Prompt response to rituximab in a patient with resistant polymyositis with complications of dysphagia and dysphonia: a case report.

Introduction and importance: Polymyositis is an inflammatory process, primarily affecting proximal muscles, characterized by elevated muscle enzymes and distinctive electromyography patterns. Case presentation: The authors present a case of a 33-year-old male patient experiencing complications of polymyositis, including pharyngeal and laryngeal involvement leading to dysphagia and dysphonia. Steroids and intravenous immunoglobulin (IVIG) therapy proved ineffective. Subsequently, rituximab was administered, resulting in significant improvement in dysphagia, dysphonia, and proximal muscles within 3 days of the initial rituximab dose. Additionally, there was a remarkable decrease in creatine phosphokinase (CPK) levels. Clinical discussion: Immune-mediated myopathies (IMM) are rare diseases characterized by muscle inflammation and weakness. This case of probable polymyositis, diagnosed through clinical features and elevated CPK, was complicated by the patient's lack of response to glucocorticoids and IVIG therapy. Remarkably, rituximab treatment led to rapid improvement in muscle strength and symptoms, highlighting its potential effectiveness in refractory cases of polymyositis. Conclusions: Primary treatment for cases of polymyositis typically involves the use of glucocorticoids. However, approximately half of the patients do not respond adequately to corticosteroids alone. Alternatives, in such cases, encompass IVIG therapy and rituximab.

Intermanufacturer assessment of diagnostic performance of angiogenic ratio vs glycosylated fibronectin in women with suspected pre-eclampsia.

OBJECTIVE: To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio with that of a point-of-care test for glycosylated fibronectin (GlyFn) in women with suspected pre-eclampsia (PE). METHODS: This was a prospective, single-center, double-blinded, non-interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt-1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo-Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (Diabetomics). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt-1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt-1/PlGF ratio was classified as high or low using platform-specific thresholds equivalent to a Roche sFlt-1/PlGF ratio of 38, which were derived using Passing-Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 µg/mL and 510 µg/mL). RESULTS: Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty-eight (37.3%) women had a sFlt-1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt-1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt-1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 µg/mL and > 510 µg/mL, respectively. The negative predictive value (NPV) of the sFlt-1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 µg/mL and > 510 µg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt-1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 µg/mL and > 510 µg/mL. CONCLUSIONS: The predictive performance of different manufacturers' assays for the sFlt-1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt-1/PlGF ratio and GlyFn using a cut-off of 263 µg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Efficacy of BRAF/MEK-inhibitor therapy for epithelioid glioblastoma with a novel BRAFV600 mutation.

Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs' presence in the patient's cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.

Tick-borne pathogens isolated from ticks, rodents, and a shrew in Gangwon and Gyeonggi provinces in the Republic of Korea.

The prevalence of tick-borne pathogens (TBP), Orientia tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals, namely wild rodents, is now widely investigated. This study is to present the prevalence and distribution of O. tsutsugamushi, Rickettsia and Borrelia spp. in wild small animals and ticks collected from Gyeonggi and Gangwon provinces, Republic of Korea (ROK) in 2014. A total of 131 wild small animals, rodents and shrews, and 2,954 ticks were collected from Gyeonggi and Gangwon provinces from May to November 2014. The wild small animals (KR1-9) and ticks (K1-17) were grouped in accordance with capture dates and locations. Among the wild small animals, a total of 393 tissues and blood samples were extracted from six selected small animal series (KR1-3, KR6-8). Also, each date and location-grouped ticks were identified for its species and pooled according to the stage of development. Molecular identification for Rickettsia, Orientia, and Borrelia species was performed using polymerase chain reaction (PCR). To detect TBPs among wild small animals and ticks, primer sets targeting the 56 kDa protein encoding gene of Orientia spp., outer membrane protein B gene (OmpB) of Rickettsia spp., and 5S-23S intergenic spacer region (IGS) gene of Borrelia spp. were used. Of the 393 wild small animals' blood and tissue samples, 199 (50.6%) were positive for Orientia spp., 158 (40.2%) were positive for Borrelia spp., and 55 (14.0%) were positive for Rickettsia spp. Moreover, a total of 14 tick pools (n = 377) was positive for Rickettsia spp. (n=128, 34.0%) and Borrelia spp. (n=33, 8.8%). High prevalence of Orientia spp. and Rickettsia spp. in rodents and shrews were observed. This study presents significant insights by presenting data collected in 2014 that the prevalence of TBP was already high in mid 2010s. This study highlights the sustainable routine surveillance model for TBP.

[Clinical systematics of chronic delusional psychoses in schizophrenia and schizophrenia-spectrum pathology]. / Klinicheskaya sistematika khronicheskikh bredovykh psikhozov pri shizofrenii i patologii shizofrenicheskogo spektra.

OBJECTIVE: To develop a systematics of chronic delusional psychoses in schizophrenia and pathology of the schizophrenic spectrum that takes into account psychopathological structure (the mechanism of delusional formation) and the trajectories of the disease course (the ratio of negative/positive dimensions). MATERIAL AND METHODS: The study sample was recruited from the large Moscow psychiatric hospital in 2019-2024 and included 126 patients (94 male, 32 female, mean age 36.5±12.1 years) hospitalized with ICD-10 diagnosis of paranoid schizophrenia (F20.00) or delusional disorder (F22). A clinical-psychopathological method was used. RESULTS: The study identifies three variants of paranoid domains, the typology of which takes into account both the psychopathological structure and the trajectories of their development, which determine the dominance of predominantly negative or positive symptoms throughout the disease: 1) psychosis with delusional interpretations and predominant orientation of symptoms towards the negative pole of the schizophrenia psychopathology (n=37, 29.4%); 2) psychosis with hallucinatory delusions and predominant direction of symptoms towards the positive pole of the schizophrenia psychopathology (n=50, 39.7%); and 3) «combined¼ hallucinatory-delusional psychosis with a simultaneous orientation of symptoms to the negative/positive poles of the schizophrenia psychopathology (n=39, 30.9%). Detailed phenomenological characteristics of each of the three presented variants are given. CONCLUSION: The developed three-component taxonomy confirms, on the model of chronic delusional psychoses appearing in schizophrenia and the pathology of the schizophrenia spectrum, the concept of simultaneous representation of two relatively independent domains determined by neurobiological processes in the schizophrenia psychopathology positive and negative disorders.

[Anxiety-depressive disorders in patients before and in the long terms after aortic replacement]. / Trevozhno-depressivnye rasstroistva u patsientov do i v otdalennye sroki posle protezirovaniya aorty.

OBJECTIVE: To study the structure and dynamics of anxiety-depressive disorders in patients with dissection/aneurysm of the ascending aorta and aortic arch before and in the long term after surgical treatment and to identify factors associated with disturbances in psycho-emotional status. MATERIAL AND METHODS: We examined 124 patients with dissection/aneurysm of the ascending aorta and arch before and in the long-term period after aortic replacement, assessing anxiety and depression using the Generalized Anxiety Disorder (GAD-7) and Beck Depression Questionnaires. Multivariate regression analysis was used to identify factors associated with clinically significant anxiety and depressive disorders. RESULTS: Average scores on the GAD and the depression scale before surgery decreased from 6.5 (4.0-9.0) and 12.0 (8.0-16.0) to 3.0 (2.0-5.0) and 6.0 (3.0-10.0) (p<0.05) respectively, in the long-term postoperative period. There was no significant decrease in the proportion of patients with clinically significant levels of GAD and depression (p>0.05). Before surgery, clinically significant anxiety and depressive disorders are associated with older age, chronic cerebrovascular insufficiency (CCI) and atrial fibrillation (AF) in the hospital period. After surgery, clinically significant GAD was associated with older age, CCI, and a history of stroke. Depressive disorders were associated with older age and a history of stroke. CONCLUSION: In all patients with aortic disease, GAD and depression of varying severity are recorded; clinically significant GAD and depression are recorded in 19.2 and 23.2% of cases. In the long-term postoperative period, there is no significant decrease in the proportion of patients with clinically significant levels of GAD and depression, which amounted to 10.1 and 13.1%. Clinically significant anxiety and depressive disorders before and after surgery are associated with older age and the history of cerebrovascular disorders. In addition, the baseline clinically significant anxiety and depressive disorders showed an association with the subsequent development of AF in the early postoperative period.

Unmet Surgical Need among Adults in A Mixed Urban-Rural Community in Nigeria: A Survey of 1,993 Adults Using the Sosas Survey Tool.

INTRODUCTION: Community-based prevalence studies are known to be more accurate than hospital-based records. However, such community-based prevalence studies are uncommon in low- and middle-income countries including Nigeria. Allocation of resources and prioritization of health care needs by policy makers require data from such community-based studies to be meaningful and sustainable. This study aims to assess the prevalence of common surgical conditions amongst adults in Nigeria. METHODS: A descriptive cross-sectional community-based study to determine the prevalence of congenital and acquired surgical conditions in adults in a mixed rural-urban area of Lagos was conducted. The study population comprised resident members in the Ikorodu Local Government Area (LGA) of Lagos State. Data was collected using a modified version of the interviewer-administered questionnaire, the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey tool. Data was analysed using the REDCap analytic tool. RESULTS: Eight hundred and fifty-six households were surveyed with a yield of 1,992 adults. There were 95 adults who complained of surgical conditions giving a prevalence rate of 5%. Vast majority of reported conditions were acquired deformities (n=94) while only 1 congenital deformity was reported. Others included breast lumps, anterior neck swelling, and groin swellings. CONCLUSION: The most common surgical complaints in our setting among adults were acquired conditions of the extremities and open wounds/sores. With an estimated population of 90 million adults and approximately 1,200 orthopaedic and general surgeons respectively, the surgeon-to-affected population ratio is 1:10,000. There is a large gap to be filled in terms of surgical manpower development.

INTRODUCTION: Les études de prévalence communautaires sont connues pour être plus précises que les dossiers hospitaliers. Cependant, de telles études de prévalence communautaires sont rares dans les pays à revenu faible et intermédiaire, y compris le Nigeria. L'allocation des ressources et la priorisation des besoins de santé par les décideurs nécessitent des données issues de telles études communautaires pour être significatives et durables. Cette étude vise à évaluer la prévalence des affections chirurgicales courantes chez les adultes au Nigeria. MÉTHODES: Une étude descriptive transversale basée sur la communauté pour déterminer la prévalence des conditions chirurgicales congénitales et acquises chez les adultes dans une zone rurale-urbaine mixte de Lagos a été menée. La population étudiée comprenait des membres résidents de la zone de gouvernement local (LGA) d'Ikorodu, dans l'État de Lagos. Les données ont été collectées à l'aide d'une version modifiée du questionnaire administré par un enquêteur, l'outil d'enquête Surgeons OverSeas Assessment of Surgical Need (SOSAS). Les données ont été analysées à l'aide de l'outil analytique REDCap. RÉSULTATS: Huit cent cinquante-six ménages ont été enquêtés, ce qui a donné 1 992 adultes. Quatre-vingt-quinze adultes se sont plaints de conditions chirurgicales, donnant un taux de prévalence de 5 %. La grande majorité des conditions rapportées étaient des déformations acquises (n=94) tandis qu'une seule déformation congénitale a été signalée. Les autres incluaient des nodules mammaires, des gonflements antérieurs du cou et des gonflements inguinaux. CONCLUSION: Les plaintes chirurgicales les plus courantes dans notre cadre parmi les adultes étaient des conditions acquises des extrémités et des plaies ouvertes/ulcères. Avec une population estimée à 90 millions d'adultes et environ 1 200 chirurgiens orthopédiques et généralistes respectivement, le ratio chirurgien-population affectée est de 1:10,000. Il y a un grand écart à combler en termes de développement de la main-d'œuvre chirurgicale. MOTS CLÉS: Prévalence, Charge de morbidité, Chirurgie, Plaies.

Biomarkers and Cognition Study, Singapore (BIOCIS): Protocol, Study Design, and Preliminary Findings.

BACKGROUND: The focus of medicine is shifting from treatment to preventive care. The expression of biomarkers of dementia and Alzheimer's disease (AD) appear decades before the onset of observable symptoms, and evidence has emerged supporting pharmacological and non-pharmacological interventions to treat modifiable risk factors of dementia. However, there is limited research on the epidemiology, clinical phenotypes, and underlying pathobiology of cognitive diseases in Asian populations. OBJECTIVES: The objectives of the Biomarkers and Cognition Study, Singapore(BIOCIS) are to characterize the underlying pathobiology of Cognitive Impairment through a longitudinal study incorporating fluid biomarker profiles, neuroimaging, neuropsychological and clinical outcomes in a multi-ethnic Southeast Asian population. DESIGN, SETTING, PARTICIPANTS: BIOCIS is a 5-year longitudinal study where participants are assessed annually. 2500 participants aged 30 to 95 will be recruited from the community in Singapore. To investigate how pathology presents with or without minimal clinical symptoms and vice versa, CI and unimpaired individuals will be recruited. Participants will undergo assessments to characterise biomarkers of dementia through neuroimaging, fluid biomarkers, cognitive assessments, behavioural and lifestyle profiles, retinal scans and microbiome indicators. RESULTS: Since commencement of recruitment in February 2022, 1148 participants have been enrolled, comprising 1012 Chinese, 62 Indian, and 35 Malay individuals. Mean age and education is 61.32 years and 14.34 years respectively with 39.8% males. 47.9 % of the cohort are employed and 32.06% have a family history of dementia. The prevalence of cerebral small vessel disease is 90.2% with a mean modified Fazekas white matter hyperintensity score of 4.1. CONCLUSION: The BIOCIS cohort will help identify novel biomarkers, pathological trajectories, epidemiology of dementia, and reversible risk factors in a Southeast Asian population. Completion of BIOCIS longitudinal data could provide insights into risk-stratification of Asians populations, and potentially inform public healthcare and precision medicine for better patient outcomes in the prevention of Alzheimer's disease and dementia.

Panoramic Radiography in the Evaluation of the Relationship of Maxillary Molar Teeth and Maxillary Sinuses on the Deep Learning Models Improved with the Findings Obtained by Cone Beam Computed Tomography.

BACKGROUND: Panoramic radiography (PR) is available to determine the contact relationship between maxillary molar teeth (MMT) and the maxillary sinus floor (MSF). However, as PRs do not provide clear and detailed anatomical information, advanced imaging methods can be used. AIM: The aim of this study was to evaluate the diagnostic performance of deep learning (DL) applications that assess the relationship of the MSF to the first maxillary molar teeth (fMMT) and second maxillary molar teeth (sMMT) on PRs with data confirmed by cone beam computed tomography (CBCT). METHODS: A total of 2162 fMMT and sMMT were included in this retrospective study. The contact relationship of teeth with MSF was compared among DL methods. RESULTS: DL methods, such as GoogLeNet, VGG16, VGG19, DarkNet19, and DarkNet53, were used to evaluate the contact relationship between MMT and MSF, and 85.89% accuracy was achieved by majority voting. In addition, 88.72%, 81.19%, 89.39%, and 83.14% accuracy rates were obtained in right fMMT, right sMMT, left fMMT, and left sMMT, respectively. CONCLUSION: DL models showed high accuracy values in detecting the relationship of fMMT and sMMT with MSF.

First evaluation and detection of ivermectin resistance in gastrointestinal nematodes of sheep and goats in South Darfur, Sudan.

In Sudan, resistance to benzimidazoles has been reported recently in cattle and goats from South Darfur. Herein, ivermectin efficacy against gastrointestinal nematodes (GINs) was evaluated in sheep and goats in three study areas in South Darfur. The faecal egg count reduction test (FECRT) was used to evaluate the efficacy of ivermectin in sheep and goats naturally infected with GINs in the region of Bulbul (goats: n = 106), Kass (goats: n = 40) and Nyala (Domaia (sheep: n = 47, goats: n = 77) and the University farm (goats: n = 52)), using different treatment plans, and the efficacy was evaluated 12 days after treatment. Ivermectin efficacy was also evaluated in goats experimentally infected using local Haemonchus contortus isolates from Kass and Nyala. Nematodes surviving ivermectin treatment in goats in Bulbul and Nyala were harvested and larvae used to infect worm-free male sheep (n = 6, ≤6 months old). Infected sheep were dosed subcutaneously with ivermectin every eight days with increasing doses from 0.2 mg/kg to 1.6 mg/kg bodyweight (bw). Reduced ivermectin efficacy was identified in sheep and goats in the four study locations. Using a paired statistic, the efficacy of a therapeutic dose in sheep was 75.6% (90% upper credible limit (UCrL): 77.5%), while twice the recommended dose led to a reduction of 92.6% (90% UCrL: 93.3%). In goats, the FECRs of a therapeutic dose were 72.9-95.3% (90% UCrL range: 73.6-95.7%) in Bulbul, Nyala Domaia, Nyala University farm and Kass. Twice the dose recommended for goats in Bulbul revealed a 90% UCrL of 87.6%. All post-treatment faecal cultures contained only Haemonchus spp. larvae. The experimental infection trials in sheep and goats supported our findings from field trials and calculated upper 90% CrL of below 98.9%. For the first time highly ivermectin resistant H. contortus populations have been identified in sheep and goats in Sudan, and resistance was experimentally confirmed.

A Comprehensive Study on Implant Stability Quotient (ISQ) in View of Resonance Frequency and Spectrum Analysis.

PURPOSE: To investigate how well an implant stability quotient (ISQ) represents resonance frequency. MATERIALS AND METHODS: Benchtop experiments on standardized samples that replicated a mandibular premolar site were conducted to correlate an ISQ value and a resonance frequency to synthetic bone density and an incremental insertion torque; then, a frequency spectrum analysis was performed to check the validity of the resonance frequency analysis (RFA). Brånemark Mk III implants (4 × 11.5 mm; Nobel Biocare) were placed in Sawbones test models of five different densities (40, 30, 40/20, 20, and 15 PCF). An incremental insertion torque was recorded during implant placement. To perform stability measurements, the test models were partially clamped in a vise (unclamped volume: 10 × 20 × 34 mm). A MulTipeg (Integration Diagnostics) was attached to the implants, and a Penguin (Integration Diagnostics) RFA measured ISQ. Simultaneously, the MulTipeg motion was monitored via a laser Doppler vibrometer and processed by a spectrum analyzer to obtain the resonance frequency. Tightness of the clamp was adjusted to vary the resonance frequency. A statistical analysis produced a linear correlation coefficient (R) among the measured ISQ, resonance frequency, and incremental insertion torque. RESULTS: The resonance frequency had high correlation to the incremental insertion torque (R = 0.978), confirming the validity of using RFA for this study. Measured ISQ data were scattered and had low correlation to the resonance frequency (R = 0.214) and the incremental insertion torque (R = 0.386). The spectrum analysis revealed the simultaneous presence of multiple resonance frequencies. CONCLUSIONS: For the designed benchtop tests, resonance frequency does indicate implant stability in view of Sawbones density and incremental insertion torque. However, ISQ measurements do not correlate to the resonance frequency and may not reflect the stability when multiple resonance frequencies are present simultaneously.

[Prevention and treatment of COVID-19 based on post-genomic pharmacological analysis: Systematic computer analysis of 290,000 scientific articles on COVID-19].

The COVID-19 pandemic has highlighted pressing challenges in biomedical research methodology. It has become obvious that the rapid and effective development of treatments for "new" viral infections is impossible without the coordination of interdisciplinary research and in-depth analysis of data obtained within the framework of the post-genomic paradigm. Presents the results of a systematic computer analysis of 290,000 scientific articles on COVID-19, with an emphasis on the results of post-genomic studies of SARS-CoV-2. The futility of the overly simplified approach, which considers only one "most important receptor protein", only one "key virus gene", etc., is shown. It is shown how post-genomic technologies will make it possible to find informative biomarkers of severe coronavirus infection, including those based on complex immune disorders associated with COVID-19.

[Study of antitumor effects of human placenta hydrolysate on PC-3, OAW-42, BT-474 cell cultures].

AIM: To investigate the antitumor effects of human placenta hydrolysate (HPH) peptides on three hormone-dependent human cell lines: prostate adenocarcinoma, breast carcinoma, and ovarian cancer by metabolic analysis of cell cultures. MATERIALS AND METHODS: The effect of HPH on tumor and control tumor cell lines was evaluated. Study stages: (A) de novo peptide sequencing by collision-induced dissociation mass spectrometry; (B) detection of peptides with anti-tumor properties; (C) expert analysis of the obtained lists of peptides. RESULTS: Dose-dependent cytotoxic effects of HPH on three tumor cell lines are shown: PC-3 (human prostate adenocarcinomas), OAW-42 (human ovarian cancer), BT-474 (human breast carcinomas), and IC50 constants (1.3-2.8 mg/ml) were obtained. The analysis of the HPH peptide fraction showed more than 70 peptides with antitumor properties in the composition of this HPH, including kinase inhibitors: mitogen-activated protein kinases, kappa-bi nuclear factor inhibitor kinase, AKT serine/threonine kinase 1, protein kinase C zeta, interleukin-1 receptor-associated kinase 4 and cyclin-dependent kinase 1. CONCLUSION: The results of the study indicate not only the oncological safety of the HPH used in therapy but also the mild antitumor effects of this HPH at high concentrations.

Selenium Deficiency as a Risk Factor for Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a multifactorial disease. Although the specific aetiology and pathogenesis of PPCM are unknown, several hypotheses have been proposed, including selenium deficiency. However, the risk of PPCM from selenium deficiency was not previously quantified. This posthoc analysis of peripartum cardiomyopathy in Nigeria (PEACE) registry data aimed to determine if selenium deficiency is an independent risk factor for PPCM. METHODS: Apparently healthy women who delivered within the previous 8 weeks and PPCM patients in Kano, Nigeria, were compared for selenium deficiency (<70µg/L) and other relevant socio-demographic and clinical characteristics. Selenium level was measured at recruitment for each subject. Independent predictors of PPCM were determined using logistic regression models. RESULTS: 159 PPCM patients and 90 age-matched controls were consecutively recruited. 84.9% of the patients and 3.3% of controls had selenium deficiency. Selenium deficiency independently increased the odds for PPCM by 167-fold while both unemployment and lack of formal education independently increased the odds by 3.4-fold. CONCLUSION: Selenium deficiency was highly prevalent among PPCM patients in Kano, Nigeria, and significantly increased the odds for PPCM. These results could justify screening of women in their reproductive years for selenium deficiency, particularly those living in regions with high incidence of PPCM. The results also call for the setting up of a definitive clinical trial of selenium supplementation in PPCM patients with selenium deficiency, to further define its benefits in the treatment of PPCM.

CONTEXTE: La cardiomyopathie péripartum (CMPP) est une maladie multifactorielle. Bien que l'étiologie spécifique et la pathogenèse de la CMPP soient inconnues, plusieurs hypothèses ont été proposées, notamment la carence en sélénium. Cependant, le risque de CMPP lié à la carence en sélénium n'a pas été précédemment quantifié. Cette analyse post-hoc des données du registre de la cardiomyopathie péripartum au Nigéria (PEACE) visait à déterminer si la carence en sélénium est un facteur de risque indépendant de la CMPP. MÉTHODES: Des femmes apparemment en bonne santé ayant accouché dans les 8 semaines précédentes et des patientes atteintes de CMPP à Kano, au Nigéria, ont été comparées pour la carence en sélénium (<70µg/L) et d'autres caractéristiques socio-démographiques et cliniques pertinentes. Le taux de sélénium a été mesuré au recrutement pour chaque sujet. Les prédicteurs indépendants de la CMPP ont été déterminés à l'aide de modèles de régression logistique. RÉSULTATS: 159 patientes atteintes de CMPP et 90 témoins appariés selon l'âge ont été recrutés consécutivement. 84,9% des patientes et 3,3% des témoins présentaient une carence en sélénium. La carence en sélénium augmentait indépendamment les chances de CMPP de 167 fois, tandis que le chômage et le manque d'éducation formelle augmentaient indépendamment les chances de 3,4 fois. CONCLUSION: La carence en sélénium était très répandue parmi les patientes atteintes de CMPP à Kano, au Nigéria, et augmentait significativement les chances de CMPP. Ces résultats pourraient justifier le dépistage de la carence en sélénium chez les femmes en âge de procréer, en particulier celles vivant dans des régions à forte incidence de CMPP. Les résultats appellent également à la mise en place d'un essai clinique définitif sur la supplémentation en sélénium chez les patientes atteintes de CMPP présentant une carence en sélénium, afin de définir davantage ses avantages dans le traitement de la CMPP. MOTS-CLÉS: Cardiomyopathie Péripartum; Carence en Sélénium; Facteur de Risque.

Performance of wearable sleep trackers during nocturnal sleep and periods of simulated real-world smartphone use.

GOAL AND AIMS: To test sleep/wake transition detection of consumer sleep trackers and research-grade actigraphy during nocturnal sleep and simulated peri-sleep behavior involving minimal movement. FOCUS TECHNOLOGY: Oura Ring Gen 3, Fitbit Sense, AXTRO Fit 3, Xiaomi Mi Band 7, and ActiGraph GT9X. REFERENCE TECHNOLOGY: Polysomnography. SAMPLE: Sixty-three participants (36 female) aged 20-68. DESIGN: Participants engaged in common peri-sleep behavior (reading news articles, watching videos, and exchanging texts) on a smartphone before and after the sleep period. They were woken up during the night to complete a short questionnaire to simulate responding to an incoming message. CORE ANALYTICS: Detection and timing accuracy for the sleep onset times and wake times. ADDITIONAL ANALYTICS AND EXPLORATORY ANALYSES: Discrepancy analysis both including and excluding the peri-sleep activity periods. Epoch-by-epoch analysis of rate and extent of wake misclassification during peri-sleep activity periods. CORE OUTCOMES: Oura and Fitbit were more accurate at detecting sleep/wake transitions than the actigraph and the lower-priced consumer sleep tracker devices. Detection accuracy was less reliable in participants with lower sleep efficiency. IMPORTANT ADDITIONAL OUTCOMES: With inclusion of peri-sleep periods, specificity and Kappa improved significantly for Oura and Fitbit, but not ActiGraph. All devices misclassified motionless wake as sleep to some extent, but this was less prevalent for Oura and Fitbit. CORE CONCLUSIONS: Performance of Oura and Fitbit is robust on nights with suboptimal bedtime routines or minor sleep disturbances. Reduced performance on nights with low sleep efficiency bolsters concerns that these devices are less accurate for fragmented or disturbed sleep.

Evaluation of apolipoprotein A5 variants: A cohort of patients with severe hypertriglyceridemia from Turkiye.

BACKGROUND: This study aims to show the clinical and biochemical features in patients with severe hypertriglyceridemia (HTG) associated with rare variants in the apolipoprotein A-V (APOA5) gene. MATERIALS AND METHODS: Demographics, blood lipid levels, body mass index (BMI) and APOA5 mutation subtypes were collected from the endocrinology clinic registry and analyzed for a retrospective cohort study of ten patients with severe HTG and APOA5 gene variants. RESULTS: Of the 10 cases, four were female, and six were male. The median age was 45.0 years (min-max: 21-60 years), the median triglyceride was 2429.5 mg/dL (27.5 mmol/L) (min-max: 1351-4087 mg/dL, 15.3-46.2 mmol/L), and the mean BMI was calculated as 30.4 ± 4.4 kg/m2 (min-max: 24.9-41.0 kg/m2). Four cases had diabetes mellitus (DM); two were on intensive insulin therapy, and two were on basal insulin therapy. The mean hemoglobin A1c was 9.2 ± 1.2 % (min-max: 8.3-11.0 %). Among the study group, eight different APOA5 gene mutations were detected. These variants were heterozygous in 2 patients and homozygous (bi-allelic) in 8 patients. One patient was homozygous for APOA5 p.Ser19Trp, a relatively common polymorphism that is a risk variant for HTG. CONCLUSION: We report a cohort of patients with biallelic and single copy APOA5 variants, who were diagnosed later in life. Most had secondary factors, such as DM or obesity with increased BMI. Most rare APOA5 variants found in our patients were of uncertain significance. Our results add to the growing evidence that rare variants in certain candidate genes may predispose to developing HTG, together with secondary factors such as obesity. The genetic basis of HTG in many other patients is still unknown and remains the subject of further investigation.

Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

Interventions to Improve Adherence to Medication on Multidrug-Resistant Tuberculosis Patients: A Scoping Review.

INTRODUCTION: Inappropriate treatment and non-adherence use of anti-tuberculosis (TB) drugs trigger the spread of multidrug-resistant tuberculosis (MDR-TB) strains and causes an emerging public health threat worldwide. Therefore, non-adherence to MDR-TB treatment leading to prolonged medication period, increase incidence of adverse event and financial burden, thus it requires interventions to achieve a therapeutic outcome. OBJECTIVE: This scoping review aims to provide an overview of interventions to improve the adherence level to medication of MDR-TB patients. MATERIALS AND METHODS: A review of observational studies was conducted to discuss the accuracy, tolerability and ease of use of tonometers in measuring IOP in children with glaucoma. Three databases (PubMed, Web of Science, Scopus) were used in a scoping review. The data were synthesised using Rayyan AI. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to guide this review. RESULTS: A total of 11 articles were included in this review to describe the various interventions in MDR-TB treatment adherence. Psychological counselling or education intervention was the most popular intervention, and it significantly increased adherence levels among MDR-TB patients. Increased adherence level patients also reported by interventions with Medication Event Reminder Monitor (MERM), Video Directly Observed Therapy (VDOT), 30-day recall and Visual Analogue Scale (VAS), Financial Support, mHealth Application and directly observed therapy, short course (DOTS) and DOTS-Plus programs. However, we found that Electronic Dose Monitoring (EDM) device intervention has less effect on MDR-TB patients' adherence. CONCLUSION: The recovery of patients can be facilitated through MDR-TB treatment adherence interventions. It is acknowledged that the studies included in this review exhibit heterogeneity, with a majority showing significant improvement. Therefore, further study was required to investigate the specific on developing highly personalised interventions tailored to specific population or context, as well as to assess the cost-effectiveness of such interventions.

Emerging artificial intelligence-aided diagnosis and management methods for ischemic strokes and vascular occlusions: A comprehensive review.

Large-vessel occlusion (LVO) stroke is a promising field for the use of AI, especially machine learning (ML) because optimal results are highly dependent on timely diagnosis, communication, and treatment. In order to better understand the current state of artificial intelligence (AI) in relation to LVO strokes, its efficacy, and potential future applications, we searched relevant literature to perform a comprehensive evaluation of the topic. The databases PubMed, Embase, and Scopus were extensively searched for this review. Studies were then screened using title and abstract criteria and duplicate studies were excluded. By using pre-established inclusion and exclusion criteria, it was decided whether or not to include full-text papers in the final analysis. The studies were analyzed, and the relevant information was retrieved. In recognizing LVO on computed tomography, ML approaches were very accurate. There is a shortage of AI applications for thrombectomy patient selection, despite the fact that certain research accurately evaluates individual patient eligibility for endovascular therapy. Machine learning algorithms may reasonably predict clinical and angiographic outcomes as well as associated factors. AI has shown promise in the diagnosis and treatment of people who have just suffered a stroke. However, the usefulness of AI in management and forecasting remains restricted, necessitating more studies into machine learning applications that can guide decision making in the future.

Tasa de resangrado vítreo posterior a vitrectomía o facovitrectomía en pacientes con retinopatía diabética proliferativa: estudio retrospectivo / Vitreous rebleeding rate after vitrectomy or phacovitrectomy in patients with proliferative diabetic retinopathy: A retrospective study

Antecedentes: La complicación más común tras la vitrectomía en pacientes es el resangrado en cavidad vítrea. Es importante detectar los distintos factores que pueden incrementar la tasa de resangrado vítreo en estos pacientes. Objetivo: Realizar una revisión retrospectiva de la tasa de resangrado de cavidad vítrea posterior a vitrectomía o facovitrectomía. Método: Estudio retrospectivo, descriptivo y comparativo de pacientes con diagnóstico de retinopatía diabética proliferativa con procedimiento de facovitrectomía o vitrectomía. Se obtuvieron datos de antecedentes personales patológicos, tipo de intervención quirúrgica y grado del cirujano que realizó el procedimiento. Resultados: Se revisaron 1.227 expedientes de pacientes diabéticos sometidos a vitrectomía o facovitrectomía. El 65% presentaron hipertensión arterial sistémica. La tasa de filtración glomerular promedio fue del 63,50 (±32,36) ml/min/1,73m2 y la de hemoglobina glucosilada (HbA1c) del 8% (4,6 al 15%). En la comparación de variables se obtuvo una diferencia significativa de la tasa de resangrado vítreo comparando la facovitrectomía con la vitrectomía (p=0,003), y al relacionar la vitrectomía con el resangrado, se obtuvo una razón de momios de 1,44. Conclusión: Los resultados obtenidos muestran una menor tasa de resangrado en los pacientes con retinopatía diabética proliferativa sometidos a facovitrectomía.(AU)

Background: The most common complication after vitrectomy is the rebleeding in vitreous cavity. It is important to detect the different factors that can increase the vitreous rebleeding rate in these patients. Objective: To carry out a retrospective review of the rate of vitreous rebleeding after vitrectomy or phacovitrectomy. Method: Retrospective, descriptive and comparative study of patients with a diagnosis of proliferative diabetic retinopathy with phacovitrectomy or vitrectomy procedure. Personal background data, type of surgical intervention and grade of the surgeon who carried out the procedure were obtained. Results: One thousand two hundred twenty-seven files of diabetic patients with vitrectomy or phacovitrectomy were reviewed. Sixty-five percent presented systemic arterial hypertension. The average glomerular filtration rate was 63.50 (±32.36)ml/min/1.73m2 and glycosylated hemoglobin (HBA1C) of 8% (4.6-15%). In the comparison of variables, a significant difference in the rate of vitreous rebleeding was obtained comparing phacovitrectomy with vitrectomy (P=.003), in the relationship between vitrectomy with vitreous rebleeding, an odds ratio of 1.44 was obtained. Conclusion: The results obtained show a lower rate of rebleeding in patients undergoing phacovitrectomy in patients with proliferative diabetic retinopathy.(AU)