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Sepsis is a major cause of mortality among critically ill children, particularly affecting neonates and children under five. Gram-negative bacteria (GNB) have emerged as significant pathogens in pediatric intensive care units (PICUs), contributing to high rates of antimicrobial resistance and complicating treatment outcomes. This systematic review aims to determine the prevalence and antibiotic resistance patterns of Gram-negative bacterial infections in pediatric sepsis cases within PICUs and to identify associated risk factors. An extensive search was conducted in PubMed and MEDLINE for studies published between 2019 and 2024, focusing on studies involving pediatric patients in PICUs with documented GNB infections. After a rigorous selection process, 11 articles were included in the review. The prevalence of GNB in PICUs varied widely across the studies, ranging from 5% to 65.7%, with a mean prevalence of 38.5%. Common pathogens included Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. The rate of multidrug-resistant Gram-negative pathogens ranged from 18.2% to 63.7%, with a mean of 47%. Key risk factors identified included previous PICU stays, invasive procedures, and prior antibiotic use. The findings underscore the significant burden of Gram-negative bacterial infections and the high levels of antibiotic resistance in PICUs. There is an urgent need for enhanced diagnostic practices, targeted infection control measures, and robust antimicrobial stewardship programs to manage and mitigate the impact of these infections. Future research should focus on validating these findings and developing effective interventions to improve patient outcomes in pediatric settings.

Abstract TV viewing is associated with health risks, but existing measures of TV viewing are imprecise due to relying on self-report. We developed the Family Level Assessment of Screen use in the Home (FLASH)-TV, a machine learning pipeline with state-of-the-art computer vision methods to measure children’s TV viewing. In three studies, lab pilot (n = 10), lab validation (n = 30), and home validation (n = 20), we tested the validity of FLASH-TV 3.0 in task-based protocols which included video observations of children for 60 min. To establish a gold-standard to compare FLASH-TV output, the videos were labeled by trained staff at 5-second epochs for whenever the child watched TV. For the combined sample with valid data (n = 59), FLASH-TV 3.0 provided a mean 85% (SD 8%) accuracy, 80% (SD 17%) sensitivity, 86% (SD 8%) specificity, and 0.71 (SD 0.15) kappa, compared to gold-standard. The mean intra-class correlation (ICC) of child’s TV viewing durations of FLASH-TV 3.0 to gold-standard was 0.86. Overall, FLASH-TV 3.0 correlated well with the gold standard across a diverse sample of children, but with higher variability among Black children than others. FLASH-TV provides a tool to estimate children’s TV viewing and increase the precision of research on TV viewing’s impact on children’s health.

Abstract Sexual dysfunction (SD) is a common non-motor symptom in people with Parkinson’s disease (PD) yet underreported and undertreated specifically in many ethnic PD groups because of religious, social and personal perceptions. We conducted the first single-centre cross-sectional study in the United Arab Emirates of SD in 513 consecutive patients who agreed to complete the survey questionnaires. Data was collected on SD using the Nonmotor Symptoms Scale (NMSS), Index of Erectile Function, and Female Sexual Function Index. Our results show that the non-Emirati group had higher NMSS-SD scores than the Emirati group. SD was reported independent of ethnicity, race and disease stage (p

Abstract Road traffic crashes (RTCs) disproportionately impact low and middle-income countries (LMICs). Current interventions in LMICs primarily target road user behavior, neglecting systemic issues and casting drivers as mere contributors. Given Iran’s unique cultural, financial, and social intricacies, this study aims to explore the latent causes of RTCs, prioritizing drivers’ experiences and encompassing insights from various traffic system components. Applying a qualitative approach, data were collected through 46 semi-structured interviews with 38 participants, including drivers and experts from traffic-related organizations. Content analysis identified ten themes as contributing to driving errors. Direct factors included fatigue influenced by economic and occupational conditions, distraction from internal and external sources, reckless behaviors influenced by traffic culture and environment, and Inadequate driving skills due to training. Macro-scale challenges in road infrastructure, vehicle quality, education, and accident investigations were highlighted. The lack of a centralized traffic safety authority and a predominant focus on penalizing drivers overshadowed systemic issues. The study offers valuable insights into the complex interplay of factors contributing to driving errors in LMICs, advocating for a paradigm shift towards holistic, systemic interventions beyond individual driver behavior and challenging the conventional blame-centric view associated with driving errors.

Objective We aimed to assess the prevalence of clonal haematopoiesis (CH) in patients with giant cell arteritis (GCA) compared with controls and individuals with other autoimmune diseases (AIDs) and to identify high-risk clinical/genetic profiles that could influence disease outcomes.Methods In a prospective observational study at three hospitals, we included 49 patients diagnosed with GCA, 48 patients with other AIDs and 27 control participants. We used next-generation sequencing to detect clonal haematopoiesis (CH) among them.Results CH was detected in 55.1% of patients with GCA, 59.3% of controls and 18.8% of patients with other AIDs. The most commonly mutated genes in GCA and control groups were DNMT3A and TET2. No significant differences in CH prevalence were found between patients with GCA and controls or other AID when adjusted for age and sex. Cluster analysis revealed two distinct groups within the patients with GCA, one of which displayed a higher prevalence of TET2 and JAK2 variants, and was associated with worse prognosis.Conclusions CH is prevalent among patients with GCA but does not differ significantly from controls or other autoimmune conditions. However, specific genetic profiles, particularly mutations in TET2 and JAK2, are associated with a higher risk cluster within the GCA cohort. This observation highlights the interest of detecting CH in patients with GCA in both routine practice and clinical trials for better risk stratification. Further prospective studies are needed to determine if management tailored to the genetic profile would improve outcomes.

Background: Cannabis use is highly prevalent and detrimental among people with HIV (PWH). Legislative changes in several states altered the legality and accessibility of cannabis. We examined pre-post legislative changes in current, daily, and severe use in PWH in clinical care. Methods: PWH engaged in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort from 3 sites/states were asked about past 3-month cannabis use on a routine clinical assessment of health behavior before and after legalization. A fourth site in a state without legalization served as a comparator. We used linear regression to estimate changes in use prevalence from 1 year before to 1 year after legalization. Results: Among PWH (n=7885), from 1 year before to 1 year after legalization, cannabis use prevalence increased slightly in Boston, MA (32–38 %), Birmingham, AL (26–27 %), and San Diego, CA (25–29 %); and decreased in Seattle, WA (44–41 %). Contemporaneously, daily cannabis use increased modestly (less than 5 %) at all sites. Severe use (cannabis-specific ASSIST score ≥27) decreased or plateaued at all sites. No site showed significant change in prevalence trends of current, daily, or severe use 1 year before and after legalization in linear regression (p >0.05). Conclusion: Few changes prevailed in cannabis use patterns around dates of legalization among PWH in care in the U.S. Relaxation of cannabis policy does not appear to result in an immediate increase in use among PWH.

Background In recent years, there has been a notable increase in the level of attention devoted to exploring capabilities of nanoparticles, specifically gold nanoparticles AuNPs, within context of modern times. AuNPs possess distinct biophysical properties, as a novel avenue as an antibacterial agent targeting Streptococcus Mutans and Candida Albicans. The aim of this study to create a nano-platform that has the potential to be environmentally sustainable, in addition to exhibiting exceptional antimicrobial properties against Streptococcus Mutans as well as Candida Albicans. Methods this study involved utilization of Pelargonium Graveolens leaves extract as a cost effective and environmentally sustainable approach for the green synthesis of AuNPs. Subsequently, physicochemical characteristics were assessed employing a variety of analytical methods, including as transmission electron microscopy, X-ray diffraction, Field Emission Scanning Electron Microscope, Zeta potential, Ultraviolet visible absorption spectroscopy, and Energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. The antimicrobial efficacy against Streptococcus Mutans and Candida Albicans was evaluated. Nanoparticles of various shapes, including hexagonal, spherical, semi-spherical, and triangular, were synthesized. These nanoparticles exhibited a mean particle size of 294nm and demonstrated low degree of aggregation. These nanoparticles exhibited long-term stability and were capable of facilely combining with diverse bioactive compounds. Results The study demonstrated that AuNPs which is synthesized by green methods display potent antimicrobial properties. Conclusion Utilization of Pelargonium Graveolens AuNPs may exhibit a promising potential as an antibacterial agent against Streptococcus Mutans and Candida Albicans. Nanoparticles (NPs) have the potential to serve as a novel approach for addressing pathogen infections as well as for biomedical, dental and pharmaceutical purposes in the future.

Abstract The Yunshang black goat is a renowned mutton specialist breed mainly originating from China that has excellent breeding ability with varying litter sizes. Litter size is an important factor in the economics of goat farming. However, ruminal microbiome structure might be directly or indirectly regulated by pregnancy-associated factors, including litter sizes. Therefore, the current experiment aimed to evaluate the association of different litter sizes (low versus high) with ruminal microbiome structure by 16S rRNA gene sequencing and metabolomic profiling of Yunshang black does. A total of twenty does of the Yunshang Black breed, approximately aged between 3 and 4 years, were grouped (n = 10 goats/group) into low (D-l) and high (D-h) litter groups according to their litter size (the lower group has ≤ 2 kids/litter and the high group has ≧ 3 kids/litter, respectively). All goats were sacrificed, and collected ruminal fluid samples were subjected to 16S rRNA sequencing and LC–MS/MC Analysis for ruminal microbiome and metabolomic profiling respectively. According to PCoA analysis, the ruminal microbiota was not significantly changed by the litter sizes among the groups. The Firmicutes and Bacteroidetes were the most dominant phyla, with an abundance of 55.34% and 39.62%, respectively. However, Ruminococcaceae_UCG-009, Sediminispirochaeta, and Paraprevotella were significantly increased in the D-h group, whereas Ruminococcaceae_UCG-010 and Howardella were found to be significantly decreased in the D-l group. The metabolic profiling analysis revealed that litter size impacts metabolites as 29 and 50 metabolites in positive and negative ionic modes respectively had significant differences in their regulation. From them, 16 and 24 metabolites of the D-h group were significantly down-regulated in the positive ionic mode, while 26 metabolites were up-regulated in the negative ionic mode for the same group. The most vibrant identified metabolites, including methyl linoleate, acetylursolic acid, O-desmethyl venlafaxine glucuronide, melanostatin, and arginyl-hydroxyproline, are involved in multiple biochemical processes relevant to rumen roles. The identified differential metabolites were significantly enriched in 12 different pathways including protein digestion and absorption, glycerophospholipid metabolism, regulation of lipolysis in adipocytes, and the mTOR signaling pathway. Spearman’s correlation coefficient analysis indicated that metabolites and microbial communities were tightly correlated and had significant differences between the D-l and D-h groups. Based on the results, the present study provides novel insights into the regulation mechanisms of the rumen microbiota and metabolomic profiles leading to different fertility in goats, which can give breeders some enlightenments to further improve the fertility of Yunshang Black goats.

Abstract Ascomycetes, basidiomycetes and deuteromycetes can degrade wood, but less attention has been paid to basidiomycetes involved in Esca, a major Grapevine Trunk Disease. Using a wood sawdust microcosm system, we compared the wood degradation of three grapevine cultivars inoculated with Fomitiporia mediterranea M. Fisch, a basidiomycete responsible for white-rot development and involved in Esca disease. The grapevine cultivar Ugni blanc was more susceptible to wood degradation caused by F. mediterranea than the cultivars Cabernet Sauvignon and Merlot. Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy showed that F. mediterranea preferentially degrades lignin and hemicellulose over cellulose (preferential, successive or sequential white-rot). In addition, co-inoculation of sawdust with two cellulolytic and xylanolytic bacterial strains of Paenibacillus (Nakamura) Ash ( Paenibacillus sp. (S231-2) and P. amylolyticus (S293)), enhanced F. mediterranea ability to degrade Ugni blanc. The NMR data further showed that the increase in Ugni blanc sawdust degradation products was greater when bacteria and fungi were inoculated together. We also demonstrated that these two bacterial strains could degrade the wood components of Ugni blanc sawdust. Genome analysis of these bacterial strains revealed numerous genes predicted to be involved in cellulose, hemicellulose, and lignin degradation, as well as several other genes related to bacteria-fungi interactions and endophytism inside the plant. The occurrence of this type of bacteria-fungus interaction could explain, at least in part, why necrosis develops extensively in certain grapevine varieties such as Ugni blanc.

Background: Since December 2019, when a new coronavirus disease 2019 (COVID-19) was detected in Wuhan, China, over 774 million confirmed COVID-19 cases and over seven million deaths have been reported globally, as of 7 January 2024 (WHO, 2024). Venous thromboembolism is a recognized complication of COVID-19. This study aimed to investigate the prevalence of pulmonary embolism (PE) diagnosed by CT pulmonary angiography (CTPA) in COVID-19 patients and the features of the associated factors. Methods and Results: The study included 162 patients from the Imam Abdulrahman Al-Faisal Hospital who had COVID-19-confirmed infections while hospitalized in the ICU. Patients were diagnosed as COVID-19 positive by RT-PCR and underwent CTPA examination on the Discovery 16-slice CT scanner (Siemens, Germany) following standard protocol. For contrast enhancement, non-ionic, iodinated, intravenous contrast material (Omnipaque 350 mg) was used. PE was detected by CTPA in 87(53.7%) COVID-19 patients. The D-dimer level was significantly higher in the PE group than in the non-PE group. The frequency of renal impairment in the PE group was 2.3 times higher than in the non-PE group. The ICU duration was longer in the PE group than in non-PE group (12.9±11.3 and 8.6±7.2 days, P=0.005). The death rate was 17.2% in the PE group and 1.3% in the non-PE group (P=0.001). The heart and respiratory rates, blood pressure, BMI, BUN, and creatinine levels did not differ in the study groups. The frequency of diabetes, hypertension, asthma, COPD, and smoking were comparable in the groups. Conclusion: CTPA is very important in diagnosing PE in COVID-19 patients. CTPA-diagnosed PE is significantly associated with D-dimer, ICU duration, and death.

Abstract Background Large conductance calcium-activated potassium (BKCa) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BKCa channel opener) could induce migraine-like headache in persons with PPTH. Methods This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period. Results Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001). Conclusions Our results indicate that BKCa channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BKCa channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BKCa channel blockers in managing PPTH. ClinicalTrials.gov Identifier NCT05378074.

Background: Temporal arteritis is a large-vessel vasculitis mostly seen in the elderly. Amyloidosis may be secondary to a chronic inflammation of body organs. Here, we present the second case report of temporal arteritis complicated by amyloidosis that was successfully treated by tocilizumab. Case presentation: A 64-year-old female presented complaining of fatigue, fever, and diarrhea accompanied by abdominal pain. One year before presentation, she was diagnosed with temporal arteritis. She was treated with 15 mg/day oral prednisone for the last 6 months, with partial remission, but persistence of the fatigue and an elevated erythrocyte sedimentation rate (ESR, 56 mm/h). Physical examination showed tenderness of both temporal arteries and a soft abdomen. Colon tissue biopsy showed amyloid depositions in the vessels and stroma that were positive for Congo red staining. Tocilizumab was started with 8 mg/kg intravenous, the diarrhea resolved, and the arthralgia improved within 1 month, with a decrease in the ESR to 8 mm/h, and a C-reactive protein (CRP) level of 0.98 mg/dl. Monthly tocilizumab therapy remains efficacious 12 months later and was stopped due to lack of tocilizumab from the hospital. No side effects of tocilizumab were registered. Conclusion: Chronic inflammation may be complicated by amyloidosis in patients with rheumatic diseases and genetic predisposition. Therefore, it is important to screen for intestinal Amyloid A (AA) amyloidosis in individuals with gastrointestinal disorders complicated by rheumatic disorders. AA amyloidosis may be complicated by temporal arteritis and presented with gastrointestinal symptoms such as diarrhea.

الخلفية: يمثل استئصال المرارة بالتنظير الشكل الرئيسي للتداخلات الجراحية من أجل تحصي الصفراء، وعلى الرغم من امتلاكها بعض المزايا فيما يتعلق بالشفاء الأسرع ومدة الاستشفاء الأقصر فإنها لا تخلو من بعض المشاكل مثل الألم التالي للجراحة الذي يعتبر من التحديات الصحية الهامة. الهدف: كان الهدف من هذه الدراسة تقييم التطبيق الموضعي لليدوكائين 2% داخل البريتوان بعد استئصال المرارة التنظيري على الألم التالي للجراحة والحاجة للمسكنات الأفيونية. المواد والطرق: كانت هذه دراسة مقارنة تحليلية(مستقبلية) شملت 100 مريضاً من الخاضعين لاستئصال المرارة تنظيرياً في وحدة الجراحة العامة، مستشفى تشرين الجامعي، اللاذقية، خلال الفترة ما بين 2023-2024. تم تقسيم المرضى عشوائياً إلى مجموعتين متساويتين هما الليدوكائين(50 حالة) ومجموعة الشاهد(50 حالة) مع مقارنة الحصيلة النهائية بين المجموعتين. النتائج: من بين 100 مريض، بلغ عدد الذكور 31 مريض(31%) والاناث 69 مريضة(69%). كان متوسط عمر المرضى 45.44 ±13.7 سنة و 66% من المرضى من الدرجة I تبعاً لتصنيف ASA. لم يلاحظ وجود فروقات هامة إحصائياً بين مجموعتي الدراسة فيما يتعلق بالعمر، الجنس، مشعر كتلة الجسم، تصنيف ASA، مدة العمل الجراحي وزمن التخدير(P>0.05). كان تواتر كل من الألم في الكتف بعد الجراحة، الغثيان والإقياء في مجموعة الليدوكائين مقابل الشاهد على الشكل التالي:(88% مقابل 96%،p:0.1)، (38% مقابل 44%،p:0.5) و(20% مقابل 24%،p:0.4) على التوالي. بالإضافة لذلك، كانت الحاجة للمسكنات أقل بشكل هام إحصائياً في مجموعة الليدوكائين(92% مقابل 100%،p:0.04) مع متوسط زمن أخذ المسكنات بعد الجراحة أطول في مجموعة الليدوكائين(4.5±1.4 ساعة مقابل 2.92±0.8 ساعة في مجموعة الشاهد مع p:0.001). كان متوسط سلم الألم في الكتف والبطن أقل بشكل هام إحصائياً في مجموعة الليدوكائين مقارنة مع الشاهد خلال الساعات الستة الأولى بعد الجراحة(p

Background In recent years, there has been a notable increase in the level of attention devoted to exploring capabilities of nanoparticles, specifically gold nanoparticles AuNPs, within context of modern times. AuNPs possess distinct biophysical properties, as a novel avenue as an antibacterial agent targeting Streptococcus Mutans and Candida Albicans. The aim of this study to create a nano-platform that has the potential to be environmentally sustainable, in addition to exhibiting exceptional antimicrobial properties against Streptococcus Mutans as well as Candida Albicans. Methods this study involved utilization of Pelargonium Graveolens leaves extract as a cost effective and environmentally sustainable approach for the green synthesis of AuNPs. Subsequently, physicochemical characteristics were assessed employing a variety of analytical methods, including as transmission electron microscopy, X-ray diffraction, Field Emission Scanning Electron Microscope, Zeta potential, Ultraviolet visible absorption spectroscopy, and Energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. The antimicrobial efficacy against Streptococcus Mutans and Candida Albicans was evaluated. Nanoparticles of various shapes, including hexagonal, spherical, semi-spherical, and triangular, were synthesized. These nanoparticles exhibited a mean particle size of 294nm and demonstrated low degree of aggregation. These nanoparticles exhibited long-term stability and were capable of facilely combining with diverse bioactive compounds. Results The study demonstrated that AuNPs which is synthesized by green methods display potent antimicrobial properties. Conclusion Utilization of Pelargonium Graveolens AuNPs may exhibit a promising potential as an antibacterial agent against Streptococcus Mutans and Candida Albicans. Nanoparticles (NPs) have the potential to serve as a novel approach for addressing pathogen infections as well as for biomedical, dental and pharmaceutical purposes in the future.

Abstract Background Phosphodiesterase 3 (PDE-3) inhibition have been implicated in the neurobiologic underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to ascertain whether PDE-3 inhibition can elicit migraine-like headache in persons with PPTH. Methods We tested cilostazol, which inhibits PDE-3, in a randomized, double-blind, placebo-controlled, two-way crossover study involving persons with PPTH attributed to mild traumatic brain injury. The randomized participants were allocated to receive oral administration of either 200-mg cilostazol or placebo (calcium tablet) on two separate experiment days. The primary end point was the incidence of migraine-like headache during a 12-hour observation window post-ingestion. The secondary endpoint was the area under the curve (AUC) for reported headache intensity scores during the same observation window. Results Twenty-one persons underwent randomization and completed both experiment days. The mean participants’ age was 41.4 years, and most (n = 17) were females. During the 12-hour observation window, 14 (67%) of 21 participants developed migraine-like headache post-cilostazol, in contrast to three (14%) participants after placebo (P =.003). The headache intensity scores were higher post-cilostazol than after placebo (P

Background. The incidence of kidney stones has been raised all over the world. Nephrolithiasis is the most common cause of illnesses in western countries and has been rising in its incidence in developing countries. PCNL describe the management of large renal calculi when measuring >20 mm and even for smaller ones of lower pole with excellent stone-free rate reach to 98%. Aim. To evaluate the mini-percutaneous nephrolithotomy (mini-PCNL) safety used to cure upper ureteral and renal stones with assessing the complication and procedure outcome in Iraqi patients. Method. This is a prospective study done between October 2022 and September 2023 in Ghazi Al-Hariri for Surgical Specialties Hospital, Medical city, with 100 patients enrolled who underwent mini-PCNL. All patients had upper ureteral and renal stones (size ≥20 mm). The nephroscope tube was utilized. The stones were destroyed by pneumatic lithotripter. Complications and outcomes were determined immediately postoperative via X-ray of the ureters, kidneys and bladder. Ultra-sonography also used to determine safety and efficacy of procedure. Results. The cases mean age was 55.8 ± 12.3 years, and their BMI was 29.5 ± 5.9 kg/m2. The size of mean stone was 22.5 ± 17.9 mm. The stone-free rate (SFR) was 94.7%. The post-operative hospital stay mean was 3.6 ± 2.7 days. The Hb drop mean was 0.6 ± 0.3 g/dL. There were none of our cases had organ trauma or any complications. Thirty cases required additional subsequent extra-corporeal shock wave lithotripsy. Conclusion. The mini-PCNL is effective and safe in cases of upper ureteral and renal stones ≥20 mm. Researches with a larger multi-center cohorts may be needed to validate these techniques.

Safeguarding patients from emerging infectious diseases demands strategies that prioritise patient well-being and protection. Immunobridging is an established trial methodology which has been increasingly employed to ensure patient protection and provide clinicians with swift access to vaccines. It uses immunological markers to infer the effectiveness of a new drug through a surrogate measure of efficacy. Recently, this method has also been employed to authorise novel drugs, such as COVID-19 vaccines, and this article explores the concepts behind immunobridging trials, their advantages, issues, and significance in the context of COVID-19 and other infectious diseases. Our goal is to improve awareness among clinicians, patient groups, regulators, and health leaders of the opportunities and issues of immunobridging, so that fewer patients are left without protection from infectious diseases, particularly from major pathogens that may emerge.

HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes ROBO1 (log2FoldChange = 4.32, FDR = 1.35E-11) and SLC38A5 (log2FoldChange = 3.36 FDR = 1.59E-07). ROBO1, an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial SLC38A5, an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis.

Abstract Local tissue damage following snakebite envenoming remains a poorly researched area. To develop better strategies to treat snakebites, it is critical to understand the mechanisms through which venom toxins induce envenomation effects including local tissue damage. Here, we demonstrate how the venoms of two medically important Indian snakes (Russell's viper and cobra) affect human skeletal muscle using a cultured human myoblast cell line. The data suggest that both venoms affect the viability of myoblasts. Russell’s viper venom reduced the total number of cells, their migration, and the area of focal adhesions. It also suppressed myogenic differentiation and induced muscle atrophy. While cobra venom decreased the viability, it did not largely affect cell migration and focal adhesions. Cobra venom affected the formation of myotubes and induced atrophy. Cobra venom-induced atrophy could not be reversed by small molecule inhibitors such as varespladib (a phospholipase A2 inhibitor) and prinomastat (a metalloprotease inhibitor), and soluble activin type IIb receptor (a molecule used to promote regeneration of skeletal muscle), although the antivenom (raised against the Indian ‘Big Four’ snakes) has attenuated the effects. However, all these molecules rescued the myotubes from Russell’s viper venom-induced atrophy. This study demonstrates key steps in the muscle regeneration process that are affected by both Indian Russell’s viper and cobra venoms and offers insights into the potential causes of clinical features displayed in envenomed victims. Further research is required to investigate the molecular mechanisms of venom-induced myotoxicity under in vivo settings and develop better therapies for snakebite-induced muscle damage.

Abstract Background About one-third of persons with migraine experience transient neurologic symptoms, referred to as aura. Despite its widespread prevalence, comprehensive clinical descriptions of migraine with aura remain sparse. Therefore, we aimed to provide an in-depth phenotypic analysis of aura symptoms and characteristics in a cross-sectional study of a large sample of adults diagnosed with migraine with aura. Methods Data were extracted from the baseline characteristics of participants in the Registry for Migraine (REFORM) study – a single-center, prospective, longitudinal cohort study. Participants were adults diagnosed with migraine aura, reporting ≥ 4 monthly migraine days in the preceding 3 months. Trained personnel conducted in-person semi-structured interviews, capturing details on the nature, duration, localization, and progression of individual aura symptoms. Results Of the 227 enrolled participants with migraine with aura, the mean age was 41.1 years, with a predominant female representation (n = 205 [90.3%]). Visual aura was present in 215 (94.7%) participants, somatosensory aura in 81 (35.7%), and speech and/or language aura in 31 (13.7%). A single type of aura was observed in 148 (65.2%) participants, whilst 79 (34.8%) reported multiple aura types. Most participants (n = 220 [96.9%]) described their aura symptoms as positive or gradually spreading. Headache in relation to aura was noted by 218 (96.0%) participants, with 177 (80.8%) stating that the onset of aura symptoms preceded the onset of headache. Conclusions This study offers a detailed clinical depiction of persons with migraine with aura, who were predominantly enrolled from a tertiary care unit. The findings highlight potential gaps in the available literature on migraine with aura and should bolster clinicians’ acumen in diagnosing migraine with aura in clinical settings.

Abstract Background Migraine is a multiphasic neurovascular disorder, where headache can be succeeded by postdromal symptoms. However, there are limited research on postdromal symptoms. This study aimed to investigate the proportion of individuals with migraine from a tertiary care unit reporting postdromal symptoms in adherence with the ICHD-3 definition. We also aimed to examine how the means of enquiry might influence the estimated proportions. Additionally, we explored whether any clinical features might affect the likelihood of reporting postdromal symptoms. Finally, we assessed to what extend the postdromal symptoms might impact the disease burden. Methods In a cross-sectional study, we enrolled adult participants diagnosed with migraine who were asked to report their postdromal symptoms (i.e., unprompted reporting). Subsequently, a 16-item list was used to further ascertain the occurrence of postdromal symptoms (i.e., prompted reporting). Clinical characteristics were obtained through a semi-structured interview. Moreover, electronic questionnaires were used to assess the disease burden, i.e., the Six-Item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and the World Health Organization Disability Assessment 2.0 (WHODAS 2.0). Results Among 631 participants with migraine, a higher proportion experienced at least one postdromal symptom when prompted (n = 509 [80.7%]) compared with unprompted reporting (n = 421 [66.7%], P

Introduction: Emergency medicine (EM) is one of few specialties with variable training lengths. Hiring a three-year graduate to continue fellowship training in a department that supports a four-year residency program can lead to conflicts around resident supervision. We sought to understand hiring and clinical supervision, or staffing, patterns of non-Accreditation Council for Graduate Medical Education (ACGME) fellowships hosted at institutions supporting four-year residency programs. Methods: We performed a web-based, cross-sectional survey of non-ACGME fellowship directors (FD) hosted at institutions supporting four-year EM residency programs. We calculated descriptive statistics. Our primary outcome was the proportion of programs with four-year EM residencies that hire non-ACGME fellows graduating from three-year EM residencies. Results: Of 119 eligible FDs, 88 (74%) completed the survey. Seventy FDs (80%) indicated that they hire graduates of three-year residencies. Fifty-six (80%) indicated that three-year graduates supervise residents. Most FDs (74%) indicated no additional requirements exist to supervise residents outside of being hired as faculty. The FDs cited department policy, concerns about quality and length of training, and resident complaints as reasons for not hiring three-year graduates. A majority (10/18, 56%) noted that not hiring fellows from three-year programs negatively impacts recruitment and gives them access to a smaller applicant pool. Conclusion: Most non-ACGME fellowships at institutions with four-year EM programs recruit three-year graduates and allow them to supervise residents. This survey provides programs information on how comparable fellowships recruit and staff their departments, which may inform policies that fit the needs of their learners, the fellowship, and the department.

Abstract Background: Immunoglobulin E (IgE) has a role in mediating allergic reactions and their powerful effector functions, but numerous factors influence its value. Objective: To find any difference in total and specific IgE serum levels at the different age groups and residences. Materials and Methods: Eighty-seven asthmatic children, including 57 males and 30 females with asthma aged between 1 and 16 years old, 32.2% living in rural and 67.8% living in urban, were collected at Kerbala Teaching Hospital for Children. All asthmatic children in this study were subjected to measuring total IgE level using AccuBind IgE ELISA kit, Human Chlamydia pneumoniae IgG using Cpn IgG ELISA kit, and Human C. pneumoniae IgE using Cpn IgE ELISA kit. Results: There was a significant positive linear correlation between age and total IgE level and a significant negative correlation between age and C. pneumoniae IgE in asthmatic children (0.255, P = 0.017, -0.233, P = 0.03, respectively). Further, there was a significant positive linear correlation between total IgE and C. pneumoniae IgE under age controlling (0.225, P = 0.019). In urban residents, the asthmatic children more than eleven years old had a low C. pneumonia IgE serum level (5.845 ± 1.821 ng/L) compared with asthmatic children who lived in rural areas (8.206 ± 2.793 ng/L). Depending on age groups, there was a significant difference (P = 0.047) in C. pneumonia IgE serum levels in asthmatic children who lived in urban areas. Conclusion: C. pneumonia-specific IgE decreased in early adulthood urban asthmatic children.

Background The increasing prevalence of diabetic ketoacidosis (DKA) related admissions poses a significant burden on the healthcare systems globally. However, data regarding the predictors of healthcare resource utilization in DKA is limited and inconsistent. This study aimed to identify key predictors of hospital length of stay (LOS), readmission and recurrent DKA episodes.Methods We undertook a retrospective cross-sectional analysis of all DKA admissions from 2015 to 2021 across four hospitals in Qatar. The primary outcomes were the length of stay (LOS), 90-day readmission and 6-month and 1-year DKA recurrence.Results We included 922 patients with a median age of 35 years (25–45). 62% were males with type-1 diabetes-mellitus (T1DM) and type-2 DM (T2DM), present in 52% and 48% of patients. The median LOS was 2.6 days (IQR 1.1–4.8), and the median DKA resolution time was 18 h (10.5–29). Male-gender, new-onset DM, higher Charlson Comorbidity Index (CCI), lower haemoglobin, sodium and potassium, higher urea, longer DKA duration and MICU admission predicted a longer LOS in a multivariate regression analysis. None of the factors were significantly associated with 90-day readmission. Patients with pre-existing T1DM were more likely to have a six-month DKA recurrence than pre-existing T2DM. Patients with a 6-month DKA recurrence, female gender and T1DM had higher odds of 12-month recurrence, whereas a consult with a diabetes educator at the index admission was associated with decreased odds of recurrence.Conclusions/interpretation This is the most extensive study from the Middle-East region reporting on LOS, readmissions and the recurrence of DKA. Results from this study with a diverse population may be valuable for physicians and healthcare systems to decrease the diabetes-related healthcare burden in DKA patients.

Abstract The human aryl hydrocarbon receptor (AHR) undergoes continuous shuttling between nucleus and cytoplasm. Binding to exogenous or endogenous ligands promotes its rapid nuclear import. The proposed mechanism for the ligand-dependent import is based on exposing the bipartite nuclear localisation signal (NLS) to members of the importin (IMP) superfamily. Among this, the molecular interactions involved in the basal import still need to be clarified. Utilizing fluorescently fused AHR variants, we recapitulated and characterized AHR localization and nucleo-cytoplasmic shuttling in living cells. Analysis of AHR variants carrying NLS point mutations demonstrated a mandatory role of first (13RKRRK17) and second (37KR-R40) NLS segments on the basal import of AHR. Further experiments indicated that ligand-induced import is mainly regulated through the first NLS, while the second NLS is supportive but not essential. Additionally, applying IMPα/β specific inhibitors, ivermectin (IVM) and importazole (IPZ), slowed down the ligand-induced import and, correspondingly, decreased the basal nuclear accumulation of the receptor. In conclusion, our data show that ligand-induced and basal nuclear entry of AHR rely on the same mechanism but are controlled uniquely by the two NLS components.

Some changes appeared in women’s menstrual cycle after receiving the coronavirus disease 2019 (COVID-19) vaccine, but the information about the pattern and characteristics of these symptoms was unclear. This study was conducted to estimate the prevalence of menstruation change and evaluate the association between COVID-19 vaccination and the occurrence of such disturbance. An online web-based survey was conducted during March–April 2022 that targeted 729 COVID-19 vaccinated women aged between 18 and 45 years in the Jazan region of Kingdom of Saudi Arabia. The tool collected demographic information, psychological data, and COVID-19 post-vaccination side effects. The overall prevalence of menstrual change among the women was 60.9% (95% CI 57.3–64.4). 66.3% and 64.1% of women, respectively, in the age group of 25–34 and 35–45 years were more affected. Most of the detected abnormalities were related to delayed menstruation and changes in pain intensity. Menstrual disturbances that occur after immunization are transient and have no long-term implications. Menstrual disorders are prevalent before vaccination, but there is a considerable increase following vaccination. Because there is no apparent cause for these post-vaccine disturbances, and their effects are difficult to anticipate, it is preferable to warn those concerned and encourage them to learn more about the biological changes causing these problems.

Abstract Networks are essential for analyzing complex systems. However, their growing size necessitates backbone extraction techniques aimed at reducing their size while retaining critical features. In practice, selecting, implementing, and evaluating the most suitable backbone extraction method may be challenging. This paper introduces netbone, a Python package designed for assessing the performance of backbone extraction techniques in weighted networks. Its comparison framework is the standout feature of netbone. Indeed, the tool incorporates state-of-the-art backbone extraction techniques. Furthermore, it provides a comprehensive suite of evaluation metrics allowing users to evaluate different backbones techniques. We illustrate the flexibility and effectiveness of netbone through the US air transportation network analysis. We compare the performance of different backbone extraction techniques using the evaluation metrics. We also show how users can integrate a new backbone extraction method into the comparison framework. netbone is publicly available as an open-source tool, ensuring its accessibility to researchers and practitioners. Promoting standardized evaluation practices contributes to the advancement of backbone extraction techniques and fosters reproducibility and comparability in research efforts. We anticipate that netbone will serve as a valuable resource for researchers and practitioners enabling them to make informed decisions when selecting backbone extraction techniques to gain insights into the structural and functional properties of complex systems.

Abstract Background Although the involvement of calcitonin gene-related peptide (CGRP) in migraines is well-established, its specific role in investigating the aura phase, which often precedes the headache, remains largely unexplored. This study aims to instigate CGRP’s potential in triggering aura, thus establishing its role in the early stages of migraine. Methods In this open-label, non-randomized, single-arm trial, 34 participants with migraine with aura received continuous intravenous infusion of CGRP (1.5 µg/min) over 20 min on a single experimental day. Participants were required to be free of headache and report no use of acute medications 24 h before infusion start. The primary endpoint was the incidence of migraine aura during the 12-hour observational period after the start of infusion. Results Thirteen (38%) of 34 participants developed migraine aura after CGRP infusion. In addition, 24 (71%) of 34 participants developed migraine headache following CGRP infusion. Conclusions Our findings suggest that CGRP could play an important role in the early phases of a migraine attack, including during the aura phase. These insights offer a new perspective on the pathogenesis of migraines with aura. They underscore the need for additional research to further explore the role of CGRP in these initial stages of a migraine attack, and potentially inform future development of therapeutic interventions. Trial registration ClinicalTrials.gov Identifier: NCT04592952. Graphical Abstract

مقدمة: يعتبر الداء السكري أكثر الإضطرابات الاستقلابية شيوعاً حول العالم، وقرح القدم السكرية أحد أهم المضاعفات الصحية المرتبطة بالداء السكري المزمن وهي السبب الرئيسي لبتر الساق غير الرضي. هدفت الدراسة الحالية إلى تقييم تأثير تطبيق تقنية الضغط السلبي على درجة التئام قرح القدم السكرية لدى مرضى السكري من النمط الثاني في مشفى تشرين الجامعي في اللاذقية. المناهج: وفق المنهج التجريبي طبقت الدراسة على عينة عشوائية شملت 30 مريضاً من كلا الجنسين في قسم جراحة الأوعية، تم تقسيمهم إلى مجموعتين تجريبية (15 مريضاً) خضعت لتغيير ضماد قرح القدم باستخدام تقنية الضغط السلبي، وضابطة (15مريضاً) خضعت لتغيير الضماد بالطريقة الروتينية المعتمدة في المشفى. تم تقييم درجة التئام القرح ودرجة القرح باستخدام مقياس ريسفتش ومقياس درجة القرح خلال الأيام (1،5 ,10،15، 20) بعد بدء تطبيق الضماد. النتائج: أظهرت النتائج وجود فروق ذات دلالة إحصائية مهمة جداً في متوسطات رتب درجة التئام قرح القدم السكرية (U=44,P=0.004)، ووجود فروق ذات دلالة إحصائية مهمة في اجمالي درجة القرح (X2=10.09، p=0.018) مقارنة بمرضى المجموعة الضابطة. الاستنتاجات: تقنية الضغط السلبي لها دور في تحسين شفاء قرح القدم السكرية، لذلك توصي الدراسة بضرورة اعتمادها كطريقة ضماد روتينية لمرضى قرح القدم السكرية واجراء المزيد من الأبحاث حولها وذلك لتحسين شفاء المرضى والتقليل من الحاجة لإجراء بتر الأطراف السفلية.

Background: Patient satisfaction is increasingly recognized as a vital indicator of healthcare service quality. It aids in identifying healthcare system shortcomings and improving patient trust. Factors influencing patient satisfaction during anesthesia services have been studied globally, but there is a lack of research in the context of lipoabdominoplasty under combined lumbar spinal-epidural anesthesia (CLSEA). Objective: To evaluates patient satisfaction with lipoabdominoplasty under CLSEA, focusing on various intraoperative factors that may affect satisfaction. Patients and Methods: This prospective observational cross-sectional study included adult patients undergoing lipoabdominoplasty under CLSEA without complications. Patients completed a structured questionnaire assessing satisfaction with intraoperative care. The questionnaire addressed factors related to the information provided, decision-making involvement, physical comfort, emotional support, and respect for patient values. Results: The questionnaire encompassed three types of questions: anesthesia quality, factors causing intraoperative annoyance, and patient-team interaction. The majority of patients found epidural anesthesia favorable. Factors causing moderate annoyance included surgery duration, stress, fixed position, feeling cold, and shivering. Patients reported low annoyance with factors like team discussions, anxiety, surgical light, dizziness, thirst, itching, nausea, vomiting, noise, pain, and dyspnea. Patients generally had a high rate of good reactions toward the surgical team, but less than 50% requested more respect and thorough medication information. Conclusion: This study offers insights into patient satisfaction with lipoabdominoplasty under CLSEA, shedding light on factors affecting their experiences. The findings underline the importance of addressing patient concerns and expectations to enhance overall satisfaction and quality of care.

Schwann cells are found in the peripheral nervous system and can sometimes appear as benign hamartoma lesions in various parts of the body. Although rare in the gastrointestinal (GI) tract, they have been observed in the colon. Recently, mucosal Schwann cell hamartomas of the GI tract have been studied, and it was discovered that they had yet to be investigated up to 2009. In this context, we present the case of a 60-year-old man who was found to have lesions in the transverse colon during a routine colonoscopy. No further investigations were conducted since these lesions have not been associated with any risk of malignancy transformation and have not been linked to any inherited syndromes.

Abstract Background Erenumab has demonstrated effectiveness for prevention of migraine attacks, but the treatment is costly, and a considerable proportion of patients do not respond to it. The Registry for Migraine study (REFORM) was initiated to discover biomarkers that can predict response to erenumab in patients with migraine. The specific objective was to investigate differences in erenumab efficacy based on clinical information, blood-based biomarkers, structural and functional magnetic resonance imaging (MRI), and response to intravenous infusion of calcitonin gene-related peptide (CGRP). In this first report of the REFORM study, we provide a comprehensive description of the study methodology, and present the baseline characteristics of the study population. Methods The REFORM study was a single-center, prospective, longitudinal cohort study in adults with migraine who were scheduled to receive preventive treatment with erenumab as part of a separate, open-label, single-arm phase IV trial. The study included four periods: a 2-week screening period (Weeks -6 to -5), 4-week baseline period (Week -4 to Day 1), 24-week treatment period (Day 1 to Week 24), and a 24-week follow-up period without treatment (Week 25 to Week 48). Demographic and clinical characteristics were recorded using a semi-structured interview, whilst outcome data were obtained using a headache diary, patient-reported outcomes, blood sampling, brain MRI, and responsiveness to intravenous infusion of CGRP. Results The study enrolled 751 participants, with a mean age ± SD of 43.8 ± 12.2 years, of which 88.8% (n = 667) were female. At enrollment, 64.7% (n = 486) were diagnosed with chronic migraine, and 30.2% (n = 227) had history of aura. The mean monthly migraine days (MMDs) was 14.5 ± 7.0. Concomitant preventive medications were used by 48.5% (n = 364) of the participants, and 39.9% (n = 300) had failed ≥ 4 preventive medications. Conclusion The REFORM study enrolled a population with a high migraine burden and frequent use of concomitant medications. The baseline characteristics were representative of patients with migraine in specialized headache clinics. Future publications will report the results of the investigations presented in this article. Trial registration The study and sub-studies were registered on ClinicalTrials.gov (NCT04592952; NCT04603976; and NCT04674020).

Abstract Miniaturized electrical stimulation (ES) implants show great promise in practice, but their real-time control by means of biophysical mechanistic algorithms is not feasible due to computational complexity. Here, we study the feasibility of more computationally efficient machine learning methods to control ES implants. For this, we estimate the normalized twitch force of the stimulated extensor digitorum longus muscle on n = 11 Wistar rats with intra- and cross-subject calibration. After 2000 training stimulations, we reach a mean absolute error of 0.03 in an intra-subject setting and 0.2 in a cross-subject setting with a random forest regressor. To the best of our knowledge, this work is the first experiment showing the feasibility of AI to simulate complex ES mechanistic models. However, the results of cross-subject training motivate more research on error reduction methods for this setting.

Background and aims: Usually non-daily smokers do not consider themselves smokers, and they are at a higher level of health risks due to smoking compared to non-smokers. This study aimed to identify the prevalence of non-daily smoking (NDS) and its associated factors among university students. Methods: This cross-sectional web-based study was performed in Tabriz, Iran. A proportional random sample of 3666 students from all universities of Tabriz were recruited from July to August, 2019, and an online questionnaire was used to collect data. Predictors of NDS were investigated using a multiple logistic regression model. Results: A total of 15.7% and 7.8% of the students were daily and NDSs, respectively. Compared to the non-smokers, the NDSs were more likely to exhibit high-risk behaviors such as substance abuse (odd ratio [OR]=2.96; 95% CI: 2.12-4.13), alcohol drinking (OR=2.54; 95% CI: 1.78-3.62), hookah smoking experience (OR=9.30; 95% CI: 6.06-14.25), and regular hookah use (OR=24.22; 95% CI: 14.86-39.46). Compared to daily smokers, NDSs were more likely to be female gender (OR=0.16; 95% CI: 0.10-0.24), denial of being a smoker (OR=11.69; 95% CI: 6.86-19.91), not addicted to nicotine (OR=10.02; 95% CI: 4.21-23.85), and less likely to have an intention for quitting in recent months (OR=2.27; 95% CI: 1.28-4.04). Conclusion: Non-daily smokers do not consider themselves smokers and have no intention to quit smoking. They are more prone to present high-risk health behaviors. Health policymakers should pay more attention to NDSs while planning smoking cessation programs.

Currently, allergen-specific immunotherapy (AIT) for ragweed allergy is still based on natural allergen extracts. This study aimed to analyse the ability of four commercially available AIT vaccines (CLUSTOID, TYRO-SIT, POLLINEX Quattro Plus and Diater Depot) regarding their ability to induce IgG antibodies against ragweed pollen allergens in rabbits. Accordingly, the IgG reactivity of AIT-induced rabbit sera was tested for ten different ragweed pollen allergens (Amb a 1, 3, 4, 5, 6, 8, 9, 10, 11 and 12) by an ELISA. Furthermore, the ability of rabbit AIT-specific sera to block allergic patients’ IgE binding to relevant ragweed allergens (Amb a 1, 4, 6, 8 and 11) and to inhibit allergen-induced basophil activation was evaluated by an IgE inhibition ELISA and a mediator release assay. Only two AIT vaccines (Diater Depot > CLUSTOID) induced relevant IgG antibody levels to the major ragweed allergen Amb a 1. The IgG responses induced by the AIT vaccines against the other ragweed allergens were low and highly heterogeneous. Interestingly, the kinetics of IgG responses were different among the AIT vaccines and even within one AIT vaccine (Diater Depot) for Amb a 1 (long-lasting) versus Amb a 8 and Amb a 11 (short-lived). This could be due to variations in allergen contents, the immunogenicity of the allergens, and different immunization protocols. The IgE inhibition experiments showed that rabbit AIT-specific sera containing high allergen-specific IgG levels were able to inhibit patients’ IgE binding and prevent the mediator release with Diater Depot. The high levels of allergen-specific IgG levels were associated with their ability to prevent the recognition of allergens by patients’ IgE and allergen-induced basophil activation, indicating that the measurement of allergen-induced IgG could be a useful surrogate marker for the immunological efficacy of vaccines. Accordingly, the results of our study may be helpful for the selection of personalized AIT vaccination strategies for ragweed-allergic patients.

Key Clinical Message Posterior reversible encephalopathy syndrome may occur secondary to abrupt cessation of antihypertensive therapy. A gradual reduction in blood pressure and counseling regarding medication adherence are crucial to prevent adverse consequences. Abstract Posterior reversible encephalopathy syndrome (PRES) is a reversible clinical radiographic syndrome with headache, hypertensive encephalopathy, seizures, and visual disturbances as common modes of presentation. PRES can be attributed to several risk factors. We reported the case of a 66‐year‐old Asian female with PRES following nonadherence to antihypertensive treatment. Initially, her computed tomography scan of the head was normal. After 48 h, we again ordered a head CT scan, which showed lesions suggestive of hypertensive encephalopathy. We immediately reduced 20%–25% of mean arterial pressure, followed by a gradual blood pressure lowering to avoid adverse consequences. We did a follow‐up CT scan of the head at 2 weeks, showing the resolution of early lesions. Hence, we made a diagnosis of PRES. In these patients, it is crucial to ensure medication adherence to avoid complications.

Background: Esophageal cancer, a highly aggressive and often fatal gastrointestinal disease, frequently reaches advanced unresectable stages. The standard treatment involves definitive chemoradiation due to concerns about regional failure. To address this, intensified radiation dosages and advanced techniques like Intensity-Modulated Radiation Therapy (IMRT) and Three-Dimensional Conformal Radiation Therapy (3D-CRT) are being explored. This study aimed to compare dosimetric factors in patients with esophageal carcinoma undergoing IMRT versus 3D-CRT treatments. Methods: Twenty patients were alternately assigned to receive either treatment. Each patient's alternate virtual plan resulted in a total of forty plans. Dosimetric evaluations included coverage of the Planning Target Volume (PTV) and dose-volumes of lungs, heart, and spinal cord. Treatment consisted of 50.4 Gy radiation with concurrent weekly paclitaxel and carboplatin chemotherapy. Statistical analysis was conducted using the two-tailed Paired t-Test. Results: Dosimetric evaluations revealed no significant distinctions in PTV parameters such as maximum dose, minimum dose, mean dose, D2%, D50%, and V95% between IMRT and 3D-CRT plans. However, IMRT exhibited improvements in D98% and Homogeneity Index. While Conformity Index did not differ significantly, IMRT displayed reduced lung irradiation in various aspects such as Dmean, V20, and V30, while 3D-CRT showed lower irradiation in V5 and V10. IMRT effectively spared the heart with lowered heart irradiation in V30. Spinal cord Dmax remained consistent across both techniques. Conclusions: IMRT demonstrated better dose homogeneity and superior lung and heart sparing capabilities compared to 3D-CRT in treating esophageal carcinoma. While both techniques had similar dose conformity, IMRT's potential to reduce long-term radiation-induced lung and heart complications through improved sparing of these organs is noteworthy.

BackgroundOlder adults with polypharmacy are more prone to medication errors. People with low educational attainment have more difficulties in taking their medications.ObjectivesThis study aimed to identify the extent of medication self-administration errors (MSEs) and the contributing factors among illiterate and low-literate community-dwelling older adults with polypharmacy.MethodThe present cross-sectional study was conducted among people aged 60 and above. The data were collected using the sociodemographic, clinical, and Belief about Medicines Questionnaires (BMQ). To determine the extent of MSE, a medication error checklist was used. The negative binomial hierarchical regression model in the five blocks was performed.ResultsThe final sample size was 276 people. The frequency of MSEs in the last 6 months was 69.2%. Sixteen percent of participants had made four or more mistakes. The most common MSEs were forgetting, improper taking of medications with food, improper timing, incorrect dosage (lower dose), and forgetting the doctor's instructions. Near 18% of participants reported adverse events following their mistakes. The significant predictors of MSEs were being completely illiterate (p = 0.021), the higher number of doctor visits per year (p = 0.014), irregularly seeing doctors (p < .001), the higher number of medications (p < .001), and having poor medication beliefs (p < .001).ConclusionDespite the high prevalence of MSEs among older patients, practical strategies to deal with them at their homes have not been established among health systems. MSE as a multifactorial event can be caused by a collection of internal and external factors. Further studies to identify the role of patients, clinicians, procedures, and systems in developing MSEs as interconnected components are needed.

Rheumatic diseases are common progressive diseases that associated with chronic pain. Most patients seek to reduce the pain of these diseases by using dietary supplements (DS). Yet, most DS have limited benefits to reduce pain and/or disease progression. Therefore, this study aimed to explore the perceptions of community pharmacists about the efficacy, safety, and quality of the DS for treatment of rheumatic diseases (DSTRD) in the Iraqi pharmaceutical market. A qualitative study was conducted during February-2023 through face-to-face interview with community pharmacists with ≥6 months of working experience. The interviews were guided through semi-structured open-ended questions. The interviews were recorded using iPhone-11. A hybrid framework-model was used to analyze the data. Interviews were performed with 20 pharmacists. Only 30% of pharmacists considered DSTRD to be effective, whereas 75% of them perceived DSTRD to be safe. One-quarter of the participants considered the quality of DSTRD to be good. All interviewed pharmacists reported that prescribing DSTRD become a common practice. Eleven participants reported that deals with pharmaceutical companies are the main trigger for prescribing DSTRD. Three-quarter of participating pharmacists mentioned that they educate their patient about the dispensed DSTRD. However, only 10% of them educate patients about the possible side effects and interactions of DSTRD. In conclusion, most of the participating pharmacists have doubts about the efficacy, safety, and quality of DSTRD in the Iraqi market. The prescribing of such products by physicians is common and usually triggered by deals with pharmaceutical companies. Pharmacist-education to the patient on these supplements is poor.

Objective When considering proposals to improve diets, it is important to understand how factors like price and income can affect saturated fat (SF) intake and demand. In this study, we examine and estimate the influence of price and income on intake across 160 countries, by age and sex, and derive sensitivity measures (price elasticities) that vary by age, sex and world region.Design We econometrically estimate intake responsiveness to income and prices across countries, accounting for differences by world region, age and sex. Intake data by age, sex and country were obtained from the 2018 Global Dietary Database. These data were then linked to global price data for select food groups from the World Bank International Comparison Programme and income data from the World Development Indicators Databank (World Bank).Results Intake differences due to price were highly significant, with a 1% increase in price associated with a lower SF intake (% energy/d) of about 4.3 percentage points. We also find significant differences across regions. In high-income countries, median (age 40) intake reductions were 1.4, 0.8 and 0.2 percentage points, given a 1% increase in the price of meat, dairy, and oils and fats, respectively. Price elasticities varied with age but not sex. Intake differences due to income were insignificant when regional binary variables were included in the analysis.Conclusion The results of this study show heterogeneous associations among prices and intake within and across countries. Policymakers should consider these heterogeneous effects as they address global nutrition and health challenges.

تؤدي العمليات الجراحية الكبرى إلى استجابات فيزيولوجية عميقة ومضاعفات عديدة، يعتبر التركيز على العناية التمريضية المتخصصة خلال مرحلة الافاقة هو الإدراك بأنه يمكن الوقاية من وقوع الوفيات وإدارة المضاعفات. يرتبط استخدام مقياس new fast trackبنتائج سريرية مفيدة، وقد تم استخدامه في العديد من الجراحات ولكنه نادرا ما تم تطبيقه بالاشتراك مع جراحة أمراض النساء. الهدف: أجريت هذه الدراسة لتحديد تأثير تطبيق مقياس New fast track على المضاعفات المباشرة التالية لجراحة استئصال الرحم البطني. أدوات البحث وطرائقه: اجري البحث على عينة قوامها 30 مريضة في غرفة الافاقة وقسم الجراحة النسائية في مشفى تشرين الجامعي قسمت بالتساوي على مجموعتين بحيث تم تطبيق مقياسnew fast track على مريضات المجموعة التجريبية وعددهن 15 وتركت مريضات المجموعة الضابطة وعددهن 15 لروتين المشفى تم تقييم المضاعفات المباشرة الحاصلة لدى مريضات العينة الضابطة والتجريبية وذلك لمدة 24 ساعة من العمل الجراحي باستخدام اداتين مطورتين وهما استمارة البيانات الديموغرافية الحيوية واستمارة المضاعفات المباشرة بعد العمل الجراحي وترجمة الاداة الثالثة وهو مقياس new fast track . النتائج: أوضحت النتائج فعالية تطبيق مقياس new fast track. إذ انخفضت نسبة حدوث المضاعفات المتعلقة بالغثيان والاقياء وانخفاض درجة الحرارة في المجموعة التجريبية بشكل ملحوظ إضافة إلى انخفاض حدوث مضاعفات اخرى مثل الالم والنزف وتسرع القلب مقارنة بمريضات المجموعة الضابطة التي تركت لروتين المستشفى الا ان مدة التخريج من غرفة الافاقة كانت اطول. الاستنتاجات: تقترح معلومات الدراسة أن تطبيق مقياس new fast track في غرفة الافاقة يساهم في خفض معدل حدوث المضاعفات المباشرة التالية لاستئصال الرحم البطني.

Objective: This in vitro study compares the accuracy and trueness of various 3D-printed denture teeth. Methods: A total of 30 specimens were created using various 3D-printed resins, 10 each using Asiga DentaTOOTH resin (Asiga, Australia), Formlabs Denture Teeth Resin (Formlabs GmbH, Germany), and NextDent C&B MFH (Micro Filled Hybrid) resin (Nextdent B.V., Netherlands), respectively. A prefabricated mandibular first molar was scanned using a desktop laser scanner (E3, 3Shape A/S) to create a standard tessellation language file, which served as a “reference tooth” scan. That file was sent to each corresponding printer for printing according to manufacturer recommendations. The printed teeth were scanned with an intraoral scanner (TRIOS 3, 3shape, Copenhagen, Denmark). Trueness and precision were assessed using 3D morphometric analysis software (Geomagic Control X, 3D Systems, Rock Hill, SC, USA). One-way ANOVA was used to analyze the data (α = 0.05). Root mean square error and mean deviations were also calculated. Data analysis was carried out using SPSS (IBM Corp., New York, NY, USA) software. One-way ANOVA with Tukey’s post hoc analysis was used. P-values of

Abstract Background Pituitary adenylate cyclase-activating polypeptide (PACAP), structurally related to vasoactive intestinal peptide (VIP), is one of the important mediators in the pathogenesis of migraine and is known to dilate cranial arteries and induce headache and migraine. Our objective was to determine whether Lu AG09222—an investigational humanized monoclonal antibody directed against PACAP ligand—would inhibit the PACAP-signaling cascade by abolishing its vasodilatory and headache-inducing abilities. Methods In a randomized, double-blind, parallel-group, single-dose, placebo-controlled study of Lu AG09222, healthy volunteers aged 18–45 years without history of headache disorders were randomly allocated to three treatment sequences (1:2:2) on two experimental infusion visits with 9 ± 3 days’ interval: placebo + saline + saline (n = 5), placebo + PACAP38 + VIP (n = 10), and Lu AG09222 + PACAP38 + VIP (n = 10). The primary outcome measure was area under the curve (AUC) of the change in superficial temporal artery (STA) diameter from 0 to 120 min after start of infusion of PACAP38. The study was conducted at the Danish Headache Center in Copenhagen, Denmark. Results In participants who received Lu AG09222 + PACAP38 infusion, there was a significantly lower STA diameter (mean (SE) [95% CI] AUC ‒35.4 (4.32) [‒44.6, ‒26.3] mm × min; P

Abstract Stenotrophomonas maltophilia, an environmental aerobic non-fermentative Gram-negative bacilli, has gained attention in many nosocomial outbreaks. COVID-19 patients in intensive care unit have extended hospital stay and are severely immunosuppressed. This study aimed to determine the prevalence and risk factors of S. maltophilia pneumonia in critical COVID-19 patients. A total of 123 COVID-19 patients in ICU admitted between March 2020 and March 2021 were identified from the authors’ institutional database and assessed for nosocomial pneumonia. Demographic data and factors predisposing to S. maltophilia pneumonia were collected and analyzed. The mean age was 66 ± 13 years and 74% were males. Median APACHE and SOFA scores were 13 (IQR = 8–19) and 4 (3–6), respectively. The Median NEWS2 score was 6 (Q1 = 5; Q3 = 8). The Median ICU stay was 12 (Q1 = 7; Q3 = 22) days. S. maltophilia was found in 16.3% of pneumonia patients, leading to a lengthier hospital stay (34 vs. 20 days; p

Abstract Objective To examine whether white matter hyperintensities (WMHs) and cerebral microbleeds (CMBs) are more prevalent in people with persistent post-traumatic headache attributed to mild traumatic brain injury (TBI), compared with healthy controls. Methods A magnetic resonance imaging (MRI) study of adults with persistent post-traumatic headache attributed to mild TBI and age- and gender-matched healthy controls. A semi-structured interview and validated self-report instruments were used to record data on demographics, clinical characteristics, and comorbidities. Imaging data were obtained on a 3T MRI Scanner using a 32-channel head coil. Participants and controls underwent a single MRI session, in which fluid-attenuated inversion recovery was used to visualize WMHs, and susceptibility-weighted imaging was used to detect CMBs. The primary outcomes were (I) the difference in the mean number of WMHs between participants with persistent post-traumatic headache and healthy controls and (II) the difference in the mean number of CMBs between participants with persistent post-traumatic headache and healthy controls. All images were examined by a certified neuroradiologist who was blinded to the group status of the participants and controls. Results A total of 97 participants with persistent post-traumatic headache and 96 age- and gender-matched healthy controls provided imaging data eligible for analyses. Among 97 participants with persistent post-traumatic headache, 43 (44.3%) participants presented with ≥ 1 WMH, and 3 (3.1%) participants presented with ≥ 1 CMB. Compared with controls, no differences were found in the mean number of WMHs (2.7 vs. 2.1, P = 0.58) and the mean number of CMBs (0.03 vs. 0.04, P = 0.98). Conclusions WMHs and CMBs were not more prevalent in people with persistent post-traumatic headache than observed in healthy controls. Future studies should focus on other MRI techniques to identify radiologic biomarkers of post-traumatic headache.

Abstract Background Brucellosis is a zoonotic disease caused by Gram-negative bacteria. It has variable manifestations (gastrointestinal, hepatobiliary, skeletal). Neurobrucellosis may develop at any stage of the disease (acute, subacute, and chronic phases) and affects the central and peripheral nervous systems. Acute peripheral neuropathy mimicking Guillain–Barré syndrome caused by brucellosis is rarely reported: only four cases in children were found in the literature review. Case presentation We report a case of a 4-year-old Syrian boy who presented with fever, weakness of lower limbs, backache, and fatigue. The patient lived in a brucellosis endemic area. A physical examination including a neurological examination showed mild paresthesia and muscle weakness. He had a stiff neck with Kernig’s sign with an absence of deep tendon reflexes in the lower extremities. Proprioception in the lower extremities was impaired, but he did not have any sensory problems. Abdominal cutaneous reflexes were absent. Brucellosis and Guillain–Barré syndrome were found in laboratory investigations and on electroneurogram (ENG). The patient was treated with sulfamethoxazole + trimethoprim, rifampicin, gentamicin, and dexamethasone, with an improvement. Conclusion This case demonstrates a rare case of brucellosis neurologic manifestation. Brucellosis should be kept in mind in all patients with acute paralysis, especially in those who live in endemic areas.

Aim. To determine morphological and morphometric changes in the structure of the mucous membrane of the large intestine and their relationship with the content of short-chain volatile fatty acids and fecal calprotectin in patients with inflammatory bowel disease. Materials and methods. We examined 68 patients with inflammatory bowel disease, including 30 women and 38 men aged 20–66 years, 55 patients were with ulcerative colitis and 13 patients – with Crohn’s disease. Histological examination focused on changes in the mucous membrane of the large intestine. Determination of short-chain volatile fatty acids in feces was performed using gas chromatography. Calprotectin content was measured in fecal samples by enzyme-linked immunosorbent assay. Results. Significant correlations were found between epithelial disruption and changes in crypt architecture, infiltration density, and histological activity. The higher degree of inflammation in patients with severe course was combined with a lower level of tissue nonspecific protection, which was detected by the number of goblet cells, eosinophilic and neutrophilic leukocytes. There was a decrease in the fecal concentration of butyric acid in patients with nonspecific ulcerative colitis and Crohn’s disease compared with controls, but a more significant decrease was observed in patients with severe nonspecific ulcerative colitis. The data have confirmed the association between inflammatory bowel disease and the content of short-chain volatile fatty acids, fecal calprotectin in coprofiltrate, which was evidenced by the presence of correlations between low content of short-chain volatile fatty acids and eosinophilic infiltration (r = -0.412; fecal calprotectin levels and disease severity (r = 0.589; P = 0.001), atrophy (r = 0.458; Р < 0.05), infiltration density (r = 0.434; Р < 0.05). Conclusions. All patients with inflammatory bowel disease are characterized by a specific histological picture, which reflected the different degrees of inflammation. Morphometric parameters more accurately show significant atrophic changes in the mucous membrane of the large intestine. The data have confirmed the association between inflammatory bowel disease and the content of short-chain volatile fatty acids and calprotectin in coprofiltrate.

Introduction: Primary Sjögren syndrome (pSS) is an immune systemic disease, that may affect the central nervous system. A severe headache unresponsive to treatment is the headache which is persistently nonresponsive to narcotic analgesics. Case presentation: A 48-year-old woman with a 10-year history of pSS was seen in January 2021, complaining of a headache one week previously. The headache was characterised by a dull persistent pressing intensity and was not responding to paracetamol, NSAIDs or codeine. She had no previous history, nor family history. Physical examination revealed bilateral parotid glands enlargement. Laboratory tests showed anaemia, and elevated levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), with positive anti-La and anti-Ro antibodies. She was given topical treatment and different doses of Predlone, in addition to methotrexate10 mg/week. She had received three pulses of methylprednisolone and was started on azathioprine with a mild response to the headaches, so she received two initial IV doses of rituximab 375 mg/m2, then every 2 weeks, with a clinical and laboratory response. Two years later, she had no headache. Discussion: Headache that may presented in pSS are tension headaches, migraines and cluster headaches. The therapy is disease-modifying antirheumatic drugs, hydroxychloroquine, glucocorticoids and biotherapeutics. Rituximab is used in the treatment of some patients with pSS, especially where it can affect systemic symptoms. Conclusion: Rituximab treatment may be an option for severe headache in patients with pSS. The mechanism is unknown but may be due to depletion of brain auto-reactive B cells. Further research is needed.