warped spatial Gaussian process models which can support various desirable features such as flexible marginal distributions, which can be skewed, leptokurtic and/or heavy-tailed. The resulting model is widely applicable in a range of spatial field reconstruction applications. To utilise the model in applications in practice, it is important to carefully characterise the statistical properties of the Tukey g-and-h random fields. In this work, we both study the properties of the resulting warped Gaussian processes as well as using the characterising statistical properties of the warped processes to obtain flexible spatial field reconstructions. In this regard, we derive five different estimators for various important quantities often considered in spatial field reconstruction problems. These include the multi-point Minimum Mean Squared Error (MMSE) estimators; the multiple point Maximum A-Posteriori (MAP) estimators; an efficient class of multiple-point linear estimators based on the Spatial-Best Linear Unbiased (S-BLUE) estimators; and two multi-point threshold exceedance based estimators, namely the Spatial Regional and Level Exceedance estimators. Simulation results and real data examples show the benefits of using the Tukey g-and-h transformation as opposed to standard Gaussian spatial random fields in a real data application for environmental monitoring.

Abstract: Laryngoscopy for tracheal intubation has been developed for many decades. Among various conventional laryngoscopes, videolaryngoscopes (VL) have been applied in different patient populations, including difficult airways. The safety and effectiveness of VL have been repeatedly studied in both normal and difficult airways. The superiority of VL then has been observed and is advocated as the standard of care. In contrast to laryngoscopy, the development of video-assisted intubating stylet (VS, also named as styletubation) has been noticed two dec-ades ago. Since then, sporadic clinical experiences of use have appeared in literature. In this re-view article, we presented our vast use experiences of the styletubation (more than 55,000 pa-tients since 2016). We found this technique is swift (the time to intubate: from 3 s to 10 s), smooth (first-attempt success rate: 100%), safe (no airway complications), and easy (high subjective satis-faction and fast learning curve for the novice trainees) in both normal and difficult airway sce-narios. We therefore propose styletubation technique can be feasibly applied as universal rou-tine use for tracheal intubation.

Objective:Over the last two decades one of the main surgical treatment for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) surgery was the insertion of non-absorbable mesh to restore continence and prolapse respectively. Over time complications arose including mesh-associated pain syndrome (MAPS), mesh exposure, mesh-erosion, chronic bladder/vaginal infections, and dyspareunia. Consequently, women chose surgical mesh removal to counter these problems. However, little is known about the demographics, medical co-morbidities, mesh types involved and the timing from mesh insertion to mesh removal. This retrospective study will look at which of these factors may be closely associated with mesh removal surgery.Design:Retrospective studySetting:Female Pelvic Medicine and Reconstructive Surgery (FPMRS) Clinic at University College London Hospitals NHS Foundation Trust.Population:All patients presenting to the FPMRS Clinic between June 2011 to December 2019, requesting mesh removal surgery with a history of MAPS and other mesh complications were included in this study. Methods:Patient demographics including age, ethnicity, obstetric history, and medical co-morbidities; type of mesh/anatomical route used; onset of symptoms; and time from insertion to removal were recorded. Main Outcome Measures:Determination of correlation coefficients between patient demographics, patient reported symptoms and mesh removal surgery. Results:Three hundred and forty-five women with a history of MAPS were included in the study. Women in the 40-60 year old cohort accounted for 54.4% of mesh removal surgery; 54.8% had a BMI under 30 and almost 90% were Caucasian. 96.5% had had children, with over 77% having had a vaginal delivery. 91.9% of patients reported other health conditions including 18.8% with a concomitant history of mental health problems and 15.4% with a history of heart disease. Over 80% of women undergoing mesh removal surgery had a continence mesh (49% retropubic and 32% obturator continence mesh) removed, whereas 20% had an abdominal prolapse and/or vaginal prolapse mesh removed. The average time from mesh insertion to mesh removal was seven years, with the prevalence of mesh removal surgery averaging 85% (range 50 - 100%) depending on the comorbidity determined. Conclusions:All women presented to the clinic with a history of MAPS and other comorbidities which may have influenced their decision to pursue mesh removal surgery. There were no specific predictors, other than chronic pain associated with mesh, determining which women underwent surgery, though those with continence mesh were more likely to do so.

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SAPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

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

Detection and measurement of pain are crucial in designing effective pain management interventions to alleviate suffering and prevent functional decline in the medical domain. Traditional methods of pain identification rely on verbal patient reports or observable signs, which can be imprecise or subjective due to variability in patient self-assessments. Hence, there is a pressing need for automated methods to standardize pain measurement procedures. This paper proposes a novel facial expression-based automated pain assessment system as a behavioral indicator for pain evaluation. Our system integrates a fusion structure comprising Convolutional Neural Networks (CNNs) and Tensor-based extended Quantitative Expression Descriptors Analysis (TXQEDA). This innovative approach allows for joint learning of robust pain-related facial expression features from raw facial images, combining RGB appearance with shape-based latent representation. We extensively evaluated our proposed model using the UNBC-McMaster dataset for pain classification and intensity estimation. Our results demonstrate the efficacy of the proposed technique, achieving an impressive accuracy of 99.10% for pain level classification. Furthermore, our system excels in pain intensity estimation, showcasing its potential to provide precise and reliable assessments of pain severity. Overall, our research underscores the importance of automated pain assessment systems in improving patient care and clinical outcomes. By leveraging advanced deep learning techniques and fusion strategies, our proposed model offers a promising approach for standardizing pain measurement procedures and enhancing the quality of pain management interventions.

The inhibition of kynurenine aminotransferase II (KATII) is a target for treating several diseases with an excess of kynurenic acid (KYNA). KATII inhibitors exist, but they have adverse side effects, given their irreversible inhibition mechanism. This study aimed to discover potent and safe inhibitors of KATII by using computational and in vitro methods. We identified herbacetin and (-)-Epicatechin as reversible KATII inhibitors from a small library of natural compounds, whose Glide docking scores (-8.66 kcal mol-1 and-8.16 kcal mol-1, respectively) and MM/GBSA binding energies (-50.30 kcal mol-1 and -51.35 kcal mol-1, respectively), which are higher scores than the standard inhibitor, PF-04859989 (-7.12 kcal mol-1 and -38.41 kcal mol-1, respectively). The ADMET analysis showed that herbacetin and (-)-Epicatechin have suitable pharmacokinetic parameters, are moderately bioavailable, and have a safe toxicity profile. Their KATII inhibitory activity is in the range of IC50 values of 5.98± 0.18 µM and 8.76 ± 0.76 µM, respectively. Furthermore, the MTT assay for cell toxicity showed that the two compounds do not alter HepG2 cell viability at their required concentration for KATII inhibition. These results show that herbacetin and(-)-Epicatechin are suitable for KATII inhibition and appropriate candidates for further development of KATII inhibitors.

COVID-19 pandemic that started in China has spread within 3 months to the entire globe. We tested the hypothesis that the vaccination against tuberculosis by BCG correlates with a better outcome for COVID-19 patients. Our analysis covers 55 countries complying with predetermined thresholds on the population size and number of deaths per million (DPM). We found a strong negative correlation between the years of BCG administration and the DPM along with the progress of the pandemic, corroborated by permutation tests. The results from multivariable regression tests with 23 economic, demographic, health-related, and pandemic restriction quantitative properties, substantiate the dominant contribution of BCG years to the COVID-19 outcomes. The analysis of countries according to an age-group partition reveals that the strongest correlation is attributed to the coverage in BCG vaccination of the young population (0-24 years). Furthermore, a strong correlation and statistical significance are associated with the degree of BCG coverage for the most recent 15 years, but no association was observed in these years for other broadly used vaccination protocols for measles and rubella. We propose that BCG immunization coverage, especially among the most recently vaccinated contributes to attenuation of the spread and severity of the COVID-19 pandemic.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

With the increasing occurrence of rotator cuff injuries every year, there is a great need for a reliable treatment option. Wharton’s Jelly contains several components that can positively impact the replacement and repair of musculoskeletal defects. The overall objective of this study is to evaluate the improvement of patient-reported pain scales after applying Wharton’s Jelly (WJ) in rotator cuff defects. Eighty-seven patients with rotator cuff defects who failed at least eight weeks of conservative treatment were selected from the retrospective repository. 2cc of WJ flowable allograft was applied to the specific affected anatomy, the most common being supraspinatus tendon, biceps tendon insertion, labral tear, and subscapularis tear. No adverse reactions were reported. Statistically significant improvements were found from the initial to Day 90 in all scales. Patient satisfaction was calculated using minimal clinically important differences. No statistically significant differences were found in mean changes between gender, BMI, and age. Scanning Electron Microscopy images reveal the similarities between the collagen matrix in WJ and the rotator cuff. The significant improvement in patient outcomes coincides with current literature analyzing WJ applications with other structural defects around the body. WJ is a promising alternative for musculoskeletal defects when the standard of care fails.

While the majority of previous studies assessing pain-related variables in psychopaths used electric shocks, little is known about the effectiveness of alternative pain-inducing methods to increase emotional responses such as fear and anxiety. A small sample of healthy undergraduate men (N = 15) was recruited to assess the effectiveness of a heat stimulus to induce pain in an immediate versus delayed punishment paradigm. Although pain catastrophizing, anxiety, and threat of pain did not increase throughout the experiment, participants experienced a significant increase of fear of pain and pain intensity, indicating that the heat stimulus was effective in inducing pain. Furthermore, subjects were slower in initiating the pain stimulus during the first five trials, but no time difference was found during the 15 remaining trials. No correlation was found between psychopathic traits and pain-related variables, with the exception of inconsistent results within the Fearless Dominance factor. Findings are discussed in terms of improvement for a larger scale study involving psychopathic individuals.

Building energy demand impacts a myriad of interconnected economic, societal, and environmental aspects. As a result, Buildings Energy Models (BEM) play an important role in the process of urban design and planning. While previous studies have investigated the effects of building interventions on energy efficiency, their applicability may be limited due to the BEM’s high computational complexity. This limits their ability to systematically study important aspects of energy demand on a large scale. The development of Machine Learning Models (MLM) allows to design the required detailed analysis and solutions, while reducing the computational burden, making MLM attractive for urban designers. The capability of MLM to generalize well for multiple contexts (in our case, multiple buildings) is a crucial contributor to their applicability. However, the validation process in a wider context is often overlooked, therefore its generalization capabilities are not quantified. In this paper, we present a framework to train and validate a surrogate model derived from a physics-based BEM. Our method employs a Multiple Linear Regression model to predict Energy Use Intensity (EUI) for office buildings in Singapore using 36 input parameters (covariates), based on a training dataset of 23,000 samples. Model validation is performed by comparing the results of the Surrogate Model (SM) to a widely used BEM for a sample of 120 buildings. Our results indicate that the SM has an accuracy of NRMSE of 13%, NMBE of −3.56%, and R2 of 0.92, which suggests it can effectively and accurately predict building EUI. We also conduct a sensitivity analysis, which indicates that the parameters associated with internal loads and internal space usage are the most influential. Additionally, we present a reduced order model trained with only the 11 most influential parameters, which exhibits negligible loss in accuracy compared to the full SM while providing reduced complexity. Finally, we demonstrate an application of our SM to evaluate energy efficiency under uncertainty scenarios. The analytically derived results indicate a potential reduction of EUI of offices in Singapore from 227kWh/m2 to 99kWh/m2 by altering the building parameters that were identified as most influential.

Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.

Spinal cord stimulation (SCS) is a therapeutic modality for the treatment of various chronic pain conditions that has rapidly evolved over the past 50 years. Unfortunately, over time, patients implanted with SCS undergo a habituation phenomenon leading to decreased pain relief. Consequently, discovery of new stimulation waveforms and SCS applications have shown to prolong efficacy and reduce explantation rates. This article explores various SCS waveforms, their applications and proposes a graded approach to habituation mitigation. We suspect the neural habituation phenomenon parallels that seen in pharmacology. Consequently we urge further exploration of early introduction of these stimulation strategies to abate spinal cord stimulation habituation.

Knee osteoarthritis (KO) is an important health condition, affecting one third of the people aged 65 years or more. Pain is the main cause of disability. Pain management in KO includes pharmacological and non-pharmacological modalities. Patient education, lifestyle changes, physical exercise and physical agents are prescribed as a first approach for pain control. Laser therapy is part of many therapeutical protocols, with two forms, low-level laser therapy (LLLT) and high-intensity laser therapy (HILT). The paper aimed at stressing the advantages of HILT, based on a greater wavelength, higher energy delivery and deeper tissue penetration. Research on 23 published trials revealed that analgesic effect is rapid, cumulative and long lasting. Compared to sham, to LLLT or to other associations of therapeutical modalities, HILT provided significantly better results on pain reduction and functional improvement. Ultrasound examination showed reduction of intraarticular inflammation.

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we will discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.

Poly-DADMAC (PD) is a commonly used organic polymer in water treatment, known for its effectiveness as a coagulant. However, its presence as a residue in water raises concerns related to membrane fouling and the potential formation of carcinogenic compounds. Therefore, fast and simple quantification is necessary to efficiently control and monitor the optimal dose of poly-DADMAC with minimal negative effects. This study introduces a new colorimetric quantification method for poly-DADMAC, based on complexation with a cationic dye (fast green- FG). The method was examined through varying conditions which included different analytical and commercial poly-DADMAC formulations and concentrations. The experiments confirm its effectiveness in quantifying poly-DADMAC with a detection limit of 3.22 µg L^-1 (0.02 µM based on monomers' molecular weight), which is one order of magnitude lower than regulatory requirements (50 µg L^-1). To validate the method, the effect of pH was examined, and implementation demonstrations were conducted on cyanobacteria and cowshed polluted water samples. This research introduces a fast, cost-effective innovative method to accurately quantify poly-DADMAC, enhancing water treatment strategies for high-quality purification and water reuse

In this study, we aimed to explore the oral bacteria and fungi that can help discern oral squamous cell carcinoma (OSCC) and investigate the correlations between multiple key pathogens. Methods: Twelve participants (8 females and 4 males; mean age, 54.33 ± 20.65 years) were prospectively recruited into three groups: Group 1: healthy control, Group 2: patients with stomatitis, and Group 3: patients with OSCC, with 4 individuals in each group. Unstimulated whole saliva samples from these participants were analyzed using real-time PCR to assess the presence and abundance of 14 major oral bacterial species and Candida albicans. Results: The analysis revealed significant differences for certain microorganisms, namely Treponema denticola (T. denticola), Lactobacillus casei (L. casei), and Candida albicans. T. denticola was most abundant in the OSCC group (5,358,692.95 ± 3,540,767.33), compared to the stomatitis (123,355.54 ± 197,490.86) and healthy control (9,999.21 ± 11,998.40) groups. L. casei was undetectable in the healthy control group, but was significantly more abundant in the stomatitis group (1,653.94 ± 2,981.98) and even higher in the OSCC group (21,336.95 ± 9,258.79) (p = 0.001). A similar trend was observed for C. albicans, with DNA copy numbers rising from the healthy control (464.29 ± 716.76) to the stomatitis (1,861.30 ± 1,206.15) to the OSCC group (9,347.98 ± 5,128.54) (p = 0.006). The amount of T. denticola was positively correlated with L. casei (r=0.890, p<0.001) and C. albicans (r=0.724, p=0.008). L. casei's DNA copy number was strongly correlated with C. albicans (r=0.931, p<0.001). These three oral microbes exhibited strong positive correlations with each other and had various direct or indirect relationships with other species. Conclusions: In the OSCC group, T. denticola, L. casei, and C. albicans exhibited strong positive correlations with one another, further emphasizing the need for a deeper understanding of the complex microbial interactions in the OSCC environment.

Ice-binding proteins (IBPs) have several functions that permit their hosts to thrive in the presence of ice. The ability of IBPs to control ice growth makes them potential additives in various industries ranging from food storage and cryopreservation to anti-icing systems. For IBPs to be used in commercial applications, however, methods are needed to produce sufficient quantities of high-quality proteins. Here, we describe a new method for IBP purification, termed falling water ice purification (FWIP). The method is based on the affinity of IBPs for ice. A crude IBP solution is allowed to flow continuously over the large chilled vertical surface of a commercial ice machine. The temperature of the surface is lowered gradually until ice crystals are produced, to which the IBPs bind but other solutes do not. As in other ice affinity methods, FWIP does not require molecular tags and is suitable for purifying recombinant IBPs as well as IBPs from natural sources. The advantage of FWIP over other ice affinity methods is that it exploits an ice machine designed to produce large volumes of clear ice daily. This system can be easily scaled up and suits the purification of industrial quantities of IBPs. The FWIP method significantly advances the use of IBPs in research and industry.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Many studies utilize sensors to measure foot plantar pressure and analyze gait patterns, often focusing on assessing weight-bearing symmetry or asymmetry compared to control groups. However, a critical question arises: does the selection of the control group significantly impact study outcomes? Does chronic low back pain affect foot plantar pressure measurements? This experimental study involved 23 participants, including healthy individuals and those without foot disorders but with chronic low back pain. Dynamic foot pressure measurements were conducted using the Ortopiezometr, and data were analyzed using the "Steps" program. Participants were divided into two groups: Group 1 comprised completely healthy individuals, while Group 2 consisted of individuals without foot problems but with moderate chronic low back pain. The findings highlight a prevalence of energy release in the forefoot sensors compared to the hindfoot for both the right and left legs in most cases. Even among healthy volunteers, achieving perfect symmetry in the maximum values on the sensors for the right and left feet was a challenge. Results showed no statistically significant differences in energy released on specific sensors or duration of gait phases between the groups. Essentially, this suggests that foot pressure patterns are comparable between healthy individuals and those with low back pain. The use of sensor-equipped inserts for pedobarographic examinations indicates that, in cases of degenerative changes in the lumbar and sacral spine without accompanying acute pain, gait patterns resemble those of the healthy population.

While Spinal Cord Stimulation (SCS) provides satisfaction to almost 2/3 of Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients implanted for refractory chronic back and/or leg pain when not adequately addressed the back pain component, leaves patients in a therapeutic cul-de-sac. Peripheral Nerve field Stimulation (PNfS) has shown interesting results addressing back pain in the same population. Far from placing these two techniques in opposition, we suggest that these approaches could be combined to better treat PSPS-T2 patients. We designed a RCT (CUMPNS), with a 12-month follow-up, to assess the potential added value of PNfS, as a salvage therapy, in PSPS-T2 patients experiencing a “Failed SCS Syndrome” in the back pain component. Fourteen patients were included in this study and randomized into 2 groups (“SCS + PNfS” group/n=6 vs “SCS only” group/n=8). The primary objective of the study was to compare the percentage of back pain surface decrease after 3 months, using a computerized interface to obtain quantitative pain mappings, combined with multi-dimensional SCS outcomes. Back pain surface decreased significantly greater for the ”SCS+PNfS” group (80.2% ± 21.3%) compared to the “SCS only” group (13.2% ± 94.8%) (p=0.012), highlighting the clinical interest of SCS+PNfS, in cases where SCS fails to address back pain.

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

Use of fingerprints found at a crime scene is a common practice for identifying suspects in criminal investigations. Over the past two decades, attempts have been made to obtain additional information from fingerprints, beyond locating suspects as part of an investigation. This includes gender, age and nationality. Researchers demonstrated 75%-90% accuracy in gender classification based on fingerprint images. Nonetheless, despite promising results, these studies have several significant shortcomings with respect to their practical feasibility. First, they ignore the low quality and quantity of fingerprints collected from the crime scene since typically the scene of a crime has only one fingerprint collected, and the fingerprint might be partially or of poor quality as well. Second, as most results are based on a single database, public or private, it is difficult to generalize the most suitable method. Third, studies miss the untapped potential of Data-Centric AI (DCAI) approaches for improving results. The aim of this study was to compare, for the first time, the gender classification from a fingerprint using several datasets and with varying fingerprint image quality. The results from four databases are compared, three public and one internal private database. In addition, we utilize the latest Data-Centric AI (DCAI) approaches for improving classification results. The results demonstrate that a conservative Convolutional Neural Networks (CNN) such as VGG is sufficient for this task. Classification accuracy ranges from 80% to 95% depending on the quality of the fingerprint, with DCAI approaches adding 1%-4% improvement. For partially or low-quality fingerprint images, the periphery of a fingerprint is the most significant area for determining gender. The source code is also provided here for practical application.

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

The multidimensionality of chronic pain forces us to look beyond isolated pain assessment such as pain intensity, which does not consider multiple key parameters, particularly in patients suffering from post-operative Persistent Spinal Pain Syndrome (PSPS-T2). Our ambition was to provide a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and objective quantitative pain mapping assessments, the objective being to capture patient condition instantaneously, using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in a real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined using exploratory factor analyses to create an optimally accurate MCRI; as a single composite index, using pairwise correlations between measurements, it appeared to better represent all pain dimensions than any other classical score. It appeared to be the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by changing the physician’s perception of patient condition on the basis of objective and holistic metrics, and by providing new insights to therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.

Introduction: Birth Asphyxia is a severe condition that includes many potential pathways of occurrence both in utero and during childbirth. We aimed to identify and describe specific macroscopic and microscopic placental injuries in birth asphyxia to serve as a quick tool to stratify a newborn’s potential further evolution, as hypoxic-ischemic encephalopathy can be responsible for neonatal death or severe neurologic sequelae further compromising the affected persons’ quality of life. Materials and methods: We conducted an observational prospective study over 3 years. 62 patients diagnosed with birth asphyxia which had placental histopathological examination performed were enrolled. The control group consisted of 69 term newborns that required neonatal intensive care for at least three days, in the same period, for any other reason and that also had available placental exams. In our study, placental histopathological lesions identified in birth asphyxia have been classified according to Amsterdam Criteria. Results: We analysed data gathered from both groups by applying specific statistical tests for each type of variable and hypothesis. Thus, umbilical cord abnormalities were associated with hypoxic-ischemic encephalopathy in a statistically significant manner when comparing the birth asphyxia group of newborns with the control group. Also, we identified a high statistical level of significance for maternal and fetal vascular malperfusion and the occurrence of hypoxic-ischemic syndrome when comparing the two groups (p = .00). Conclusion: The macroscopic and microscopic placental examination can provide important information on the evolution of the disease in selected newborns according to the identified lesions.

1) Background. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, characterized by extensive necrosis and detachment of the epidermis. 2) Case presentation. We present a case of a 46-year-old patient with late-stage high-grade serous ovarian cancer who was primarily treated with neoadjuvant chemotherapy and interval debulking which was followed by adjuvant chemotherapy. At first recurrence, she was again treated with chemotherapy and due to severe abdominal pain, an elastomeric pump containing analgesics, anti-inflammatories and ondansetron was administered. In the same month, she was admitted to the hospital due to severe dysphagia and in the following days, she developed haemorrhagic vesiculobullous lesions on facial skin and trunk. Stevens-Johnson syndrome was confirmed and ondansetron as a leading cause was discontinued. Despite multimodal treatment, her condition deteriorated, and she died. 3) Discussion and conclusion. Although gynaecologists rarely encounter Stevens-Johnson syndrome, high mortality of the disease should ensure a low threshold for diagnosing and treating this disease.

Binge drinking is a pattern of alcohol abuse. Its prevalence and associated risk factors are not well documented. Heavy drinking, on the other hand, has a well-studied association with bereavement . This report uses a cross-sectional, population-based survey to estimate prevalence of bingeing and its association with new bereavement. Bingeing is defined as 4 or more drinks (women) or 5 or more drinks (men) in a 2-to-4-hour setting. For the first time, the Georgia Behavioral Risk Factor Surveillance Survey (BRFSS) included a bereavement item, ‘Have you experienced the death of a family member or close friend in the years 2018 or 2019?’. Methods: Georgia BRFSS is a complex sampling survey administered annually. It is designed to represent the 8.1 million persons in the U.S. state of Georgia aged 18 years and older. Alcohol consumption patterns are routinely measured in the common core. In the 2019 field survey, the state added a new item probing for bereavement in the prior 24 months predating the pandemic of COVID-19. Imputation and weighting techniques were applied to yield population prevalence rates of new bereavement, bingeing, and their co-occurrence with other high-risk health states. Models, adjusted for age, gender, and race were used to estimate the risk for other unhealthy behaviors posed by the co-occurrence of bereavement and bingeing. Results: In Georgia, bereavement is common (45.8 %), and alcohol consumption is common (48.8 %). Bereavement and alcohol use co-occurred among 1,796,817 persons (45 % of all drinkers). The subset of co-occurring bereavement and binging totaled 608,282 persons. Within this group, the highest rates of bereavement were associated with death of a friend / neighbor (30.7%) or 3 plus deaths (31.8%). Conclusions: While bingeing is a known risk to public health, its co-occurrence with recent bereavement is a new observation. Public health surveillance systems need to monitor this co-occurrence to protect both individual and societal health. In a time of global bereavement, documenting its influence on binge drinking can support the work towards Sustainable Goal #3 – Good health and Well-Being. Keywords: BRFSS, Binge Drinking, Population Survey, Bereavement, SDG#3. Mental Health

Metabolic syndrome (MetS) refers to the group of several interconnected risk factors that collectively double the risk of cardiovascular disease. Epilepsy is linked to MetS across all age groups, though its prevalence differs across various studies. This can be understood from the perspective of seizure-related metabolic abnormalities, long-term antiepileptic drugs (AEDs) use, and a more sedentary lifestyle due to epilepsy. The factors that are considered in developing MetS for patients with epilepsy (PWE) are age, residence, level of physical activity, food intake status, epilepsy subtype, epilepsy duration, current (AEDs) use, drug responsiveness status, body-mass index (BMI), total cholesterol and LDL-cholesterol levels. A deeper understanding of the epilepsy-AED-MetS connection and the exploration of lifestyle interventions hold the promise of significantly improving the overall health and well-being of PWE. Clinicians managing PWE should closely monitor various risk factors for developing MetS and consider them when selecting AED treatment.

Background: Facial features are the first basic spring of medical knowledge in children and adults with congenital malformation. Children born with multiple contractures almost always receive the misdiagnosis of arthrogryposis multiplex. Larsen syndrome can easily be diagnosed at birth via the proper interpretations of its characteristic facial features and multiple dislocations. Instant diagnosis can facilitate the orthopaedic strategy for early treatment and follow-ups. Material and Methods: Six children (four boys and two girls, age range from a few months to 7 year-old) have been referred to our departments for diagnosis and treatment. All children received their first misdiagnosis by the paediatricians as having arthrogryposis multiplex congenita. The clinical phenotype was our first decisive tool for diagnosis. All children exhibited the classical phenotype of Larsen syndrome, dish-like facies associated with multiple joint dislocations. Radiological phenotypic characteristics confirmed our clinical diagnosis. three children out of six showed unpleasant cervical spine deformities. The first child of a-2- year old became tetraplegic after minor trauma. One child presented with rigid cervical kyphosis. The third child wasa product of first related marriage and was born congenital tetraplegia. genotype has been carried out for confirmation. Results: Three children underwent open reduction for congenital hip and knee dislocations. one child underwent spinal fusion CO-C7 because of tetraplegia. 3D reformatted and reconstruction CT scan of the craniocervical junction in two children showed unusual male segmentations along C2-3 causing effectively the development of rigid cervical kyphosis and one child with congenital tetraplegia showed serious malsegmentation of C1/C2 associated with hypoplasia of the anterior and the posterior rings of the atlas. These findings in the last two children made any surgical intervention quite sophisticated. Four of these children were compatible with the autosomal dominant type of Larsen syndrome and manifested heterozygous mutation in FLNB mapped 3p14.3, encoding and actin-binding protein, filamin B. One child showed no mutations in the FLNB, though his clinical and radiological phenotype and his family history of first related marriage were totally compatible within the diagnosis of autosomal recessive type of Larsen syndrome. Conclusion: The orthopaedic strategy in patients with Larsen syndrome can not be achieved unless a precise diagnosis is has to be established as early as possible. Arthrogryposis multiplex congenita has been the first false diagnosis which was the reason for improper management.The most diagnostic confusion /error occurs to the paediatricians is the multiple contractures which are akin to arthrogryposis multiplex congenita. In practice, arthrogryposis multiplex congenita is a symptom complex rather than a precise diagnostic entity. The second diagnostic misconception is the generalized ligamentous hyperlaxity which can mimic hypotonia. Hypotonia in a newborn can be falsely categorized within the floppy infant syndrome. We used 3D reformatted CT scan to further understand the craniocervical junction pathology in three children with cervical spine kyphosis. Strikingly, mal segmentation and defective ossifications of the atlanto-axial spine segments in a child with Larsen syndrome and congenital tetraplegia.

There is an anecdotal impression that teenage patients report exaggerated postoperative pain scores that do not correlate with their actual level of pain. Nurse and parental perception of teenagers' pain can be complemented by knowledge of patient pain behavior, pain catastrophizing thoughts, anxiety, and mood level. Two hundred two patients completed the study: 56.4% female, 89.6% White, 5.4% Black, and 5% other race. Patient ages ranged from 11 to 17 years (mean = 13.8, SD = 1.9). The patient, the parent, and the nurse completed multiple questionnaires on day one after laparoscopic surgery to assess patient pain. Teenagers and parents (r=0.56) have a high level of agreement, and teenagers and nurses (r=0.47) have a moderate level of agreement on pain scores (p &lt;0.05). The correlation between patient APBQ (Adolescent Pain Behavior Questionnaire) and teenager VAS (Visual Analog Scale ) and between nurse APBQ and teenager VAS, while statistically significant (p &lt; 0.05), is weaker (r range = 0.14-0.17). There is a moderate correlation between teenagers' pain scores and their psychological assessments of anxiety, catastrophic thoughts, and mood (r range= 0.26 – 0.39; p &lt;0.05). A multi-modal evaluation of postoperative pain can be more informative than only assessing self-reported pain scores.

Neuropathic pain (NeP) is a complex and debilitating condition that impacts millions of people globally. Although various treatment options exist, their effectiveness is often limited, and they can be accompanied by significant side effects. In recent years, there has been increasing interest in targeting the N-methyl-D-aspartate receptor (NMDAR) as a potential therapeutic approach to alleviate different types of neuropathic pain. This narrative review aims to provide a comprehensive examination of NMDAR antagonists, specifically ketamine, memantine, methadone, amantadine, carbamazepine, valproic acid, phenytoin, dextromethorphan, riluzole, and levorphanol, in the management of NeP. By analyzing and summarizing current preclinical and clinical studies, this review seeks to evaluate the efficacy of these pharmacologic agents in providing adequate relief for NeP.

Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

Tryptophan metabolism, via the kynurenine (Kyn) pathway, and microbial transformation of tryptophan to indolic compounds, are fundamental for host health; both of which are altered in colon carcinogenesis. Alterations in tryptophan metabolism begin early in colon carcinogenesis as an adaptive mechanism for the tumor to escape immune surveillance and metastasize. The microbial community is a key part of the tumor microenvironment and influences cancer initiation, promotion and treatment response. A growing awareness of the impact of the microbiome on tryptophan (Trp) metabolism in the context of carcinogenesis has prompted this review. We first compare the different metabolic pathways of Trp under normal cellular physiology to colon carcinogenesis, in both the host cells and the microbiome. Second, we review how the microbiome, specifically indoles, influence host tryptophan pathways under normal and oncogenic metabolism. We conclude by proposing several dietary, microbial and drug therapeutic modalities that can be utilized in combination to abrogate tumorigenesis.

The present study was conducted to compare embryo survival rate and treatment outcomes including pregnan-cy, miscarriage and live birth rates of IVF and ICSI vitrified-thawed embryo transfers. Authors suggested to compare treatment outcomes [clinical pregnancy, miscarriage, ectopic pregnancy, and live birth rates] after transfer of IVF versus ICSI vitrified-thawed embryos. Cohort retrospective study in the IVF unit at a university af-filiated Medical Center which included 845 frozen thawed embryo transfer cycles of vitrified embryos from treatment cycles between the years 2013-2019. Out of 845 FET cycles of vitrified thawed embryos, 223 clinical pregnancies were achieved [26.4%]. Of these 64 [28.4%] following IVF, 131 [25.6%] after ICSI and 28 [25.9%] in the sibling oocytes group [P =0.631]. Live birth rate did not differ between the three groups: 23.6%, 22.3% and 21.5% for groups IVF, ICSI and IVF+ICSI, respectively [p=0.899]. Sub analysis by age below 35 and above 35 years old revealed no statistical difference between IVF and ICSI cycles in terms of clinical pregnancy, miscarriage, ectopic pregnancy, and live birth rates between the groups. The present study suggests that the technique of insemina-tion has no adverse effect related to vitrification.

The prolonged static sitting at the workplace is considered as one of the main risks for development of musculoskeletal disorders (MSDs) and adverse health effects. Factors such as poor posture and extended sitting are perceived to be a reason for conditions such as lumbar hyperlordosis and lower back pain (LBP), even though the scientific explanation of this relationship is still unclear and raises disputes in the scientific community. This publication proposes the low back pain assessment (LBPA) dataset collected through experiment with 100 participants and consisting of photogrammetric images with intentionally placed body markers, calculated postural angles and tags correct and incorrect posture assessed by habilitated rehabilitator, as well as questionnaire-based self-reports regarding the occurrence of LBP and similar symptoms among the participants. Machine learning models trained with this data are employed for recognizing incorrect body postures. Two scenarios have been elaborated for modeling purposes: scenario 1, based on natural body posture tagged as correct and incorrect, and scenario 2, based on incorrect body postures, corrected additionally by the rehabilitator. The achieved accuracies of respectively 75.3% and 85% for both scenarios reveal the potential for future research in enhancing awareness and actively managing posture-related issues that elevate the likelihood of developing lower back pain symptoms.

Superior mesenteric artery (SMA) syndrome or Wilkie’s syndrome is a vascular compression disorder that causes abnormal compression of the third portion of the duodenum by the SMA. It has a low incidence rate, higher in young women, and is rarely associated with the Nutcracker phenomenon: a condition of compression of the left renal vein between the SMA and the aorta, which manifests as pain in the left flank and pelvis. Here we report the case of a 54-year-old woman with a history of repeated episodes of abdominal pain caused by the Nutcracker syndrome and Wilkie's syndrome.

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

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age representing the primary cause of anovulatory infertility. The nonapeptide oxytocin (OT) plays an important role in cognitive, emotional, and reproductive functions in human beings. Oxytocin receptors are expressed in several body parts including the ovaries. Despite this, the possible role played by oxytocin in symptoms of PCOS is not clear. The present systematic review aimed at understanding, the presence of possible oxytocin level alterations in PCOS, the connection between alterations of OT levels and the symptoms of PCOS, and the effect of oxytocin administration in PCOS. After a systematic search in the principal databases, seven studies, five human and two animal, were included. Most of the studies highlighted the role played by oxytocin in fertility issues related to PCOS. Studies that analyzed oxytocin basal levels in PCOS women agreed that PCOS is associated with a reduction in the serum level of oxytocin. Two studies found that in PCOS the serum levels of oxytocin were lower than healthy controls. One human and one animal study agreed about lower levels of PCOS, confirming a possible implication of a dysfunction of OT, in the pathogenesis of PCOS.

Passive plasma spectroscopy is a well-established non-intrusive diagnostic technique. Depending on the emitter and its environment which determine the dominant interactions and effects governing emission line shapes, passive spectroscopy allows the determination of electron densities, emitter and perturber temperatures as well as other quantities like abundances. However, using spectroscopy needs appropriate line shape codes retaining all the physical effects governing the emission line profiles. This requires for line shape code developers to continuously correct or improve them to increase their accuracy when applied for diagnostics. This is exactly the aim expected from code-code and code-data comparisons. In this context, the He I 492 nm emitted in a helium corona discharge at room temperature represents an ideal case since its profile results from several broadening mechanisms: Stark, Doppler, resonance and van der Waals. The importance of each broadening mechanism depends on the plasma parameters. Here the profiles of the He I 492 nm in a helium plasma computed by various codes are compared for a selected set of plasma parameters. In addition, preliminary results related to plasma parameter determination using experimental spectra from a helium corona discharge at low pressure 1- 2 bars, are presented.

Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

Transcriptionally controlled tumor protein (TCTP) is a highly conserved protein performing a large number of cellular functions by binding with various partner proteins. The importance of its roles in many diseases requires an assay method to find regulatory compounds. However, the molecular characteristics of TCTP made it difficult to search for chemicals interacting with it. In this study, a tryptophan-based assay method was designed and Y151W mutant TCTP was constructed to search binding chemicals. Since there is no tryptophan in the native sequence of TCTP, the incorporation of tryptophan in the Y151W mutant was very effective to establish the method. A flavonoid library was employed to the assay with the method. With the native and Y151W mutant TCTPs, three flavonoids such as morin, myricetin and isobavachalcone have been found to interact with TCTP. Combined with native gel electrophoresis, the binding region of isobavachalcone was suggested to be the flexible loop of TCTP. This approach can be easily applicable to find binding compounds of proteins with similar molecular characteristics of TCTP.

Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine–tryptophan–ketoglutarate (HTK) solution is a preservative used during organ transplantation. Can HTK also protect neurons from severe hypoxia (SH) following CA? We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and NADPH oxidase-4 (NOX4) expression were evaluated at different time points till 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluating NOX4 and H2O2 level in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persisted HIF-1α expression, reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK’s effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity and NOX4 gene expression were all decreased in the brain specimen of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution.

Background and Objectives: The aim of this study was to determine the job-related and individual features that influence BS and depression levels among dentists working in faculties, oral and dental health centres (ODHC) and private clinics. Materials and Methods: This prospective, cross sectional study was carried out on dentists working in different regions of Turkey. Data were collected using an on-line questionnaire created using Google Forms. The questionnaire consisted of demographic data, Maslach BS Inventory (MBI) and Beck Depression Inventory (BDI) sections. Demographics were age, height, weight, marital status, blood type, gender, monthly income, income satisfaction and having enough free time. The dentists were divided into 3 groups as faculty, private clinic and ODHC according to the institutions in which they worked. Results: Of the total 290 dentists enrolled in the study, there were 172 males and 118 females with a mean age of 36.98±5.6 years. 128 of the dentists worked in faculties, 72 in private clinics and 90 in ODHCs. It was observed that women's EE scores were higher than men's (P&lt;0.05). No statistically significant difference was found between the groups when comparing BS and depression scores according to marital status and blood group (P&gt;0.05). There was no significant relationship between emotional exhaustion (EE), depersonalisation (DP), personal accomplishment (PA) and depression scores according to age, BMI and work experience, age, work experience and BMI (P&lt;0.05). It was found that the EE scores of the dentists working in the faculty and private clinic were lower than those of the dentists working in the ODHC (P&lt;0.05). Monthly income was associated with depression (r = -0.35). Conclusions: This study showed that dentists working in ODHCs had more EE. These findings suggest that there is a need for improvement in the working conditions of dentists, particularly in ODHCs.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

Interventional management of neuropathic pain (NP) is available to the many patients who do not attain satisfactory outcomes with pharmacotherapy, but evidence supporting this is sparse and fragmented. We attempted to summarize and critically appraise the existing data to identify strategies that yield maximum benefit, orient clinicians, and identify areas that merit further investigation. A two-round Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 26-item questionnaire prepared by the authors. Consensus on each statement was defined as either at least 80% endorsement or rejection after the second round. Thirty-five and 29 panelists participated in the first and second round, respectively. Consensus was reached in 20 out of 26 statements. There is sufficient basis to treat postherpetic neuralgias and complex regional pain syndromes with progressive levels of invasiveness and failed back surgery syndrome with neuromodulation. Radiculopathies and localized NP could be treated with peripheral blocks and neuromodulation, or pulsed radiofrequency. Non-ablative radiofrequency and non-paresthetic neuromodulation are efficacious and better tolerated than ablative and suprathreshold procedures. A graded approach, from least to most invasive interventions has the potential to improve outcomes in many patients with common refractory NP conditions. Preliminary promising data warrant further research on new indications, and technical advances might enhance the safety and efficacy of current and future therapies.

The increasing prevalence of Metabolic Syndrome (MetS), a serious condition associated with elevated risks of cardiovascular diseases, stroke, and type 2 diabetes, underscores the urgent need for effective diagnostic tools. This research carefully examines the effectiveness of 16 diverse machine learning (ML) models in predicting MetS, a multifaceted health condition linked to increased risks of heart disease and other serious health complications. Utilizing a comprehensive, unpublished dataset of imbalanced blood test results, spanning from 2017 to 2022, from the Laboratory Information System of the General Hospital of Amfissa, Greece, our study embarks on a novel approach to enhance MetS diagnosis. By harnessing the power of advanced ML techniques, we aim to predict MetS with greater accuracy using non-invasive blood test data, thereby reducing the reliance on more invasive diagnostic methods. Central to our methodology is the application of the Borda count method, an innovative technique employed to refine the dataset. This process prioritizes the most relevant variables, as determined by the performance of the leading ML models, ensuring a more focused and effective analysis. Our selection of models, encompassing a wide array of ML techniques, allows for a comprehensive comparison of their individual predictive capabilities in identifying MetS. This study not only illuminates the unique strengths of each ML model in predicting MetS but also reveals the expansive potential of these methods in the broader landscape of health diagnostics. The insights gleaned from our analysis are pivotal in shaping more efficient strategies for the management and prevention of Metabolic Syndrome, thereby addressing a significant concern in public health.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

Background: Pediatric patients with polyuria polydipsia syndrome (PPS) represent a diagnostic challenge for clinicians because of the technical difficulties in performing the gold standard water deprivation test (WDT). Copeptin, a stable biomarker representing the C-terminal portion of the polypeptide chain of antidiuretic hormone, proves to be a more reliable diagnostic tool. Objective: To assess the diagnostic accuracy of copeptin baseline dosing, arginine/saline copeptin stimulation tests, and WDT. Establishing the diagnostic utility of copeptin in pediatrics, for differentiating central and nephrogenic diabetes insipidus, and primary polydipsia. Methods: comparative and non-comparative primary studies, relating to children, were included and searched for in PubMed, Cochrane Library, WOS, ScienceDirect, Scopus, Google Scholar, up to August 2024. QUADAS-2 tool was used to assess risk of bias and applicability. Meta-analyses used fixed effect models due to low heterogeneity and the HSROC model. Results: 11 studies included, with an overall Low bias, no significant applicability concerns. The mean pooled sensitivity = 0.98 (95% CI: 0.936–1.025), pooled specificity=0.947 (95% CI: 0.920–0.973), and AUC=0.972 (95% CI: 0.952–0.992), indicating excellent diagnostic accuracy. Conclusion: Stimulation methods for copeptin dosing represent effective and less invasive diagnostic test for children with PPS, and future development of standard copeptin testing protocols are needed.

Vascular anomalies are a diverse group of abnormal blood vessel developments that can occur at birth or shortly afterward. Embolization and sclerotherapy have been utilized as a treatment option for these malformations but may cause moderate to severe pain. This study aims to evaluate the utilization of peripheral nerve blocks in opioid consumption, pain scores, and length of stay. A retrospective chart review was conducted at the UPMC Children's Hospital of Pittsburgh for all patients who underwent embolization and sclerotherapy between 2011 and 2020. Patient data was collected to compare opioid consumption, pain scores, and length of stay. Eight hundred fifty-four procedures were performed on 347 patients. The morphine milligram equivalent per kilogram mean ratio between groups was 0.9 (0.86, 0.95) with a p-value of &lt;0.001. The pain score mean ratio was –1.17 (–2.2, -0.1) and a p-value of 0.027. Length of stay had a mean ratio of 0.94 (0.4, 2) and a p-value of 0.875. By decreasing opioid consumption and postoperative pain scores, peripheral nerve blocks may have utility in patients undergoing embolization and sclerotherapy while not clinically increasing the length of stay for patients. Their use should be individualized and carefully discussed with the interventional radiologist.

Background/Objectives: Catastrophization and other comorbid psychological factors that increase awareness of pain are known to hinder chronic pain recovery. Five pilot studies, reported here, indicate that increased pain awareness from frequent pain assessment may impede chronic pain recovery through similar mechanisms. Methods: All study participants were asked to use a biofeedback device at least twice daily. Studies 1 and 2 required pain assessment before and after each biofeedback session, while Studies 3-5 did not. Pain levels were measured by the McGill Pain Inventory (McGill PI) at the start and end of each study. Results: Studies 3-5 replicated our prior work, demonstrating changes in pain, anxiety, and satisfaction and recovery following a home-use biofeedback program. Participants in the studies without frequent pain assessment experienced greater overall reductions in pain compared to participants in studies that did not require pain assessment. The results are, however, statistically inconclusive due to high variability, so further research is necessary. Conclusion: The results of our study suggest that frequent pain assessment may hinder pain reduction, likely by facilitating negative thought patterns and neural circuits involved in chronic pain. These findings can be applied to developing better research designs and more effective chronic pain recovery programs.

Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress play also role in frailty (frail) and metabolic syndrome (MetS). Methods: 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed: waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n=19), NonMetS-frail (n=20), MetS-Nonfrail (n=17), and MetS-frail (n=10). Results: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggests that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors. Conclusions: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2,500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72h of cultivation. The analysis of mean PI showed significant differences between 45,X and 46,XN lineages; however there were no intraindividual differences. On the other hand, mean SCE frequencies showed no differences between the two lineages, but there were intraindividual differences in 5 patients. The absence of mean SCE frequency differences between 45,X and 46,XN lineages may indicate that both were equally unstable, as more than 70% of the 46,XN lineages had an anomalous karyotype. However, 46,XN had a higher mean PI, suggesting that the amount of cells with a karyotype distinct from 45,X may increase with time in mosaic TS women.

The human gastrointestinal tract is inhabited by trillions of commensal bacteria collectively known as the gut microbiota. Our recognition of the significance of the complex interaction between the microbiota, and its host has grown dramatically over the past years. A balanced microbial community is a key regulator of the immune response, and metabolism of dietary components, which in turn, modulates several brain processes impacting mood and behavior. Consequently, it is likely that disruptions within the composition of the microbiota would remotely affect the mental state of the host. Here, we discuss how intestinal bacteria and their metabolites can orchestrate gut-associated neuroimmune mechanisms that influence mood and behavior leading to depression. In particular, we focus on microbiota-triggered gut inflammation and its implications in shifting the tryptophan metabolism towards kynurenine biosynthesis while disrupting the serotonergic signaling. We further investigate the gaps to be bridged in this exciting field of research in order to clarify our understanding of the multifaceted crosstalk in the microbiota-gut-brain interphase, bringing about a novel microbiota-targeted therapeutics for mental illnesses.

Peritoneal fluid is an ovarian exudate from the growing follicle or corpus luteum. Therefore, the free concentrations of estrogens and progesterone are always much higher than in plasma, especially after ovulation. The peritoneum is not vascularised, and peritoneal implants and the superficial portion of deep endometriosis are likely influenced mainly by peritoneal fluid. Follicular phase progesterone concentrations are as high as during the luteal phase in plasma. This explains that most peritoneal implants are rarely proliferative and out of phase with the endometrium. From some 5 mm of depth onwards, endometriosis is rather influenced by plasma hormone concentra-tions, and the deeper parts can be proliferative as the endometrium. Because of these progesterone concentrations, progesterone resistance has to be postulated, permitting endometriosis lesions to initiate and develop. This opens the discussion of whether endometriosis is similar to the basal endometrium. These peritoneal fluid concentrations are important to understand the natural history and medical therapy of endometriosis. Most medical therapies decrease ovarian function and affect peritoneal fluid steroid hormone concentrations. It is suggested that the efficacy of medical therapy for endometriosis-associated pain is a consequence of the decreased estrogen concentrations in the peritoneal cavity and that the local effect of progestins may not be determinant for pain relief. If this is true, a history of endometriosis should not be considered a contraindication for hormone re-placement therapy.

This review article discusses the involvement of the Brain-Derived Neurotrophic Factor (BDNF) in the control of pain. BDNF, a neurotrophin known for its essential role in neuronal survival and plasticity, has garnered significant attention for its potential implications as a modulator of nociception and pain. This comprehensive review aims to provide insights into the multifaceted interactions between BDNF and pain pathways, encompassing both physiological and pathological pain conditions. I delve into the molecular mechanisms underlying BDNF's involvement in pain processing and discuss potential therapeutic applications of BDNF and its mimetics in managing pain. Furthermore, I highlight recent advancements and challenges in translating BDNF-related research into clinical practice.

In this paper, the authors seek to discuss some of the complexities involved in cross-cultural working in relation to the communication and management of pain in older people. Specifically, the paper addresses the culture construction of ageing and how pain is often constructed as a natural part of ageing. The authors also suggests that with the rise of the ideology of active-ageing many older people who are disabled or living in chronic pain, may feel a moral imperative to hide pain and ill-health. The discussion extends into looking at the impact of culture and the communication of pain, including specific idioms of distress, somaticize and the lay-management of pain through stoicism.

The human gastrointestinal gut contains about 100 trillion of microorganisms including up to 5000 different types of bacteria called the "gut microbiome". Alterations in the composition of gut microorganisms (dysbiosis) can cause threatening for life diseases. This present seeks to evaluate if finally diet and more specifically functional foods affect the intestinal microbiome, and if obesity and the metabolic syndrome (Mets) are associated with the intestinal microbiome. This systematic review was accomplished according to PRISMA guidelines mostly using the key words functional foods, microbiome, obesity, Mets, Mediterranean diet. The search was carried out of recent scien-tific articles from the databases Pubmed, Scopus, and Google Scholar. The most studies discussed in this review showed a potential therapeutic effect of the Mediterranean diet rich in beneficial nutrients, on body weight, fat deposition, in correlation with modulation of the synthesis of gut microbiome. This literature review demonstrates a possible relationship between the metabolites of the microflora, the endotoxemia, obesity and Mets. The role of probiotics, prebiotics, and polyphe-nols in the prevention of obesity and Mets is of high importance in promoting healthy aging. The future challenge is to understand how different dietary patterns can regulate the composition of the gut microflora and whether these changes could be long-term.

Heterocytous cyanobacteria are among the most prolific source of bioactive secondary metabolites, including anabaenopeptins (APTs). A terrestrial filamentous Brasilonema sp. CT11 collected in Costa Rica bamboo forest, as black mat was studied using a multidisciplinary approach: genome mining and HPLC-HRMS/MS coupled with bionformatic analyses. Herein, we report the nearly complete genome consisting 8.79 Mbp with a GC content of 42.4%. Moreover, we report on three novel tryptophane-containing APTs; anabaenopeptin 788 (1), anabaenopeptin 802 (2) and anabaenopeptin 816 (3). Further, the structure of two homologues, i.e., anabaenopeptin 802 (2a) and anabaenopeptin 802 (2b) was determined by spectroscopic analysis (NMR and MS). Both compounds were shown to exert weak to moderate antiproliferative activity against HeLa cell lines. This study also provides the unique and diverse potential of biosynthetic gene clusters and an assessment of the predicted chemical space yet to be discovered from this genus.

Crigler-Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in two forms: CNS type 1 (CNS1), the more severe form with a complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients re-sponding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risks of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interven-tions.

Global public health systems have continuously faced challenges from the advent of novel infectious illnesses, necessitating quick and efficient actions to stop their spread.First discovered in Saudi Arabia in 2012, Middle East respiratory syndrome (MERS) is a viral respiratory disorder caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). Since then, the nation has reported most cases and fatalities related to this sickness, with occasional outbreaks happening in other nations and regions. Severe sickness and high mortality are caused by MERS-CoV, especially in older persons and those with underlying chronic conditions. Through intimate contact, the virus can spread from people to dromedary camels and vice versa. It has sparked multiple epidemics both domestically and abroad in the Middle East, raising the possibility of fatalities and widespread transmission, especially in susceptible groups. The Riyadh region was the main target of the most current MERS-CoV outbreak in Saudi Arabia, which began in 2023 and ended on September 1, 2023, with 312 confirmed cases and ninety-seven fatalities. With the use of published studies and their contributions to the field, we hope to present a thorough overview of the MERS-CoV outbreak in Saudi Arabia in this review of the literature, including its epidemiological investigation, public health response, impact, and lessons learned. In addition to highlighting the importance and continued relevance of this problem, our work suggests ways to lower the risk of MERS-CoV transmission and avert further outbreaks.

Background and Objectives: The complications seen after lower impacted third molar surgery affect the quality of life of the patients. The aim of the study was to investigate the efficacy of a single preoperative dose of deflazacort on pain, swelling and trismus following impacted lower third molar surgery. Materials and Methods: This randomised, prospective, double-blind, split-mouth clinical study included 30 healthy individuals with bilaterally impacted lower third molars that was removed for orthodontic purposes between September 2017 and September 2018. Group 1 was given a placebo (single dose vitamin C tablet) and group 2 was given a single 30 mg dose of deflazacort 1 hour prior to the surgery. Pain was evaluated using the visual analog scale for 1 week postoperatively. Edema (in mm) and trismus (in mm) were evaluated preoperatively and on postoperative days 2 and 7. The Mann-Whitney U test was applied for group analysis. p values < 0.05 were considered statistically significant. Results: When postoperative pain scores were evaluated, a significant difference was found between the groups only at the 6th and 12th hours (p0.05). Even high trismus values were recorded on the 2nd day, it was observed that the trismus resolved on the 7th day. There were no significant differences in trismus between the groups at any time point (p>0.05). Evaluation of swelling showed that there was no statistically significant difference between the study and control groups at any time point (p>0.05). No side effect was detected in both the study and the control groups. Conclusions: This was the first split-mouth study evaluating the anti-inflammatory effect of deflazacort after lower impacted third molar surgery. A single dose of 30 mg deflazacort was shown to be effective in reducing pain at 6 and 12 hours postoperatively.

Migraine and neuropathic pain (NP) are evocative of painful, disabling, chronic conditions which exhibit resembling symptoms and thus considered to share a common etiology. Calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant search for more effective therapeutic targets for pain management. This scoping review overviews human studies of common pathogenic factors in migraine and NP to explore potential novel therapeutic targets. CGRP causes inflammation in the meninges; monoclonal antibodies and inhibitors target CGRP. Gluta-mate-induced hyperexcitability and subsequent sensitization are closely linked to an alteration of the tryptophan (Trp)-kynurenine (KYN) metabolic system; the Trp-KYN system may serve as a potential target. Microglial overaction is observed in migraine and NP; modifying the microglial activity may be a possible approach. Cytokine-induced inflammation is a leading hypothesis of the pathogenesis of the conditions; alleviating neuroinflammation may complement a pain-relieving armamentarium. Transient receptor potential (TRP) ion channels evoke the release of several substances; TRP ion channels may potentially emerge as new targets. The endocannabinoid system plays a major role in the pain trafficking pathway; modification of the system may open a new path toward discovery of new analgesics. Here we highlight the mechanism of those common pathogenic factors to explore therapeutic targets for innovative pain management in migraine and NP.

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

Palmitoylethanolamide (PEA) has been prescribed for neuropathic pain for several years. This study is mainly addressed to summarize what has been published on the topic in the last decades, and how appropriate the numerous prescriptions are. Among others, it examines the innovative EquiPEA^® patent, which aims to address obstacles encountered with conventional PEA formulations. EquiPEA^® seems to partially ameliorate the bioavailability and the targeted distribution. It seems to introduce novel advancements that have the potential to enhance the therapeutic effectiveness of PEA in terms of its anti-inflammatory, antioxidant, and analgesic properties. The deep literature analysis aims to examine the potential advantages of this innovative formulation, in the context of several pathological conditions that may benefit from this molecule. In particular, it investigates the potential enhanced bioavailability and targeted delivery system of EquiPEA^®. Also, it tries to understand if it can modernize the field of therapy based on PEA, thus offering a better treatment option for individuals with long-term inflammation, oxidative stress, and neuropathic or mixed pain with a neuropathic component. The study examines the possible impact of EquiPEA^® on personalized medicine strategies and its potential for translation into clinical practice. It analyses the possibilities that EquiPEA^® has in enhancing patient outcomes in a range of central nervous system and inflammatory conditions. This narrative review makes a valuable contribution to the ongoing comprehension of PEA therapy. It establishes a foundation for further exploration in research and potential uses in clinical settings.

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden as well, if the absolute risk of infection during child-bearing age increases. Dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with low current burden and high transmission intensity. Low or declining rubella virus transmission intensity is concurrently associated with both greater disease burden and greater vaccine effectiveness. The risk of increasing burden through vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase and a large, immediate burden decrease strongly favors RCV introduction.

Abstract: Sand-cement bound screed floor layers are at risk for work-related low back pain, lumbosacral radicular syndrome and knee osteoarthritis given their working technique of level-ling screed with their trunk bended and mainly supported by their hands and knees. To reduce the exposure of the physical demands of bending of the trunk and kneeling, a manually moved screed levelling machine was developed for floor layers in the Netherlands. The aim of this pa-per is to estimate the potential health gain of the manually moved screed levelling machine on the risk of low back pain (LBP), lumbosacral radicular syndrome (LRS) and knee osteoarthritis (KOA) compared to the traditional working technique. The potential health gain was assessed using the epidemiological population estimates of the Population Attributable Fraction (PAF) and the Potential Impact Fraction (PIF) combined with work-related risk estimates for these three disorders from systematic reviews. The percentage of workers exceeding these risk esti-mates was based on worksite observations among in total 28 floor layers. For LBP, 16/18 work-ers were at risk using the traditional working technique with PAF=38%, and for the manually moved screed levelling machine this was 6/10 with PIF=13%. For LRS, these data were 16/18 with PAF=55% and 14/18 with PIF=18% and for KOA, 8/10 with PAF=35% and 2/10 with PIF=26%. A manually moved screed levelling machine might have a significant impact on the prevention of LBP, LRS and KOA among floor layers in the Netherlands and a health impact assessment is a feasible approach to assess health gains in an efficient way.