Outcomes of patients with hepaticojejunostomy anastomotic strictures undergoing endoscopic and percutaneous treatment.

Background and study aims The increase in hepaticojejunostomies has led to an increase in benign strictures of the anastomosis. Double balloon enteroscopy-assisted ERCP (DBE-ERCP) and percutaneous transhepatic biliary drainage (PTBD) are treatment options; however, there is lack of long-term outcomes, with no consensus on management. We performed a retrospective study assessing the outcomes of patients referred for endoscopic management of hepaticojejunostomy anastomotic strictures (HJAS). Patients and methods All consecutive patients at a tertiary institution underwent endoscopic intervention for suspected HJAS between 2009 and 2021 were enrolled. Results Eighty-two subjects underwent DBE-ERCP for suspected HJAS. The technical success rate was 77 % (63/82). HJAS was confirmed in 41 patients. The clinical success rate for DBE-ERCP ± PTBD was 71 % (29/41). DBE-ERCP alone achieved clinical success in 49 % of patients (20/41). PTBD was required in 49 % (20/41). Dual therapy was required in 22 % (9/41). Those with liver transplant had less technical success compared to other surgeries (72.1 % vs 82.1 % P  = 0.29), less clinical success with DBE-ERCP alone (40 % vs 62.5 % P  = 0.16) and required more PTBD (56 % vs 37.5 % P  = 0.25). All those with ischemic biliopathy (n = 9) required PTBD for clinical success, required more DBE-ERCP (4.4 vs 2.0, P = 0.004), more PTBD (4.7 vs 0.3, P  < 0.0001), longer treatment duration (181.6 vs 99.5 days P  = 0.12), and had higher rates of recurrence (55.6 % vs 30.3 % P  = 0.18) compared to those with HJAS alone. Liver transplant was the leading cause of ischemic biliopathy (89 %). The overall adverse event rate was 7 %. Conclusions DBE-ERCP is an effective diagnostic and therapeutic tool in those with altered gastrointestinal anatomy and is associated with low complication rates.

Barrett's esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies.

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett's in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett's with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett's by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett's is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.

Current endoscopic closure techniques for the management of gastrointestinal perforations.

Acute gastrointestinal perforations occur either from spontaneous or iatrogenic causes. However, particular attention should be made in acute iatrogenic perforations as timely diagnosis and endoscopic closure prevent morbidity and mortality. With the increasing use of diagnostic endoscopy and advances in therapeutic endoscopy worldwide, the endoscopist must be able to recognize and manage perforations. Depending on the size and location of the defect, a variety of endoscopic clips, stents, and suturing devices are available. This review aims to prepare and guide the endoscopist to use the right tools and techniques for optimal patient outcomes.

Enabling Green Crowdsourced Social Delivery Networks in Urban Communities.

With the ever-increasing popularity of wearable devices, data on the time and location of popular walking, running, and bicycling routes is expansive and growing rapidly. These data are currently used primarily for route discovery and mobile context awareness, as it provides precise and updated information about urban dynamics. We leverage these data to build ad hoc transportation flows, and we present a novel model that creates delivery networks from these zero-emission transportation flows. We evaluate the model using data from two popular datasets, and our results indicate that such networks are indeed possible, and can help reduce traffic, emissions, and delivery times. Moreover, we demonstrate how our results can be consistently reproduced in different cities with different subsets of carriers. We then extend our work into predicting routes of vehicles, hence possible delivery flows, based on the traces history. We conclude this paper by laying the groundwork for a future real-world study.

Acute physiological comparison of sub-maximal exercise on a novel adapted rowing machine and arm crank ergometry in people with a spinal cord injury.

STUDY DESIGN: Non-randomized crossover trial. OBJECTIVES: The objective of this study was to assess the oxygen uptake during exercise using the Adapted ROWing machine (AROW) compared to the more commonly used Arm Crank Ergometry (ACE) for people with spinal cord injury/disease (SCI/D) with or without trunk stability. SETTING: Canada, Vancouver. METHODS: Participants were from a convenience sample of 14 adults with SCI/D (age 21-63 y) which include those with lumbar to low cervical impairments currently exercising at least once per week using cardiovascular exercise equipment at our Physical Activity Research Centre. The interventions were non-randomized steady-state exercise bouts at self-selected low and moderate workloads on the AROW and ACE for 5 min each. Our primary outcomes were the rate of oxygen consumption (mL/kg/min) and the Borg 0-10 Rating Scale of Perceived Exertion (RPE). RESULTS: A repeated measures two-way ANOVA (p < 0.05) indicated that exercising on the AROW resulted significantly greater oxygen consumption and perceived exertion than ACE at similar sub-maximal workloads which may be explained by the differences in efficiency between the devices (Partial eta squared = 0.84, F stat = 48.25; Partial eta squared = 0.86, F stat = 53.54). CONCLUSIONS: We have demonstrated that this form of upper extremity exercise had a greater RPE and VO2 on the ACE at a given workload. Thus, the AROW could provide a functional upper extremity workout that can be used for daily exercise for those with varying levels of SCI.

Translational autoregulation of the S. cerevisiae high-affinity polyamine transporter Hol1.

Polyamines, small organic polycations, are essential for cell viability, and their physiological levels are homeostatically maintained by post-transcriptional regulation of key biosynthetic enzymes. In addition to de novo synthesis, cells can also take up polyamines; however, identifying cellular polyamine transporters has been challenging. Here we show that the S. cerevisiae HOL1 mRNA is under translational control by polyamines, and we reveal that the encoded membrane transporter Hol1 is a high-affinity polyamine transporter and is required for yeast growth under limiting polyamine conditions. Moreover, we show that polyamine inhibition of the translation factor eIF5A impairs translation termination at a Pro-Ser-stop motif in a conserved upstream open reading frame on the HOL1 mRNA to repress Hol1 synthesis under conditions of elevated polyamines. Our findings reveal that polyamine transport, like polyamine biosynthesis, is under translational autoregulation by polyamines in yeast, highlighting the extensive control cells impose on polyamine levels.

Tele-Rehabilitation to Combat Rehabilitation Service Disruption During COVID-19 in Hong Kong: Observational Study.

BACKGROUND: A tele-rehabilitation platform was developed to improve access to ambulatory rehabilitation services in Hong Kong. The development was completed in October 2019 and rolled out for use to occupational therapists, physiotherapists, and speech therapists. During the COVID-19 pandemic, rehabilitation services were severely interrupted. Tele-rehabilitation was used extensively to meet the demand for rehabilitation service delivery. OBJECTIVE: The aims of this study were to (1) describe the design and development process of a tele-rehabilitation service, and (2) study how the tele-rehabilitation platform was used to overcome the disruption of rehabilitation service during the COVID-19 pandemic. METHODS: Tele-rehabilitation was developed utilizing 4 core determinants of Unified Theory of Acceptance and Use of Technology as guiding principles. A generic prescription platform, called the activity-based prescription system, and a mobile app, called the Rehabilitation App, were built. Five outcomes were used to examine the utilization of tele-rehabilitation both before and during the pandemic: throughput, patient demographic, patient conditions, workforce, and satisfaction from patients and staff. RESULTS: There was a tremendous increase in the use of tele-rehabilitation during pandemic. The total number of patients (up until July 2020) was 9101, and the main age range was between 51 to 70 years old. Tele-rehabilitation was used for a much wider scope of patient conditions than originally planned. More than 1112 therapists, which constituted 50.6% of the total workforce (1112/2196), prescribed tele-rehabilitation to their patients. Moreover, there was a high satisfaction rate from patients, with a mean rating of 4.2 out of 5, and a high adherence rate to prescribed rehabilitation activities (107840/131995, 81.7%). CONCLUSIONS: The findings of our study suggested that tele-rehabilitation in the form of a generic prescription platform and mobile app can be an effective means to provide rehabilitation to patient. During the COVID-19 pandemic, tele-rehabilitation has been used extensively and effectively to mitigate service disruption. Our findings also provide support that there is a high level of satisfaction with tele-rehabilitation; however, a longer duration study is required to demonstrate the sustained use of tele-rehabilitation, especially after the pandemic.

Ovary unusual colonic lesion.

We describe an unusual endoscopic finding, caused by a dominant ovarian follicle compressing a low-lying ascending colon just inferior to a patulous retroverted cecum. Endoscopically detected extra-colonic lesions represent a diverse group of pathologies, and it is important the endoscopist has an appreciation of the varied number of benign and malignant causes-including those of gynecological origin.

Genome-wide binding analysis of 195 DNA binding proteins reveals "reservoir" promoters and human specific SVA-repeat family regulation.

A key aspect in defining cell state is the complex choreography of DNA binding events in a given cell type, which in turn establishes a cell-specific gene-expression program. Here we wanted to take a deep analysis of DNA binding events and transcriptional output of a single cell state (K562 cells). To this end we re-analyzed 195 DNA binding proteins contained in ENCODE data. We used standardized analysis pipelines, containerization, and literate programming with R Markdown for reproducibility and rigor. Our approach validated many findings from previous independent studies, underscoring the importance of ENCODE's goals in providing these reproducible data resources. We also had several new findings including: (i) 1,362 promoters, which we refer to as 'reservoirs,' that are defined by having up to 111 different DNA binding-proteins localized on one promoter, yet do not have any expression of steady-state RNA (ii) Reservoirs do not overlap super-enhancer annotations and distinct have distinct properties from super-enhancers. (iii) The human specific SVA repeat element may have been co-opted for enhancer regulation and is highly transcribed in PRO-seq and RNA-seq. Collectively, this study performed by the students of a CU Boulder computational biology class (BCHM 5631 -Spring 2020) demonstrates the value of reproducible findings and how resources like ENCODE that prioritize data standards can foster new findings with existing data in a didactic environment.

Novel Application of Steroid Eluting Stent in Petrous Apex Cholesterol Granuloma.

Objective This study describes the safety and efficacy of mometasone furoate eluting stents in the management of petrous apex cholesterol granuloma approached through an endonasal endoscopic route and assesses the restenosis rate. Methods Consecutive patients undergoing endoscopic endonasal marsupialization of a petrous apex cholesterol granuloma at a tertiary referral center who had a mometasone furoate eluting stent placed intraoperatively were reviewed in a retrospective fashion. Postoperative endoscopy was used to determine success of surgery and stenting. Results Five patients were included in the study, three were primary cases and two patients had revision surgeries performed. The steroid eluting stent was placed successfully and safely in all patients with no dural or vascular injuries. The average follow-up duration was 10.6 months. There was no restenosis in three patients and one patient had an immediate restenosis that was debrided in clinic (revision case). This was patent at the 16 months follow-up. One patient also developed stenosis, 4 months after surgery due to sphenoid sinusitis. Conclusion Mometasone furoate eluting stents are safe and effective in the primary management of petrous apex cholesterol granuloma. Further studies are needed to assess their efficacy in revision cases and for long term results.

Hypoxia-induced remodelling of goldfish membranes.

Hypoxia-tolerant animals use metabolic suppression as an essential strategy to survive low oxygen. Ectotherms can alter membrane lipid composition in response to changes in environmental temperature, but it is currently unknown whether chronic hypoxia can also elicit membrane restructuring. The goal of this study was to investigate a possible physiological link between membrane remodelling and metabolic suppression in goldfish exposed to prolonged hypoxia (4 weeks at 10% air saturation). We have tested the hypothesis that chronic hypoxia would modulate membrane lipid composition in ways that are consistent with known mechanisms of ion pump inhibition. Because homeoviscous membrane restructuring could interfere with the response to hypoxia, measurements were made at 2 temperatures. Results show that hypoxic goldfish suppress metabolic rate by 74% (at 13 °C) and 63% (at 20 °C). This study is the first to reveal that cold-acclimated animals undergo extensive, tissue-specific restructuring of membrane lipids as they reach minimal metabolic rates. However, hypoxia does not affect membrane composition in fish acclimated to 20 °C. The strong membrane response of cold-acclimated fish involves increases in cholesterol abundance (in white muscle and gills) and in fatty acid saturation, mainly caused by a reduction in %22:6 (docosahexaenoic acid in gills and liver). Major ion pumps like Na+/K+-ATPase are known to be inhibited by cholesterol and activated by 22:6. Because ion pumping by membrane-bound ATPases accounts for a large fraction of basal cellular energy use, we propose that the membrane responses reported here could be a novel mechanism to promote metabolic suppression in cold-acclimated animals.

Sinonasal Quality of Life Outcomes After Extended Endonasal Approaches to the Skull Base.

Introduction Endoscopic endonasal skull base surgery (EESBS) leads to significant alterations in sinonasal anatomy and physiology. However, there is limited data available on quality of life (QOL) outcomes following EESBS. Methods A retrospective review of patients undergoing EESBS from January 2014 to April 2017 was performed. Records were reviewed for clinical history, operative details, and 22-item Sinonasal Outcomes Test (SNOT-22) scores. Unadjusted and adjusted linear regression models were utilized to compare change in SNOT-22 scores from baseline in patients who underwent a simple sella approach (SA) or an extended beyond sella approach (BSA). Results A total of 108 patients were in the SA group, while 61 patients were in the BSA group. SNOT-22 scores were available at baseline and 3 months for 84 patients, while 6-month scores were available for 49 patients. SNOT-22 scores for all patients were not significantly different at 3 months ( p = 0.40) or at 6 months ( p = 0.58). Unadjusted linear regression model did not show an association between the type of approach and change in SNOT-22 score at 3 months ( p = 0.07) and 6 months ( p = 0.28). Adjusted regression model showed a significant decrease in SNOT-22 scores at 3 months ( p = 0.04) for the BSA group, but there was no significant change in SNOT-22 score at 6 months ( p = 0.22). Conclusion Patients undergoing EESBS had no significant change in outcomes at 3 and 6 months. A more extensive BSA was not associated with worse QOL outcomes as measured by SNOT-22.

In vitro behavior and UV response of melanocytes derived from carriers of CDKN2A mutations and MC1R variants.

Coinheritance of germline mutation in cyclin-dependent kinase inhibitor 2A (CDKN2A) and loss-of-function (LOF) melanocortin 1 receptor (MC1R) variants is clinically associated with exaggerated risk for melanoma. To understand the combined impact of these mutations, we established and tested primary human melanocyte cultures from different CDKN2A mutation carriers, expressing either wild-type MC1R or MC1RLOF variant(s). These cultures expressed the CDKN2A product p16 (INK4A) and functional MC1R. Except for 32ins24 mutant melanocytes, the remaining cultures showed no detectable aberrations in proliferation or capacity for replicative senescence. Additionally, the latter cultures responded normally to ultraviolet radiation (UV) by cell cycle arrest, JNK, p38, and p53 activation, hydrogen peroxide generation, and repair of DNA photoproducts. We propose that malignant transformation of melanocytes expressing CDKN2A mutation and MC1RLOF allele(s) requires acquisition of somatic mutations facilitated by MC1R genotype or aberrant microenvironment due to CDKN2A mutation in keratinocytes and fibroblasts.

VEGF signaling regulates the fate of obstructed capillaries in mouse cortex.

Cortical capillaries are prone to obstruction, which over time, could have a major impact on brain angioarchitecture and function. The mechanisms that govern the removal of these obstructions and what long-term fate awaits obstructed capillaries, remains a mystery. We estimate that ~0.12% of mouse cortical capillaries are obstructed each day (lasting >20 min), preferentially in superficial layers and lower order branches. Tracking natural or microsphere-induced obstructions revealed that 75-80% of capillaries recanalized within 24 hr. Remarkably, 30% of all obstructed capillaries were pruned by 21 days, including some that had regained flow. Pruning involved regression of endothelial cells, which was not compensated for by sprouting. Using this information, we predicted capillary loss with aging that closely matched experimental estimates. Genetic knockdown or inhibition of VEGF-R2 signaling was a critical factor in promoting capillary recanalization and minimizing subsequent pruning. Our studies reveal the incidence, mechanism and long-term outcome of capillary obstructions which can also explain age-related capillary rarefaction.

Preoperative Imaging Findings and Cost in Adults With Postlingual Deafness Prior to Cochlear Implant.

OBJECTIVE: To assess the imaging findings of computed topography (CT) and magnetic resonance imaging (MRI) in adults with postlingual deafness and otherwise normal clinical history and physical exam. Additionally, determine the influence and implications of these findings with respect to surgical outcomes and cost. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: Adults with postlingual deafness with no history of prior ear surgery, chronic ear disease, meningitis, otosclerosis, or head trauma. INTERVENTIONS: Cochlear implantation of 1 or both ears, with preoperative CT, MRI, or both. MAIN OUTCOME MEASURES: Imaging results were classified as normal, abnormal affecting surgery, incidental requiring follow-up, or incidental not requiring follow-up. Average cost of each imaging modality was determined. RESULTS: A total of 128 patients met the inclusion criteria. Of these, 82 (64.1%) had both CT and MRI performed, 33 (25.8%) had CT, and 13 (10.2%) had MRI prior to cochlear implant (CI). Scans were normal in 125 (97.7%) of cases. Of the remaining 3 (2.3%) patients, there were incidental findings requiring follow-up. All implants were placed successfully, and in no instance did the results of the scan influence the surgery. The average cost of imaging per patient was $4707. CONCLUSION: In adults with postlingual deafness with an otherwise benign clinical history, CT and MRI are unlikely to affect or preclude surgery. With new MRI safe cochlear implants, imaging can be performed safely postoperatively if needed.

Solar-powered hearing aids for children with impaired hearing in Vietnam: a pilot study.

BACKGROUND: Hearing loss is a barrier to speech and social and cognitive development. This can be especially pronounced in children living in low- and middle-income countries with limited resources. AIM: To determine the feasibility, durability and social impact of ComCare GLW solar-powered hearing aids provided for Vietnamese children with hearing impairment. METHODS: A retrospective review of data from an international, multi-discipline humanitarian visit was performed. Hearing aids were given to 28 children enrolled at the Khoai Chau Functional Rehabilitation School, Hung Yen Province, Vietnam. Device inspection and observational assessments were performed by teachers using a modified Parents' Evaluation of Aural/Oral Performance of Children and an Infant Hearing Program Amplification Benefit Questionnaire. Qualitative interviews were undertaken to assess the study aims. RESULTS: Hearing aids were well tolerated for use during regular school hours. All units remained functional during the study period (12 months). Teachers noted increased student awareness and responsiveness to surrounding sounds, but the degree of response to amplification varied between children. There was no significant improvement in speech development as all subjects had prelingual deafness. Teachers felt confident in troubleshooting any potential device malfunction. CONCLUSIONS: A solar-powered hearing aid may be a viable option for children in low- and middle-income countries. This study demonstrates that device distribution, maintenance and function can be established in countries with limited resources, while providing feasibility data to support future studies investigating how similar devices may improve the quality of life of those with hearing loss.

Correlation between sinus and lung cultures in lung transplant patients with cystic fibrosis.

BACKGROUND: Lung transplantation has revolutionized the treatment of end-stage pulmonary disease due to cystic fibrosis. However, infection of the transplanted lungs can lead to serious complications, including graft failure and death. Although many of these patients have concurrent sinusitis, it is unclear whether bacteria from the sinuses can infect the allograft. METHODS: This is a single-institution retrospective study of all patients who underwent lung transplantation for cystic fibrosis from 2005 to 2015 at Duke University Hospital. Pre- and posttransplant nasal and pulmonary cultures obtained via nasal endoscopy and bronchoalveolar lavage (BAL), respectively, were analyzed. RESULTS: A total of 141 patients underwent 144 lung transplants. Sinus cultures were available for 76 patients (12 pretransplant, 42 posttransplant, 22 both pre- and posttransplant). Pretransplant BAL cultures were available for 139 patients, and posttransplant BAL cultures were available for all patients. Pseudomonas aeruginosa (PsA) and methicillin-resistant Staphylococcus aureus (MRSA) were the most common organisms cultured. There was a significant correlation between pretransplant sinus and posttransplant BAL cultures for PsA (p = 0.003), MRSA (p = 0.013), and Burkholderia cepacia (p = 0.001). CONCLUSION: There was a high correlation between pretransplant sinus cultures and posttransplant BAL cultures for PsA, MRSA, and Burkholderia sp. This suggests that the paranasal sinuses may act as a reservoir for allograft colonization in patients with cystic fibrosis. Further studies are needed to determine whether treatment of sinusitis affects allograft colonization and transplant outcomes.