Search

Hussein M Ismail,1,2 Abeer S Algrafi,2 Osama Amoudi,3 Sameh Ahmed,4 Sultan S Al-Thagfan,5 Hassan Shora,6 Mohammed Aljohani,7 Mohammed Almutairi,7 Fahad Alharbi,7 Abdullah Alhejaili,7 Majed Alamri,7 Abdullah Muhawish,7 Ayat Abdallah8,9 1Department of cardiology, College of Medicine, Suez Canal University, Ismailia, Egypt; 2Department of medicine, College of Medicine, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia; 3Madinah Cardiac Center, Adult cardiology, Al-Madinah Al-Munawara, Saudi Arabia; 4Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia; 5Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia; 6Department of molecular biology/biochemistry, Port Said University, Port Said, Egypt; 7Medical intern, Taibah University, Al-Madinah Al-Munawara, Saudi Arabia; 8Epidemiology and Preventive Medicine Department, National Liver Institute, Shebin El-Kom, Egypt; 9Department of Family and Community Medicine, Taibah University, Al-Madinah Al-Munawara, Saudi ArabiaCorrespondence: Hussein M IsmailDepartment of Cardiology, College of Medicine, Suez Canal University, Ismailia, EgyptEmail husseinismail@med.suez.edu.eg; drhussein72@gmail.comBackground: Vitamin D deficiency is considered an emerging health problem that affects at least one billion patients worldwide. Calcitriol 1,25(OH)2D3 has several systemic effects, including anti-inflammatory, anti-thrombotic and anti-atherosclerotic impacts that explain its cardioprotective effects. The precise association between vitamin D and its metabolites and the value of supplements in acute coronary syndrome (ACS) is still controversial. This study aims to search the association between vitamin D2, D3, and metabolites and ACS in patients undergoing coronary angiography.Materials and Methods: This was a case–control study on 73 consecutive adult patients with ACS undergoing coronary angiography compared to 50 controls without coronary artery disease and matched for age and sex from June 2019 till July 2019. Echocardiography and coronary angiography were done for all cases. Plasma vitamin D and its metabolites were measured at admission for all participants along with chemistry profiles.Results: Vitamin D and its metabolites were statistically significantly lower in ACS patients than the controls. Multivariate regression analysis revealed that low levels of 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) significantly predicted ACS occurrence; the other significant predictors were high systolic blood pressure (BP), high total cholesterol, and low high-density lipoprotein-cholesterol. Interestingly, vitamin D2 and D3 did not significantly predict ACS (p> 0.05). We did not find a statistically significant association between the number of affected coronary vessels and vitamin D metabolites. Moreover, there was no statistically significant correlation between vitamin D and its metabolites and left ventricular ejection fraction measured by echocardiography.Conclusion: There was a strong association between vitamin D and all its metabolites with ACS. Significantly, low 25(OH)D and 1,25(OH)2D predicted ACS, but vitamin D2 and D3 did not. Large randomized controlled trials are needed to verify the beneficial values of vitamin D supplementation in ACS patients.Keywords: vitamin D3, vitamin D2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3, acute coronary syndrome, coronary artery disease

Plenty of disease types exist in world communities that can be explained by humans’ lifestyles or the economic, social, genetic, and other factors of the country of residence. Recently, most research has focused on studying common diseases in the population to reduce death risks, take the best procedure for treatment, and enhance the healthcare level of the communities. Kidney Disease is one of the common diseases that have affected our societies. Sectionicularly Kidney Tumors (KT) are the 10th most prevalent tumor for men and women worldwide. Overall, the lifetime likelihood of developing a kidney tumor for males is about 1 in 466 (2.02 percent) and it is around 1 in 80 (1.03 percent) for females. Still, more research is needed on new diagnostic, early, and innovative methods regarding finding an appropriate treatment method for KT. Compared to the tedious and time-consuming traditional diagnosis, automatic detection algorithms of machine learning can save diagnosis time, improve test accuracy, and reduce costs. Previous studies have shown that deep learning can play a role in dealing with complex tasks, diagnosis and segmentation, and classification of Kidney Tumors, one of the most malignant tumors. The goals of this review article on deep learning in radiology imaging are to summarize what has already been accomplished, determine the techniques used by the researchers in previous years in diagnosing Kidney Tumors through medical imaging, and identify some promising future avenues, whether in terms of applications or technological developments, as well as identifying common problems, describing ways to expand the data set, summarizing the knowledge and best practices, and determining remaining challenges and future directions.

Les fractures du bassin, le plus souvent multiples, sont fréquemment instables et surviennent le plus souvent dans des contextes traumatiques violents. Le traitement orthopédique de ces lésions est souvent pénible pour le patient et pour le personnel médical nécessitant une décharge au lit ou parfois des tractions qui peuvent aller jusqu'à 45 jours et peut compromettre la statique et la marche, le traitement chirurgical à ciel ouvert est un geste difficile, grevé d'une morbidité non négligeable avec un risque vasculaire (plexus veineux), nerveux (racines sacrées) ou septique notamment à prendre en compte, elle est donc généralement réservée aux formes neurologiques et fortement déplacées. La fixation percutanée sous radioscopie dans les fractures instables du bassin type B et C permet la synthèse des lésions postérieures source d'instabilité en fixant l'os coxal avec le corps de S1 ou S2 et la reprise rapide de la rééducation et de la marche.

La fracture de l'extrémité supérieure de l'humérus est la troisième fracture en fréquence chez les sujets âgés et leur répartition est bimodale touchant préférentiellement le sujet âgé ostéoporotique après un traumatisme à faible énergie ou plus rarement le sujet jeune par mécanisme à forte cinétique. Le traitement des fractures complexes de l'humérus proximal est le sujet de nombreuses controverses Le clou Telegraph constitue une approche thérapeutique très efficace pour les fractures déplacées de l'extrémité supérieure de l'humérus, de technique chirurgicale facile mais avec une courbe d'apprentissage et permettant un protocole de rééducation dans l'immédiat de l'intervention. C'est un matériel d'enclouage antérograde de 15 cm de long, plein verrouillé en proximal et en distal, le verrouillage proximal est assuré par 4 vis spongieuses, de filetage long, stables dans le clou et cela confère une solidité tout-à-fait remarquable à ce montage alors que le verrouillage distal est assuré au niveau du V deltoïdien en zone avasculaire et là où il n'y a pas de passage nerveux. L'étude présentée concerne 19 patients traités par un clou Telegraph court dans le traitement des fractures de l'extrémité supérieure de l'humérus entre 2013 et 2015 et elle a pour but d'analyser les résultats radio-cliniques et d'évaluer la répercussion de cette technique sur la fonction de l'épaule. Le clou Telegraph proposé depuis plus de 12 ans à peu près, a rencontré et continue de rencontrer un réel succès. Il permet de traiter très efficacement les fractures simples type 2 et 3, mais aussi les fractures impactées en valgus à 4 fragments. L'ostéosynthèse par clou Telegraph est une solution efficace, rapide et reproductible dans le traitement chirurgical des fractures de l'extrémité supérieur de l'humérus même en cas des fractures complexes et permet une reprise rapide de la mobilité de l'épaule.

La prise en charge d'une fracture au voisinage d'une prothèse de la hanche dépend de différents facteurs. En marge des facteurs liés à l'état physiologique du patient ou à l'expérience du chirurgien l'analyse précise de la fracture et de ses conséquences est essentielle.Le but de cette étude est d'évaluer les résultats des différents méthodes, proposer des indications en fonction des critères liés au terrain, au type et à la localisation de la fracture et à l'état de la fixation prothétique au moment de la fracture.

L'ostéome ostéoïde est une tumeur bénigne ostéoblastique relativement rare, constituée d'une petite lésion de tissu charnu et vascularisé, appelé nidus, cernée d'une ostéocondensation réactionnelle. Il représente 2 à 3% de l'ensemble des tumeurs osseuses et 10 à 20 % des tumeurs osseuses bénignes et survient généralement entre 10 et 25 ans (extrêmes : 5-53 ans), avec une nette prédominance masculine. La localisation intra-articulaire est rare représentant environ 10 à 13% descas. La clinique et les images radiologiques, souvent atypiques, rendent son diagnostic ardu. Le risque de traitement inadéquat est important. Jusqu'à 40% d'arthroscopies inappropriées ont été rapportés. Le cas rapporté illustre cette situation.

Nous rapportons le cas d'un ostéochondrome de l'omoplate ayant un aspect radiologique et une localisation inhabituelle chez un jeune homme de 24 ans qui consulte pour une déformation de son épaule gauche avec une bosse postérieure refoulant son omoplate. Un bilan radiologique standard a montré une exostose pédiculée à la partie supérieure de l'omoplate. La tomodensitométrie était en faveur d'une exostose volumineuse. La résection chirurgicale de la tumeur et l'examen anatomo-pathologique ont permis de confirmer le diagnostic d'un ostéochondrome. Après un recul de dix mois, les résultats fonctionnels étaient très bons.

Nous rapportons le cas d'une rupture post-traumatique du tendon tibial postérieur survenue lors d'une fracture bimalléolaire de la cheville. Le diagnostic a été posé lors de l'intervention chirurgicale. La réparation du tendon, non dégénératif, a été réalisée en même temps que l'ostéosynthèse. Bien que rare, cette possibilité de lésion tendineuse lors des fractures de la cheville ne doit pas êtreoubliée. Des douleurs résiduelles, un déficit de l'inversion active du pied, une modification de l'arche médiane du pied et à terme une évolution vers un pied plat valgus doivent faire évoquer rétrospectivement le diagnostic.

Il s'agit d'une jeune fille de 19 ans, sans antécédents pathologiques notables, qui consulte pour des douleurs du poignet gauche d'allure inflammatoire, avec perte de la force de préhension, sans déficit vasculo-nerveux, évoluant pendant 2 ans. Le bilan radiologique (A) a montré des images lacunaire intéressant le scaphoïde carpien, le trapèze, le trapézoïde et le grand os. Une biopsie (B) a été faite, révélant une tumeur a cellules géantes. La patiente a bénéficié dune exérèse chirurgicale (C) de la tumeur en bloc. Les suites postopératoires étaient simples et sans complications.

Il s'agit d'un jeune homme de 33 ans, sans antécédents pathologiques notables, qui consulte pour une énorme tumeur (A) bourgeonnante et ulcérée de l'avant bras droit évoluant depuis 3 ans. Une biopsie a été faite ayant conclue pour une tumeur nerveuse de haut grade de malignité. L'IRM (B) a montré une tumeur mesurant 141/64/69mm correspondant à un neurofibrosarcome du nerf interosseux postérieur. La prise en charge thérapeutique du patient a consisté en une amputation au niveau du tiers inferieur du bras (C).

Il s'agit d'un enfant de 5ans, sans antécédent pathologique notable, victime d'une chute de sa hauteur à la cour de l'école, occasionnant chez lui une douleur et une impotence fonctionnelles totales du membre inférieur gauche. L'examen clinique trouve un membre inférieur raccourci en adduction et rotation interne. Le bilan radiologique montre une luxation postérieure pure de la hanche sans lésion associée (A). La prise en charge en urgence a consisté en une réduction de la luxation sous anesthésie générale (B), suivie de la mise en place d'une traction non collée pendant 3 semaines.

Les fractures luxations du cotyle sont le plus souvent dues à des traumatismes de haute énergie. Elles constituent une urgence thérapeutique, l'association de la luxation à une fracture du cotyle fait apparaître la question du choix thérapeutique entre traitement orthopédique et traitement médical. L'objectif de l'étude est de mettre le point sur l'aspect thérapeutique dans ces lésions mais aussi leurs pronostics à long terme. Nous rapportons une étude rétrospective portant sur 40 cas colligés au service d'orthopédie du centre hospitalier universitaire de Rabat. Nous avons évalué les résultats de notre prise en charge mais aussi le pronostic à court et à long terme. Dans notre série, vingt cinq patients ont bénéficié d'un traitement orthopédique alors que les quinze restants ont été opérés, la voie d'abord la plus utilisée est la voie postérieure. Les résultats fonctionnels ont été évalués, après un recul de 3 à 8 ans, selon la cotation de Merle d'Aubigné. Nous avons obtenu 90% de résultats satisfaisants. La comparaison de nos résultats à ceux de la littérature montre que le résultat des traitements orthopédiques et chirurgicaux dépend essentiellement du type de fracture. Le pronostic à long terme reste imprévisible. La survenue des complications tardives telle que la nécrose céphalique et de l'arthrose reste toujours imprévisible, ce qui impose un suivi régulier et prolongé des patients.

Il s'agit d'un jeune homme de 22ans, sans antécédents pathologiques notables, consulte pour une masse indolore au niveau de la région fessière augmentant insidieusement de volume, mobile par rapport aux deux plans, sans signes inflammatoires en regard (A). Un bilan radiologique a mis en évidence une tumeur kystique d'allure bénigne mesurant 18cm de grand axe (B). Le patient a bénéficié d'une résection chirurgicale en bloc de la tumeur (C). Un examen anatomopathologique de la pièce opératoire a été réalisé objectivant un kyste épidermoïde géant. Les kystes épidermoïdes sont les kystes les plus communs de la peau, ils sont généralement petits et de croissance lente et atteignent rarement plus de 05cm de diamètre.

Context: Staging preclinical type 1 diabetes (T1D) and monitoring the response to disease-modifying treatments rely on the oral glucose tolerance test (OGTT). However, it is unknown whether OGTT-derived measures of beta-cell function can detect subtle changes in metabolic phenotype, thus limiting their usability as endpoints in prevention trials., Methods: We characterized the metabolic phenotype of individuals with islet autoimmunity in the absence (Stage 1) or presence (Stage 2) of dysglycemia. Participants were screened at a TrialNet site and underwent a 5-point, 2-hour OGTT. Standard measures of insulin secretion (AUC C-peptide, HOMA2-B) and sensitivity (HOMA-IR, HOMA2-S, Matsuda Index) and oral minimal model derived insulin secretion (phi total), sensitivity (SI), and clearance were adopted to characterize the cohort., Results: Thirty participants with Stage 1 and 27 with Stage 2 T1D were selected. Standard metrics of insulin secretion and sensitivity did not differ between Stage 1 and Stage 2 T1D, while the oral minimal model revealed lower insulin secretion (p<0.001) and sensitivity (p=0.034) in those with Stage 2 T1D, as well as increased insulin clearance (p=0.006). A higher baseline phi total was associated with reduced odds of disease progression, independent of Stage [OR 0.92 (0.86, 0.98), p=0.016]., Conclusion: The oral minimal model describes the differential metabolic phenotype of Stage 1 and Stage 2 T1D and identifies phi total as a progression predictor. This supports its use as a sensitive tool and endpoint for T1D prevention trials., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.)

Inhibition of the adenosine 2A receptor (A 2A R) is recognized as a promising immunotherapeutic strategy but is challenged by the ubiquity of A 2A R function in the immune system. To develop a safe yet efficacious immunotherapy, the discovery of a novel negative allosteric modulator (NAM) was preferred. Leveraging an in-house, sensitive, high-throughput screening cellular assay, novel A 2A R NAM scaffolds were identified, followed by an extensive structure-activity relationship (SAR) study, leading to the discovery of potent 2-amino-3,5-dicyanopyridine derivatives. The allosteric mode of action of active compounds was confirmed by progressive fold-shift assay, nonlinearity of the Schild plot analysis, biophysical measurements, and retained satisfactory potencies in high-adenosine concentrations. Further correlation of A 2A R engagement and downstream signaling was done in a human blood translational assay, clearly showcasing the potential of A 2A R allosteric modulation as a novel approach for efficient and safer cancer immunotherapies.

Context: Obesity is prevalent in type 1 diabetes (T1D) and is problematic with higher risk for diabetes complications. It is unknown to what extent gut microbiome changes are associated with obesity and T1D., Objective: This work aimed to describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized statistically significant gut microbial and metabolite differences in lean T1D youth (body mass index [BMI]: 5%-<85%) vs those with obesity (BMI: ≥95%)., Methods: We analyzed stool samples for gut microbial (using metagenomic shotgun sequencing) and short-chain fatty acid (SCFA) differences in lean (n = 27) and obese (n = 21) T1D youth in a pilot study. The mean ± SD age was 15.3 ± 2.2 years, glycated hemoglobin A1c 7.8 ± 1.3%, diabetes duration 5.1 ± 4.4 years, 42.0% female, and 94.0% were White., Results: Bacterial community composition showed between sample diversity differences (β-diversity) by BMI group (P = .013). There was a higher ratio of Prevotella to Bacteroides in the obese group (P = .0058). There was a differential distribution of significantly abundant taxa in either the lean or obese groups, including increased relative abundance of Prevotella copri, among other taxa in the obese group. Functional profiling showed an upregulation of branched-chain amino acid (BCAA) biosynthesis in the obese group and upregulation of BCAA degradation, tyrosine metabolism, and secondary bile acid biosynthesis in the lean group. Stool SCFAs were higher in the obese vs the lean group (P < .05 for all)., Conclusion: Our findings identify a gut microbiome and microbial metabolite signature associated with obesity in T1D. These findings could help identify gut microbiome-targeted therapies to manage obesity in T1D., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Multiple hereditary exostoses (MHE) is a rare skeletal disorder inherited as an autosomal dominant disorder. It is characterized by widespread multiple osteochondromas that grow near bone growth plates, leading to pain and deformities that significantly impact physical and emotional well-being and disrupt daily activities, social interactions, and psychological health, leading to considerable disability. This case report describes a 15-year-old boy with a family history of MHE who developed a large osteochondroma at his right elbow. We aim to present the surgical management of extraordinarily large-size proximal radius osteochondroma, fortunately, caused by a benign underlying condition despite typically carrying more chances of transformation into malignancy.‎ To the best of our knowledge, it would be the largest proximal radius osteochondroma documented in the literature., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Sulaiman et al.)

Background/objectives: Vitamin K2 analogs are associated with decreased vascular calcification, which may provide protective benefits for individuals with coronary artery disease (CAD) by stimulating anti-calcific proteins like matrix Gla protein and adjusting innate immune responses. This study addresses a significant gap in understanding the association between serum levels of vitamin K2 analogs in different CAD types and examines their correlations with clinical risk parameters in CAD patients., Methods: This case-control study enrolled CAD patients and healthy controls to assess and compare serum concentrations of two vitamin K2 analogs including menaquinone-4 (MK-4) and menaquinone-7 (MK-7) via ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). CAD risk factors were evaluated and related to serum levels of vitamin K2 analogs. The CAD group was further subdivided into stable angina, STEMI, NSTEMI, and unstable angina groups to investigate potential differences in vitamin K2 analog levels., Results: Patients experiencing acute coronary syndrome exhibited notably reduced serum levels of MK-4 and MK-7 (1.61 ± 0.66, and 1.64 ± 0.59 ng/mL, respectively) in comparison to the control group (2.29 ± 0.54, and 2.16 ± 0.46 ng/mL, respectively), with MK-4 and MK-7 displaying stronger associations with CAD risk indicators. Notable variations in vitamin K2 analog levels were found between CAD patients and control groups ( p < 0.001). Unstable angina patients showed the lowest serum levels of MK-4 and MK-7., Conclusions: The present study demonstrated a higher prevalence rate of vitamin K2 deficiency among patients with CAD. The most pronounced decrease in MK-4 and MK-7 was observed in unstable angina patients. Moreover, these outcomes indicate the imperative requirement for an integrative approach that incorporates metabolic, lipid, and vitamin K2-related pathways in the risk stratification and management of CAD.

Objective: We assessed whether there is an impactful glucose fraction independent of insulin secretion in autoantibody-positive individuals. Research Design and Methods: Baseline 2-h oral glucose tolerance test data from the TrialNet Pathway to Prevention (TNPTP; n = 6190) and Diabetes Prevention Trial-Type 1 (DPT-1; n = 705) studies were used. Linear regression of area under the curve (AUC) glucose versus Index60 was performed to identify two fractions: dependent (dAUCGLU) or independent (iAUCGLU) of insulin secretion. Results: The lack of correlation ( r = 0.06) of iAUCGLU and the inverse correlation of dAUCGLU ( r = -0.59) with the first-phase insulin response from DPT-1 were consistent with the independent and dependent designations of the glucose fractions. Correlations of AUC C-peptide were inverse with dAUCGLU and positive with iAUCGLU (TNPTP: r = -0.72, r = 0.57; DPT-1: r = -0.56, r = 0.60). The explained variance of AUC C-peptide increased markedly after separating AUC glucose into its fractions (from 4% to 85% in TNPTP; from 1% to 67% in DPT-1). The independent fraction contributed more to the increased glycemia of impaired glucose tolerance (IGT) than did the dependent fraction. Both dAUCGLU and iAUCGLU predicted IGT and type 1 diabetes (T1D) ( P < 0.0001 for all). However, whereas dAUCGLU was more predictive of T1D (chi-square: 849 vs. 249), iAUCGLU was more predictive of IGT (chi-square: 451 vs. 176). Conclusions: A glucose fraction independent of insulin secretion was identified that was appreciable in autoantibody-positive individuals. It provides insight into the relation between glucose and C-peptide, contributes substantially to the glycemia of IGT, and predicts both T1D and IGT, particularly the latter.

Background: Orthodontic education, besides some other factors, influences the confidence level of recently graduated dentists to diagnose subjects seeking orthodontic treatment and provide treatment plans. This study aims to explore the factors that influence the confidence level of undergraduate dental students to diagnose subjects seeking orthodontic treatment and provide treatment plans after graduation., Methods: A qualitative study was undertaken using focus groups and interviews. Purposive sampling was used, focus groups and face to face semi-structured interviews were adopted as the method of data collection. Three focus groups were evaluated including fifth-year undergraduate, postgraduate orthodontic students, and recently graduated general dentists. In addition, eleven interviews were performed with the fifth-year undergraduate students. Data collection ceased upon reaching data saturation, with thematic analysis employed for qualitative data analysis., Results: Six themes and two sub-themes were extracted from the data. More focus on the theory was highly noticed, and most of the participants exhibited a low level of self confidence in extrapolating orthodontic diagnosis and establishing treatment plans after graduation. In addition, they believed that practical teaching sessions mostly deal with wire bending and demanded to expand the clinical orthodontic knowledge to be able to indicate the right diagnosis and initiate proper treatment plans., Conclusions: Clinical and practical training alongside theoretical foundation represent key factors in orthodontic education required to obtain confidence in orthodontic practice among dental undergraduate students and alumni. The findings help in enhancing undergraduate programs via providing a clinically oriented orthodontic education from student perceptions., (© 2024 American Dental Education Association.)

Background: Knockout (KO) ferrets with the cystic fibrosis transmembrane conductance regulator (CFTR) exhibit distinct phases of dysglycemia and pancreatic remodeling prior to cystic fibrosis-related diabetes (CFRD) development. Following normoglycemia during the first month of life (Phase l), hyperglycemia occurs during the subsequent 2 months (Phase Il) with decreased islet mass, followed by a period of near normoglycemia (Phase Ill) in which the islets regenerate. We aimed to characterize islet hormone expression patterns across these Phases., Methods: Immunofluorescence staining per islet area was performed to characterize islet hormone expression patterns in age matched CFTR KO and wild type (WT) ferrets, focusing on the first three phases., Results: In Phase I, insulin staining intensity was higher in CF ( p  < 0.01) than WT but decreased in Phase III ( p  < 0.0001). Glucagon was lower in CF during Phases I and increased in Phase III, while proinsulin decreased ( p  < 0.0001) Phases II and III. CF sections showed lower proinsulin-to-insulin ratio in Phase I ( p  < 0.01) and in Phase III ( p  < 0.05) compared to WT. Conversely, glucagon-to-insulin ratio was lower in CF in Phase I ( p  < 0.0001) but increased in Phase III ( p  < 0.0001). Mender's coefficient overlap showed higher overlap of insulin over proinsulin in CF sections in Phase II ( p  < 0.001) and Phase III ( p  < 0.0001) compared to WT. Mender's coefficient rate was higher in CF sections during Phase II ( p  < 0.001)., Conclusion: CF ferret islets revealed significant immunofluorescent staining changes compared to WT during various phases of disease, providing insights into CRFD pathophysiology.

Indoor residual spraying (IRS) and the use of insecticide-treated bednets for malaria vector control have contributed substantially to a reduction in malaria disease burden. However, these control tools have important shortcomings including being donor-dependent, expensive, and often failing because of insufficient uptake. We assessed the safety and efficacy of a user-friendly, locally tailored malaria vector control approach dubbed "Hut Decoration for Malaria Control" (HD4MC) based on the incorporation of a WHO-approved insecticide, Actellic ® 300 CS, into a customary hut decoration practice in rural Uganda where millions of the most vulnerable and malaria-prone populations live in mud-walled huts. Three hundred sixty households were randomly assigned to either the HD4MC (120 households), IRS (120 households) or control group without any wall treatment (120 households). Entomological indices were assessed using pyrethrum spray catching, CDC light traps and human landing catches. The Actellic ® 300 CS toxicity on acetylcholinesterase activity among applicators of HD4MC was evaluated using the Test-mate (Model 400) erythrocyte acetylcholinesterase (AChE) test V.2, whereas toxicity in household occupants was monitored clinically. The Actellic ® 300 CS level in house dust was analyzed using reversed-phase high-performance liquid chromatography (RP-HPLC). Entomological indices were compared between the three study arms at 1.5, 3 and 6 months post-intervention. HD4MC- and IRS-treated huts had a significantly reduced malaria vector density and feeding rate compared to control huts. There was no significant reduction in acetylcholinesterase activity at 1.5 and 24 h post exposure. Actellic ® 300 CS exposure did not result in any serious adverse events among the household occupants. In conclusion, HD4MC was safe and had comparable efficacy to canonical IRS.

Purpose: Insulin resistance plays a pivotal role in the preclinical stages of type 1 diabetes (T1D)., Objective: This study aims at exploring the genetic, metabolic, and immunological features associated with insulin resistance among individuals at risk of developing T1D., Methods: We retrospectively selected relatives of individuals with T1D from participants in the TrialNet Pathway to Prevention study. They were categorized into two groups: high-H (n = 27) and low-H (n = 30), based on the upper and lower quartiles of insulin resistance assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Genetic predisposition was determined using the T1D Genetic Risk Score 1 (GRS1). Additionally, glucose control was evaluated through an oral glucose tolerance test and levels of metabolic hormones and inflammatory cytokines were measured in the serum. Flow cytometry analysis was employed to assess frequency and phenotype of islet-specific CD8 T cells., Results: While GRS1 were similar between the low-H and high-H groups, high-H individuals displayed a distinct metabolic profile, characterized by compensatory hyperinsulinemia, even while maintaining normoglycemia. Circulating cytokine levels were similar between the two groups. However, immune profiling revealed a central memory and activated profile of GAD65-specific CD8 T cells, along with an increased frequency of insulin-specific CD8 T cells in high-H individuals. The enrichment in insulin-specific CD8 T cells was independent of body mass., Conclusion: These findings highlight the intricate interplay between insulin resistance, genetic factors, and immune activation in the context of T1D susceptibility, indicating potential connections between insulin resistance and immune responses specific to islet cells., Competing Interests: Declarations. Competing interests: The authors have no relevant financial or non-financial interests to disclose. Ethics approval: This research study was conducted retrospectively from data obtained for clinical purposes. On selected subjects immunological parameters were tested on biobanked biological material. This study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The OSR Ethics Committee approved this study (IRB# NHPROT32803-TN01). Consent to participate: Informed consent was obtained from all individual or from legal guardians’ participants included in the study., (© 2024. The Author(s).)

Background: The surveillance of serious and superficial skin fungal infections in Iraq has not been conducted. Limited information exists on their incidence and prevalence., Objectives: This study aimed to analyze, compute and estimate the prevalence and burden of fungal infections, as no previous data is available and no studies has been attempted in Iraq., Methods: In the present study the data were collected and reviewed from published data on epidemiology of fungal infections nationally, internationally, from unpublished postgraduate master and PhD theses, hospital records and private clinic records. External sources of data from other countries were used for diseases which lacked sufficient local data., Results: We estimated 985,628 annual serious infections comprising of 2.26 % of the total population. When including superficial fungal infections group of the skin, this rises to 2,075,113 infections at 4.76 % of the total population. The most common serious and skin infections were recurrent Candida vaginitis, fungal rhinosinusitis and tinea capitis comprising 61.5 %, 21.8 %, and 22.4 % of all infections although the total incidence of superficial fungal infections was also high at 1,071,485. Respiratory fungal disease is also common comprising 14.0 % of infections. We predicted the following annual burden per 100,000; oral candidiasis at 247.9, esophageal candidiasis at 6.04, candidemia at 5.0, Candida peritonitis at 0.75, recurrent Candida vaginitis at 5461, allergic bronchopulmonary aspergillosis at 35, severe asthma with fungal sensitisation at 46, invasive aspergillosis at 7.9, chronic pulmonary aspergillosis at 11.7, chronic fungal rhinosinusitis at 496, mucormycosis at 0.99, fungal keratitis at 14.0, and total dermatophytosis at 1631, the most severe being tinea capitis at 366. Many of these estimates were made with data sourced from other nations, so additional data from Iraq is required to validate or modify these estimates., Conclusion: Recurrent Candida vaginitis, fungal rhinosinusitis, and tinea capitis are considered to be the most frequent fungal diseases present in Iraq., Competing Interests: Declaration of competing interest None of the authors have a conflict of interest with the contents of this manuscript, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aims/hypothesis: We aimed to analyse TrialNet Anti-CD3 Prevention (TN10) data using oral minimal model (OMM)-derived indices to characterise the natural history of stage 2 type 1 diabetes in placebo-treated individuals, to describe early metabolic responses to teplizumab and to explore the predictive capacity of OMM measures for disease-free survival rate., Methods: OMM-estimated insulin secretion, sensitivity and clearance and the disposition index were evaluated at baseline and at 3, 6 and 12 months post randomisation in placebo- and teplizumab-treated groups, and, within each group, in slow- and rapid-progressors (time to stage 3 disease >2 or ≤ 2 years). OMM metrics were also compared with the standard AUC C-peptide. Percentage changes in CD8 + T memory cell and programmed death-1 (PD-1) expression were evaluated in each group., Results: Baseline metabolic characteristics were similar between 28 placebo- and 39 teplizumab-treated participants. Over 12 months, insulin secretion declined in placebo-treated and rose in teplizumab-treated participants. Within groups, placebo slow-progressors (n=14) maintained insulin secretion and sensitivity, while both declined in placebo rapid-progressors (n=14). Teplizumab slow-progressors (n=28) maintained elevated insulin secretion, while teplizumab rapid-progressors (n=11) experienced mild metabolic decline. Compared with rapid-progressor groups, insulin clearance significantly decreased between baseline and 3, 6 and 12 months in the slow-progressor groups in both treatment arms. In aggregate, both higher baseline insulin secretion (p=0.027) and reduced 12 month insulin clearance (p=0.045) predicted slower progression. A >25% loss of insulin secretion at 3 months had specificity of 0.95 (95% CI 0.86, 1.00) to identify rapid-progressors and correctly classified the 2 year risk for progression in 92% of participants, with a sensitivity of 0.19 (95% CI 0.08, 0.30). OMM-estimated insulin secretion outperformed AUC C-peptide to differentiate groups by treatment or to predict progression. Metabolic changes were paralleled by relative frequency of change in PD-1 + CD8 + T effector memory cells., Conclusions/interpretation: OMM measures characterise the metabolic heterogeneity in stage 2 diabetes, identifying differences between rapid- and slow-progressors, and heterogeneous impacts of immunotherapy, suggesting the need to account for these differences when designing and interpreting clinical trials., Competing Interests: Data availability: The datasets generated during and/or analysed in the current study are available from the corresponding author upon reasonable request. Funding: AG is supported by BreakthroughT1D (formerly Juvenile Diabetes Research Foundation) (3-SRA-2022-1186-S-B and 3-SRA-2023-1422-S-B). EKS is supported by funding from R01DK121929, R01DK133881, the Ralph W. and Grace M. Showalter Research Trust and the grant 2021258 from the Doris Duke Charitable Foundation through the COVID-19 Fund to Retain Clinical Scientists collaborative grant programme, made possible through the support of grant 62288 from the John Templeton Foundation. CEM is supported by NIH grants R01 DK093954, DK127308, U01DK127786, and UC4DK104166, VA Merit Award I01BX001733, 2-SRA-2019-834-S-B and JDRF 2-SRA-2018-493-A-B, and the Helmsley Charitable Trust. AP is supported by Breakthrough T1D Transition Award (1-FAC-2025-1632-A-N). KCH received support from NIH grants DK057846, and AI66387, and DK106993 (Type 1 Diabetes TrialNet). HMI is supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number K23DK129799. AM received support for this project from NIH DK106993 (Type 1 Diabetes TrialNet). The Type 1 Diabetes TrialNet Study Group is a clinical trials network currently funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through cooperative agreements U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085453, U01 DK085461, U01 DK085465, U01 DK085466, U01 DK085476, U01 DK085499, U01 DK085504, U01 DK085509, U01 DK103153, U01 DK103180, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK097835 and U01 DK106993; JDRF; and the American Diabetes Association. Additional support for clinical studies was provided by the National Center for Research Resources through Clinical Translational Science Awards UL1TR000142, UL1TR002366, UL1TR000445, UL1TR000064, UL1TR002537, UL1TR001082, UL1TR000114, UL1TR001857, UL1TR002529, UL1TR001872 and by the Immune Tolerance Network (UM1 AI09565). MacroGenics donated the study agents and provided funds for additional site monitoring. Authors’ relationships and activities: EKS has received compensation for educational lectures on diabetes screening from Medscape, the American Diabetes Association, Sanofi and Health Matters CME; for serving as the Chair of the Steering Committee for Clinical Advances in Type 1 Diabetes: Screening, Staging, and Treatment; for serving on the Sanofi Drug Agnostic Type 1 Diabetes Screening Committee; and for consulting for DRI Healthcare and Sanofi. BMN received honoraria for speaking on type 1 diabetes prevention by the Med Learning Group. Over the last 5 years, AM reports serving on scientific advisory boards for Dompé Farmaceutici SpA, ProventionBio, Vertex Pharmaceuticals and Abata Therapeutics; and serving on data and safety monitoring boards funded by NovoNordisk and the Leona M. and Harry B. Helmsley Charitable Trust; her institution has received grant funding on her behalf from the NIH, JDRF, the Cystic Fibrosis Foundation, Abbott Diabetes, ProventionBio, Intrexon (now Precigen) and Caladrius Biosciences; she has received study supplies for investigator-initiated studies from NovoNordisk, Medtronic and Abbott Diabetes. CEM has served on advisory boards related to T1D research clinical trial initiatives including Dompe, Isla Technologies, MaiCell Technologies, and Avotres. CEM serves as President of the Immunology of Diabetes Society (IDS), Co-Executive Director of nPOD, Investigator and Study Chair in TrialNet, and Co-PI of the NIH Integrated Islet Distribution Program (IIDP). These activities have not dealt directly with topics covered in this manuscript. CEM is a co-inventor on Patent (16/291,668): Extracellular Vesicle Ribonucleic Acid (RNA) Cargo as a Biomarker of Hyperglycemia and Type 1 Diabetes. CEM has received investigator-initiated grant funding from Astellas and Lilly Pharmaceuticals and in-kind research support from BMS and Nimbus for an unrelated project. KCH has consulted for Sanofi and is on the Scientific Advisory Boards of Sonoma Biotherapeutics and NexImmune. He is a co-inventor for a patent for use of teplizumab for delay of type 1 diabetes but receives no royalties. HMI has consulted for Rise Therapeutics and Sanofi. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: AG researched data, performed analyses, interpreted results and wrote the first draft of the manuscript. EKS planned analyses, interpreted results and reviewed and edited the manuscript. DC obtained data, performed analyses and reviewed and edited the manuscript. CE-M, KCH, BMN, HMI and AP contributed to discussion and reviewed and edited the manuscript. AM researched data, planned analyses, interpreted results and reviewed and edited the manuscript. All authors approved the final version of the manuscript. AG is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis., (© 2024. The Author(s).)

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb + ) children and adults who are at risk of (confirmed single IAb + ) or living with (multiple IAb + ) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb + ; (2) when people who are IAb + are initially identified there is a need for confirmation using a second sample; (3) single IAb + individuals are at lower risk of progression than multiple IAb + individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care., (© 2024. American Diabetes Association and European Association for the Study of Diabetes.)

Background Incorporating nanoparticles into resin infiltrant (RI) can alter its physical properties, including microleakage. This study aimed to examine the microleakage properties of RI modified with 2.5% and 5% zinc oxide (ZnO) and magnesium oxide (MgO) nanoparticles on artificially induced carious lesions (ACLs) in bovine teeth. Materials and methods Modified RIs were applied to five sound and 30 ACLs on bovine incisors. They were divided into seven groups based on the procedure (Group 1: sound enamel (SE), Group 2: artificial caries lesion only (ACL), Group 3: RI, Group 4: RI+ 2.5% ZnO, Group 5: RI + 5% ZnO, Group 6: RI + 2.5% MgO, Group 7: RI + 5% MgO). The samples were subjected to 5000 thermal cycles and then exposed to methylene blue solution for 24 hours in an incubator. The teeth were sectioned and examined with a stereomicroscope to assess the depth of methylene blue penetration (MBP), quantifying microleakage according to the following scoring: 0 = no penetration, 1 = outer half of enamel, 2 = inner half of enamel, 3 = outer half of dentin, and 4 = inner half of dentin. An ANOVA test was conducted to assess the significance of differences among the groups. Post-hoc tests, including Tukey's HSD (honestly significant difference) test, were performed to identify specific group differences and determine which differences were statistically significant. Results SE samples (Group 1) showed minimal penetration, with 100% scoring 1, indicating high resistance to MBP. The ACL group had significant penetration, with 77.78% scoring 3 and 22.22% scoring 2. The RI group completely prevented MBP, with all samples scoring 0. Both RI+2.5% ZnO (Group 4) and RI+2.5% MgO (Group 6) were highly effective, with 88.89% scoring 0 and 11.11% scoring 1. RI+5% ZnO (Group 5) and RI+5% MgO (Group 7) also prevented MBP but had slightly higher minimal penetration, with 77.78% scoring 0 and 22.22% scoring 1. Significant differences were observed between the ACL group and all other groups, underscoring the effectiveness of RI treatments. No significant differences were found between RI+ZnO and RI+MgO at both concentrations, indicating similar effectiveness. Conclusions The study demonstrated that RI modified with 2.5% and 5% ZnO and MgO nanoparticles effectively reduced microleakage in ACLs on bovine teeth compared to untreated lesions. These modifications significantly inhibited MBP, particularly in enamel and dentin, indicating their potential to enhance the durability and effectiveness in clinical applications. This research emphasizes the promising role of nanoparticle-modified RI in minimizing microleakage and optimizing treatment outcomes. Further research is needed to confirm these findings and refine protocols., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: Scientific and Ethics Committee of the University of Sulaimani, College of Dentistry Issued protocol number 46/21 on 01/09/2021. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khursheed et al.)

Duchenne muscular dystrophy (DMD) is the most common muscular disorder affecting children. It affects nearly 1 male birth over 5000. Oxidative stress is a pervasive feature in the pathogenesis of DMD. Recent work shows that the main generators of ROS are NADPH oxidases (NOX), suggesting that they are an early and promising target in DMD. In addition, skeletal muscles of mdx mice, a murine model of DMD, overexpress NOXes. We investigated the impact of diapocynin, a dimer of the NOX inhibitor apocynin, on the chronic disease phase of mdx 5Cv mice. Treatment of these mice with diapocynin from 7 to 10 months of age resulted in decreased hypertrophy of several muscles, prevented force loss induced by tetanic and eccentric contractions, improved muscle and respiratory functions, decreased fibrosis of the diaphragm and positively regulated the expression of disease modifiers. These encouraging results ensure the potential role of diapocynin in future treatment strategies., Competing Interests: Declaration of Competing Interest The author declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Context: Metabolic measures are frequently used to predict type 1 diabetes (T1D) and to understand effects of disease-modifying therapies., Objective: Compare metabolic endpoints for their ability to detect preventive treatment effects and predict T1D., Methods: Six-month changes in metabolic endpoints were assessed for (1) detecting treatment effects by comparing placebo and treatment arms from the randomized controlled teplizumab prevention trial, a multicenter clinical trial investigating 14-day intravenous teplizumab infusion and (2) predicting T1D in the TrialNet Pathway to Prevention natural history study. For each metabolic measure, t-Values from t tests for detecting a treatment effect were compared with chi-square values from proportional hazards regression for predicting T1D. Participants in the teplizumab prevention trial and participants in the Pathway to Prevention study selected with the same inclusion criteria used for the teplizumab trial were studied., Results: Six-month changes in glucose-based endpoints predicted diabetes better than C-peptide-based endpoints, yet the latter were better at detecting a teplizumab effect. Combined measures of glucose and C-peptide were more balanced than measures of glucose alone or C-peptide alone for predicting diabetes and detecting a teplizumab effect., Conclusion: The capacity of a metabolic endpoint to detect a treatment effect does not necessarily correspond to its accuracy for predicting T1D. However, combined glucose and C-peptide endpoints appear to be effective for both predicting diabetes and detecting a response to immunotherapy. These findings suggest that combined glucose and C-peptide endpoints should be incorporated into the design of future T1D prevention trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)