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BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments. OBJECTIVE: We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. METHODS: We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium. RESULTS: We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD. CONCLUSION: Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.

KRASG12C inhibitors, such as sotorasib and adagrasib, have revolutionized cancer treatment for patients with KRASG12C-mutant tumors. However, patients receiving these agents as monotherapy often develop drug resistance. To address this issue, we evaluated the combination of the PAK4 inhibitor KPT9274 and KRASG12C inhibitors in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). PAK4 is a hub molecule that links several major signaling pathways and is known for its tumorigenic role in mutant Ras-driven cancers. We found that cancer cells resistant to KRASG12C inhibitor were sensitive to KPT9274-induced growth inhibition. Furthermore, KPT9274 synergized with sotorasib and adagrasib to inhibit the growth of KRASG12C-mutant cancer cells and reduce their clonogenic potential. Mechanistically, this combination suppressed cell growth signaling and downregulated cell-cycle markers. In a PDAC cell line-derived xenograft (CDX) model, the combination of a suboptimal dose of KPT9274 with sotorasib significantly reduced the tumor burden (P= 0.002). Similarly, potent antitumor efficacy was observed in an NSCLC CDX model, in which KPT9274, given as maintenance therapy, prevented tumor relapse following the discontinuation of sotorasib treatment (P= 0.0001). Moreover, the combination of KPT9274 and sotorasib enhances survival. In conclusion, this is the first study to demonstrate that KRASG12C inhibitors can synergize with the PAK4 inhibitor KPT9274 and combining KRASG12C inhibitors with KPT9274 can lead to remarkably enhanced antitumor activity and survival benefits, providing a novel combination therapy for patients with cancer who do not respond or develop resistance to KRASG12C inhibitor treatment.

Abstract Background Pericardiocentesis offers a definitive diagnostic and a life-saving therapeutic modality through removal of pericardial fluid and relief of high intrapericardial pressure. Percutaneous pericardiocentesis has been performed via different approaches depending on different institutional experiences. In this paper, we present our institutional experience and review the current literature of the different approaches for performing percutaneous pericardiocentesis. Materials and methods We evaluated consecutive patients who underwent echocardiographic-guided pericardiocentesis via the apical approach for pericardial effusion between the period of April 1st, 2022, and April 1st, 2023, at University of Arkansas for Medical Sciences (UAMS). Health records were reviewed for clinical presentations, available imaging findings, procedural outcomes, and short-term follow up. Results A total of eight consecutive cases of pericardiocentesis via the apical approach were found. Seven were successful. No complications were reported. Six patients had evidence of tamponade physiology on echocardiogram. Conclusion Historically, pericardiocentesis has been most performed via the subxiphoid approach. However, an ultrasound-guided apical approach offers a safe and effective alternative and may be preferable in patients with challenging anatomies.

Abstract Background Interstitial lung disease (ILD) is an increasingly recognized complication of rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. Many risk factors for RA-related ILD were reported. The current study aims to explore the features and risk factors of Saudi patients with RA-ILD. Methods This is a multicenter, retrospective, observational study of patients with RA-ILD. Clinical and radiological data from patients with RA-ILD were obtained from electronic medical records, including demographics, clinical characteristics, laboratory tests, pulmonary function tests, ECHO, and HRCT images. Result Out of 732 patients, 57 had RA-ILD. The mean age at the time of ILD diagnosis was 61.9 (± 12.2) years. RA-ILD diagnosis was significantly less among females (p = 0.008). Patients who ever smoked had significantly more RA-ILD (p 0.05). The most common symptoms of RA-ILD were cough (55.6%) and dyspnea (30.2%), and the most common ILD pattern was Non-specific Interstitial Pneumonia (NSIP) (55.6%) followed by Usual Interstitial Pneumonia (UIP) (38.9%). Traction bronchiectasis (75.5%) and glass ground opacities (73.6%) were also observed. The mean FVC and DLCO at baseline were 64.6% and 53.3%, respectively. Conclusion In this cohort of patients, Saudi RA-ILD patients had a predominant NSIP pattern conversely to what is seen globally. These findings could be explained by the lower rates of smoking in our patient population. Future prospective national studies are needed to confirm the current findings and better evaluate RA-ILD epidemiology and risk factors.

Background: Malignant pericardial effusion (Eff) is often asymptomatic and has an unknown prevalence, due to its occult presentation. The condition often is identified postmortem on autopsy, and it is associated with a poor prognosis. Given the late presentation of malignant pericardial Effs, a minimal volume of literature has examined the epidemiology, clinical characteristics, and outcomes of these complex patients. We conducted a systematic review to advance present understanding of this condition. Methods: A search of 4 databases resulted in 41 case reports meeting criteria. Inclusion criteria were being a patient aged > 18 years who presented with pericardial Eff in the setting of malignancy. Intervention was medical and/or surgical therapy, and the outcome was mortality. Results: For the 41 patients included, the median age was 54 years, and the majority were male patients (58%). Dyspnea was the leading symptom (90%), and cardiac tamponade was present in 78% of cases. Common cancers included lung, gastrointestinal, and renal neoplasms (59%). Pericardiocentesis occurred in 98% of cases, with a median fluid extraction volume of 1000 mL. Death occurred in 44%, primarily due to disease progression and/or metastasis. Conclusions: This study presents the largest systematic review on malignancy-induced pericardial Effs to date. Notably, solid tumours, and specifically lung adenocarcinomas, are common culprits. Malignant pericardial Effs are often severe, with a majority of patients presenting with cardiac tamponade. Overall, treatment options are limited, and the associated mortality rate is high. Résumé: Contexte: L’épanchement péricardique malin (EPM) est un état généralement asymptomatique, de prévalence inconnue en raison de son tableau clinique occulte. Il est souvent reconnu post-mortem, à l’autopsie, et est associé à un pronostic médiocre. En raison de la consultation tardive pour un EPM, les données publiées relatives à l’épidémiologie, aux caractéristiques cliniques et à l’issue de ces cas complexes sont limitées. Nous avons réalisé une analyse systématique dans le but d’élargir les connaissances sur cette affection. Méthodologie: Une recherche réalisée dans quatre bases de données a permis de repérer 41 rapports de cas qui répondaient aux critères de recherche. Les critères d’inclusion étaient les suivants : être âgé de plus de 18 ans; présenter un épanchement péricardique en présence d’un cancer; intervention pharmacologique et/ou chirurgicale; issue mortelle. Résultats: L’âge médian des 41 patients inclus était de 54 ans; la majorité d’entre eux étaient des hommes (58 %). Le symptôme principal était la dyspnée (90 %), et une tamponnade cardiaque était présente dans 78 % des cas. Les cancers les plus fréquents étaient le cancer du poumon, le cancer gastro-intestinal et les néoplasmes rénaux (59 %). Une péricardiocentèse a été réalisée dans 98 % des cas. Le volume de drainage médian était de 1 000 mL. Quarante-quatre pour cent des sujets sont décédés, principalement en raison de la progression de la maladie et/ou de métastases. Conclusions: Cette étude est la plus vaste analyse systématique réalisée à ce jour sur l’EPM. Les tumeurs solides, et plus particulièrement les adénocarcinomes pulmonaires, sont des causes fréquentes. L’EPM est souvent grave, la majorité des patients présentant une tamponnade cardiaque. Les traitements disponibles sont généralement limités, et le taux de mortalité associé est élevé.

Agustina Rayes, Mariano J. Aramburo, Julio Djenderedjian, Aníbal Jáuregui, María Elena Barral, María José Valdez, Cecilia Simón.

Critical land is a condition of land that is no longer able to carry out its functions properly because it has experienced physical, chemical, and biological damage. One area that has the potential to experience critical land problems is the Cikapundung Sub-watershed, West Java. This research aims to identify the existence of critical land in the Cikapundung Sub-watershed area by integrating the Geographic Information System, Sentinel-2 Imagery, and DEMNAS as well as mapping the distribution of land criticality levels in the Cikapundung Sub-watershed at a detailed scale (1:25,000). The research was carried out from May to August 2023. The research was carried out using spatial analysis methods by overlaying thematic maps of each critical land parameter consisting of maps of land cover, erosion, and slope. The results of overlaying all critical land parameter maps were then analyzed using a scoring method to classify the level of land criticality and create a critical land distribution map in the Cikapundung Sub-watershed area. The results of identifying critical land in the Cikapundung Sub-watershed area produced five classes of land criticality, namely uncritical, potentially critical, rather critical, critical, and very critical. The identification results show that there are 4210.94 ha (13.83%) of land identified as critical land in the Cikapundung Sub-watershed area. The results of mapping the level of land criticality in the Cikapundung Sub-watershed show that the Cikapundung Sub-watershed area which is included in the forest area is dominated by the moderately critical land criticality class, while the Cikapundung Sub-watershed area which is outside the forest area is dominated by the uncritical land criticality class.

Background and Aim: Artemisia annua (AA), used as a growth promoter in poultry, lowers feed costs and enhances economic efficiency. This study aimed to assess the impact of varying AA concentrations on broiler chicken growth, gene expression, and profitability. Materials and Methods: Two hundred 1-day-old male Cobb chicks were randomly allocated into four treatment groups, each containing five replicates and 10 birds. The experimental groups consisted of G1 (basal diet), G2 (basal diet with 0.3% AA), G3 (basal diet with 0.6% AA), and G4 (basal diet with 0.9% AA). The birds had continuous access to feed and water throughout the study. The experiment lasted for 42 days. we measured the growth performance (Feed intake, Life weight), carcass traits (weight after slaughter, dressed carcass, heart, gizzard, spleen, giblet and thymus weight), liver and spleen antioxidants (CAT, GSH, SOD), and gene expression of anti-inflammatory and immune- related genes. Results: The primary findings revealed that the addition of 0.6% AA had a positive impact (p < 0.05) on all investigated variables compared with the control and other groups. Dietary supplementation with 0.6% AA led to increased breast, giblet, skeleton, and total yield, and net return compared with the control group. Supplementation with AA exhibited antioxidant, anti-inflammatory, and immunological effects through improved levels of antioxidant superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in tissue homogenates of the liver and spleen. It also upregulated the relative messenger RNA levels of anti-inflammatory interleukin (IL)-10, SOD, CAT, and GSH-Px, whereas IL-1β and tumor necrosis factor-alpha were downregulated. Conclusion: The study found that AA is a promising replacement for antibiotics in poultry farming as a growth promoter for chickens. 0.6% AA in the broiler diet yielded the best results, striking a balance between superior performance and robust economic benefits.

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p

A finely tuned balance between excitation and inhibition (E/I) is essential for proper brain function. Disruptions in the GABAergic system, which alter this equilibrium, are a common feature in various types of neurological disorders, including autism spectrum disorders (ASDs). Mutations in Phosphatase and Tensin Homolog (PTEN), the main negative regulator of the phosphatidylinositol 3-phosphate kinase/Akt pathway, are strongly associated with ASD. However, it is unclear whether PTEN deficiencies can differentially affect inhibitory and excitatory signaling. Using the Caenorhabditis elegans neuromuscular system, where both excitatory (cholinergic) and inhibitory (GABAergic) inputs regulate muscle activity, we found that daf-18/PTEN mutations impact GABAergic (but not cholinergic) neurodevelopment and function. This selective impact results in a deficiency in inhibitory signaling. The defects observed in the GABAergic system in daf-18/PTEN mutants are due to reduced activity of DAF-16/FOXO during development. Ketogenic diets (KGDs) have proven effective for disorders associated with E/I imbalances. However, the mechanisms underlying their action remain largely elusive. We found that a diet enriched with the ketone body β-hydroxybutyrate during early development induces DAF-16/FOXO activity, therefore improving GABAergic neurodevelopment and function in daf-18/PTEN mutants. Our study provides valuable insights into the link between PTEN mutations and neurodevelopmental defects and delves into the mechanisms underlying the potential therapeutic effects of KGDs.

Background Throughout the Syrian conflict, the Syrian government has intentionally attacked health facilities, violating International Humanitarian Law. Previous studies have qualitatively described health system disruptions following attacks on healthcare or established associations between armed conflict and health service utilisation, but there are no quantitative studies exploring the effects of health facility attacks. Our unprecedented study addresses this gap by quantifying the effects of health facility attacks on health service use during the Syrian conflict.Methods This retrospective observational study uses 18 537 reports capturing 2 826 627 consultations from 18 health facilities in northwest Syria and 69 attacks on these facilities. The novel study applies case time series design with a generalised non-linear model and stratification by facility type, attack mechanism and corroboration status.Results The study found significant, negative associations between health facility attacks and outpatient, trauma and facility births. On average, a health facility attack was associated with 51% and 38% reductions in outpatient, RR 0.49 (95% CI 0.43 to 0.57) and trauma consultations, RR 0.62 (95% CI 0.53 to 0.72), the day after an attack, with significant reductions continuing for 37 and 20 days, respectively. Health facility attacks were associated with an average 23% reduction in facility births, the second day after an attack, RR 0.77 (95% CI 0.66 to 0.89), with significant reductions continuing for 42 days.Conclusions Attacks on health facilities in northwest Syria are strongly associated with significant reductions in outpatient, trauma and facility births. These attacks exacerbate the adverse effects of armed conflict and impede the fundamental right to health. The findings provide evidence that attacks on health facilities, violations of international humanitarian law by themselves, also negatively affect human rights by limiting access to health services, underscoring the need to strengthen health system resilience in conflict settings, expand systematic reporting of attacks on healthcare and hold perpetrators accountable.

The performance of ultrasonic transducers is largely determined by the piezoelectric properties and geometries of their active elements. Due to the brittle nature of piezoceramics, existing processing tools for piezoelectric elements only achieve simple geometries, including flat disks, cylinders, cubes and rings. While advances in additive manufacturing give rise to free-form fabrication of piezoceramics, the resultant transducers suffer from high porosity, weak piezoelectric responses, and limited geometrical flexibility. We introduce optimized piezoceramic printing and processing strategies to produce highly responsive piezoelectric microtransducers that operate at ultrasonic frequencies. The 3D printed dense piezoelectric elements achieve high piezoelectric coefficients and complex architectures. The resulting piezoelectric charge constant, d33, and coupling factor, kt, of the 3D printed piezoceramic reach 583 pC/N and 0.57, approaching the properties of pristine ceramics. The integrated printing of transducer packaging materials and 3D printed piezoceramics with microarchitectures create opportunities for miniaturized piezoelectric ultrasound transducers capable of acoustic focusing and localized cavitation within millimeter-sized channels, leading to miniaturized ultrasonic devices that enable a wide range of biomedical applications.

Abstract Although patients experiencing food insecurity commonly screen positive for a myriad of social determinants of health (SDOH) needs and chronic medical conditions influenced by diet, few studies have investigated associations within both uninsured and food insecure populations. We screened patients for food insecurity using the USDA six-item short form between October 2021 and April 2022. We then evaluated associations of food security status with nine separate SDOH needs and eight chronic medical conditions. In this cross-sectional study, of the 190 patients seen at a student-run free clinic serving patients without health insurance, 135 (71%) completed the SDOH survey. We identified chronic medical conditions via retrospective chart review and analyzed associations using multivariable logistic regressions adjusted for age and sex. Uninsured participants experiencing food insecurity (n = 22,16.3%) requested more support for: medications (adjusted odds ratio [AOR] = 7.28; 95% Confidence Interval [95% CI] = 2.33–23.2); p-value [P] =

Abstract Introduction Despite the growing use of immune checkpoint inhibitors (ICI) in cancer treatment, data regarding ICI-associated pericardial disease are primarily derived from case reports and case series. ICI related pericardial disease can be difficult to diagnose and is associated with significant morbidity. We conducted a systematic review to further characterize the epidemiology, clinical presentation, and outcomes of this patient population. Methods A search of four databases resulted in 31 studies meeting inclusion criteria. Patients > 18 years old who presented with ICI mediated pericardial disease were included. Intervention was medical + surgical therapy and outcomes were development of cardiac tamponade, morbidity, and mortality. Results Thirty- eight patients across 31 cases were included. Patients were majority male (72%) with a median age of 63. Common symptoms included dyspnea (59%) and chest pain (32%), with 41% presenting with cardiac tamponade. Lung cancer (81%) was the most prevalent, and nivolumab (61%) and pembrolizumab (34%) were the most used ICIs. Pericardiocentesis was performed in 68% of patients, and 92% experienced symptom improvement upon ICI cessation. Overall mortality was 16%. Discussion This study provides the most comprehensive analysis of ICI-mediated pericardial disease to date. Patients affected were most commonly male with lung cancer treated with either Nivolumab or Pembrolizumab. Diagnosis may be challenging in the setting of occult presentation with normal EKG and physical exam as well as delayed onset from therapy initiation. ICI-associated pericardial disease demonstrates high morbidity and mortality, as evidenced by a majority of patients requiring pericardiocentesis.

Abstract Introduction Nail psoriasis is highly prevalent among patients with psoriasis yet remains one of the most challenging areas to treat. To better understand the treatment landscape for psoriatic nail disease, more studies are needed that compare the effectiveness of different biologics for patients with nail psoriasis. This study contributes to this objective by directly comparing the effectiveness of approved biologics in improving nail psoriasis for patients up to month 12 in a real-world setting. Methods Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. This study assessed the change in modified Nail Psoriasis Severity Index (mNAPSI) score from baseline to months 3, 6 and 12 for 763 patients and compared the effectiveness of anti-interleukin (IL)-17A biologics versus other approved biologics, as well as ixekizumab versus secukinumab, guselkumab, risankizumab and adalimumab. Comparative adjusted analyses used frequentist model averaging (FMA). Least square mean difference (LSMD) in mNAPSI scores are presented as observed. Results Irrespective of the severity of nail psoriasis at baseline, the anti-IL-17A cohort had greater mean mNAPSI reductions from baseline compared to the other biologics cohort through month 12, reaching significance at months 3 and 6 in the adjusted analysis. For patients with moderate-to-severe nail psoriasis, ixekizumab showed numerically higher mean reductions in mNAPSI scores compared to all other studied biologics, reaching significance versus guselkumab at all timepoints and risankizumab at month 6. Conclusion This real-world study showed that patients with moderate-to-severe psoriasis and any severity of concomitant nail involvement had significantly faster and more substantial improvements in nail psoriasis up to month 6 in the anti-IL-17A cohort compared to the other biologics cohort. Of the individual biologics studied, ixekizumab showed the highest numerical improvements in nail psoriasis at month 12. Trial registration EUPAS24207.

The objective of this experiment was to evaluate the impact of dietary supplementation with rumen-protected fat (calcium soaps of fatty acids, CSFA) and/or hormonal superovulation using equine chorionic gonadotropin (eCG) on ovarian activity, changes in ovarian hormones, and reproductive performance in Barki ewes under semiarid conditions. A total of 39 non-pregnant Barki ewes, with an average body weight of 34.7 ± 0.25 kg and an average age of 3–4 years, were divided into four groups. The first group (9 ewes) served as the control, while the second group (10 ewes) received double doses of PGF2α, administered 9 d apart, and was superovulated with 600 IU (international unit) eCG. The third group (10 ewes) was supplemented with 30 g per head per day of rumen-protected fat. The fourth group (10 ewes) underwent the same superovulation protocol as the second group and was also supplemented with 30 g per head per day of rumen-protected fat. All the ewes were fed a basal diet. Ovarian activity was detected using ultrasonography during the estrus phase in all the groups, after which all the ewes were naturally bred with Barki rams. The results demonstrated significant (P) increases in estradiol 17-β (E2) and progesterone (P4) levels in the treated groups compared to the control group. Ewes in all the treated groups exhibited large follicles, with an overall mean diameter (≥5 mm) significantly higher than that of ewes in the control group. Although there were no significant differences between the treated and control groups, the ewes treated with CSFA and/or the eCG hormone showed tendencies to improve the reproductive traits of Barki ewes. Overall, the findings of this study demonstrated a positive effect of CSFA alone or in combination with an estrous synchronization protocol on ovarian activity in Barki ewes, as indicated by the number and size of follicles and the presence of large-sized follicles.

ABSTRACTAmong hospitalized patients worldwide, infections caused by multidrug-resistant (MDR) bacteria are a major cause of morbidity and mortality. This study aimed to isolate MDR bacteria from five intensive care units (ICUs) at Tripoli University Hospital (TUH). A prospective cross-sectional study was conducted over a seven-month period (September 2022 to March 2023) across five ICUs at TUH. A total of 197 swabs were collected from Patients’, healthcare workers’ and ICUs equipment. Samples collected from patients were nasal swabs, oral cavity swabs, hand swabs, sputum specimens, skin swabs, umbilical venous catheter swabs, and around cannula. Swabs collected from health care workers were nasal swabs, whereas ICUs equipment’s samples were from endotracheal tubes, oxygen masks, and neonatal incubators. Identification and antimicrobial susceptibility test was confirmed by using MicroScan auto SCAN 4 (Beckman Coulter). The most frequent strains were Gram negative bacilli 113 (57.4%) with the predominance of Acinetobacter baumannii 50/113 (44%) followed by Klebsiella pneumoniae 44/113 (40%) and Pseudomonas aeruginosa 6/113 (5.3%). The total Gram positive bacterial strains isolated were 84 (42.6%), coagulase negative Staphylococci 55 (66%) with MDRs (89%) were the most common isolates followed by Staphylococcus aureus 15 (17.8%). Different antibiotics were used against these isolates; Gram- negative isolates showed high resistance rates to ceftazidime, gentamicin, amikacin and ertapenem. A. baumannii were the most frequent MDROs (94%), and the highest resistance rates in Gram-positive strains were observed toward ampicillin, oxacillin, ampicillin/sulbactam and Cefoxitin, representing 90% of total MDR Gram-positive isolates. ESBL and MRS were identified in most of strains. The prevalence of antibiotic resistance was high for both Gram negative and Gram positive isolates. This prevalence requires strict infection prevention and control intervention, continuous monitoring, implementation of effective antibiotic stewardship, immediate, concerted and collaborative action to monitor its prevalence and spread in the hospital.

ABSTRACTBackground: Feasibility studies with non-French speaking migrants in France are needed to inform appropriate adaptation of psychosocial intervention procedures.Objective: To test the WHO Problem Management Plus (PM+) intervention protocol for Arabic-speaking migrants in the Paris metropolitan region.Methods: Between 2019 and 2021 we recruited participants from three accommodation centres receiving asylum seekers or migrants experiencing social and economic difficulties. Participants experiencing psychological distress underwent five PM + sessions with trained helpers. Feasibility was evaluated through 15 interviews with 8 participants, 4 helpers, and 3 study supervisors. Interview topics covered PM + implementation in general and for each component. We also sought to understand problems with delivery and gathered suggestions for improvement. Data were analysed thematically using a deductive approach.Results: We found implementation of PM + to be feasible, with predominantly positive reactions from participants, helpers and study staff. All intervention components were considered beneficial, with breathing exercises considered easy to implement and often sustained. Selection of problems and strategies to address them were described as challenging to execute. Psychosocial support from and rapport with helpers and the use of the native language were considered key strengths of the programme. However, we observed the need for complementary or higher intensity psychological support in some cases. Findings also highlighted the importance of addressing distress among non-specialist helpers delivering PM + . Finally, local guidance to social resources were suggested to be added in the protocol.Conclusion: PM + was well-liked and feasible, with cultural adjustments and increased access to community resources for migrants needed.

BACKGROUND: Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortiums (PIDTCs) prospective and retrospective studies of SCID. OBJECTIVE: Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed. METHODS: We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes. RESULTS: According to PIDTC 2022 Definitions, 18 of 353 patients eligible per 2014 Criteria were considered not to have SCID, whereas 11 of 26 patients ineligible per 2014 Criteria were determined to have SCID. Of note, very low numbers of autologous T cells (

ObjectiveNorthern Syria faces a large burden of influenza-like illness (ILI) and severe acute respiratory illness (SARI). This study aimed to investigate the trends of Early Warning and Response Network (EWARN) reported ILI and SARI in northern Syria between 2016 and 2021 and the potential impact of SARS-CoV-2.MethodsWe extracted weekly EWARN data on ILI/ SARI and aggregated cases and consultations into 4-week intervals to calculate case positivity. We conducted a seasonal-trend decomposition to assess case trends in the presence of seasonal fluctuations.ResultsIt was observed that 4-week aggregates of ILI cases (n = 5,942,012), SARI cases (n = 114,939), ILI case positivity, and SARI case positivity exhibited seasonal fluctuations with peaks in the winter months. ILI and SARI cases in individuals aged ≥5 years surpassed those in individuals aged