Profile of and risk factors for early unplanned readmissions in patients with acute necrotizing pancreatitis.

INTRODUCTION: Acute necrotizing pancreatitis (ANP) complicates up to 15% of acute pancreatitis cases. ANP has historically been associated with a significant risk for readmission, but there are currently no studies exploring factors that associate with risk for unplanned, early (<30-day) readmissions in this patient population. METHODS: We performed a retrospective review of all consecutive patients presenting to hospitals in the Indiana University (IU) Health system with pancreatic necrosis between December 2016 and June 2020. Patients younger than 18 years of age, without confirmed pancreatic necrosis and those that suffered in-hospital mortality were excluded. Logistic regression was performed to identify potential predictors of early readmission in this group of patients. RESULTS: One hundred and sixty-two patients met study criteria. 27.7% of the cohort was readmitted within 30-days of index discharge. The median time to readmission was 10 days (IQR 5-17 days). The most frequent reason for readmission was abdominal pain (75.6%), followed by nausea and vomiting in (35.6%). Discharge to home was associated with 93% lower odds of readmission. We found no additional clinical factors that predicted early readmission. CONCLUSION: Patients with ANP have a significant risk for early (<30 days) readmission. Direct discharge to home, rather than short or long-term rehabilitation facilities, is associated with lower odds of early readmission. Analysis was otherwise negative for independent, clinical predictors of early unplanned readmissions in ANP.

[Guidelines on the urological management of the adult patient with spinal dysraphism (spina bifida)]. / Recommandations sur la gestion du risque et la prise en charge urologique du patient adulte atteint de dysraphisme spinal (spina bifida).

INTRODUCTION: Improved life expectancy and prenatal screening have changed the demographics of spina bifida (spinal dysraphism) which has presently become a disease of adulthood. Urinary disorders affect almost all patients with spinal dysraphism and are still the leading cause of mortality in these patients. The aim of this work was to establish recommendations for urological management that take into account the specificities of the spina bifida population. MATERIALS AND METHODS: National Diagnosis and Management Guidelines (PNDS) were drafted within the framework of the French Rare Diseases Plan at the initiative of the Centre de Référence Maladies Rares Spina Bifida - Dysraphismes of Rennes University Hospital. It is a collaborative work involving experts from different specialties, mainly urologists and rehabilitation physicians. We conducted a systematic search of the literature in French and English in the various fields covered by these recommendations in the MEDLINE database. In accordance with the methodology recommended by the authorities (Guide_methodologique_pnds.pdf, 2006), proposed recommendations were drafted on the basis of this literature review and then submitted to a review group until a consensus was reached. RESULTS: Bladder dysfunctions induced by spinal dysraphism are multiple and varied and evolve over time. Management must be individually adapted and take into account all the patient's problems, and is therefore necessarily multi-disciplinary. Self-catheterisation is the appropriate micturition method for more than half of the patients and must sometimes be combined with treatments aimed at suppressing any neurogenic detrusor overactivity (NDO) or compliance alteration (anticholinergics, intra-detrusor botulinum toxin). Resort to surgery is sometimes necessary either after failure of non-invasive treatments (e.g. bladder augmentation in case of NDO resistant to pharmacological treatment), or as a first line treatment in the absence of other non-invasive alternatives (e.g. aponeurotic suburethral tape or artificial urinary sphincter for sphincter insufficiency; urinary diversion by ileal conduit if self-catheterisation is impossible). CONCLUSION: Spinal dysraphism is a complex pathology with multiple neurological, orthopedic, gastrointestinal and urological involvement. The management of bladder and bowel dysfunctions must continue throughout the life of these patients and must be integrated into a multidisciplinary context.

The addition of flexible endoscopic suturing to stenting for the management of transmural esophageal wall defects: a single tertiary center experience.

BACKGROUND AND AIMS: Endoscopic stenting is the standard of care for full thickness esophageal wall defects. The aim of this study is to evaluate outcomes of endoscopic closure of esophageal defects using stenting, with or without endoscopic suturing. METHODS: This is a single-center retrospective study of patients with esophageal wall defects who underwent endoscopic interventions. Outcomes of stenting with or without endoscopic suturing of the defect were assessed. Univariate and multivariate logistic regression models were used to examine factors associated with successful defect closure. RESULTS: One hundred and fourteen patients with esophageal wall defects underwent 254 endoscopies with an overall complete closure rate of 75.8%. Twenty-three (20.2%) patients underwent primary closure using endoscopic suturing and subsequent esophageal stenting, while 91 (79.8%) underwent esophageal stenting only. The dual modality group (versus the stent-only group) had similar defect closure rates (84.2 vs. 73.8%, p = 0.55) and time to stent migration (37 vs. 12.5 days, p = 0.07), but was associated with longer procedure times (60 vs. 36 min, p < 0.01) and fewer additional endoscopic procedures (13.6 vs. 43.2%, p = 0.01). Stent suturing significantly decreased migration (35.5 vs. 58.5%, p = 0.04), was associated with fewer additional endoscopies (15.4 vs. 50%, p < 0.01) and reduced need for additional stents (7.7 vs. 34.3%, p < 0.01). On multivariate analysis, chronic defects (> four weeks old) were 81% less likely to close compared to acute (≤ 4 weeks) defects (OR 0.19, CI 0.04-0.77, p = 0.02), and large diameter stents (23 mm) were associated with higher odds of defect closure (OR 3.36, CI 1.02-11.4, p = 0.04). CONCLUSION: Endoscopic treatment of esophageal wall defects is safe, effective, and more likely to be successful in acute defects using larger caliber stents. Stent suturing reduces migration, need for additional endoscopic procedures, and stent exchanges. Further comparative studies with larger cohorts are needed to validate our results.

A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Paroxysmal atrial fibrillation with high vs. low arrhythmia burden: atrial remodelling and ablation outcome.

AIMS: The relation between atrial tachyarrhythmia (ATA) burden in paroxysmal atrial fibrillation (AF), atrial remodelling, and efficacy of catheter ablation (CA) is unknown. We investigated whether high vs. low-burden paroxysmal AF patients have distinct clinical characteristics or electro-mechanical properties of the left atrium (LA) and whether burden impacts outcome of CA. METHODS AND RESULTS: Atrial tachyarrhythmia burden, defined as the percentage of time spent in ATA, was assessed by insertable cardiac monitors in 105 patients before and after CA. Clinical characteristics and electro-mechanical properties of LA were compared between patients with high vs. low ATA burden. Catheter ablation efficacy was assessed by reduction in ATA burden and 1-year freedom from any ATA. Median ATA burden was 2.7% (highest tertile 9.3%). Clinical characteristics and electrical properties of LA (refractoriness, conduction velocity, low voltage) did not differ between high (≥9.3%) vs. low ATA burden (<9.3%) patients. High ATA burden patients had larger LA diameter (46.5 ± 6 vs. 42.5 ± 6mm, P < 0.01), volume (93.8 ± 22 vs. 80.4 ± 21mL, P = 0.01), and lower LA reservoir and contractile strain (19.7 ± 6 vs. 24.7 ± 6%, P < 0.01; 10.3 ± 3 vs. 12.8 ± 4%, P = 0.01). Catheter ablation reduced ATA burden by 100% (100-100) in both groups (P = 1.0). Freedom from ATA after CA was equally high (83% vs. 89%, P = 0.38). CONCLUSION: Paroxysmal AF patients with high ATA burden have altered LA mechanical properties, reflected by larger size and impaired function. Despite mechanical remodelling of the atria, they are excellent responders to CA. Most likely the lack of fibrosis and/or advanced electrical remodelling explain why pulmonary veins remain the dominant trigger for AF in this patient cohort.

Exploring avenues for best use of cytotechnologists in non-gynaecological cytology: Double screening or independent sign-out.

OBJECTIVE: Cytotechnologist (CT) screening workload has been decreasing due to the falling number of Papanicolaou tests. This continuing trend has prompted exploration of ways to best employ the CT skillset. One potential way of more effective use is by having two CTs double screen non-gynaecological (NGC) cases to assess whether this improves screening quality and concordance with pathologists. Another is evaluating the CT's performance on low-complexity negative NGC cases for a potential independent CT sign-out without pathologist review. METHODS: In total, 1119 NGC cases were reviewed; 577 screened by two CTs and 542 screened by one CT. All cases were signed out by a pathologist and all CT interpretations were compared to the pathologist final diagnoses. The disagreements were classified based on degree of discrepancy. The extra workload by adding the second screener was assessed. RESULTS: The agreement rate between the CT's screening interpretation and pathologist's interpretation did not improve by adding a second CT compared to a single screener (91.5% vs 92.9%, respectively). CT to pathologist concordance was very high on low complexity NGC cases (voided urine, fluid, sputum) whether screened and interpreted as negative by one CT (97.3%) or two CTs (99.3%). CONCLUSION: Double screening of NGC cases by two cytotechnologists prior to pathologist sign-out does not improve screening quality and is not cost-effective. The high concordance between the CTs and pathologists in this limited group of low complexity negative cases suggests that such cases could be signed out independently by cytotechnologists.

Impact of laser fiber tip cleavage on power output for ureteroscopy and stone treatment.

PURPOSE: Holmium:YAG laser is the most used laser for urolithiasis. Generally, we use metallic scissors to cut the fiber tip to restore its effectiveness. Many cleaving methods have been described to avoid fiber damage and to restore its greatest power to the fiber. There is a lack of information regarding which cleaving method should be used and its effect on the fiber. In order to compare these effects, we studied different cleavage methods in terms of power output and its effects on the fiber. METHODS: New single-use 272-µm fibers were used with a holmium:YAG laser lithotripter. Five kinds of fiber tips were compared: a new intact fiber, cleaved with ceramic scissors, cleaved with metallic scissors, first cleaved then stripped and first stripped then cleaved. The fibers were used against synthetic stones (BegoStone®) similar to calcium oxalate monohydrate, with fragmentation (SP, 5 Hz, 1.5 J) and dusting (LP, 15 Hz, 0.5 J) settings. We measured power output at 0, 1, 5, 10 and 15 min. RESULTS: For fragmentation parameters, there was a statistical difference between the 5 groups at 0 and 1 min of laser use (p < 0.05) and none for time period over 1 min (p = 0.077-0.658). For dusting parameters, there was a statistical difference between the 5 groups at 0 min of laser use (p < 0.05) and none for time period over 0 min (p = 0.064-1). CONCLUSION: Cleaving the fiber tip may restore its effectiveness to the fiber, but only for a limited time, although it may preserve the scopes from damage.

The diagnostic yield of ultrasound of the head in healthy infants presenting with the clinical diagnosis of benign macrocrania.

AIM: To investigate the frequency of sonographic findings that required neurosurgical consultation for all referred outpatients suspected to have benign macrocrania (BMC). MATERIALS AND METHODS: A retrospective review was performed from September 2011 until June 2015 for all outpatients referred to the ultrasound (US) department for BMC. Electronic medical records, US images, and reports were reviewed in conjunction with follow-up imaging. Each review consisted of gender, specialty of referring physician, first head circumference, head circumference at or closest to the time of the head US, the last head circumference, and any neurological issue prior to the US, at the time of US, or following the US, and clinical outcomes. Statistical analysis employed the Kruskal-Wallis rank sum test and Fischer's exact test (chi square test of independence) that compared normal/BMC patients from the patients requiring a neurosurgical consultation. RESULTS: One hundred and thirty (40.9%) had a normal head US, 181 patients (56.9%) had sonographic findings of BMC, and seven (2.2%) patients had an abnormal head US that required a neurosurgical consultation. Of the 181 patients with BMC, 23 underwent follow-up imaging with 22 patients having unchanged BMC or a normal head US and one patient developing mild ventriculomegaly that was stable on follow-up imaging. Three of the seven patients (1%) aged 1.8, 2.3, and 13.1 months with abnormal head US requiring neurosurgical consultation, had mild ventriculomegaly that was stable on follow-up imaging. Four of the seven patients (1.2%) that required neurosurgical consultation needed a neurosurgical procedure. Between the two US subgroups (normal and BMC), no statistical significance was noted regarding age of patient at US, head circumference at clinical and radiological presentation (p>0.05) except for the first head circumference clinically documented which demonstrated statistical significance (p<0.03). CONCLUSION: Short interval surveillance including head circumference and assessment for the development of bulging anterior fontanelle and neurological abnormalities may be more cost effective than US in the initial evaluation of patients clinically suspected to have BMC.

Specific physical trainability in elite young soccer players: efficiency over 6 weeks' in-season training.

The aim of the present study was to compare the effects of 3 training protocols (plyometric [PLYO], agility [AG], or repeated shuttle sprints [RS]) on physical performance in the same population of young soccer players. Forty-two youth-level male players (13.6±0.3-years; 1.65±0.07 m; 54.1±6.5 kg; body fat: 12.8±2.6%) participated in a short-term (6-week) randomized parallel fully controlled training study (pre-to-post measurements): PLYO group, n=10; AG group, n=10; RS group, n=12; and control group [CON] n=10. PLYO training = 9 lower limb exercises (2-3 sets of 8-12 repetitions). The AG group performed planned AG drills and direction changes. RS training consisted of 2-4 sets of 5-6x 20 to 30 m shuttle sprints (20 seconds recovery in between). Progressive overload principles were incorporated into the programme by increasing the number of foot contacts and varying the complexity of the exercises. Pre/post-training tests were: bilateral standing horizontal jump, and unilateral horizontal jumps, sprint (30 m with 10 m lap time), agility (20 m zigzag), and repeated sprint ability (RSA) (i.e. 6x30 m shuttle sprints: 2x15 m with 180° turns). Significant main effects for time (i.e. training application) and group (training type) were detected. Improvements in horizontal jumping were higher (p<0.01: ES=large) in PLYO. The RS group improved significantly more (p<0.01; ES=large) than other groups: 30 m sprint, RSAbest and RSAmean performances. Significantly greater increases in 20 m zigzag performance were observed following AG and RS training (4.0 and 3.8%, respectively) compared with PLYO (2.0%) and CON training (0.8%). No significant differences were reported in the RSAdec between groups. Elite young male soccer players' physical performances can be significantly and specifically improved either using PLYO or AG or RSA training over short-term in-season training.

Screening for mutations in RPGR and RP2 genes in Jordanian families with X-linked retinitis pigmentosa.

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous disease causing progressive degeneration of retinal photoreceptor cells. X-linked RP (XLRP), in which photoreceptor degeneration begins in early childhood and complete blindness often occurs by the fourth decade of life, constitutes the most severe form of this disease. Two genes commonly associated with XLRP have previously been cloned: retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (RP2). We sought to identify mutations in these genes in Jordanian families suffering from this disease. Five unrelated Jordanian families with confirmed XLRP were screened for such mutations using direct sequencing. Three mutations were identified in the ORF15 exon of RPGR. The silent g.ORF15+470G>A substitution and the g.ORF15+1822insA insertion in the 3ꞌ-untranslated region were found in both normal and affected male family members at comparable frequencies, and thus were considered normal variants. The third mutation, g.ORF15+588G>A, in which alanine is substituted by threonine, was found in all affected men and one unaffected man in the two families harboring this variant. Thus, this mutation may be pathogenic, but with incomplete penetrance. No RP2 mutations were found among the examined families. Mutation screening of RP patients is essential to understand the mechanism behind this disease and develop treatments. A complete family history is required to identify its inheritance pattern and provide genetic counseling for patients and their families.

Hybrid Self-Adaptive Evolution Strategies Guided by Neighborhood Structures for Combinatorial Optimization Problems.

This article presents an Evolution Strategy (ES)--based algorithm, designed to self-adapt its mutation operators, guiding the search into the solution space using a Self-Adaptive Reduced Variable Neighborhood Search procedure. In view of the specific local search operators for each individual, the proposed population-based approach also fits into the context of the Memetic Algorithms. The proposed variant uses the Greedy Randomized Adaptive Search Procedure with different greedy parameters for generating its initial population, providing an interesting exploration-exploitation balance. To validate the proposal, this framework is applied to solve three different [Formula: see text]-Hard combinatorial optimization problems: an Open-Pit-Mining Operational Planning Problem with dynamic allocation of trucks, an Unrelated Parallel Machine Scheduling Problem with Setup Times, and the calibration of a hybrid fuzzy model for Short-Term Load Forecasting. Computational results point out the convergence of the proposed model and highlight its ability in combining the application of move operations from distinct neighborhood structures along the optimization. The results gathered and reported in this article represent a collective evidence of the performance of the method in challenging combinatorial optimization problems from different application domains. The proposed evolution strategy demonstrates an ability of adapting the strength of the mutation disturbance during the generations of its evolution process. The effectiveness of the proposal motivates the application of this novel evolutionary framework for solving other combinatorial optimization problems.

Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females.

This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE) in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS) or high-intensity interval training (HIIT at 100% MAS), with matched 15 s recovery at 50% MAS, thrice weekly, or a no-training control group. The HIIT and MIIT groups showed improved (p < 0.05) body mass (BM), BMI Z-score, and percentage of body fat (%BF). Only the HIIT group showed decreased waist circumference (WC) (p = 0.017). The effect of exercise on maximal oxygen uptake (VO2max) was significant (p = 0.019, ES = 0.48 and p = 0.010, ES = 0.57, HIIT and MIIT, respectively). The decrease of rate-pressure product (RPP) (p < 0.05, ES = 0.53 and ES = 0.46, HIIT and MIIT, respectively) followed the positive changes in resting heart rate and blood pressures. Blood glucose, insulin level and the homeostasis model assessment index for insulin decreased (p < 0.05) in both training groups. Significant decreases occurred in blood leptin (p = 0.021, ES = 0.67 and p = 0.011, ES = 0.73) and in RPE (p = 0.001, ES = 0.76 and p = 0.017, ES = 0.57) in HIIT and MIIT, respectively. In the post-intervention period, blood leptin was strongly associated with %BF (p < 0.001) and VO2max (p < 0.01) in the HIIT and MIIT groups, respectively, while RPE was strongly associated with BM (p < 0.01) in the HIIT group. The results suggest that high-intensity interval training may produce more positive effects on health determinants in comparison with the same training mode at a moderate intensity.

Reasons for referral, intervention approaches and demographic characteristics of clients with intellectual disability attending adult psychiatric outpatient services in the Kingdom of Bahrain.

BACKGROUND: Relatively little information is available regarding the use of psychiatric services by individuals with intellectual disability (ID) in Arab countries. The current study aimed to identify (1) the reasons for referral; (2) demographic characteristics of individuals referred; (3) previous contact with child psychiatric services; (4) psychiatric diagnoses; (5) level of ID; (6) nature of interventions; and (7) patterns of medication usage in individuals attending a specialist psychiatric service for individuals with an ID in the Kingdom of Bahrain. METHOD: Case file analysis was used. Files that recorded attendance at the specialist service within a specific calendar year were selected. A total of 537 files were available for review and 79 contained records indicating the individual had been seen within the year. RESULTS: The primary referral reason to adult psychiatric services was the presence of behavioural disturbance. Pharmacological intervention was the dominant treatment choice and no individual was recommended for psychological/behavioural intervention. Psychiatric diagnosis was not recorded in over 90% of cases. CONCLUSION: Services in the Kingdom of Bahrain for individuals with ID rely exclusively on pharmacological approaches for the treatment of behavioural disorders. Implications for best practice guidelines are discussed.

[Quality of life survey of 3,738 patients treated with intravitreal injections for age-related macular degeneration]. / Enquête de qualité de vie auprès de 3738 patients traités par injections intravitréennes pour leur dégénérescence maculaire liée à l'âge.

PURPOSE: To evaluate the peri- and post-intravitreal injection (IVI) symptoms reported by patients who have been repeatedly injected for age-related macular degeneration (AMD) and to analyze these according to the protocols of the injector. MATERIALS AND METHODS: Multi-center, cross-sectional, consecutive, analytical survey. RESULTS: The IVI protocols of 106 injectors differed in terms of the number of instillations of povidone-iodine, its contact time, and rinsing of the ocular surface post-injection. In total, 3,738 patients responded to the survey, 60.1% of whom were women; 36.4% had received more than 20 IVIs; 50.7% of patients reported irritation upon application of povidone-iodine. Post-IVI, depending on the symptom in question, between 44.8% and 57.4% of patients reported symptoms of ocular surface change. The number of instillations of povidone-iodine, its contact time with the ocular surface, and abundant rinsing post-IVI increased the immediate symptoms. Patients who received more IVIs were more prone to experiencing gritty eyes, and the incidence of acute pain increased in patients who had previously received over 20 IVIs. Women and patients previously treated for dry eye or glaucoma were at greater risk of worse symptoms. CONCLUSION: Comparing injecting centers' practices with patients' self-assessments showed an aggravation of symptoms of ocular surface changes related to povidone-iodine. This survey contributes to providing data for the implementation of a protocol to improve the quality of life of patients injected repeatedly for AMD.

Investigation of relaxor and diffuse dielectric phase transitions of Ba1-XBixTi0.8Fe0·2O3 materials.

Different doping elements have been used to enhance the dielectric properties of BaTiO3 ceramic. In this work, the effect of substitution of Ba by Bi in A site and Ti by Fe in B site on structural, dielectric and electrical properties of Ba1-xBixTi0.80Fe0·20O3 ceramics at (x = 0.00, 0.05, 0.10 and 0.15) was investigated by X-ray diffraction, Raman spectroscopy, Scanning Electron Microscopy (SEM), Mössbauer spectroscopy as well as dielectric measurements. The Rietveld refinement results revealed that the prepared compounds crystallize in both tetragonal (P4mm) and hexagonal (P63/mmc) phases for x = 0.00 and 0.05 while at x = 0.10 and 0.15, the hexagonal phase disappears and only the tetragonal phase is fitted. The Raman spectra confirmed the disappearance of hexagonal phase in benefit of tetragonal phase as the Bi3+ substitution increases. Based on Mössbauer analyses results, all the samples are in paramagnetic state at room temperature and the Fe is oxidized under Fe3+ without the presence of Fe2+ or Fe4+ ions. The dielectric measurements as function of temperature are studied and tree broad and relaxor phase transitions were detected: from rhombohedral to orthorhombic phase TR-O and to tetragonal ferroelectric phase TO-T then to cubic paraelectric phase Tm. These phase transitions were displaced to the lower temperature with increasing of Bi3+ substitution. The values of ε'r increase gradually with increasing of Bi3+contents which confirmed the enhancement of dielectric properties of BaTi0·80Fe0·20O3 by Bi substitution on Ba site. The diffuse phase transitions were described by fitting the modified Uchino relation. The Cole-Cole analyses showed that both the grain and grain boundaries resistivity values are higher for Bi3+ substituted samples which are responsible to the dielectric properties improvement.

A novel deletion in ZBTB24 in a Lebanese family with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2.

The immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disease characterized by targeted chromosome breakage, directly related to a genomic methylation defect. It manifests with phenotypic and clinical variability, with the most consistent features being developmental delay, facial anomalies, cytogenetic defects and immunodeficiency with a reduction in serum immunoglobulin levels. From the molecular point of view, ICF syndrome was always divided into ICF type I (ICF1) and ICF type 2 (ICF2). Mutations in DNMT3B gene are responsible for ICF1, while mutations in ZBTB24 have been reported to be responsible for ICF2. In this study, we describe a Lebanese family with three ICF2 affected brothers. Sanger sequencing of the coding sequence of ZBTB24 gene was conducted and revealed a novel deletion: c.396_397delTA (p.His132Glnfs*19), resulting in a loss-of-function of the corresponding protein. ZBTB24 belongs to a large family of transcriptional factors and may be involved in DNA methylation of juxtacentromeric DNA. Detailed molecular and functional studies of the ZBTB24 and DNMT3B genes are needed to understand the pathophysiology of ICF syndrome.

Clinicians' attitudes to depression in Europe: a pooled analysis of Depression Attitude Questionnaire findings.

BACKGROUND: Depression in primary care is common but under-recognized and suboptimally managed. Health professionals' attitudes are likely to play an important part in their recognition and management of depression. OBJECTIVES: To pool findings from studies using the Depression Attitude Questionnaire (DAQ) to provide greater detail of clinicians' attitudes and the measure's psychometric properties. METHODS: Electronic databases and grey literature were searched for relevant studies. Data from eligible studies were requested and pooled analysis conducted. RESULTS: Twenty studies were eligible and data were obtained from 12 of these involving GPs (n = 1543) and nurses (n = 984). Responses showed strong disagreement that depression is due to ageing or weakness. European GPs were more positive about depression treatments than UK GPs; nurses were more favourable about psychotherapy than GPs. UK GPs especially strongly opposed notions that depression is best managed by psychiatrists. Trends over time indicated increasing acknowledgement of psychological therapies and the nurse's role in depression management. Factor analysis indicated that many DAQ items fitted weakly within an overall model. The most parsimonious solution involved two factors: a positive view of depression and its treatment response and professional confidence in depression management. CONCLUSIONS: Individual DAQ items appear to measure key aspects of clinicians' attitudes to depression, and item responses indicate important differences between professions and geographical settings as well as changes over time. There are problems with the DAQ as a scale: its internal consistency is weak, and several items appear specific to particular professions or service structures, indicating that this questionnaire should be revised.

Chemical modulation of the metabolism of an endophytic fungal strain of Cophinforma mamane using epigenetic modifiers and amino-acids.

Endophytic fungi are capable of producing a great diversity of bioactive metabolites. However, the presence of silent and lowly expressed genes represents a main challenge for the discovery of novel secondary metabolites with different potential uses. Epigenetic modifiers have shown to perturb the production of fungal metabolites through the induction of silent biosynthetic pathways leading to an enhanced chemical diversity. Moreover, the addition of bioprecursors to the culture medium has been described as a useful strategy to induce specific biosynthetic pathways. The aim of this study was to assess the effects of different chemical modulators on the metabolic profiles of an endophytic fungal strain of Cophinforma mamane (Botryosphaeriaceae), known to produce 3 thiodiketopiperazine (TDKP) alkaloids (botryosulfuranols A-C), previously isolated and characterized by our team. Four epigenetic modifiers, 5-azacytidine (AZA), sodium butyrate (SB), nicotinamide (NIC), homoserine lactone (HSL) as well as 2 amino acids, l-phenylalanine and l-tryptophan, as bioprecursors of TDKPs, were used. The metabolic profiles were analysed by UHPLC-HRMS/MS under an untargeted metabolomics approach. Our results show that the addition of the two amino acids in C. mamane culture and the treatment with AZA significantly reduced the production of the TDKPs botryosulfuranols A, B and C. Interestingly, the treatment with HSL significantly induced the production of different classes of diketopiperazines (DKPs). The treatment with AZA resulted as the most effective epigenetic modifier for the alteration of the secondary metabolite profile of C. mamane by promoting the expression of cryptic genes.

Anxiety, depression and stress among internally displaced persons and host community in an armed conflict region: A comparative study.

This study compares the psychological profile of Internally Displaced Persons (IDPs) and individuals living in host communities in the war-affected setting. We conducted a cross-sectional survey from October-November 2019. Subjects were recruited from six IDPs camps and the surrounding host communities within the metropolis of Maiduguri, Nigeria by convenience sampling. Data were collected using the Hausa version of Depression Anxiety Stress Scale-21, and analysed by logistic regression using adjusted odds ratio (AOR) at 95% Confidence Interval (CI). A total of 562 subjects were recruited. Living in IDP camp was the most significantly predictor of depression, anxiety, and stress. The common predictors were living in an IDP camp, and marital status (separated). Aged 18-29years was a protective factor compared to those ≥50years. Living in IDP camps, separated from partners, lack of education and pre-conflict employment were significant predictors of depression, anxiety and stress.

Echo-endoscopy: new therapeutic frontiers.

Endoscopic ultrasound (EUS) has been established as a valuable diagnostic modality as it offers high-resolution imaging and fine-needle biopsy, which is essential in detecting and staging malignancies. Since the introduction of EUS-guided fine needle aspiration (EUS-FNA) in 1992, numerous novel EUS-based interventions and techniques have emerged. Currently, established interventional EUS techniques include celiac plexus block and neurolysis, drainage of pancreatic pseudocysts and pelvic fluid collections, and implantation of fiducial markers and radioactive seeds into the malignant tumors. Emerging EUS-guided experimental techniques include antitumor injection, ablation of tumors, and vascular access. Diagnostic and therapeutic access to the biliary tree and pancreatic duct is increasingly being used for failed ERCP procedures or inaccessible ducts. Interventional EUS is a very promising technique with many potential applications. The future holds promise for substantial progress in EUS-guided therapeutic interventions and their applications in clinical gastroenterology.