Slow-release RGD-peptide hydrogel monoliths

We report on the formation of hydrogel monoliths formed by functionalized peptide Fmoc-RGD (Fmoc: fluorenylmethoxycarbonyl) containing the RGD cell adhesion tripeptide motif. The monolith is stable in water for nearly 40 days. The gel monoliths present a rigid porous structure consisting of a network of peptide fibers. The RGD-decorated peptide fibers have a β-sheet secondary structure. We prove that Fmoc-RGD monoliths can be used to release and encapsulate material, including model hydrophilic dyes and drug compounds. We provide the first insight into the correlation between the absorption and release kinetics of this new material and show that both processes take place over similar time scales

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Slow-Release RGD-Peptide Hydrogel Monoliths

We report on the formation of hydrogel monoliths formed by functionalized peptide Fmoc-RGD (Fmoc: fluorenylmethoxycarbonyl) containing the RGD cell adhesion tripeptide motif. The monolith is stable in water for nearly 40 days. The gel monoliths present a rigid porous structure consisting of a network of peptide fibers. The RGD-decorated peptide fibers have a β-sheet secondary structure. We prove that Fmoc-RGD monoliths can be used to release and encapsulate material, including model hydrophilic dyes and drug compounds. We provide the first insight into the correlation between the absorption and release kinetics of this new material and show that both processes take place over similar time scales

Study protocol: a randomised controlled trial of a telephone delivered social wellbeing and engaged living (SWEL) psychological intervention for disengaged youth

Internationally, from 12.2-23.4% of youth (aged 16-24 years) are not in employment, education or training (NEET). These disengaged youth are more likely to experience social exclusion, increased psychological distress and poor quality of life. Youth at risk of disengagement are less likely to access traditional support services, requiring development of innovative interventions.The trial is a single blind, three arm, randomised controlled trial evaluating the effectiveness of a telephone delivered psychological intervention for disengaged youth (12-25 years). Participants will be randomised to receive either (i) SWEL, (ii) Befriending, or (iii) Single Session Psycho-Education. Therapy will be over an 8 week period with a minimum of four and maximum of eight sessions for the SWEL or Befriending conditions, or a single session for the Psycho-Education condition. Outcomes will be assessed at baseline and at 2, 8 and 14-month follow-up with the primary outcome being re-engagement in education, training or employment.This large, multi-site, randomised controlled trial will inform the delivery of services for young people at risk of disengaging from education or training. The provision of psychological therapy by telephone increases access by youth - especially those in rural and remote areas - both to the trial and the treatment, if adopted by services. The outcomes of this trial could have meaningful societal impact for a vulnerable population. It is expected that recruitment, intervention and retention will present challenges for the trial given the focus on disengaged youth.ANZCTR, ACTRN12614001212640 , Registered 18 Nov 2014. Retrospectively registered.Ethics approval has been obtained from the participating institutions. Results of the trial will be submitted for publication in peer reviewed journals and findings presented at scientific conferences and to key service providers and policy makers

Predictors of Hospital Readmission after Bariatric Surgery.

BACKGROUND: Identification of factors that might predict readmission after bariatric surgery could help surgeons target high-risk patients. The purpose of this study was to identify comorbidities, surgical variables, and postoperative complications associated with readmission. STUDY DESIGN: Patients with bariatric surgery as their primary procedure were identified from the 2012 American College of Surgeons (ACS) NSQIP database. Patient variables, operative times, and major postoperative complications were analyzed for predictors of readmission. The ACS NSQIP estimated probability of morbidity (MORBPROB) was also considered. Chi-square tests and Poisson regression were used for statistical analysis to identify significant predictors. RESULTS: There were 18,186 patients who met inclusion criteria. There were 1,819 who had a laparoscopic gastric band, 9,613 who had laparoscopic Roux-en-Y gastric bypass (RYGB), 6,439 who had gastroplasties (vertical banded gastroplasty and sleeve), and 315 who had open RYGB. Age, sex, BMI, American Society of Anesthesiologists (ASA) class, diabetes, hypertension, steroid use, type of procedure, and operative time all were significantly associated with readmission within 30 days of operation. All major postoperative complications were significant predictors of readmission. Patients expected to be at high risk based on the ACS NSQIP MORBPROB had a significantly higher rate of readmissions. The overall readmission rate for patients undergoing bariatric surgery was 5%. The readmission rate among patients with any major complication was 31%. CONCLUSIONS: Bariatric surgery is a low-risk procedure. Complexity of operation, ASA class, prolonged operative time, and major postoperative complications are important determinants of high risk for readmission. The ACS NSQIP MORBPROB may be a useful tool to identify and target patients at risk for readmission

One-Year Follow-Up of COVID-19 Impact on Surgical Education: Clinical Training Restored but Surgical Trainee Emotional Well-Being Still at Risk.

BackgroundA previous survey documented the severe disruption of the coronavirus disease 2019 pandemic on surgical education and trainee well-being during the initial surge and systemic lockdowns. Herein, we report the results of a follow-up survey inclusive of the 2020 to 2021 academic year.Study designA survey was distributed to education leaders across all surgical specialties in summer 2021. We compared the proportion of participants reporting severe disruption in key areas with those of the spring 2020 survey. Aggregated differences by year were assessed using chi-square analysis.ResultsIn 2021, severe disruption of education programs was reported by 14% compared with 32% in 2020 (p < 0.0001). Severe reductions in nonemergency surgery were reported by 38% compared with 87% of respondents in 2020. Severe disruption of expected progression of surgical trainee autonomy by rank also significantly decreased to 5% to 8% in 2021 from 15% to 23% in 2020 among respondent programs (p < 0.001). In 2021 clinical remediation was reported for postgraduate year 1 to 2 and postgraduate year 3 to 4, typically through revised rotations (19% and 26%) and additional use of simulation (20% and 19%) maintaining trainee promotion and job placement. In 2021, surgical trainees' physical safety and health were reported as less severely impacted compared with 2020; however, negative effects of isolation (77%), burnout (75%), and the severe impact on emotional well-being (17%) were prevalent.ConclusionsOne year after the initial coronavirus disease 2019 outbreak, clinical training and surgical trainee health were less negatively impacted. Disruption of emotional well-being remained high. Future needs include better objective measures of clinical competence beyond case numbers and the implementation of novel programs to promote surgical trainee health and well-being

Impact of the COVID-19 pandemic on surgical trainee education and well-being spring 2020-winter 2020: A path forward

BackgroundThe time course and longitudinal impact of the COVID -19 pandemic on surgical education(SE) and learner well-being (LWB)is unknown.Material and methodsCheck-in surveys were distributed to Surgery Program Directors and Department Chairs, including general surgery and surgical specialties, in the summer and winter of 2020 and compared to a survey from spring 2020. Statistical associations for items with self-reported ACGME Stage and the survey period were assessed using categorical analysis.ResultsStage 3 institutions were reported in spring (30%), summer (4%) [p < 0.0001] and increased in the winter (18%). Severe disruption (SD) was stage dependent (Stage 3; 45% (83/184) vs. Stages 1 and 2; 26% (206/801)[p < 0.0001]). This lessened in the winter (23%) vs. spring (32%) p = 0.02. LWB severe disruption was similar in spring 27%, summer 22%, winter 25% and was associated with Stage 3.ConclusionsSteps taken during the pandemic reduced SD but did not improve LWB. Systemic efforts are needed to protect learners and combat isolation pervasive in a pandemic

Lived Experiences of Surgical Residents During the COVID-19 Pandemic: A Qualitative Assessment

OBJECTIVE: As the COVID-19 pandemic dynamically changes our society, it is important to consider how the pandemic has affected the training and wellness of surgical residents. Using a qualitative study of national focus groups with general surgery residents, we aim to identify common themes surrounding their personal, clinical, and educational experiences that could be used to inform practice and policy for future pandemics and disasters. DESIGN: Six 90-minute focus groups were conducted by a trained qualitative researcher who elicited responses on six predetermined topics. De-identified transcripts and audio recordings were later analyzed by two independent researchers who organized responses to each topic into themes. SETTING: Focus groups were conducted virtually and anonymously. PARTICIPANTS: General surgery residents were recruited from across the country. Demographic information of potential participants was coded, and subjects were randomly selected to ensure a diverse group of participants. RESULTS: The impact of the COVID-19 pandemic on residents\u27 clinical, educational, and personal experiences varied depending on the institutional response of the program and the burden of COVID-19 cases geographically. Many successes were identified: the use of telehealth and virtual didactics, an increased sense of camaraderie amongst residents, and flexibility in scheduling. Many challenges were also identified: uncertainty at work regarding personal protective equipment and scheduling, decreased case volume and educational opportunities, and emotional trauma and burnout associated with the pandemic. CONCLUSIONS: These data gathered from our qualitative study highlight a clear, urgent need for thoughtful institutional planning and policies for the remainder of this and future pandemics. Residency programs must ensure a balanced training program for surgical residents as they attempt to master the skills of their craft while also serving as employed health care providers in a pandemic. Furthermore, a focus on wellness, in addition to clinical competency and education, is vital to resident resilience and success in a pandemic setting