The Successful Management of Stroke in Evans Syndrome by Anticoagulation with Warfarin, Intravenous Immunoglobulin (IVIG), and High-Dose Corticosteroid.

Evans syndrome (ES) is a rare autoimmune disorder characterised by autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia and autoimmune neutropenia. The precise pathogenesis of ES remains unclear, but it is believed to involve immune-mediated destruction of erythrocytes and platelets. Thrombotic complications, such as stroke, are critical yet largely unrecognised in ES. Here, we present a case of an 80-year-old male with ES who developed multiple strokes, emphasising the complex management challenges associated with this condition. The patient, known for stage IIB lung adenocarcinoma, presented with right-sided weakness and was diagnosed with a stroke of undetermined aetiology. He was started on warfarin for secondary prevention alongside intravenous immunoglobulin (IVIG) and corticosteroids for ES. Stroke in ES is rarely reported, and the optimal management remains inconclusive due to its rarity. The patient's management was guided by existing guidelines for stroke prevention and anticoagulation in the setting of antiphospholipid syndrome. While anticoagulants are recommended for venous thromboembolism prophylaxis in AIHA, there are no clear guidelines for stroke prevention in ES. This case underscores the necessity of individualised treatment approaches and highlights the gaps in evidence regarding stroke management in ES. Future research is essential to determine the optimal management of stroke in this complex clinical scenario. LEARNING POINTS: Evans syndrome is a rare autoimmune disorder characterised by the coexistence of autoimmune haemolytic anaemia and immune thrombocytopenia, which potentially increase venous and arterial thrombotic risk.Managing strokes in Evans syndrome remains challenging due to its rarity and lack of definitive guidelines, necessitating individualised treatment approaches.Future prospective studies are warranted to determine the optimal patient population that needs secondary prevention with anticoagulants following a stroke in the context of Evans syndrome.

Exercise-induced pain within endurance exercise settings: Definitions, measurement, mechanisms and potential interventions.

Pain can be defined as an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage. Though consistent with this definition, different types of pain result in different behavioural and psychophysiological responses. For example, the transient, non-threatening, acute muscle pain element of exercise-induced pain (EIP) is entirely different from other pain types like delayed onset muscle soreness, muscular injury or chronic pain. However, studies often conflate the definitions or assume parity between distinct pain types. Consequently, the mechanisms through which pain might impact exercise behaviour across different pain subcategories may be incorrectly assumed, which could lead to interventions or recommendations that are inappropriate. Therefore, this review aims to distinguish EIP from other subcategories of pain according to their aetiologies and characteristics, thereby providing an updated conceptual and operational definition of EIP. Secondly, the review will discuss the experimental pain models currently used across several research domains and their relevance to EIP with a focus on the neuro-psychophysiological mechanisms of EIP and its effect on exercise behaviour and performance. Finally, the review will examine potential interventions to cope with the impact of EIP and support wider exercise benefits. HIGHLIGHTS: What is the topic of this review? Considerations for future research focusing on exercise-induced pain within endurance exercise settings. What advances does it highlight? An updated appraisal and guide of research concerning exercise-induced pain and its impact on endurance task behaviour, particularly with reference to the aetiology, measurement, and manipulation of exercise-induced pain.

Traumatic Penile Injury: An Analysis of the Patient Age with Aetiological Type and Injury Severity in a Single Centre.

BACKGROUND: Penile trauma is associated with debilitating complications. Apart from its sparse literature, contextually relevant evidence on aetiology and standardized severity grading, and its stratification by legal age are needed. This study aimed to describe the frequency, aetiology and injury severity grade of patients, and explore the association of specific factors by legal age. SUBJECTS, MATERIALS AND METHODS: A single-centre retrospective cross-sectional study was conducted in our centre. Male patients with penile trauma managed by urologists were included. Data on age, year of presentation, aetiology, penile injury extent and co-existing genitourethral injuries were obtained. Descriptive and inferential statistics were undertaken using SPSS and MedCalc. Pvalue < 0.05 was considered significant. RESULTS: Forty-two patient records were analyzed. The median age and interquartile range for legal minors and legal adults were 9.5 (5.0-14.8) years and 31.0 (22.5-41.0) years, and they constituted 28.6% (n=12) and 71.4% (n=30) of the study population respectively. Penile trauma was isolated in 26.2% (n=11) of the total population.Its annual frequency was below the median volume between 2001 and 2008 but shifted to a rate above the average level between 2017 and 2021. The rate of conveyor belt-related aetiology and high-grade trauma was 41.7% and 75.0% in legal minors while it was 26.1% and 53.3% respectively in legal adults. CONCLUSIONS: Grade IV trauma was the most predominant while conveyor belt injury was the most common cause of the injury. Albeit limitations of statistical comparison, the rate of conveyor belt injury and high-grade trauma was numerically high in legal minors.

CONTEXTE: Les traumatismes du pénis sont associés à des complications débilitantes. Outre la rareté de la littérature, des preuves contextuel l ement per tinentes sur l ' étiol ogie et l a classification standardisée de la gravité, ainsi que leur stratification par âge légal, sont nécessaires. Cette étude visait à décrire la fréquence, l'étiologie et le degré de gravité des blessures des patients, et à explorer l'association de facteurs spécifiques par âge légal. SUJETS, MATÉRIELS ET MÉTHODES: Une étude rétrospective transversale monocentrique a été réalisée dans notre centre. Les patients masculins ayant subi un traumatisme pénien pris en charge par des urologues ont été inclus. Les données sur l'âge, l'année de présentation, l'étiologie, l'étendue de la blessure pénienne et les blessures génito-urétrales coexistantes ont été obtenues. Des statistiques descriptives et inférentielles ont été réalisées à l'aide de SPSS et MedCalc. Une valeur de p < 0,05 a été considérée comme significative. RÉSULTATS: Quarante-deux dossiers de patients ont été analysés. L'âge médian et l'intervalle interquartile pour les mineurs légaux et les adultes légaux étaient de 9,5 (5,0-14,8) ans et 31,0 (22,5-41,0) ans, représentant respectivement 28,6 % (n=12) et 71,4 % (n=30) de la population étudiée. Le traumatisme pénien était isolé chez 26,2 % (n=11) de la population totale. Sa fréquence annuelle était inférieure au volume médian entre 2001 et 2008, mais a dépassé le niveau moyen entre 2017 et 2021. Le taux d'étiologie liée aux tapis roulants et de traumatismes graves était de 41,7 % et 75,0 % chez les mineurs légaux, contre 26,1 % et 53,3 % respectivement chez les adultes légaux. CONCLUSIONS: Le traumatisme de grade IV était le plus prédominant, tandis que les blessures causées par les tapis roulants étaient la cause la plus courante de lésion. Bien que limitées par des comparaisons statistiques, les taux de blessures par tapis roulant et de traumatismes graves étaient numériquement élevés chez les mineurs légaux. MOTS-CLÉS: Facteurs d'âge, Étiologie, Score de gravité des blessures, Pénis.

Etiology-specific incidence and mortality of diarrheal diseases in the African region: a systematic review and meta-analysis.

BACKGROUND: Diarrheal diseases substantially affect public health impact in low- and middle-income countries (LMIC), particularly in Africa, where previous studies have indicated a lack of comprehensive data. With a growing number of primary studies on enteric infections in Africa, this study aimed to estimate the incidence and mortality of diarrheal pathogens across all ages in Africa in the year 2020. We also explored different methodological assumptions to allow comparison with other approaches. METHODS: Through a systematic review and meta-analysis of data from African LMICs, we estimated the etiology proportions for diarrheal diseases and deaths. We combined the etiology proportions with incidence data collected from a population survey in Africa from 2020 and mortality data from the Global Health Observatory of WHO. RESULTS: We estimated 1,008 billion diarrhea cases (95% UI 447 million-1,4 billion) and 515,031 diarrhea deaths (95% UI 248,983-1,007,641) in the African region in 2020. In children under five, enteroaggregative E. coli (EAEC) (44,073 cases per 100,000 people, 95% UI 18,818 - 60,922) and G. lamblia (36,116 cases per 100,000 people, 95% UI 15,245 - 49,961) were the leading causes of illness. Enteroinvasive E. coli (EIEC) (155 deaths per 100,000 people, 95% UI 106.5-252.9) and rotavirus (61.5 deaths per 100,000 people, 95% UI 42.3-100.3) were the primary causes of deaths. For children over five and adults, Salmonella spp. caused the largest number of diarrheal cases in the population of children ≥ 5 and adults (122,090 cases per 100,000 people, 95% UI 51,833 - 168,822), while rotavirus (16.4 deaths per 100,000 people, 95% UI 4.2-36.7) and enteroaggregative E. coli (EAEC) (14.6 deaths per 100,000 people, 95% UI 3.9-32.9) causing the most deaths. Geographically, the highest incidence of diarrhea was in Eastern Africa for children under five (114,389 cases per 100,000 people, 95% UI 34,771 - 172,884) and Central Africa for children over five and adults (117,820 cases per 100,000 people, 95% UI 75,111-157,584). Diarrheal mortality was highest in Western Africa for both children below five and above (children < 5: 194.5 deaths per 100,000 people, 95% UI 120-325.4; children ≥ 5 and above: 33.5 deaths per 100,000 people, 95% UI 12.9-75.1). CONCLUSION: These findings provide new information on the incidence and mortality of sixteen pathogens and highlight the need for surveillance and control of diarrheal infectious diseases in Africa. The cause-specific estimates are crucial for prioritizing diarrheal disease prevention in the region.

Sex ratio and age of onset in AQP4 antibody-associated NMOSD: a review and meta-analysis.

BACKGROUND: Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data. METHODS: A systematic search of databases was conducted according to the PRISMA guidelines. Articles reporting sex distribution and age of onset for AQP4 antibody-associated NMSOD were reviewed. An initially inclusive approach involving exploration with regression meta-analysis was followed by an analysis of just AQP4 antibody positive cases. RESULTS: A total of 528 articles were screened to yield 89 articles covering 19,415 individuals from 88 population samples. The female:male sex ratio was significantly influenced by the proportion of AQP4 antibody positive cases in the samples studied (p < 0.001). For AQP4 antibody-positive cases the overall estimate of the sex ratio was 8.89 (95% CI 7.78-10.15). For paediatric populations the estimate was 5.68 (95% CI 4.01-8.03) and for late-onset cases, it was 5.48 (95% CI 4.10-7.33). The mean age of onset was significantly associated with the mean life expectancy of the population sampled (p < 0.001). The mean age of onset for AQP4 antibody-positive cases in long-lived populations was 41.7 years versus 33.3 years in the remainder. CONCLUSIONS: The female:male sex ratio and the mean age of onset of AQP4 antibody-associated NMOSD are significantly higher than MS. The sex ratio increases with the proportion of cases that are positive for AQP4 antibodies and the mean age of onset increases with population life expectancy.

Aetiology and predictors of outcome in non-shockable in-hospital cardiac arrest: A retrospective cohort study from the Swedish Registry for Cardiopulmonary Resuscitation.

BACKGROUND: Non-shockable in-hospital cardiac arrest (IHCA) is a condition with diverse aetiology, predictive factors, and outcome. This study aimed to compare IHCA with initial asystole or pulseless electrical activity (PEA), focusing specifically on their aetiologies and the significance of predictive factors. METHODS: Using the Swedish Registry of Cardiopulmonary Resuscitation, adult non-shockable IHCA cases from 2018 to 2022 (n = 5788) were analysed. Exposure was initial rhythm, while survival to hospital discharge was the primary outcome. A random forest model with 28 variables was used to generate permutation-based variable importance for outcome prediction. RESULTS: Overall, 60% of patients (n = 3486) were male and the median age was 75 years (IQR 67-81). The most frequent arrest location (46%) was on general wards. Comorbidities were present in 79% of cases and the most prevalent comorbidity was heart failure (33%). Initial rhythm was PEA in 47% (n = 2702) of patients, and asystole in 53% (n = 3086). The most frequent aetiologies in both PEA and asystole were cardiac ischemia (24% vs. 19%, absolute difference [AD]: 5.4%; 95% confidence interval [CI] 3.0% to 7.7%), and respiratory failure (14% vs. 13%, no significant difference). Survival was higher in asystole (24%) than in PEA (17%) (AD: 7.3%; 95% CI 5.2% to 9.4%). Cardiopulmonary resuscitation (CPR) durations were longer in PEA, 18 vs 15 min (AD 4.9 min, 95% CI 4.0-5.9 min). The duration of CPR was the single most important predictor of survival across all subgroup and sensitivity analyses. Aetiology ranked as the second most important predictor in most analyses, except in the asystole subgroup where responsiveness at cardiac arrest team arrival took precedence. CONCLUSIONS: In this nationwide registry study of non-shockable IHCA comparing asystole to PEA, cardiac ischemia and respiratory failure were the predominant aetiologies. Duration of CPR was the most important predictor of survival, followed by aetiology. Asystole was associated with higher survival compared to PEA, possibly due to shorter CPR durations and a larger proportion of reversible aetiologies.

Metabolic dysfunction-associated steatotic liver disease has become the most common cause of hepatocellular carcinoma in Sweden: A nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, and can lead to hepatocellular carcinoma (HCC), a leading cause of cancer-related death. We aimed to determine the extent to which MASLD is an increasing cause of HCC in Sweden and to determine clinical characteristics associated with underlying MASLD. Using the Swedish quality registry for liver cancer (SweLiv), we identified all adults with a diagnosis of HCC in Sweden between 2012 and 2018. Baseline data were retrieved from SweLiv and other nationwide registers. Totally, 3494 patients with HCC were identified. Of them, 757 patients (22%) had MASLD-HCC. The proportion with MASLD-HCC increased from 19% in 2012 to 25% in 2018 (ptrend = 0.012), and MASLD was since 2017 the leading cause of HCC, surpassing hepatitis C. MASLD was the fastest growing cause of HCC with a 33% increment during the study period. Compared to other patients with HCC, those with MASLD-HCC were older (75 vs. 67 years, p < .001), less commonly had cirrhosis (61% vs. 82%, p < .001), had larger tumours (median 5.5 vs. 4.3 cm, p < .001), and more often extrahepatic metastasis (22% vs. 16%, p < .001). Patients with HCC caused by MASLD or by other causes were equally likely to be diagnosed in an early stage (Barcelona Clinic Liver Cancer 0-A, 27% vs. 30%, p = .129). MASLD is now the leading cause of HCC in Sweden.

Therapeutic potential and recent progression of BTK inhibitors against rheumatoid arthritis.

Rheumatoid arthritis (RA) is a complex chronic inflammatory illness that affects the entire physiology of human body. It has become one of the top causes of disability worldwide. The development and progression of RA involves a complex interplay between an individual's genetic background and various environmental factors. In order to effectively manage RA, a multidisciplinary approach is required, as this disease is complicated and its pathophysiological mechanism is not fully understood yet. In majority of arthritis patients, the presence of abnormal B cells and autoantibodies, primarily anti-citrullinated peptide antibodies and rheumatoid factor affects the progression of RA. Therefore, drugs targeting B cells have now become a hot topic in the treatment of RA which is quite evident from the recent trends seen in the discovery of various B cell receptors (BCRs) targeting agents. Bruton's tyrosine kinase (BTK) is one of these recent targets which play a role in the upstream phase of BCR signalling. BTK is an important enzyme that regulates the survival, proliferation, activation and differentiation of B-lineage cells by preventing BCR activation, FC-receptor signalling and osteoclast development. Several BTK inhibitors have been found to be effective against RA during the in vitro and in vivo studies conducted using diverse animal models. This review focuses on BTK inhibition mechanism and its possible impact on immune-mediated disease, along with the types of RA currently being investigated, preclinical and clinical studies and future prospective.

Enhanced liver fibrosis (ELF) score predicts hepatic decompensation and mortality.

Background & Aims: In community pathways for detection of liver disease the most common reason for referral is fibrosis assessment. We investigated the impact of adding the Enhanced Liver Fibrosis (ELF) score as a second-line test (subsequent to an indeterminate or high Fibrosis-4 index [FIB-4] and/or non-alcoholic fatty liver disease fibrosis score) to guide referral and prognostication in our multi-aetiology pathway. Methods: Patients with ELF results from the intelligent Liver Function Testing (iLFT) pathway were recruited. Case note review was undertaken to compare ELF with endpoints of cirrhosis, hepatic decompensation, and mortality (liver-related and all-cause death). Results: In total, 1,327 individuals were included with a median follow-up of 859 days and median ELF score of 10.2. Overall sensitivity for cirrhosis at the 9.8 threshold was 94% (100% for metabolic-associated steatotic liver disease, 89% for alcohol-related liver disease). Determination of the ELF score as a second-line test reduced the referral rate by 34%. ELF scores predicted hepatic outcomes; each unit change was associated with increased decompensation (adjusted Hazard Ratio [aHR] 2.215, 95% CI: 1.934-2.537) and liver-related mortality (aHR 2.024, 95% CI: 1.674-2.446). ELF outperformed FIB-4 for risk of liver-related mortality, particularly in the short-term (area under the curve [AUC] 94.3% vs. 82.8% at six months). Where FIB-4 was indeterminate, ELF had higher AUC for all outcomes within at least 2 years. ELF ≥13 was associated with particularly high rates of decompensation (26% within 90 days) and all-cause mortality (38% at 1 year). Conclusions: The addition of ELF reduced the number of individuals referred for fibrosis assessment following iLFT pathway testing and provided useful prognostic information. Individuals with ELF scores ≥13 were considered at high-risk of negative outcomes warranting urgent clinical assessment. Impact and implications: Primary care pathways for suspected liver disease are increasingly common and often lead to increased specialist hepatology referrals for fibrosis assessment. This study, using clinical follow-up for liver-related outcomes, provides further evidence supporting ELF testing to safely reduce referrals in a two-step approach when combined with other simple fibrosis markers. Additionally, ELF scores predict liver-related morbidity and mortality, with ELF scores ≥13 indicating particularly high-risk patients. This study may help inform the implementation of diagnostic pathways for early detection of liver disease and highlights the need for urgent review of individuals with very high ELF scores.

Immersive virtual reality as a novel approach to investigate the association between adverse events and adolescent paranoid ideation.

PURPOSE: Paranoid ideation is common among adolescents, yet little is known about the precursors. Using a novel immersive virtual reality (VR) paradigm, we tested whether experiences of bullying, and other interpersonal/threatening events, are associated with paranoid ideation to a greater degree than other types of (i) non-interpersonal events or (ii) adverse childhood experiences. METHODS: Self-reported exposure to adverse life events and bullying was collected on 481 adolescents, aged 11-15. We used mixed effects (multilevel) linear regression to estimate the magnitude of associations between risk factors and paranoid ideation, assessed by means of adolescents' reactions to ambiguously behaving avatars in a VR school canteen, adjusting for putative confounders (gender, year group, ethnicity, free school meal status, place of birth, family mental health problems). RESULTS: Lifetime exposure to interpersonal/threatening events, but not non-interpersonal events or adverse circumstances, was associated with higher levels of state paranoid ideation, with further evidence that the effect was cumulative (1 type: ϐadj 0.07, 95% CI -0.01-0.14; 2 types: ϐadj 0.14, 95% CI 0.05-0.24; 3 + types: ϐadj 0.24, 95% CI 0.12-0.36). More tentatively, for girls, but not boys, recent bullying was associated with heightened paranoid ideation with effect estimates ranging from ϐadj 0.06 (95% CI -0.02-0.15) for physical bullying to ϐadj 0.21 (95% CI 0.10-0.32) for cyber bullying. CONCLUSIONS: Our data suggest a degree of specificity for adversities involving interpersonal threat or hostility, i.e. those that involve unwanted interference and/or attempted control of an individual's personal boundaries being associated with heightened levels of state paranoid ideation among adolescents.

Genetic intratumour heterogeneity and clonal evolution in extramammary Paget's disease.

All tumour cells in a patient have shared and non-shared genetic alterations, and the diversity of mutations is described as intratumoural heterogeneity (ITH). Multiregion sequencing is a genome sequencing analytical technique used for multiple, spatially-separated biopsy tissues that may further our understanding of ITH and tumour evolution. Although genetic mutations in extramammary Paget's disease (EMPD) have recently been detected by next-generation sequencing analysis, there have been no reports of ITH based on multiregion sequencing in EMPD. Thus, we clarified the landscape of ITH and tumour evolution in EMPD. We performed whole-exome sequencing on 35 tissues (30 tumour tissues and five normal skin samples as a paired control), collected from five patients with EMPD. The rate of private mutations was significantly higher than that of ubiquitous and shared mutations. Ubiquitous mutations were not present in driver genes, and most driver genes exhibited private and shared mutations. The most frequent base substitution was C>T in almost all lesions, and most mutational signatures corresponded to signature 1, 2, 3, and 8. The types of proposed aetiology in most lesions were based on age and AID/APOBEC family and BRCA1/BRCA2 mutations. Evolutionary trees were characterized by short trunks and long branches due to the extremely high ratio of private mutations. In contrast, pathogenic factors, such as base substitutions, mutational signatures, and proposed aetiology, were shared. Tumour evolution in EMPD appears to be characterized by a high level of genetic ITH with shared background factors.

Clinical characteristics and phylogenetic analysis of human enteric adenovirus type 41 (HAdV-F41) from children with gastroenteritis during SARS-CoV-2 pandemic.

Human adenovirus type 41 (HAdV-F41) usually causes pediatrics gastroenteritis. However, it was reported to be associated with the outbreaks of severe acute hepatitis of unknown aetiology (SAHUA) in pediatrics during COVID-19 pandemic. In this study, we investigated the prevalence of enteric HAdV-F41 in 37,920 paediatric gastroenteritis cases from 2017 to 2022 in Guangzhou, China. All children presented were tested negative for SARS-CoV-2 during the "zero-COVID" period. The main clinical symptom of the children was diarrhea (96.5%). No fatalities nor liver abnormal symptoms was found. In 2021, one year since the pandemic of COVID-19, the prevalence of HAdV-F41 abruptly increased from 3.71% to 8.64% (P < 0.001). All of HAdV-F41 circulating worldwide were classified into eight different subtypes (G1-G8) based on the phylogenetic clustering permutation of the four capsid genes of HAdV-F41. G3 was the predominant subtype (56.2%; 77/137). CRV5 isolates from SAHUA cases belong to this subtype, in which N312D and H335D mutations in the short fiber knob were identified in both Guangzhou and CRV5 isolates, presumably changing the virus tropism by directly interacting with the heparin sulfate (HS) receptor. Additionally, a novel recombinant G6 subtype, which is unique and only circulating in China was first identified in this study. This is the first study highlighting the prevalence of HAdV-F41 in paediatric cases of gastroenteritis during COVID-19 pandemic in China. The clinical and viral evolution finding of HAdV-F41 provide insight into the clinical characteristics of children with HAdV-F41 infections as well as the uncertain role of HAdV-F41 in the cause of SAHUA.

Exploring Temporomandibular Disorders (TMDs) and Occlusion Debate in Dentistry: Biting Into Controversy.

Some conditions known as temporomandibular disorders (TMDs) affect surrounding muscles and jaw joints. In dentistry, there has been discussion and research on the connection between TMDs and occlusion, which is how the upper and lower teeth meet. Although some dental experts have proposed a direct link between TMDs and occlusion, the specifics of this relationship are still unclear and have many facets. More particularly, the research facets of "occlusion" remain one of the most contentious subjects in TMDs. This abstract aims to provide an overview of TMDs and occlusion, summarizing the key points from the literature. The etiological factors contributing to the TMDs, including occlusal, psychological, and hormonal factors, are also analyzed. The second part of the article includes the concept of malocclusion, emphasizing its significance in masticatory function and overall health. Anterior open and posterior open bites and the potential influence of occlusal factors on TMDs are elucidated.

Deciphering the Complex Immunopathogenesis of Alopecia Areata.

Alopecia areata (AA) is an autoimmune-mediated disorder in which the proximal hair follicle (HF) attack results in non-scarring partial to total scalp or body hair loss. Despite the growing knowledge about AA, its exact cause still needs to be understood. However, immunity and genetic factors are affirmed to be critical in AA development. While the genome-wide association studies proved the innate and acquired immunity involvement, AA mouse models implicated the IFN-γ- and cytotoxic CD8+ T-cell-mediated immune response as the main drivers of disease pathogenesis. The AA hair loss is caused by T-cell-mediated inflammation in the HF area, disturbing its function and disrupting the hair growth cycle without destroying the follicle. Thus, the loss of HF immune privilege, autoimmune HF destruction mediated by cytotoxic mechanisms, and the upregulation of inflammatory pathways play a crucial role. AA is associated with concurrent systemic and autoimmune disorders such as atopic dermatitis, vitiligo, psoriasis, and thyroiditis. Likewise, the patient's quality of life (QoL) is significantly impaired by morphologic disfigurement caused by the illness. The patients experience a negative impact on psychological well-being and self-esteem and may be more likely to suffer from psychiatric comorbidities. This manuscript aims to present the latest knowledge on the pathogenesis of AA, which involves genetic, epigenetic, immunological, and environmental factors, with a particular emphasis on immunopathogenesis.

Fournier's gangrene originating from the perianal region or the urogenital area: does it make a difference?

OBJECTIVE: Fournier's gangrene (FG) is a rare and serious disorder which is associated with high mortality. In the literature, there is no study evaluating clinician-, patient- and disease-related factors affecting disease outcomes according to aetiological variation in FG. In our study, laboratory results and Uludag Fournier's Gangrene Severity Index (UFGSI) score, clinical characteristics and mortality rates were compared between FG originating from perianal or from urogenital regions. METHOD: Platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) and UFGSI risk scores were calculated in patients with FG at presentation to the emergency department. The patients were assigned to two groups according to FG aetiology. RESULTS: It was observed that the number of debridement interventions and the need for colostomy were significantly greater in the perianal FG group, while the need for flap or reconstruction was significantly (p=0.002) higher in the genitourinary FG group. No significant difference was detected in mortality between groups and the difference in aetiology had no significant effect on the results of the neutrophil-to-lymphocyte ratio, LRINEC or UFGSI scores. CONCLUSION: Laboratory results and UFGSI score were helpful in assessing disease severity independently from aetiology. The higher number of debridement interventions to protect anal function in the perianal group and the greater need for reconstructive surgery in the urogenital group were identified as factors that prolonged length of hospital stay.

Uncommon pathogens causing infective endocarditis.

Infective endocarditis is caused by a wide range of aetiological agents. The microbiology, epidemiology, and treatment of this disease have changed considerably in the last two decades. Staphylococci and streptococci are known to be the classical causative agents; however, blood culture-negative endocarditis caused by fastidious and slow-growing organisms is now common. The list of uncommon pathogens causing endocarditis has expanded in recent years. This is a narrative literature review of the aetiological agents of endocarditis that are rarely encountered in clinical practice, their epidemiology, the characteristics of these pathogens, the clinical presentations of the cases, and their management.

Effect of a powered and a manual toothbrush in subjects susceptible to gingival recession: A 36-month randomized controlled clinical study.

OBJECTIVE: The objective of this long-term clinical study was to evaluate the influence of a newly developed powered toothbrush (PT) on the size and number of pre-existing gingival recessions (GR) in comparison to a manual toothbrush (MT). METHODS: This was a prospective, single-blind, parallel-group, randomized controlled clinical study. Participants without periodontitis, but with at least two teeth (index teeth) showing GR ≥2 mm were randomized to brush either twice daily with a MT or with a PT with a linear magnetic drive causing the round brush head to produce gentle micro vibrations along with oscillating-rotating movements. Primary outcome parameter was the mean change of GR at the index teeth over 36 months. RESULTS: Totally 87 out of 92 participants completed the study (MT/PT: n = 42/n = 45). At the 36-month evaluation the mean (standard deviation) change of GR at index teeth differed significantly between MT 0.17 (0.77) and PT -0.10 (0.63) (p = 0.013). Furthermore, the amount of GR sites which improved ≥1 mm or remained stable during the study period did not differ between MT and PT, but the number of sites worsened ≥1 mm was significantly in favour for PT (MT 23 (25.5%) versus PT 10 (10.6%); p = 0.009). A binary logistic regression identified tooth type (OR = 2.991 for pre-/molar (1.096 [95% CI 1.002-8.933]; p = 0.050)) and manual brushing (OR = 3.341 (1.206 [95% CI 1291-8648]; p = 0.013)) as risk factors for recession impairment at the index teeth. There were no differences between groups for adverse events. CONCLUSION: In a population with pre-existing gingival recessions and consequently a high risk of developing further recession the PT seems to be favourable with regard to further development of GR.

The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

BACKGROUND: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. METHODS: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. RESULTS: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). CONCLUSIONS: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

High percentage of midpiece defects in Brangus bull sperm with no reduction in sperm kinematics.

The study investigated midpiece defects in sperm from a 5-year-old Brangus bull with a high rate of semen batch rejection, due to morphologically abnormal sperm, with no reduction in sperm kinematics. A comprehensive evaluation was conducted over a 16-month period, involving 28 ejaculates. Notably, despite the high proportion of midpiece defects (average 37.73%, from 3% to 58%), the study revealed stable sperm production, with no discernible differences in the kinematic data before and after cryopreservation. Electron microscopy identified discontinuities in the mitochondrial sheath, characteristic of midpiece aplasia (MPA). The anomalies were attributed to be of genetic origin, as other predisposing factors were absent. Additionally, the electron microscopy unveiled plasma membrane defects, vacuoles and chromatin decondensation, consistent with previous findings linking acrosome abnormalities with midpiece defects. The findings underscored the necessity of conducting thorough laboratory evaluations before releasing cryopreserved semen for commercialization. Despite substantial morphological alterations, the initial semen evaluation data indicated acceptable levels of sperm kinematics, emphasizing the resilience of sperm production to severe morphological changes. This case report serves as a contribution to the understanding of midpiece defects in bull sperm, emphasizing the need for meticulous evaluation and quality control in semen processing and commercialization.

Narrative review of occupational exposures and noncommunicable diseases.

OBJECTIVE: Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities. METHODS: We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality. RESULTS: We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels. CONCLUSIONS: By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.