A Perspective of the Epidemiology of Rabies in South Africa, 1998-2019.

Despite the implementation of various control strategies aimed at eliminating canine-mediated rabies, the disease is still endemic in up to 150 countries across the world. Rabies remains endemic to South Africa, with various reservoir species (both wildlife species and domestic dogs) capable of maintaining rabies infection, and the epidemiology of the disease is yet to be adequately defined. As such, this study used surveillance data collected between 1998 and 2019 from the two diagnostic laboratories in the country for a statistical space-time analysis to determine regions where significant disease clusters could occur. In addition, the robustness of surveillance activities across the country was evaluated through the mathematical evaluation and visualization of testing rates based on the average number of samples tested per species group. In our study, various significant disease clusters were detected for domestic animals, wildlife and livestock. The significant disease clusters for domestic animals and livestock were primarily restricted to eastern South Africa, while the significant disease clusters in wildlife species were detected across northern and western South Africa. Furthermore, the testing rates identified districts from various provinces where surveillance activities could be considered inadequate, consequently influencing the geographical range of the observed clusters. These results could be used to direct intervention campaigns towards high-risk areas, while also allocating the required resources to improve surveillance in the surrounding areas where surveillance was deemed inadequate.

Fecal Microbiota Transplantation for Sleep Disturbance in Postacute COVID-19 Syndrome.

BACKGROUND & AIMS: Postacute COVID-19 syndrome (PACS) is associated with sleep disturbance, but treatment options are limited. The etiology of PACS may be secondary to alterations in the gut microbiome. Here, we report the efficacy of fecal microbiota transplantation (FMT) in alleviating post-COVID insomnia symptoms in a nonrandomized, open-label prospective interventional study. METHODS: Between September 22, 2022, and May 22, 2023, we recruited 60 PACS patients with insomnia defined as Insomnia Severity Index (ISI) ≥8 and assigned them to the FMT group (FMT at weeks 0, 2, 4, and 8; n = 30) or the control group (n = 30). The primary outcome was clinical remission defined by an ISI of <8 at 12 weeks. Secondary outcomes included changes in the Pittsburgh Sleep Quality Index, Generalized Anxiety Disorder-7 scale, Epworth Sleepiness Scale, Multidimensional Fatigue Inventory, blood cortisol and melatonin, and gut microbiome analysis on metagenomic sequencing. RESULTS: At week 12, more patients in the FMT than the control group had insomnia remission (37.9% vs 10.0%; P = .018). The FMT group showed a decrease in ISI score (P < .0001), Pittsburgh Sleep Quality Index (P < .0001), Generalized Anxiety Disorder-7 scale (P = .0019), Epworth Sleepiness Scale (P = .0057), and blood cortisol concentration (P = .035) from baseline to week 12, but there was no significant change in the control group. There was enrichment of bacteria such as Gemmiger formicilis and depletion of microbial pathways producing menaquinol derivatives after FMT. The gut microbiome profile resembled that of the donor in FMT responders but not in nonresponders at week 12. There was no serious adverse event. CONCLUSIONS: This pilot study showed that FMT could be effective and safe in alleviating post-COVID insomnia, and further clinical trials are warranted. CLINICALTRIALS: gov, Number: NCT05556733.

DESCRIPTION OF FEMALE DENDRITOBILHARZIA PULVERULENTA (BRAUN, 1901) SKRJABIN, 1924 FROM TWO NEW AVIAN HOSTS IN NAMIBIA WITH PHYLOGENETIC ANALYSES AND COMMENTS ON SEVERAL TAXONOMICALLY UNCERTAIN AVIAN SCHISTOSOME SEQUENCES.

During a 2021 parasitological survey of birds in the Nyae Nyae-Khaudum Dispersal Area (Kavango-Zambezi Transfrontier Conservation Area, Namibia), we collected 9 specimens of Dendritobilharzia pulverulenta (Braun, 1901) Skrjabin, 1924 infecting the blood (heart lumen) of a white-backed duck, Thalassornis leuconotus (Eyton, 1838) (Anseriformes: Anatidae), and a fulvous whistling duck, Dendrocygna bicolor (Vieillot, 1816) (Anatidae). These flukes were fixed for morphology and preserved for DNA extraction. We assigned our specimens to DendritobilharziaSkrjabin and Zakharow, 1920 because they were strongly dorso-ventrally flattened in both sexes and had an intestinal cyclocoel with a zig-zag common cecum with lateral dendritic ramifications, numerous testes posterior to the cyclocoel and flanking the dendritic ramifications, and a tightly compacted convoluted ovary as well as lacking an oral sucker, ventral sucker, and gynaecophoric canal. Further, our specimens were morphologically identical to previously published descriptions of D. pulverulenta. Sequences of the 28S from our specimens were nearly identical to those identified as D. pulverulenta from North America (New Mexico), and our 28S phylogenetic analysis recovered D. pulverulenta within a polytomy of other Gigantobilharziinae spp. The CO1 phylogenetic analysis recovered a monophyletic Dendritobilharzia and, with low taxon sampling, a monophyletic Gigantobilharzia. This is the first record of a species of Dendritobilharzia infecting these ducks as well as the first record of an adult Dendritobilharzia from sub-Saharan Africa. The original description of adult D. pulverulenta (type locality: northern Sudan) was based on 2 males only, and hence the present study is the first description of female D. pulverulenta from Africa (the continent of the type locality). We reassign 2 Gigantobilharziinae spp. based on morphology and nucleotide evidence: Gigantobilharzia ensenadense (Lorenti, Brant, Gilardoni, Diaz, and Cremonte, 2022) Dutton and Bullard, n. comb., and Gigantobilharzia patagonense (Lorenti, Brant, Gilardoni, Diaz, and Cremonte, 2022) Dutton and Bullard, n. comb. We also comment on several avian schistosome sequences whose identities need confirmation or that likely have been misidentified.

The gut microbiome associates with phenotypic manifestations of post-acute COVID-19 syndrome.

The mechanisms underlying the many phenotypic manifestations of post-acute COVID-19 syndrome (PACS) are poorly understood. Herein, we characterized the gut microbiome in heterogeneous cohorts of subjects with PACS and developed a multi-label machine learning model for using the microbiome to predict specific symptoms. Our processed data covered 585 bacterial species and 500 microbial pathways, explaining 12.7% of the inter-individual variability in PACS. Three gut-microbiome-based enterotypes were identified in subjects with PACS and associated with different phenotypic manifestations. The trained model showed an accuracy of 0.89 in predicting individual symptoms of PACS in the test set and maintained a sensitivity of 86% and a specificity of 82% in predicting upcoming symptoms in an independent longitudinal cohort of subjects before they developed PACS. This study demonstrates that the gut microbiome is associated with phenotypic manifestations of PACS, which has potential clinical utility for the prediction and diagnosis of PACS.

A loss-of-function mutation in KCNJ11 causing sulfonylurea-sensitive diabetes in early adult life.

AIMS/HYPOTHESIS: The ATP-sensitive potassium (KATP) channel couples beta cell electrical activity to glucose-stimulated insulin secretion. Loss-of-function mutations in either the pore-forming (inwardly rectifying potassium channel 6.2 [Kir6.2], encoded by KCNJ11) or regulatory (sulfonylurea receptor 1, encoded by ABCC8) subunits result in congenital hyperinsulinism, whereas gain-of-function mutations cause neonatal diabetes. Here, we report a novel loss-of-function mutation (Ser118Leu) in the pore helix of Kir6.2 paradoxically associated with sulfonylurea-sensitive diabetes that presents in early adult life. METHODS: A 31-year-old woman was diagnosed with mild hyperglycaemia during an employee screen. After three pregnancies, during which she was diagnosed with gestational diabetes, the patient continued to show elevated blood glucose and was treated with glibenclamide (known as glyburide in the USA and Canada) and metformin. Genetic testing identified a heterozygous mutation (S118L) in the KCNJ11 gene. Neither parent was known to have diabetes. We investigated the functional properties and membrane trafficking of mutant and wild-type KATP channels in Xenopus oocytes and in HEK-293T cells, using patch-clamp, two-electrode voltage-clamp and surface expression assays. RESULTS: Functional analysis showed no changes in the ATP sensitivity or metabolic regulation of the mutant channel. However, the Kir6.2-S118L mutation impaired surface expression of the KATP channel by 40%, categorising this as a loss-of-function mutation. CONCLUSIONS/INTERPRETATION: Our data support the increasing evidence that individuals with mild loss-of-function KATP channel mutations may develop insulin deficiency in early adulthood and even frank diabetes in middle age. In this case, the patient may have had hyperinsulinism that escaped detection in early life. Our results support the importance of functional analysis of KATP channel mutations in cases of atypical diabetes.

Noninsulinoma Pancreatogenous Hypoglycemia Syndrome in a Patient With 1p36 Deletion Syndrome.

The 1p36 deletion syndrome involves a phenotypic presentation that includes central nervous system, cardiac, and craniofacial anomalies. We report the case of a 21-year-old female patient with 1p36 deletion syndrome who was found to have noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) after hospitalization for persistent falls. On admission, vital signs were normal and physical examination revealed a thin, nonverbal patient. During hospitalization and prolonged fasting (14-18 hours), she persistently developed hypoglycemia (serum glucose nadir 57 mg/dL [3.2 mmol/L] [70-100 mg/dL; 3.9-5.6 mmol/L]). Subjective symptoms of hypoglycemia were not confirmed due to patient's cognitive impairment. Hypoglycemic events continued despite feeding and dextrose-containing fluids. Further workup included a critical sample that revealed a serum glucose 59 mg/dL (3.3 mmol/L), insulin 20.6 µIU/mL (123.6 pmol/L [5-15 µIU/mL; 30.0-90 pmol/L]), proinsulin 33 pmol/L (3.6-22 pmol/L), C-peptide 1.74 ng/mL (0.58 nmol/L [0.8-3.85 ng/mL; 0.27-1.28 nmol/L]) and beta-hydroxybutyrate < 1.04 mg/dL (< 0.10 mmol/L; [< 4.2 mg/dL; < 0.4 mmol/L]). Insulin antibodies were negative. After confirmed insulin-mediated hypoglycemia, imaging studies followed. Pancreatic protocol abdominal computed tomography (CT), Ga-68 DOTATATE PET/CT scan, and endoscopic ultrasound found no pancreatic mass. Selective arterial calcium stimulation test showed a two-fold increase in insulin levels in 3/3 catheterized pancreatic territories. The patient started octreotide injections with resolution of hypoglycemia and was discharged on monthly lanreotide injections. To our knowledge, this is the first case reported of noninsulinoma pancreatogenous hypoglycemia in a patient with 1p36 deletion syndrome.

Defensiveness Toward IAT Feedback Predicts Willingness to Engage in Anti-Bias Behaviors.

People who are more defensive about their feedback on the Race-Attitudes Implicit Association Test (IAT) are less willing to engage in anti-bias behaviors. Extending on this work, we statistically clarified defensiveness constructs to predict willingness to engage in anti-bias behaviors among people who received pro-White versus no-bias IAT feedback. We replicated the finding that U.S. Americans are generally defensive toward pro-White IAT feedback, and that more defensiveness predicts less willingness to engage in anti-bias behaviors. However, people who believed their pro-White IAT feedback was an inaccurate reflection of their "true attitudes" were more willing to engage in anti-bias behaviors compared with people who received no-bias IAT feedback. These results better illuminate the defensiveness construct suggesting that receiving self-threatening feedback about bias may motivate people's willingness to engage in anti-bias behaviors in different ways depending on how people respond to that feedback.

Glycosylation in malaria parasites: what do we know?

In malaria parasites, although post-translational modification of proteins with N-. O-, and C-glycosidic bond-linked glycans is limited, it is confined to relatively fewer proteins in which the glycans are present at significant levels and may have important functions. Furthermore, several proteins are modified with glycosylphosphatidylinositols (GPIs) which represent the predominant glycan synthesized by parasites. Modification of proteins with GPIs is obligatory for parasite survival as GPI-anchored proteins (GPI-APs) play essential roles in all life cycle stages of the parasites, including development, egress, gametogenesis, motility, and host cell adhesion and invasion. Here, we discuss the current knowledge on the structures and potential functions of the glycan moieties of parasite proteins. The knowledge has important implications for the development of drugs and vaccines for malaria.

Change in Neuropsychological Test Performance Seen in a Longitudinal Study of Patients With Post-acute Sequelae of COVID-19: A 6-Month Follow-up Study.

BACKGROUND: Post-acute sequelae of COVID-19 may include physical, psychiatric, and neurocognitive symptoms. Few studies of cognitive symptoms have been longitudinal, with many following participants briefly after infection and relying on subjective complaints, screening instruments, or computerized testing. This group previously reported diminished neuropsychological (NP) test performance in over half of 60 individuals tested in-person 7 months post-COVID-19, particularly those seeking care for cognitive complaints. The current study describes the initial and 6-month follow-up results of an expanded cohort of 75 participants. OBJECTIVE: To measure longitudinal changes in neuropsychological test performance, as well as medical and psychiatric changes, post-COVID-19. METHODS: Participants underwent NP, psychiatric, and medical assessments approximately 7 months after acute COVID-19 infection. Sixty-three (84%) returned approximately 6 months later for repeat evaluation. RESULTS: At the initial visit, 29 (38.7%) met criteria for low NP performance, and 16 (21.3%) met criteria for extremely low NP performance. At 6-month follow-up, several NP domains that were significantly below normative values at the initial visit were no longer abnormal, with the exception of language. Only measures of delayed memory and fatigue showed significant improvements between the 2 time points. CONCLUSIONS: A substantial proportion of individuals recovered from acute COVID-19 infection have persistent neuropsychiatric symptoms over 1 year after infection. While the overall sample in this study showed some improvement in NP test performance relative to norms, only fatigue and delayed memory improved significantly between times 1 and 2. No individual declined in NP test performance, though relatively few individuals made significant clinical improvement, indicating the need for serial neuropsychiatric assessment and treatment supports. Longitudinal follow-up of this cohort is in progress.

Complement receptor 1 is the human erythrocyte receptor for Plasmodium vivax erythrocyte binding protein.

The discovery that Africans were resistant to infection by Plasmodium vivax (P. vivax) led to the conclusion that P. vivax invasion relied on the P. vivax Duffy Binding Protein (PvDBP) interacting with the Duffy Antigen Receptor for Chemokines (DARC) expressed on erythrocytes. However, the recent reporting of P. vivax infections in DARC-negative Africans suggests that the parasite might use an alternate invasion pathway to infect DARC-negative reticulocytes. To identify the parasite ligands and erythrocyte receptors that enable P. vivax invasion of both DARC-positive and -negative erythrocytes, we expressed region II containing the Duffy Binding-Like (DBL) domain of P. vivax erythrocyte binding protein (PvEBP-RII) and verified that the DBL domain binds to both DARC-positive and -negative erythrocytes. Furthermore, an AVidity-based EXtracelluar Interaction Screening (AVEXIS) was used to identify the receptor for PvEBP among over 750 human cell surface receptor proteins, and this approach identified only Complement Receptor 1 (CR1, CD35, or C3b/C4b receptor) as a PvEBP receptor. CR1 is a well-known receptor for P. falciparum Reticulocyte binding protein Homology 4 (PfRh4) and is present on the surfaces of both reticulocytes and normocytes, but its expression decreases as erythrocytes age. Indeed, PvEBP-RII bound to a subpopulation of both reticulocytes and normocytes, and this binding was blocked by the addition of soluble CR1 recombinant protein, indicating that CR1 is the receptor of PvEBP. In addition, we found that the Long Homology Repeat A (LHR-A) subdomain of CR1 is the only subdomain responsible for mediating the interaction with PvEBP-RII.

DON in pediatric cerebral malaria, a phase I/IIA dose-escalation safety study: study protocol for a clinical trial.

BACKGROUND: Despite treatment with highly effective antimalarial drugs, malaria annually claims the lives of over half a million children under 5-years of age in sub-Saharan Africa. Cerebral malaria (CM), defined as Plasmodium falciparum infection with coma, is the severe malaria syndrome with the highest mortality. Studies in the CM mouse model suggest that a T cell-mediated response underlies CM pathology, opening a new target for therapy in humans. This trial aims to establish the preliminary safety of one such novel therapy, the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON). METHODS: In this phase I/IIa dose-escalation clinical trial, a single dose of intravenous (IV) DON is administered to three participants groups-healthy adults and adults with uncomplicated malaria, then pediatric participants with CM-to primarily assess safety. The secondary objective of this trial is to assess pharmacokinetics of DON over a range of doses. The open-label adult portion of the trial enrolls 40 healthy adults concurrently with 40 adults with uncomplicated malaria. Cohorts of 10 participants receive a single IV dose of DON with doses escalating between cohorts from 0.1 mg/kg, 1.0 mg/kg, 5.0 mg/kg, to 10 mg/kg. Following subsequent safety review, a randomized, double-blind, and placebo-controlled pediatric study enrolls 72 participants aged 6 months to 14 years with CM. The pediatric portion of the study minimally spans three malaria seasons including a planned interim analysis after 50% of pediatric enrollments. The first half of pediatric participants receive DON 0.1 mg/kg, 1.0 mg/kg, or placebo. Dosing for the second half of pediatric participants is informed by the safety and preliminary efficacy results of those previously enrolled. The pediatric portion of the study has an exploratory outcome evaluating the preliminary efficacy of DON. Efficacy is assessed by diagnostics predictive of CM outcome: electroencephalography (EEG), magnetic resonance imaging (MRI), and transcranial doppler (TCD), measured before and after DON administration. All participants with malaria receive standard of care antimalarials in accordance with local guidelines, regardless of study drug dose group. DISCUSSION: This preliminary safety and efficacy study evaluates DON, a candidate adjunctive therapy for pediatric CM. If results support DON preliminary safety and efficacy, follow-up phase II and III clinical trials will be indicated. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov on 28 July 2022 (NCT05478720).

Larger Common River Frogs (Amietia delalandii) have Fewer and Shorter Tissue Microplastic Fibres than Smaller Frogs.

Little is known about microplastics (MPs) in adult frogs. We investigated MPs in adult Common River Frogs (Amietia delalandii) from Potchefstroom, South Africa. Five kinds of samples were analysed: natural water, water used to rinse the skin, skin, intestine, and the remainder of the body (corpus). Tissues were digested. Microplastics occurred in all frogs and sample types (1128 MPs counted). Fibres were the most prevalent MP. Fibre lengths were between 28 and 4300 µm, either polyester or polyvinyl alcohol. MPs in skin were likely derived from the ambient, and MPs in the corpus from translocation via the skin. Fibres in tissues were significantly shorter in larger frogs, a phenomenon we provisionally assign to in situ biodegradation. Microplastics in frogs can potentially be transferred through the food web to higher trophic levels. This study provides the first evidence of MPs in adult frog tissues and avenues for further investigations.

First report of a fish blood fluke from sub-Saharan Africa: Nomasanguinicola dentata (Paperna, 1964) Warren and Bullard, 2023 infecting African sharptooth catfish, Clarias gariepinus (Burchell, 1822) Teugles, 1982 in the Kavango River, Namibia, and a revised phylogeny for Sanguinicolidae Poche, 1926.

We herein provide a supplemental description of Nomasanguinicola dentata (Paperna, 1964) Warren and Bullard, 2023 (Digenea: Sanguinicolidae) and provide a revised 28S phylogeny to test relationships among freshwater fish blood flukes. We examined the heart of three African sharptooth catfish, Clarias gariepinus (Burchell, 1822) Teugles, 1982 from the Kavango River (northeastern Namibia) that was infected with adults of N. dentata. This blood fluke differs from N. canthoensis by having a body 5.3-6.7 longer than wide (vs. 3.5-4.6), an anterior esophageal swelling 7-8% (vs. 14-24%) of total esophageal length, a posterior esophageal swelling 3-5% (vs. 8-10%) of total esophageal length, a pre-cecal (vs. wholly post-cecal) testis, and an ovary that does not extend laterally beyond the nerve cords. The 28S sequence for N. dentata differed from that of N. canthoensis by 144 bp (9% difference). The phylogenetic analysis recovered these species as sister taxa and Sanguinicolidae as monophyletic. This is the first report of a fish blood fluke from sub-Saharan Africa, and the first report of a species of Nomasanguinicola from Africa in ∼40 yrs.

Improving the reliability and validity of the IAT with a dynamic model driven by similarity.

The Implicit Association Test (IAT), like many behavioral measures, seeks to quantify meaningful individual differences in cognitive processes that are difficult to assess with approaches like self-reports. However, much like other behavioral measures, many IATs appear to show low test-retest reliability and typical scoring methods fail to quantify all of the decision-making processes that generate the overt task performance. Here, we develop a new modeling approach for IATs based on the geometric similarity representation (GSR) model. This model leverages both response times and accuracy on IATs to make inferences about representational similarity between the stimuli and categories. The model disentangles processes related to response caution, stimulus encoding, similarities between concepts and categories, and response processes unrelated to the choice itself. This approach to analyzing IAT data illustrates that the unreliability in IATs is almost entirely attributable to the methods used to analyze data from the task: GSR model parameters show test-retest reliability around .80-.90, on par with reliable self-report measures. Furthermore, we demonstrate how model parameters result in greater validity compared to the IAT D-score, Quad model, and simple diffusion model contrasts, predicting outcomes related to intergroup contact and motivation. Finally, we present a simple point-and-click software tool for fitting the model, which uses a pre-trained neural network to estimate best-fit parameters of the GSR model. This approach allows easy and instantaneous fitting of IAT data with minimal demands on coding or technical expertise on the part of the user, making the new model accessible and effective.

Healthcare and successive natural disasters: Lessons still to be learned.

This article explores the increasing impact of natural disasters on healthcare leadership and disaster preparedness, particularly in Fort McMurray, Alberta. It underscores the importance of building disaster resilience in healthcare, distinguishing between emergencies, disasters, and catastrophes, and advocating for a multi-dimensional resilience approach. The need for robust electronic communication channels and comprehensive family-oriented evacuation plans, considering family and pet safety, is emphasized. The protection of vulnerable patients, the importance of resilient healthcare infrastructure, and dedicated protective equipment for first responders are also discussed. The article highlights the critical role of government support in flood prevention and disaster preparedness. Through the experiences of Fort McMurray, the article demonstrates the necessity of comprehensive disaster planning and the crucial role of healthcare systems in rapid recovery and adaptation in the face of disasters. It aims to contribute to an improved understanding and strategies for managing such critical situations in the future.

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms. METHODS: In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803. FINDINGS: Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036). INTERPRETATION: Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions. FUNDING: Health and Medical Research Fund of Hong Kong, Hui Hoy and Chow Sin Lan Charity Fund, and InnoHK of the HKSAR Government. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Effect of Real-Time Computer-Aided Polyp Detection System (ENDO-AID) on Adenoma Detection in Endoscopists-in-Training: A Randomized Trial.

BACKGROUND: The effect of computer-aided polyp detection (CADe) on adenoma detection rate (ADR) among endoscopists-in-training remains unknown. METHODS: We performed a single-blind, parallel-group, randomized controlled trial in Hong Kong between April 2021 and July 2022 (NCT04838951). Eligible subjects undergoing screening/surveillance/diagnostic colonoscopies were randomized 1:1 to receive colonoscopies with CADe (ENDO-AID[OIP-1]) or not (control) during withdrawal. Procedures were performed by endoscopists-in-training with <500 procedures and <3 years' experience. Randomization was stratified by patient age, sex, and endoscopist experience (beginner vs intermediate level, <200 vs 200-500 procedures). Image enhancement and distal attachment devices were disallowed. Subjects with incomplete colonoscopies or inadequate bowel preparation were excluded. Treatment allocation was blinded to outcome assessors. The primary outcome was ADR. Secondary outcomes were ADR for different adenoma sizes and locations, mean number of adenomas, and non-neoplastic resection rate. RESULTS: A total of 386 and 380 subjects were randomized to CADe and control groups, respectively. The overall ADR was significantly higher in the CADe group than in the control group (57.5% vs 44.5%; adjusted relative risk, 1.41; 95% CI, 1.17-1.72; P < .001). The ADRs for <5 mm (40.4% vs 25.0%) and 5- to 10-mm adenomas (36.8% vs 29.2%) were higher in the CADe group. The ADRs were higher in the CADe group in both the right colon (42.0% vs 30.8%) and left colon (34.5% vs 27.6%), but there was no significant difference in advanced ADR. The ADRs were higher in the CADe group among beginner (60.0% vs 41.9%) and intermediate-level (56.5% vs 45.5%) endoscopists. Mean number of adenomas (1.48 vs 0.86) and non-neoplastic resection rate (52.1% vs 35.0%) were higher in the CADe group. CONCLUSIONS: Among endoscopists-in-training, the use of CADe during colonoscopies was associated with increased overall ADR. (ClinicalTrials.gov, Number: NCT04838951).

Longitudinal Assessment of Pancreas Volume by MRI Predicts Progression to Stage 3 Type 1 Diabetes.

OBJECTIVE: This multicenter prospective cohort study compared pancreas volume as assessed by MRI, metabolic scores derived from oral glucose tolerance testing (OGTT), and a combination of pancreas volume and metabolic scores for predicting progression to stage 3 type 1 diabetes (T1D) in individuals with multiple diabetes-related autoantibodies. RESEARCH DESIGN AND METHODS: Pancreas MRI was performed in 65 multiple autoantibody-positive participants enrolled in the Type 1 Diabetes TrialNet Pathway to Prevention study. Prediction of progression to stage 3 T1D was assessed using pancreas volume index (PVI), OGTT-derived Index60 score and Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), and a combination of PVI and DPTRS. RESULTS: PVI, Index60, and DPTRS were all significantly different at study entry in 11 individuals who subsequently experienced progression to stage 3 T1D compared with 54 participants who did not experience progression (P < 0.005). PVI did not correlate with metabolic testing across individual study participants. PVI declined longitudinally in the 11 individuals diagnosed with stage 3 T1D, whereas Index60 and DPTRS increased. The area under the receiver operating characteristic curve for predicting progression to stage 3 from measurements at study entry was 0.76 for PVI, 0.79 for Index60, 0.79 for DPTRS, and 0.91 for PVI plus DPTRS. CONCLUSIONS: These findings suggest that measures of pancreas volume and metabolism reflect distinct components of risk for developing stage 3 type 1 diabetes and that a combination of these measures may provide superior prediction than either alone.

Development of a Carbon Nanotube-Enhanced FAS Bilayer Amphiphobic Coating for Biological Fluids.

This study reports the development of a novel amphiphobic coating. The coating is a bilayer arrangement, where carbon nanotubes (CNTs) form the underlayer and fluorinated alkyl-silane (FAS) forms the overlayer, resulting in the development of highly amphiphobic coatings suitable for a wide range of substrates. The effectiveness of these coatings is demonstrated through enhanced contact angles for water and artificial blood plasma fluid on glass, stainless steel, and porous PTFE. The coatings were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), atomic force microscopy (AFM), and contact angle (CA) measurements. The water contact angles achieved with the bilayer coating were 106 ± 2°, 116 ± 2°, and 141 ± 2° for glass, stainless steel, and PTFE, respectively, confirming the hydrophobic nature of the coating. Additionally, the coating displayed high repellency for blood plasma, exhibiting contact angles of 102 ± 2°, 112 ± 2°, and 134 ± 2° on coated glass, stainless steel, and PTFE surfaces, respectively. The presence of the CNT underlayer improved plasma contact angles by 29%, 21.7%, and 16.5% for the respective surfaces. The presence of the CNT layer improved surface roughness significantly, and the average roughness of the bilayer coating on glass, stainless steel, and PTFE was measured to be 488 nm, 301 nm, and 274 nm, respectively. Mechanistically, the CNT underlayer contributed to the surface roughness, while the FAS layer provided high amphiphobicity. The maximum effect was observed on modified glass, followed by stainless steel and PTFE surfaces. These findings highlight the promising potential of this coating method across diverse applications, particularly in the biomedical industry, where it can help mitigate complications associated with device-fluid interactions.