The microbiota-gut-brain axis:An emerging therapeutic target in chemotherapy-induced cognitive impairment

Chemotherapy-induced cognitive impairment (CICI) is an ill-defined complication of chemotherapy treatment that places a significant psychosocial burden on survivors of cancer and has a considerable impact on the activities of daily living. CICI pathophysiology has not been clearly defined, with candidate mechanisms relating to both the direct cytotoxicity of chemotherapy drugs on the central nervous system (CNS) and more global, indirect mechanisms such as neuroinflammation and blood brain barrier (BBB) damage. A growing body of research demonstrates that changes to the composition of the gastrointestinal microbiota is an initiating factor in numerous neurocognitive conditions, profoundly influencing both CNS immunity and BBB integrity. Importantly, chemotherapy causes significant disruption to the gastrointestinal microbiota. While microbial disruption is a well-established factor in the development of chemotherapy-induced gastrointestinal toxicities (largely diarrhoea), its role in CICI remains unknown, limiting microbial-based therapeutics or risk prediction strategies. Therefore, this review aims to synthesise and critically evaluate the evidence addressing the microbiota-gut-brain axis as a critical factor influencing the development of CICI

The Australasian Students' Surgical Association: organizational growth amidst the challenges of the COVID-19 pandemic

[Extract] Student surgical societies play an important role in complementing university medical curricula in the delivery of surgical education, fostering interest in surgery and facilitating networking and career opportunities.1 The Australasian Students' Surgical Association (ASSA) was established in 2015 as a not-for-profit student-run organization aiming to unite the 26 student surgical societies across Australia and New Zealand.2 Through in-person conferences, Sydney-based leadership seminars and surgical workshops, the ASSA has successfully achieved its vision to support surgical education, foster student interest in surgery, and create a culture of collaboration amongst surgical societies. As the COVID-19 pandemic presented a variety of unforeseen challenges to the medical profession, student organizations across the world were required to adapt to the content and delivery of activities.3 The pandemic posed significant challenges for the ASSA to continue promoting a pre-vocational interest in surgery for Australian and New Zealand medical students and required innovative strategies to continue delivering educational opportunities. This need to adopt alternative approaches provided an opportunity for innovation and embracing technology to overcome COVID-19 related restrictions to continue achieving the goals for ASSA

OSSOS. IX. Two Objects in Neptune's 9: 1 Resonance - Implications for Resonance Sticking in the Scattering Population

We discuss the detection in the Outer Solar System Origins Survey (OSSOS) of two objects in Neptune's distant 9:1 mean motion resonance at semimajor axis $a\approx~130$~au. Both objects are securely resonant on 10~Myr timescales, with one securely in the 9:1 resonance's leading asymmetric libration island and the other in either the symmetric or trailing asymmetric island. These objects are the largest semimajor axis objects with secure resonant classifications, and their detection in a carefully characterized survey allows for the first robust resonance population estimate beyond 100~au. The detection of these objects implies a 9:1 resonance population of $1.1\times10^4$ objects with $H_r<8.66$ ($D~\gtrsim~100$~km) on similar orbits (95\% confidence range of $\sim0.4-3\times10^4$). Integrations over 4~Gyr of an ensemble of clones spanning these objects' orbit fit uncertainties reveal that they both have median resonance occupation timescales of $\sim1$~Gyr. These timescales are consistent with the hypothesis that these objects originate in the scattering population but became transiently stuck to Neptune's 9:1 resonance within the last $\sim1$~Gyr of solar system evolution. Based on simulations of a model of the current scattering population, we estimate the expected resonance sticking population in the 9:1 resonance to be 1000-4500 objects with $H_r<8.66$; this is marginally consistent with the OSSOS 9:1 population estimate. We conclude that resonance sticking is a plausible explanation for the observed 9:1 population, but we also discuss the possibility of a primordial 9:1 population, which would have interesting implications for the Kuiper belt's dynamical history.Comment: accepted for publication in A

Guideline for the diagnosis and treatment of Faecal Incontinence-A UEG/ESCP/ESNM/ESPCG collaboration

INTRODUCTION The goal of this project was to create an up-to-date joint European clinical practice guideline for the diagnosis and treatment of faecal incontinence (FI), using the best available evidence. These guidelines are intended to help guide all medical professionals treating adult patients with FI (e.g., general practitioners, surgeons, gastroenterologists, other healthcare workers) and any patients who are interested in information regarding the diagnosis and management of FI. METHODS These guidelines have been created in cooperation with members from the United European Gastroenterology (UEG), European Society of Coloproctology (ESCP), European Society of Neurogastroenterology and Motility (ESNM) and the European Society for Primary Care Gastroenterology (ESPCG). These members made up the guideline development group (GDG). Additionally, a patient advisory board (PAB) was created to reflect and comment on the draft guidelines from a patient perspective. Relevant review questions were established by the GDG along with a set of outcomes most important for decision making. A systematic literature search was performed using these review questions and outcomes as a framework. For each predefined review question, the study or studies with the highest level of study design were included. If evidence of a higher-level study design was available, no lower level of evidence was sought or included. Data from the studies were extracted by two reviewers for each predefined important outcome within each review question. Where possible, forest plots were created. After summarising the results for each review question, a systematic quality assessment using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was performed. For each review question, we assessed the quality of evidence for every predetermined important outcome. After evidence review and quality assessment were completed, recommendations could be formulated. The wording used for each recommendation was dependent on the level of quality of evidence. Lower levels of evidence resulted in weaker recommendations and higher levels of evidence resulted in stronger recommendations. Recommendations were discussed within the GDG to reach consensus. RESULTS These guidelines contain 45 recommendations on the classification, diagnosis and management of FI in adult patients. CONCLUSION These multidisciplinary European guidelines provide an up-to-date comprehensive evidence-based framework with recommendations on the diagnosis and management of adult patients who suffer from FI

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE

OSSOS. VII. 800+Trans-Neptunian Objects-The Complete Data Release

The Outer Solar System Origins Survey (OSSOS), a wide-field imaging program in 2013-2017 with the Canada-France-Hawaii Telescope, surveyed 155 deg(2) of sky to depths of m(r) = 24.1-25.2. We present 838 outer solar system discoveries that are entirely free of ephemeris bias. This increases the inventory of trans-Neptunian objects (TNOs) with accurately known orbits by nearly 50%. Each minor planet has 20-60 Gaia/Pan-STARRS-calibrated astrometric measurements made over 2-5 oppositions, which allows accurate classification of their orbits within the trans-Neptunian dynamical populations. The populations orbiting in mean-motion resonance with Neptune are key to understanding Neptune's early migration. Our 313 resonant TNOs, including 132 plutinos, triple the available characterized sample and include new occupancy of distant resonances out to semimajor axis a similar to 130 au. OSSOS doubles the known population of the nonresonant Kuiper Belt, providing 436 TNOs in this region, all with exceptionally high-quality orbits of a uncertainty sigma(a)Peer reviewe

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL

Images in clinical medicine. Medical mystery - an unusual complication of colonoscopy

A 69-year-old man presented to the emergency department with a 3-day history of left-sided lower abdominal and groin pain. The pain had begun 36 hours after the patient had undergone colonoscopy, at which time he was found to have extensive diverticular disease. He had undergone polypectomy of a moderately dysplastic tubular adenoma of the sigmoid colon. On measurement of vital signs, he had tachycardia (pulse rate, 110) and hypotension (blood pressure, 95/70 mm Hg) and was febrile (temperature, 100.7°F [38.2°C]). Physical examination revealed erythema and swelling of the left inguinoscrotal region with associated tenderness on palpation. The remainder of his abdomen was generally soft and nontender on palpation. The results of routine laboratory testing were unremarkable except for a creatine kinase level of 387 U per liter (normal range, 0 to 170), an international normalized ratio of 1.4, and a derived fibrinogen level of 6.4 g per liter (normal range, 1.5 to 4.5). A computed tomographic scan of the patient's pelvis is shown here. What is the diagnosis