Co-producing an inclusive-care model for young people transitioning from adolescent eating disorder services to adult care: A qualitative study protocol for Transition for Eating Disorder Youth intervention.

Eating disorders (EDs) present a chronic issue to child paediatric mental health services due to their high mortality and relapse rates. The transition from Child and Adolescent Mental Health Services to Adult Mental Health Services is a particularly high-risk period for young people with EDs given their high vulnerability to change, which can negatively impact treatment outcomes. However, there is lack of evidence on the feasibility of inclusive and youth-specific interventions that address the multiple and complex needs of this group during their transition to adult care. This proposed study aims to develop a newly introduced model of care called Transition for Eating Disorder Youth intervention (TEDYi) for young people aged 16-18 years with EDs transitioning from adolescent ED services to adult care. TEDYi will be co-produced with young people, carers, and staff targeting interpersonal and psychosocial needs during the transition process. The first phase of the study involves interviews with young people (N = 15) and carers (N = 15) as well as focus groups with mental health professionals (N = 15) across four ED adolescent and adult specialist services to explore their transition experiences. The second phase, consists of four Experience-Based Co-Design workshops, aimed at collaboratively developing and refining TEDYi.

Impact of sand bund removal on seagrass ecosystems: A study of macrobenthic community structure and correlation with macrophytes cover and sediments.

This study investigated the impacts of the removal of sand bund on the macrobenthos community structure, seagrass cover, and sediment particle size in Merambong Shoal, Malaysia. The reclamation project deposited sand bund in the middle of Merambong seagrass shoal, resulting in its division into northern (NS) and southern (SS) halves. Ecosystem changes were monitored over a 31-month period using the transect lines method. Bi-monthly samples were collected for assessment. The results revealed a substantial decline in macrobenthos densities compared to previous studies. However, after the removal of the sand bund, there was a significant increase in macrobenthos density, specifically Polychaeta and Malacostraca, at NS. Seagrass cover at NS was initially lower than SS but showed an increase after the complete removal of the sand blockage. Sediment particle analysis reported a higher silt percentage at NS, indicating greater sedimentation at NS, which was partially sheltered from wave actions.

Overnight declarative memory consolidation and non-rapid eye movement sleep electroencephalographic oscillations in older adults with obstructive sleep apnea.

STUDY OBJECTIVES: To compare overnight declarative memory consolidation and non-rapid eye movement (NREM) sleep electroencephalogram (EEG) oscillations in older adults with obstructive sleep apnea (OSA) to a control group and assess slow-wave activity (SWA) and sleep spindles as correlates of memory consolidation. METHODS: Forty-six older adults (24 without OSA and 22 with OSA) completed a word-pair associate's declarative memory task before and after polysomnography. Recall and recognition were expressed as a percentage of the morning relative to evening scores. Power spectral analysis was performed on EEG recorded at frontal (F3-M2, F4-M1) and central (C3-M2, C4-M1) sites. We calculated NREM absolute slow oscillation (0.25-1 Hz) and delta (0.5-4.5 Hz) EEG power, and slow (11-13 Hz) spindle density (number of events per minute of N2 sleep) and fast (13-16 Hz) spindle density. RESULTS: There were no significant differences in overnight recall and recognition between OSA (mean age 58.7 ± 7.1 years, apnea-hypopnea index (AHI) 41.9 ± 29.7 events/hour) and non-OSA (age 61.1 ± 10.3 years, AHI 6.6 ± 4.2 events/hour) groups. The OSA group had lower fast spindle density in the frontal region (p = 0.007). No between-group differences in SWA were observed. In the Control group, overnight recognition positively correlated with slow spindle density in frontal (rho = 0.555, p = 0.020) and central regions (rho = 0.490, p = 0.046). Overnight recall was not related to SWA or spindle measures in either group. CONCLUSIONS: Older adults with OSA had deficits in fast sleep spindles but showed preserved overnight declarative memory consolidation. It is possible that compensatory mechanisms are being recruited by OSA patients to preserve declarative memory consolidation despite the presence of sleep spindle deficits.

Techniques and Outcomes of Endoscopic Ultrasound Guided-Pancreatic Duct Drainage (EUS- PDD).

Endoscopic ultrasound guided-pancreatic duct drainage (EUS- PDD) is one of the most technically challenging procedures for the interventional endoscopist. The most common indications for EUS- PDD are patients with main pancreatic duct obstruction who have failed conventional endoscopic retrograde pancreatography (ERP) drainage or those with surgically altered anatomy. EUS- PDD can be performed via two approaches: the EUS-rendezvous (EUS- RV) or the EUS-transmural drainage (TMD) techniques. The purpose of this review is to provide an updated review of the techniques and equipment available for EUS- PDD and the outcomes of EUS- PDD reported in the literature. Recent developments and future directions surrounding the procedure will also be discussed.

Pure endoscopic resection versus laparoscopic assisted procedure for upper gastrointestinal stromal tumors: Perspective from a surgical endoscopist.

Management of upper gastrointestinal (UGI) tract gastrointestinal stromal tumor (GIST) has evolved significantly over the past two decades. For GIST size smaller than 5 cm, laparoscopic resection has become the current standard. To avoid postoperative gastric deformity and preserve gastric function, laparoscopic endoscopic cooperative surgery (LECS) was developed and various modifications have been reported and utilized successfully. Pure endoscopic resection techniques have also been reported at a similar period of time, which further push the boundary of incisionless surgery in managing these lesions. Both tunneling and nontunneling exposed type endoscopic full thickness resection are well described procedures for resection of small UGI GIST. In this review, a summary of these procedures is provided, and the pros and cons of each technique from the perspective of a surgical endoscopist are discussed in detail. LECS and endoscopic resection are complementary to each other. The choice of technique should be tailored to the location, morphology, and size of the target lesions, taking into account the experience of the laparoscopic surgeons and endoscopists.

Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases.

BACKGROUND: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM. METHODS: Forty-four patients with GCPM received IP PTX (40 mg/m2, Days 1, 8), oral capecitabine (1000 mg/m2 twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m2, Day 1) in 21-day cycles. Patients with synchronous GCPM underwent conversion surgery if they had good response after chemotherapy, conversion to negative cytology, no extraperitoneal metastasis, and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were compared against a matched cohort of 39 GCPM patients who received systemic chemotherapy (SC) comprising platinum/fluoropyrimidine. RESULTS: The median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p < 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%. CONCLUSIONS: IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.

A systematic scoping review of the effects of central nervous system active drugs on sleep spindles and sleep-dependent memory consolidation.

Sleep spindles are key electroencephalogram (EEG) oscillatory events that occur during non-rapid eye movement (NREM) sleep. Deficits in sleep spindles are present in populations with sleep and neurological disorders, and in severe mental illness. Pharmacological manipulation of these waveforms is of growing interest with therapeutic potential in targeting spindle deficits relating to memory impairment. This review integrates studies that provide insight into the feasibility of manipulating sleep spindles by using psychoactive drug classes, with consequent effects on sleep-dependent memory. Most studies showed that benzodiazepines and Z-drugs consistently enhanced sleep spindle activity unlike other psychoactive drug classes reviewed. However, how these spindle enhancements translate into improved sleep-dependent memory remains to be fully elucidated. From the few studies that examined both spindles and memory, preliminary evidence suggests that zolpidem may have some therapeutic potential to enhance declarative memory through boosting sleep spindle activity. There is a greater need to standardise methodological approaches for identifying and quantifying spindle activity as well as more exploratory studies to elucidate the role of spindle enhancement for other types of memory.

Gastro-esophageal reflux disease (GERD) after peroral endoscopic myotomy (POEM).

BACKGROUND: Peroral endoscopic myotomy (POEM) is gaining traction as a minimally invasive treatment of achalasia. Increased reflux is reported after POEM but the incidence, type and severity of reflux are not fully understood. We aimed to study the prevalence and nature of reflux after POEM and correlate reflux with endoscopy and pH-impedance findings. METHODS: This is a prospective cohort study of achalasia patients undergoing POEM since 2014. Data from Eckardt and GERD symptom scores, high-resolution oesophageal manometry (HRM) and gastroscopy were performed pre-procedure and repeated at 1-year follow-up. Data from 24-h pH-impedance, if performed, were also recorded. A standardized questionnaire was used to determine the severity and frequency of heartburn symptoms and the composite score for each patient was calculated. RESULTS: 58 patients underwent POEM between January 2014 and October 2018. The efficacy of POEM at 1 year was 93.0%. We observed reduction of median Integrated Relaxation Pressure (IRP) from 23.5 ± 33.1 mmHg to 13.4 ± 7.71 mmHg (p = 0.005) and mean Eckardt score improved from 6.09 ± 2.43 points to 1.16 ± 1.70 points (p < 0.001). At 1 year, 43.1% (n = 25) had symptomatic reflux. Of the 40 patients who underwent repeated gastroscopy, 60.0% (n = 24) had endoscopic evidence of oesophagitis with seven patients (18%) diagnosed with Grade C or D oesophagitis. 43.1% (n = 25) of patients had pH-impedance done post-POEM off PPIs. 14 patients (56%) had increased acid exposure. Sixteen percent of reflux episodes were acidic and 77.3% were weakly acidic. CONCLUSION: POEM was an effective treatment for achalasia. However, GERD was common after POEM with incidence of 43% on symptom score, 60% on endoscopy and 56% on pH-impedance test. Post-POEM reflux appeared to be predominantly acidic in nature. Routine surveillance for GERD after POEM is recommended.

Admission discipline and timing of admission may influence outcomes for gastrointestinal bleeding patients.

BACKGROUND: Bleeding of the gastrointestinal tract (BGIT) is a common gastrointestinal emergency. There is no consensus whether this condition should be admitted to medical or surgical discipline. Timing of presentation may also impact patient outcomes due to differences in healthcare resource availability. This study thus aims to investigate the impact of admitting discipline and timing of admission on patient outcomes in BGIT. METHODS: A 2-year tertiary institution database was retrospectively reviewed. Outcome measures included 30-day mortality, 30-day readmissions and rebleeding requiring repeat endoscopic, angiographic or surgical interventions. Secondary outcome measures included time to endoscopy, percutaneous angiographic interventions and surgery. The effect of admission discipline (medical versus surgical) and time of admission (office-hours versus after office-hours) were analysed using a propensity-score-adjusted estimate. RESULTS: A total of 1384 patients were included for analysis, medical (n = 853), surgical (n = 530); during office-hours (n = 785) and after office-hours (n = 595). After propensity-score-adjusted analysis, no significant differences in mortality or readmissions were noted between medical or surgical admissions. Patients admitted under surgery were less likely to sustain rebleeding (P = 0.004) for lower BGIT and had an earlier time to endoscopy for upper BGIT (P = 0.04). Patients admitted after office-hours had similar outcomes with those admitted during office hours apart from a delay in time to endoscopy (P = 0.02). CONCLUSION: For BGIT patients, admission to a surgical discipline compared to a medical discipline appeared to have at least equivalent patient outcomes. Patients presenting with BGIT after office-hours were more likely to experience a delay to endoscopy, although it did not affect patient mortality.

Recent advances in diagnostic upper endoscopy.

BACKGROUND: Esophageo-gastro-duodenoscopy (EGD) is an important procedure used for detection and diagnosis of esophago-gastric lesions. There exists no consensus on the technique of examination. AIM: To identify recent advances in diagnostic EGDs to improve diagnostic yield. METHODS: We queried the PubMed database for relevant articles published between January 2001 and August 2019 as well as hand searched references from recently published endoscopy guidelines. Keywords used included free text and MeSH terms addressing quality indicators and technological innovations in EGDs. Factors affecting diagnostic yield and EGD quality were identified and divided into the follow segments: Pre endoscopy preparation, sedation, examination schema, examination time, routine biopsy, image enhanced endoscopy and future developments. RESULTS: We identified 120 relevant abstracts of which we utilized 67 of these studies in our review. Adequate pre-endoscopy preparation with simethicone and pronase increases gastric visibility. Proper sedation, especially with propofol, increases patient satisfaction after procedure and may improve detection of superficial gastrointestinal lesions. There is a movement towards mandatory picture documentation during EGD as well as dedicating sufficient time for examination improves diagnostic yield. The use of image enhanced endoscopy and magnifying endoscopy improves detection of squamous cell carcinoma and gastric neoplasm. The magnifying endoscopy simple diagnostic algorithm is useful for diagnosis of early gastric cancer. CONCLUSION: There is a steady momentum in the past decade towards improving diagnostic yield, quality and reporting in EGDs. Other interesting innovations, such as Raman spectroscopy, endocytoscopy and artificial intelligence may have widespread endoscopic applications in the near future.

Maternal and fetal outcomes of Asian pregnancies after bariatric surgery.

INTRODUCTION: Obesity is a risk factor for pregnancy-induced hypertension, preeclampsia, gestational diabetes, and large gestational age pregnancy. Bariatric surgery is widely accepted to treat obesity but associated with small for gestational age fetuses. OBJECTIVE: To report maternal and fetal outcomes after bariatric surgery in morbidly obese Asian females. SETTING: University Hospital, Singapore. METHODS: We maintain a prospective cohort of patients who underwent bariatric surgery in our institution. Maternal and fetal outcomes are compared with a control group of 31 pregnancies matched for age, parity, presurgery weight, and year of delivery. RESULTS: Twenty-four pregnancies occurred in 16 patients in our postoperative cohort. Morbidly obese women in the control group were more likely to develop gestational diabetes (19.3% versus 5.0%, P = .150) and pregnancy-induced hypertension/preeclampsia (32.2% versus 0%, P = .003) compared with the postoperative group. Of fetuses, 37.5% in the bariatric group had low birth weight compared with only 9.4% fetuses in the control group (P = .016). Preoperative body mass index, short interval between conception and surgery, and poor weight gain during pregnancy did not predict for small for gestational age fetuses. Subsequent weights were available for 37.5% of the children in the surgical cohort and none of these children exhibited growth retardation. CONCLUSION: Bariatric surgery lowers the risk of maternal co-morbidities and large gestational age fetus during pregnancy. Asians are at high risk of small for gestational age pregnancies after bariatric surgery and should undergo close monitoring for fetal growth throughout their pregnancy.

Effect of bariatric surgery on glycemic profiles in multiethnic obese nondiabetic Asians.

BACKGROUND: The effect of bariatric surgery on improvement and remission of type 2 diabetes (T2D) is well studied. The effect of surgery on glycemic profiles of obese, but nondiabetic individuals is unknown. OBJECTIVES: We aimed to study changes in glycemic indices in obese nondiabetics undergoing bariatric surgery and correlate fat mass loss with changes in glycemic profiles. SETTING: University Hospital, Singapore. METHODS: A prospective database of nonT2D patients who underwent bariatric surgery between April 2009 and December 2014 was analyzed. Changes in weight, fat mass, and glycemic profiles, including glycated hemoglobin, C-peptide levels, and the homeostasis model assessment of insulin resistance were studied at 1- and 3-year follow-up. RESULTS: One hundred thirty-three nondiabetics underwent bariatric surgery in the study period. Twenty-nine (21.8%) patients were found to have impaired fasting glycemia. We observed reductions in mean fat mass from 47.4 ± 12.2 kg preoperatively to 27.8 ± 11.6 kg at 1 year. Despite mean fat mass regain to 33.9 ± 19.6 kg at 3 years, homeostasis model assessment of insulin resistance improved from severe insulin resistant state of >5.00 (7.13 ± 11.5) preoperatively to normal ranges of <3.00 (1.55 ± .91) at 3 years. CONCLUSION: Bariatric surgery results in significant sustained weight loss in obese nondiabetics and normalizes glycated hemoglobin and homeostasis model assessment of insulin resistance after surgery. It is a promising modality to prevent or delay the onset of T2D in obese nondiabetic patients. Further studies should be conducted in nondiabetics to assess the efficacy of bariatric surgery in prevention of T2D onset in the longer term.

Effects of pristine polyvinyl chloride fragments on whole body histology and protease activity in silver barb Barbodes gonionotus fry.

Silver barb Barbodes gonionotus fry were exposed to polyvinyl chloride (PVC) fragments at increasing concentrations of 0.2, 0.5 and 1.0 mg/L for 96 h, following which whole body histological evaluation and analysis of the digestive enzymes trypsin and chymotrypsin were performed. Whole body trypsin and chymotrypsin activities increased significantly in fish exposed to 0.5 and 1.0 mg/L PVC as compared those exposed to zero or 0.2 mg/L PVC. In fish exposed to all tested concentrations, PVCs were observed in both the proximal and distal intestine, and fish exposed to 0.5-1.0 and 1.0 mg/L PVC, respectively, and these particles were associated with localized thickening of the mucosal epithelium. No tissue damage was evident in any other internal organs or gills. This lack of damage may be attributed to the absence of contaminants associated with the PVC fragments and their relatively smooth surface. The increased whole body trypsin and chymotrypsin activities may indicate an attempt to enhance digestion to compensate for epithelial thickening of the intestine and/or to digest the plastics.

PD-L1 expression is mainly regulated by interferon gamma associated with JAK-STAT pathway in gastric cancer.

Despite multidisciplinary treatment for patients with advanced gastric cancer, their prognosis remains poor. Therefore, the development of novel therapeutic strategies is urgently needed, and immunotherapy utilizing anti-programmed death 1/-programmed death ligand-1 mAb is an attractive approach. However, as there is limited information on how programmed death ligand-1 is upregulated on tumor cells within the tumor microenvironment, we examined the mechanism of programmed death ligand-1 regulation with a particular focus on interferon gamma in an in vitro setting and in clinical samples. Our in vitro findings showed that interferon gamma upregulated programmed death ligand-1 expression on solid tumor cells through the JAK-signal transducer and activator of transcription pathway, and impaired the cytotoxicity of tumor antigen-specific CTL against tumor cells. Following treatment of cells with anti-programmed death ligand-1 mAb after interferon gamma-pre-treatment, the reduced anti-tumor CTL activity by interferon gamma reached a higher level than the non-treatment control targets. In contrast, programmed death ligand-1 expression on tumor cells also significantly correlated with epithelial-mesenchymal transition phenotype in a panel of solid tumor cells. In clinical gastric cancer samples, tumor membrane programmed death ligand-1 expression significantly positively correlated with the presence of CD8-positive T cells in the stroma and interferon gamma expression in the tumor. The results suggest that gastric cancer patients with high CD8-positive T-cell infiltration may be more responsive to anti-programmed death 1/-programmed death ligand-1 mAb therapy.

Impairing Cohesin Smc1/3 Head Engagement Compensates for the Lack of Eco1 Function.

The cohesin ring, which is composed of the Smc1, Smc3, and Scc1 subunits, topologically embraces two sister chromatids from S phase until anaphase to ensure their precise segregation to the daughter cells. The opening of the ring is required for its loading on the chromosomes and unloading by the action of Wpl1 protein. Both loading and unloading are dependent on ATP hydrolysis by the Smc1 and Smc3 "head" domains, which engage to form two composite ATPase sites. Based on the available structures, we modeled the Saccharomyces cerevisiae Smc1/Smc3 head heterodimer and discovered that the Smc1/Smc3 interfaces at the two ATPase sites differ in the extent of protein contacts and stability after ATP hydrolysis. We identified smc1 and smc3 mutations that disrupt one of the interfaces and block the Wpl1-mediated release of cohesin from DNA. Thus, we provide structural insights into how the cohesin heads engage with each other.

A Reversible Association between Smc Coiled Coils Is Regulated by Lysine Acetylation and Is Required for Cohesin Association with the DNA.

Cohesin is a ring-shaped protein complex that is capable of embracing DNA. Most of the ring circumference is comprised of the anti-parallel intramolecular coiled coils of the Smc1 and Smc3 proteins, which connect globular head and hinge domains. Smc coiled coil arms contain multiple acetylated and ubiquitylated lysines. To investigate the role of these modifications, we substituted lysines for arginines to mimic the unmodified state and uncovered genetic interaction between the Smc arms. Using scanning force microscopy, we show that wild-type Smc arms associate with each other when the complex is not on DNA. Deacetylation of the Smc1/Smc3 dimers promotes arms' dissociation. Smc arginine mutants display loose packing of the Smc arms and, although they dimerize at the hinges, fail to connect the heads and associate with the DNA. Our findings highlight the importance of a "collapsed ring," or "rod," conformation of cohesin for its loading on the chromosomes.

FAT1 mutations cause a glomerulotubular nephropathy.

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function.

Trypsin-modulating oostatic factor (TMOF) decreased the survival, growth and digestion enzymes of Macrobrachium rosenbergii.

Trypsin-modulating oostatic factor (TMOF) is an effective mosquito larvicide, but information on its potential toxicity to non-target organisms is limited. To investigate this, triplicate groups of 10 Macrobrachium rosenbergii were exposed to 0, 10, 50 or 100 mg/L nominal TMOF concentrations for 12 days. Tail moisture, crude protein, and hepatopancreatic glycogen/histopathology were unaffected, but increasing TMOF linearly decreased survival and growth. TMOF at the lowest concentration employed significantly decreased trypsin and chymotrypsin activities.