Real-world use of venetoclax in the treatment of paediatric and teenage/young adult haematological malignancies.

Early-phase trials of venetoclax in children and teenagers/young adults with leukaemia have yielded promising results, but there remains a paucity of real-world data. To address this, we report a cohort of 41 children treated with venetoclax for a range of haematological malignancies, demonstrating complete remission in 43.6%, with most achieving minimal residual disease (MRD) negativity. Venetoclax was particularly effective as a bridge to transplant, with bridging successful in 75% of patients. Patients with MRD <1% at initiation of venetoclax were more likely to achieve MRD negativity (81.8% vs. 34.5%, p = 0.007) and had improved overall survival (54.5% vs. 17.9%, p = 0.004).

Rationale design and synthesis of new roflumilast analogues as preferential selective and potent PDE-4B inhibitors.

In this study, we designed and synthesized novel analogues of roflumilast that exhibit selective inhibition of PDE-4B. To accomplish this target; synthesis of novel series (4a-u, 5a-i, and 6) was done, aiming at obtaining new PDE-4B inhibitors hits based on the proposed pharmacophore, 1-(cyclopropylmethoxy)-2-(difluoromethoxy) benzene moiety. Enzyme assay was used to measure the IC50 values for the PDE-4B inhibition of all the synthesized compounds along with roflumilast as a reference drug. The results demonstrated that most of the examined candidates exhibited considerable inhibitory activity against the PDE-4B enzyme. The four compounds (4i, 4k, 4p, and 4q) exhibited the highest potency (IC50 = 7.25, 7.15, 5.50, 7.19 nM, respectively) with no significant inhibition difference from roflumilast (no statistical difference at p < 0.05). Interestingly, compound 4p with 3-OH and 4-OCH3 substituents was found to be the most potent against PDE-4B enzyme (IC50 = 5.50 nM), compared to that of roflumilast (IC50 = 2.36 nM). Moreover, the most potent derivatives 4i, 4k, 4p, and 4q were further tested for PDE-4D inhibitory activity to investigate their PDE-4D/PDE-4B selectivity ratio. Compound 4k showed the highest selectivity towards PDE-4B isozyme more than the reference drug roflumilast (PDE-4D/4B IC50 ratio for compound 4k and roflumilast = 3.22 and 3.02, respectively). Additionally, compound 4p was chosen to test its selectivity for PDE-4B over PDE-8A, PDE-11A, and PDE-1B compared to thereference drug roflumilast. Compound 4p showed approximately 6-fold selectivity for PDE-4B over PDE-8A, about 5-fold selectivity for PDE-4B over PDE-11A, and about 11-fold selectivity of PDE-4B over PDE-1B. Compound 4p showed a higher selectivity towards PDE-4B than PDE-1B, more than the reference compound roflumilast. Furthermore, the most potent compounds (4i, 4k, 4p, 4q) were subjected to further investigation, and their effects on the cAMP level and percentage of inhibition of tumor necrosis factor-alpha (TNF-α) were studied and compared with reference drug roflumilast. Compound 4q showed the highest increase in the level of intracellular cAMP (6.55 ± 0.37 pmol/mL) and compound 4i showed the highest % of TNF-α inhibition (77.22 %). On the other side, a molecular docking study against PDE-4B clarified that all the examined candidates achieved nearly similar binding modes with similar orientations to that of the native roflumilast ligand and showed higher docking scores than roflumilast.

Just-In-Time Neonatal Endotracheal Intubation Simulation Training: A Randomized Controlled Trial.

OBJECTIVE: To assess if simulation-based just-in-time training (JITT, short video and simulation) is superior to video training (5-minute video) in acquiring skill in neonatal endotracheal intubation (ETI). STUDY DESIGN: A Canadian multicenter randomized trial recruited junior residents who performed neonatal ETI from July 2017 to June 2021. The primary outcomes were overall and first attempt ETI success rate. Secondary outcomes included number of attempts, duration of attempts, ETI-related complications, and residents' confidence level. Statistical analysis included generalized estimating equations, mixed model analysis, Mann-Whitney test, and χ² tests. RESULTS: Sixty-five residents performed 139 ETI. The overall success rate was similar for both groups (67% vs 70%, P = .71). However, the first attempt success rate was higher for the simulation-based JITT group (54% vs 41%, P = .035). The mean duration of attempts was shorter (35 [SD, 9] vs 62 [SD, 9] seconds, P = .048) and the median number of attempts had a tendency to be lower for the simulation-based JITT group (1 [IQR, 1; 1] vs 1 [IQR, 1; 2], P = .02). There were more mucosal trauma events in the simulation-based JITT group (P = .02). Residents in both groups reported similar confidence level in performing ETI. CONCLUSIONS: Compared with video training, simulation-based JITT for neonatal ETI did not improve overall success rate. However, simulation-based JITT improved first attempt success rate and decreased the number and the duration of ETI attempts. With its positive clinical impact, simulation-based JITT can become an educational adjunct to neonatal ETI training for residents. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02809924.

Transobturator Tension-Free Vaginal Flap Operation versus Synthetic Transobturator Tape for Treatment of Female Stress Urinary Incontinence: A Prospective Randomized Study.

INTRODUCTION: Synthetic mid-urethral slings (MUSs) are the gold standard treatment for female stress urinary incontinence (SUI). Recently, there have been reports of serious adverse events with synthetic tapes such as urethral erosion, vaginal erosion, and mesh infection. Tension-free vaginal flap (TVF) operation has been proven to be successful as a natural alternative to synthetic slings. We propose our novel technique, the transobturator tension-free vaginal flap (TO-TVF), utilizing native vaginal tissue and being suspended via transobturator route. METHODS: This prospective study was conducted on 72 female patients with SUI, presenting at Alexandria University Hospital. Patients were randomized into 2 groups, group 1: 37 patients subjected to TO-TVF and group 2: 35 patients to conventional transobturator tape (TOT). In TO-TVF, a rectangular vaginal wall flap is created. A polypropylene monofilament mesh is sutured to each edge of the vaginal flap. This is inserted like conventional outside-in TOT. Patients were subjected to PGI and UDI-6 questionnaires and urodynamic study before and 6 months postoperatively. RESULTS: Both groups showed comparable and significant improvements in questionnaires. Mean operative time for TO-TVF and conventional TOT was 26.31 ± 5.2 min and 21.8 ± 3.1 min, respectively. Cure rate was 89% in group 1 and 91.4% in group 2, which was not statistically significant. No significant intraoperative complications were encountered. We had no cases of vaginal or urethral erosion in both groups. CONCLUSIONS: TO-TVF is a cost-effective, feasible, safe, and effective surgical alternative to synthetic MUS. Synthetic mesh tissue anchoring properties are maintained for better adjustment of tension. However, long-term follow-up on a large cohort of patients is still needed.

Fate of Cryptosporidium and Giardia through conventional and compact drinking water treatment plants.

Over the past three decades, a notable rise in the occurrence of enteric protozoan pathogens, especially Giardia and Cryptosporidium spp., in drinking water sources has been observed. This rise could be attributed not only to an actual increase in water contamination but also to improvements in detection methods. These waterborne pathogens have played a pivotal role in disease outbreaks and the overall escalation of disease rates in both developed and developing nations worldwide. Consequently, the control of waterborne diseases has become a vital component of public health policies and a primary objective of drinking water treatment plants (DWTPs). Limited studies applied real-time PCR (qPCR) and/or immunofluorescence assay (IFA) for monitoring Giardia and Cryptosporidium spp., particularly in developing countries like Egypt. Water samples from two conventional drinking water treatment plants and two compact units (CUs) were analyzed using both IFA and qPCR methods to detect Giardia and Cryptosporidium. Using qPCR and IFA, the conventional DWTPs showed complete removal of Giardia and Cryptosporidium, whereas Mansheyat Alqanater and Niklah CUs achieved only partial removal. Specifically, Cryptosporidium gene copies removal rates were 33.33% and 60% for Mansheyat Alqanater and Niklah CUs, respectively. Niklah CU also removed 50% of Giardia gene copies, but no Giardia gene copies were removed by Mansheyat Alqanater CU. Using IFA, both Mansheyat Alqanater and Niklah CUs showed a similar removal rate of 50% for Giardia cysts. Additionally, Niklah CU achieved a 50% removal of Cryptosporidium oocysts, whereas Mansheyat Alqanater CU did not show any removal of Cryptosporidium oocysts. Conventional DWTPs were more effective than CUs in removing enteric protozoa. The contamination of drinking water by enteric pathogenic protozoa remains a significant issue globally, leading to increased disease rates. Infectious disease surveillance in drinking water is an important epidemiological tool to monitor the health of a population.

Laryngeal Mask Airway Clinical Use and Training: A Survey of North American Neonatal Health Care Professionals.

OBJECTIVE: The aim of this study was to explore North American neonatal health care professionals' (HCPs) experience, confidence, skill, and training with the laryngeal mask airway (LMA). STUDY DESIGN: This was a cross-sectional survey. RESULTS: The survey was completed by 2,159 HCPs from Canada and the United States. Seventy nine percent had no clinical experience with the LMA, and less than 20% considered the LMA an alternative to endotracheal intubation (EI). The majority had received LMA training; however, 28% of registered nurses, 18% of respiratory therapists, 17% of physicians, and 12% of midwives had never inserted an LMA in a mannequin. Less than a quarter of respondents agreed that the current biennial Neonatal Resuscitation Program instruction paradigm is sufficient for LMA training. All groups reported low confidence and skill with LMA insertion, and compared with all other groups, the respiratory therapists had the highest reported confidence and skill. CONCLUSION: This survey study, which is the first of its kind to include midwives, demonstrates that neonatal HCPs lack experience, confidence, skill, and training with the LMA, rarely use the device, and in general, do not consider the LMA as an alternative to EI. These findings contribute to, and support the findings of previous smaller studies, and in conjunction with the diminishing opportunities for EI, highlight the need for programs to emphasize the importance of the LMA for neonatal airway management and prioritize regular LMA training, with focus that parallels the importance placed on the skills of EI and mask ventilation. KEY POINTS: · Lack of training for laryngeal mask airway use in neonatal resuscitation.. · Neonatal health care professionals rarely use the laryngeal mask airway as an alternate airway device.. · Neonatal health care professionals lack confidence and skill with the laryngeal mask airway..

Dating admixture events is unsolved problem in multi-way admixed populations.

Advances in human sequencing technologies, coupled with statistical and computational tools, have fostered the development of methods for dating admixture events. These methods have merits and drawbacks in estimating admixture events in multi-way admixed populations. Here, we first provide a comprehensive review and comparison of current methods pertinent to dating admixture events. Second, we assess various admixture dating tools. We do so by performing various simulations. Third, we apply the top two assessed methods to real data of a uniquely admixed population from South Africa. Results reveal that current dating admixture models are not sufficiently equipped to estimate ancient admixtures events and to identify multi-faceted admixture events in complex multi-way admixed populations. We conclude with a discussion of research areas where further work on dating admixture-based methods is needed.

Does a tailored magnetic resonance imaging technique affect the surgical planning and outcomes for different cystic urethral and periurethral swellings in females? Seven years tertiary center experience.

PURPOSE: To evaluate the use of magnetic resonance imaging (MRI) in preoperative delineation and surgical planning for the management of female urethral and periurethral cystic vaginal swellings, with emphasis on postoperative surgical outcomes. MATERIALS AND METHODS: This is a retrospective analysis of females complaining of periurethral and urethral cystic swellings referred to our tertiary center, who underwent MRI for preoperative planning in the period from January 2014 till January 2021, with a total number of 57 patients. Data retrieved from the medical records included: patients' demographics, presenting symptoms and signs, preoperative radiological investigations, duration of symptoms, previous surgical intervention, detailed intraoperative data, postoperative complications, and postoperative follow-up. RESULTS: Urethral diverticulum was the commonest cystic lesion representing (64.9%) followed by Skene gland cysts in 14%, Mullerian cysts in 7%, Gartner cysts in 3.5%, and dermoid inclusion cysts in 10.5%. MRI precisely diagnosed the various pathological entities and anatomical complex lesions prior to surgery. This was confirmed after surgery and pathology analysis. All patients were followed up with a mean duration of 35 months, without any evidence of recurrence. CONCLUSION: MRI as a standalone imaging technique is mandatory for diagnosis of all urethral and periurethral cystic lesions, as it offers the most accurate diagnostic modality for delineation of these lesions and hence aids in the preoperative surgical planning, aiming to avoid recurrence and improving surgical outcomes.

Pre- and peri-operative clinical information, physiological observations and outcome measures following flexible ureterorenoscopy (FURS), for the treatment of kidney stones. A single-centre observational clinical pilot-study in 51 patients.

BACKGROUND: Kidney stone disease contributes to a significant proportion of routine urological practice and remains a common cause of worldwide morbidity. The main aim of this clinical-pilot study was to investigate the effect of flexible ureterorenoscopy (FURS) on pre- and peri-operative clinical information, physiological observations and outcome measures. METHODS: Included were 51 patients (31 males, 20 females), who underwent elective FURS, for the treatment of kidney stones. Pre-operative and peri-operative clinical information, and post-operative physiological observations and outcome measures were collected using a standard case report form. Pre-operative clinical information included age, gender, BMI, previous history of stone formation and hypertension. Pre-operative stone information included the size (mm), Hounsfield units (HU), laterality and intra-renal anatomical location. Peri-operative surgical details included surgical time in minutes; Laser use; Duration and energy of laser; and post-operative stenting. The physiological outcomes measured included systolic and diastolic blood pressure (mmHg), Likert pain score, temperature, heart rate (bpm) and respiration rate (bpm). Following initial descriptive analysis, a series of Pearson's correlation coefficient tests were performed to investigate the relationship between surgical factors other variable factors. RESULTS: A series of significant, positive correlations were observed between; age and surgical time (p = 0.014, r = 0.373); stone size and Hounsfield unit (p = 0.029, r = 0.406); surgical time and duration of laser (p < 0.001, r = 0.702); surgical time and BMI (p = 0.035, r = 0.322); baseline heart rate and Hounsfield unit (p = 0.026, r = - 0.414); base line heart rate and BMI (p = 0.030, r = 0.307).; heart rate at 120-min post FURS and age (p = 0.038, r = - 0.308); baseline pain score and BMI (p = 0.010, r = 0.361); baseline respiration rate and BMI (p = 0.037, r = 0.296); respiration rate at 240-min post FURS and BMI (p = 0.038, r = 0.329); respiration rate at 120 min post FURS and age (p = 0.022, r = - 0.330). Four patients developed post-operative complications (3-UTIs with urinary retention, 1-urosepsis). CONCLUSIONS: We report that following FURS there is an association between various physiological, clinical and surgical parameters. Although these correlations are weak, they warrant further investigation as these may be linked with untoward complications, such as infection that can occur following FURS. This data, however, will need to be validated and reproduced in larger multi-centre studies.

An overview of genes and mutations associated with Chlamydiae species' resistance to antibiotics.

BACKGROUND: Chlamydiae are intracellular bacteria that cause various severe diseases in humans and animals. The common treatment for chlamydia infections are antibiotics. However, when antibiotics are misused (overuse or self-medication), this may lead to resistance of a number of chlamydia species, causing a real public health problem worldwide. MATERIALS AND METHODS: In the present work, a comprehensive literature search was conducted in the following databases: PubMed, Google Scholar, Cochrane Library, Science direct and Web of Science. The primary purpose is to analyse a set of data describing the genes and mutations involved in Chlamydiae resistance to antibiotic mechanisms. In addition, we proceeded to a filtration process among 704 retrieved articles, then finished by focusing on 24 studies to extract data that met our requirements. RESULTS: The present study revealed that Chlamydia trachomatis may develop resistance to macrolides via mutations in the 23S rRNA, rplD, rplV genes, to rifamycins via mutations in the rpoB gene, to fluoroquinolones via mutations in the gyrA, parC and ygeD genes, to tetracyclines via mutations in the rpoB gene, to fosfomycin via mutations in the murA gene, to MDQA via mutations in the secY gene. Whereas, Chlamydia pneumoniae may develop resistance to rifamycins via mutations in the rpoB gene, to fluoroquinolones via mutations in the gyrA gene. Furthermore, the extracted data revealed that Chlamydia psittaci may develop resistance to aminoglycosides via mutations in the 16S rRNA and rpoB genes, to macrolides via mutations in the 23S rRNA gene. Moreover, Chlamydia suis can become resistance to tetracyclines via mutations in the tet(C) gene. In addition, Chlamydia caviae may develop resistance to macrolides via variations in the 23S rRNA gene. The associated mechanisms of resistance are generally: the inhibition of bacteria's protein synthesis, the inhibition of bacterial enzymes' action and the inhibition of bacterial transcription process. CONCLUSION: This literature review revealed the existence of diverse mutations associated with resistance to antibiotics using molecular tools and targeting chlamydia species' genes. Furthermore, these mutations were shown to be associated with different mechanisms that led to resistance. In that regards, more mutations and information can be shown by a deep investigation using the whole genome sequencing. Certainly, this can help improving to handle chlamydia infections and healthcare improvement by decreasing diseases complications and medical costs.

Laparoscopic repair of female genitourinary fistulae: 10-year single-center experience.

INTRODUCTION AND HYPOTHESIS: Laparoscopic repair of different female genitourinary fistulae has been recently reported, including both conventional and laparoendoscopic single-site surgery (LESS). We present our 10-year single-center experience of the laparoscopic repair of different types of female genitourinary fistulae. METHODS: A retrospective analysis of our records over the last 10 years was performed. Type of fistula, etiology, laparoscopic approach, operative data, postoperative outcome, and follow-up were recorded. RESULTS: Overall, 46 patients with laparoscopic repair of genitourinary fistulae were reported: 25 had vesicovaginal fistulae (VVF), 14 had vesicouterine fistulae (VUF), and 7 had ureterovaginal fistulae (UVF). Thirty-three patients had conventional laparoscopic repair, whereas 7 VVF and 6 VUF had LESS repair. In all patients with VVF and VUF, extravesical repair was carried out by excising the fistulous tract and closing both the bladder and the vagina or the uterus with interposing tissue in-between. In patients with UVF, extravesical ureteric re-implantation was performed. Mean operative time was 176 ± 25 min. Mean blood loss was 105 ± 25 cc. No intraoperative or postoperative complications occurred. None was converted to open surgery. Mean postoperative hospital stay was 3.2 ± 1.2 days. After a mean follow-up of 6.3 ± 3.1 years, all patients had undergone successful repair, except for one patient with complex VVF. CONCLUSIONS: Laparoscopic repair of VVF, VUF, and UVF is a feasible procedure with a high success rate and low morbidity. LESS repair of VVF and VUF has a comparable success rate to conventional laparoscopy, but with a shorter hospital stay and fewer analgesic requirements.

The role of specific biomarkers, as predictors of post-operative complications following flexible ureterorenoscopy (FURS), for the treatment of kidney stones: a single-centre observational clinical pilot-study in 37 patients.

BACKGROUND: The number of patients diagnosed and subsequently treated for kidney stones is increasing, and as such the number of post-operative complications is likely to increase. At present, little is known about the role of specific biomarkers, following flexible ureterorenoscopy (FURS) for the surgical treatment of kidney stones. The main aim of the study was to evaluate the role of kidney and infection biomarkers, in patients undergoing FURS. METHODS: Included were 37 patients (24 males, 13 females), who underwent elective FURS, for the treatment of kidney stones. Venous blood samples were collected from each patient: pre-operatively, and at 30 min, 2 and 4 h post-operatively. Changes to kidney (NGAL, Cystatin-C) and infection (MPO, PCT) biomarkers was quantified by means of ELISA, Biomerieux mini-vidas and Konelab 20 analysers. RESULTS: Four patients developed post-operative complications (3 - UTIs with urinary retention, 1 - urosepsis. NGAL concentration increased significantly following FURS (p = 0.034). Although no significant changes were seen in Cystatin C, MPO and PCT (p ≥ 0.05) some key clinical observation were noted. Limiting factors for this study were the small number of patients recruited and restriction in blood sampling beyond 4 h. CONCLUSIONS: Although not confirmative, changes seen to biomarkers such as Cystatin C, NGAL and MPO in our observational clinical pilot-study may warrant further investigation, involving larger cohorts, to fully understand the role of these biomarkers and their potential association with post-operative complications which can develop following FURS.

Simulation in Neonatal-Perinatal Medicine Fellowship Programs.

OBJECTIVE: This study aimed to investigate the use of simulation in neonatal-perinatal medicine (NPM) fellowship programs. STUDY DESIGN: This was a cross-sectional survey of program directors (PDs) and simulation educators in Accreditation Council for Graduate Medical Education (ACGME) accredited NPM fellowship programs. RESULTS: Responses were received from 59 PDs and 52 simulation educators, representing 60% of accredited programs. Of responding programs, 97% used simulation, which most commonly included neonatal resuscitation (94%) and procedural skills (94%) training. The time and scope of simulation use varied significantly. The majority of fellows (51%) received ≤20 hours of simulation during training. The majority of PDs (63%) wanted fellows to receive >20 hours of simulation. Barriers to simulation included lack of faculty time, experience, funding, and curriculum. CONCLUSION: While the majority of fellowship programs use simulation, the time and scope of fellow exposure to simulation experiences are limited. The creation of a standardized simulation curriculum may address identified barriers to simulation.

Team Stress and Adverse Events during Neonatal Tracheal Intubations: A Report from NEAR4NEOS.

OBJECTIVE: This study aimed to examine the association between team stress level and adverse tracheal intubation (TI)-associated events during neonatal intubations. STUDY DESIGN: TIs from 10 academic neonatal intensive care units were analyzed. Team stress level was rated immediately after TI using a 7-point Likert scale (1 = high stress). Associations among team stress, adverse TI-associated events, and TI characteristics were evaluated. RESULT: In this study, 208 of 2,009 TIs (10%) had high stress levels (score < 4). Oxygenation failure, hemodynamic instability, and family presence were associated with high stress level. Video laryngoscopy and premedication were associated with lower stress levels. High stress level TIs were associated with adverse TI-associated event rates (31 vs. 16%, p < 0.001), which remained significant after adjusting for potential confounders including patient, provider, and practice factors associated with high stress (odds ratio: 1.90, 96% confidence interval: 1.36-2.67, p < 0.001). CONCLUSION: High team stress levels during TI were more frequently reported among TIs with adverse events.

H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa.

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.

Needs assessment of ethics and communication teaching for neonatal perinatal medicine programs in Canada.

OBJECTIVE: To explore ethics education needs in Canadian Neonatal Perinatal Medicine (NPM) training programs. METHODS: A retrospective review of NPM trainees' performance at the National NPM Objective Structured Clinical Examination (OSCE) was undertaken for 2012 to 2017 and two distinct cross-sectional online surveys were carried out. One survey targeted recently graduated neonatologists (RGNs) who completed 2 years' training in a Canadian NPM program between 2010 and 2015; the other survey was sent to Canadian NPM training program directors (PDs). The domains of interest were: perception of education, ethics and communication topics, educational strategies, assessment of trainees' competencies, and barriers to neonatal ethics education. RESULTS: NPM trainees generally performed less well in stations involving ethics and communication relative to other domains on the National OSCE. Forty-seven RGNs (44.3%) and 12 PDs (92.3%) completed the survey. Over 90% of PDs and RGNs agreed on the importance of training in ethics and communication. Both groups highly valued training on topics related to communication. Preferred teaching strategies were experiential: observation and feedback. PDs mentioned the importance of using validated tools to regularly and formally assess trainees. They recognized challenges in regard to financial resources, physical space, and faculty training in patient-physician communication. CONCLUSIONS: National OSCE results indicate the need to improve neonatal ethics and communication training in Canadian NPM programs. RGNs and PDs identified important topics, as well as teaching and evaluation strategies. These results can be used to develop a training program for ethics and communication in NPM.

Transcutaneous posterior tibial nerve electrostimulation with low dose trospium chloride: Could it be used as a second line treatment of overactive bladder in females.

AIM: To evaluate the effect of adding low dose trospium chloride with transcutaneous posterior tibial nerve stimulation (TPTNS) in the treatment of overactive bladder (OAB) in females after failure of behavioral therapy. METHODS: We randomized 30 women with OAB, in two groups: G I received 30 min TPTNS, three times a week; GII received TPTNS plus 20 mg trospium chloride daily. OAB Symptom Score questionnaire (OABSS), Incontinence Impact Questionnaire-short form 7 (IIQ-7), 3 day voiding diary and urodynamics at weeks 0 and 8 were evaluated. RESULTS: The groups were similar before treatment. Eight weeks after treatment, the mean OABSS decreased significantly to 8.53 ± 1.30 for group II vs 10.0 ± 2.0 for GI (P < 0.024). The mean IIQ-7 score decreased significantly to 51.86 ± 17.26 in group I vs 31.99 ± 9.26 in group II (P < 0.001). Before treatment, 11 (73.3%) and 4 (26.7%) patients in each group had moderate and poor quality of life (QoL), respectively. After treatment, 6 (40%) and 14 (93.3%) had good QoL, 7 (46.7%) and 1 (6.7%) had moderate QoL in GI and GII, respectively. Two (13.3%) patients in GI had poor QoL. The mean frequency was reduced to 8.60 ± 0.83 vs 10.60 ± 2.32 for GII and GI respectively (P = 0.006). The cystometric capacity increased from 263.40 ± 50.45 to 377.80 ± 112.92 mL (P = 0.001) for GII vs 250.13 ± 56.24 to 296.40 ± 99.0 mL (P = 0.026) for GI. CONCLUSION: TPTNS combined with low dose trospium chloride proved to be more effective than TPTNS alone in the treatment of OAB in females.

The Impact of Neonatal Simulations on Trainees' Stress and Performance: A Parallel-Group Randomized Trial.

OBJECTIVES: Assess impact of neonatal simulation and simulated death on trainees' stress and performance. DESIGN: A parallel-group randomized trial (November 2011 to April 2012). SETTING: Sainte-Justine University Hospital, Montreal, Canada. SUBJECTS: Sixty-two pediatric trainees eligible, 59 consented, and 42 completed the study. INTERVENTIONS: Trainees performed two simulations where a term neonate was born pulseless. They were randomized to start with either survival (manikin responded to appropriate resuscitation) or death scenario (manikin remained pulseless despite resuscitation). MEASUREMENTS AND MAIN RESULTS: Performance was assessed using the Neonatal Resuscitation Program megacode score sheet by two reviewers. Subjective stress was assessed with a questionnaire. Three salivary cortisol (objective stress) values were compared: at baseline (T0: during lecture), presimulation (T1), and postsimulation (T2: after first scenario). Performance scores were similar in both groups in the first (83% vs 82%; p = 0.85) and second scenarios (82% vs 79 %; p = 0.87). Salivary cortisol levels at T0 (0.10 vs 0.10; p = 0.54), T1 (0.15 vs 0.11; p = 0.35), and T2 (0.23 vs 0.17; p = 0.23) did not differ between groups. Perceived stress level was six out of 10 in survival group versus seven out of 10 in death group (p = 0.19). Salivary cortisol increased significantly from T0 to T1 (p < 0.01). T2 cortisol levels were significantly higher than T1 (p< 0.001), yet this increase was not scenario dependent (p = 0.41) nor associated with performance on either scenario. Subscores for bag mask ventilation were lower than subscores for advanced resuscitation skills. CONCLUSIONS: Neonatal simulations cause significant anticipatory and participatory stress. Despite this, trainees' performance score in simulation was over 80%. Simulated death did not impact performance, magnitude of rise in salivary cortisol level, and perceived stress level. Trainees performed better at advanced resuscitation skills (which are rarely needed) compared with basic skills routinely performed in practice.

Predicting Perinatal Outcome from Prenatal Ultrasound Characteristics in Pregnancies Complicated by Gastroschisis.

INTRODUCTION: The objective of the study was to establish the predictive value of prenatal ultrasound markers for complex gastroschisis (GS) in the first 10 days of life. MATERIAL AND METHODS: In this retrospective cohort study over 11 years (2000-2011) of 117 GS cases, the following prenatal ultrasound signs were analyzed at the last second- and third-trimester ultrasounds: intrauterine growth restriction, intra-abdominal bowel dilatation (IABD) adjusted for gestational age, extra-abdominal bowel dilatation (EABD) ≥25 mm, stomach dilatation, stomach herniation, perturbed mesenteric circulation, absence of bowel lumen and echogenic dilated bowel loops (EDBL). RESULTS: Among 114 live births, 16 newborns had complex GS (14.0%). Death was seen in 16 cases (13.7%): 3 intrauterine fetal deaths, 9 complex GS and 4 simple GS. Second-trimester markers had limited predictive value. Third-trimester IABD, EABD, EDBL, absence of intestinal lumen and perturbed mesenteric circulation were statistically associated with complex GS and death. IABD was able to predict complex GS with a sensitivity of 50%, a specificity of 91%, a positive predictive value of 47% and a negative predictive value of 92%. DISCUSSION: Third-trimester IABD adjusted for gestational age appears to be the prenatal ultrasound marker most strongly associated with adverse outcome in GS.

Saturated fatty acids alter the late secretory pathway by modulating membrane properties.

Saturated fatty acids (SFA) have been reported to alter organelle integrity and function in many cell types, including muscle and pancreatic ß-cells, adipocytes, hepatocytes and cardiomyocytes. SFA accumulation results in increased amounts of ceramides/sphingolipids and saturated phospholipids (PL). In this study, using a yeast-based model that recapitulates most of the trademarks of SFA-induced lipotoxicity in mammalian cells, we demonstrate that these lipid species act at different levels of the secretory pathway. Ceramides mostly appear to modulate the induction of the unfolded protein response and the transcription of nutrient transporters destined to the cell surface. On the other hand, saturated PL, by altering membrane properties, directly impact vesicular budding at later steps in the secretory pathway, i.e. at the trans-Golgi Network level. They appear to do so by increasing lipid order within intracellular membranes which, in turn, alters the recruitment of loose lipid packing-sensing proteins, required for optimal budding, to nascent vesicles. We propose that this latter general mechanism could account for the well-documented deleterious impacts of fatty acids on the last steps of the secretory pathway in several cell types.