Results of Integrated Transmission Assessment Surveys for Lymphatic Filariasis and Malaria in Haiti, 2017-2022.

Haiti is endemic for lymphatic filariasis (LF) and malaria, two mosquito-transmitted parasitic diseases targeted for elimination. The World Health Organization recommends a transmission assessment survey (TAS-1) to determine if LF prevalence is significantly beneath putative transmission thresholds (<2% antigen prevalence in Haiti, where Culex is the primary vector for Wuchereria bancrofti) to stop mass drug administration (MDA). Repeated TASs (TAS-2 and TAS-3) are recommended at 2-3-year intervals during post-treatment surveillance. From 2017 to 2022, The Carter Center assisted the Haitian Ministry of Public Health and Population in conducting 15 TASs in 11 evaluation units (EUs) encompassing 54 of the country's 146 districts. Children 6-7 years old were assessed for circulating filarial antigen (CFA) by Filariasis Test Strip: n = 5,239 in TAS-1; n = 11,866 in TAS-2; and n = 1,842 in TAS-3, of whom eight (0.15%), 20 (0.17%), and eight (0.43%) tested positive, respectively. The number of positive results in children was less than the threshold in each EU. When available, participants (n = 16,663) were also tested for malaria by rapid diagnostic test, with 31 (0.19%) children testing positive for Plasmodium falciparum. Integrated TASs provided an efficient means to collect epidemiological data for LF and malaria in Haiti. Results indicated thresholds for stopping and maintaining the halt of MDA for LF have been achieved in all EUs, with the halt of MDA for 571,358 people in four districts and the first TAS-3 surveys conducted in Haiti. Investigations are needed to assess the potential of ongoing LF transmission, especially in areas where CFA-positive samples were detected in TAS-3.

Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer's Disease.

INTRODUCTION: ALZ-801/valiltramiprosate is a small-molecule oral inhibitor of beta amyloid (Aß) aggregation and oligomer formation being studied in a phase 2 trial in APOE4 carriers with early Alzheimer's disease (AD) to evaluate treatment effects on fluid and imaging biomarkers and cognitive assessments. METHODS: The single-arm, open-label phase 2 trial was designed to evaluate the effects of the ALZ-801 265 mg tablet taken twice daily (after 2 weeks once daily) on plasma fluid AD biomarkers, hippocampal volume (HV), and cognition over 104 weeks in APOE4 carriers. The study enrolled subjects aged 50-80 years, with early AD [Mini-Mental State Examination (MMSE) ≥ 22, Clinical Dementia Rating-Global (CDR-G) 0.5 or 1], apolipoprotein E4 (APOE4) genotypes including APOE4/4 and APOE3/4 genotypes, and positive cerebrospinal fluid (CSF) AD biomarkers or prior amyloid scans. The primary outcome was plasma p-tau181, HV evaluated by magnetic resonance imaging (MRI) was the key secondary outcome, and plasma Aß42 and Aß40 were the secondary biomarker outcomes. The cognitive outcomes were the Rey Auditory Verbal Learning Test and the Digit Symbol Substitution Test. Safety and tolerability evaluations included treatment-emergent adverse events and amyloid-related imaging abnormalities (ARIA). The study was designed and powered to detect 15% reduction from baseline in plasma p-tau181 at the 104-week endpoint. A sample size of 80 subjects provided adequate power to detect this difference at a significance level of 0.05 using a two-sided paired t-test. RESULTS: The enrolled population of 84 subjects (31 homozygotes and 53 heterozygotes) was 52% females, mean age 69 years, MMSE 25.7 [70% mild cognitive impairment (MCI), 30% mild AD] with 55% on cholinesterase inhibitors. Plasma p-tau181 reduction from baseline was significant (31%, p = 0.045) at 104 weeks and all prior visits; HV atrophy was significantly reduced (p = 0.0014) compared with matched external controls from an observational Early AD study. Memory scores showed minimal decline from baseline over 104 weeks and correlated significantly with decreased HV atrophy (Spearman's 0.44, p = 0.002). Common adverse events were COVID infection and mild nausea, and no drug-related serious adverse events were reported. Of 14 early terminations, 6 were due to nonserious treatment-emergent adverse events and 1 death due to COVID. There was no vasogenic brain edema observed on MRI over 104 weeks. CONCLUSIONS: The effect of ALZ-801 on reducing plasma p-tau181 over 2 years demonstrates target engagement and supports its anti-Aß oligomer action that leads to a robust decrease in amyloid-induced brain neurodegeneration. The significant correlation between reduced HV atrophy and cognitive stability over 2 years suggests a disease-modifying effect of ALZ-801 treatment in patients with early AD. Together with the favorable safety profile with no events of vasogenic brain edema, these results support further evaluation of ALZ-801 in a broader population of APOE4 carriers, who represent two-thirds of patients with AD. TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04693520 .

Analysis of Cerebrospinal Fluid, Plasma ß-Amyloid Biomarkers, and Cognition from a 2-Year Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer's Disease Using Quantitative Systems Pharmacology Model.

INTRODUCTION: ALZ-801/valiltramiprosate is an oral, small-molecule inhibitor of beta-amyloid (Aß) aggregation and oligomer formation in late-stage development as a disease-modifying therapy for early Alzheimer's disease (AD). The present investigation provides a quantitative systems pharmacology (QSP) analysis of amyloid fluid biomarkers and cognitive results from a 2-year ALZ-801 Phase 2 trial in APOE4 carriers with early AD. METHODS: The single-arm, open-label phase 2 study evaluated effects of ALZ-801 265 mg two times daily (BID) on cerebrospinal fluid (CSF) and plasma amyloid fluid biomarkers over 104 weeks in APOE4 carriers with early AD [Mini-Mental State Examination (MMSE) ≥ 22]. Subjects with positive CSF biomarkers for amyloid (Aß42/Aß40) and tau pathology (p-tau181) were enrolled, with serial CSF and plasma levels of Aß42 and Aß40 measured over 104 weeks. Longitudinal changes of CSF Aß42, plasma Aß42/Aß40 ratio, and cognitive Rey Auditory Verbal Learning Test (RAVLT) were compared with the established natural disease trajectories in AD using a QSP approach. The natural disease trajectory data for amyloid biomarkers and RAVLT were extracted from a QSP model and an Alzheimer's disease neuroimaging initiative population model, respectively. Analyses were stratified by disease severity and sex. RESULTS: A total of 84 subjects were enrolled. Excluding one subject who withdrew at the early stage of the trial, data from 83 subjects were used for this analysis. The ALZ-801 treatment arrested the progressive decline in CSF Aß42 level and plasma Aß42/Aß40 ratio, and stabilized RAVLT over 104 weeks. Both sexes showed comparable responses to ALZ-801, whereas mild cognitive impairment (MCI) subjects (MMSE ≥ 27) exhibited a larger biomarker response compared with more advanced mild AD subjects (MMSE 22-26). CONCLUSIONS: In this genetically defined and biomarker-enriched early AD population, the QSP analysis demonstrated a positive therapeutic effect of oral ALZ-801 265 mg BID by arresting the natural decline of monomeric CSF and plasma amyloid biomarkers, consistent with the target engagement to prevent their aggregation into soluble neurotoxic oligomers and subsequently into insoluble fibrils and plaques over 104 weeks. Accompanying the amyloid biomarker changes, ALZ-801 also stabilized the natural trajectory decline of the RAVLT memory test, suggesting that the clinical benefits are consistent with its mechanism of action. This sequential effect arresting the disease progression on biomarkers and cognitive decline was more pronounced in the earlier symptomatic stages of AD. The QSP analysis provides fluid biomarker and clinical evidence for ALZ-801 as a first-in-class, oral small-molecule anti-Aß oligomer agent with disease modification potential in AD. TRIAL REGISTRY: https://clinicaltrials.gov/study/NCT04693520.

Exploring women's bladder self-care practices: A qualitative secondary analysis.

AIMS: To describe women's experiences with a range of bladder self-care practices. DESIGN: We conducted a secondary, directed content analysis of qualitative data from the Study of Habits, Attitudes, Realities and Experiences, a multisite focus group study designed to explore adolescent and adult women's experiences, perceptions, beliefs, knowledge and behaviours related to bladder health. This study was conducted by the National Institute of Diabetes and Digestive and Kidney Diseases' Prevention of Lower Urinary Tract Symptoms Research Consortium. Study methods were informed by the Consortium's conceptual framework, based on a social ecological model adapted from Glass and McAtee's Society-Behavior-Biology Nexus. METHODS: Participants were recruited at seven geographically diverse United States research centres between July 2017 and April 2018. Data for the current analysis were collected using a semi-structured discussion group with 36 focus groups involving 316 community-dwelling adult women aged 18-93 years. Coded text was re-examined according to eight self-care behavioural domains identified through literature review and expert opinion as potentially influencing bladder health. RESULTS: Participants described many self-care practices they had adopted to prevent bladder problems or manage existing symptoms and conditions. Eight themes were identified: 'Choosing fluids, foods and medications'; 'Dressing for bladder health'; 'Promoting bodily cleanliness'; 'Managing toileting environments'; 'Timing when to void'; 'Exercising pelvic floor muscles for bladder control'; 'Limiting physical activities that challenge the bladder' and 'Staying home and navigating when away'. Thirteen subthemes were derived from five of the eight themes. CONCLUSION: Women use a broad array of self-care practices related to their bladder health. Research is needed to examine the efficacy of self-care behaviours for preventing or managing bladder symptoms and conditions, and to discern potential risks. Results have important implications for development of bladder health promotion interventions and public health messaging around women's bladder health. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study provides a comprehensive framework for understanding women's bladder self-care practices, which can be used by clinicians and public health professionals in designing interventions to promote bladder health and function. IMPACT: Women with and without lower urinary tract symptoms use a broad range of self-care practices that may affect their bladder health, including some that may be harmful. Because of the high prevalence of bladder symptoms in women, this study may help patient assessment and counselling regarding self-care practices. REPORTING METHOD: This study was reported according to the Standards for Reporting Qualitative Research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Genetic variant detection in a South African haemophilia B population.

BACKGROUND: Haemophilia B is characterised by a deficiency of factor IX (FIX) protein due to genetic variants in the FIX gene (F9). Genetic testing may have a vital role in effectively managing haemophilia B. However, in many developing countries, comprehensive genetic variant detection is unavailable. This study aimed to address the lack of genetic data in our country by conducting genetic variant detection on people affected by haemophilia B in our region. METHODS: Twenty-one participants were screened with a direct Sanger sequencing method to identify variants in the F9 gene. The identified variants were then compared to previously published variants and/or to a reference database. RESULTS AND DISCUSSION: A total of ten F9 genetic changes were detected, with five of them being novel. These identified variants were distributed across different domains of the FIX protein. Only one participant had a history of inhibitor formation against FIX replacement therapy. Notably, this participant had two distinct genetic changes present adjacent to each other. Thus, we hypothesise that the presence of multiple variants within the same functional region of the gene may increase the risk for inhibitor development. CONCLUSION: The discovery of novel pathogenic variations in the F9 gene highlights the importance of genetic analysis in specific geographical regions. The possible link between a complex variant and inhibitor formation illustrates the potential role that genetic screening has as a pre-treatment tool in predicting treatment reactions and outcomes.

Amino Acid Uptake Limitations during Human Mesenchymal Stem Cell-Based Chondrogenesis.

A mino acids are the essential building blocks for collagen and proteoglycan, which are the main constituents for cartilage extracellular matrix (ECM). Synthesis of ECM proteins requires the uptake of various essential/nonessential amino acids. Analyzing amino acid metabolism during chondrogenesis can help to relate tissue quality to amino acid metabolism under different conditions. In our study, we studied amino acid uptake/secretion using human mesenchymal stem cell (hMSC)-based aggregate chondrogenesis in a serum-free induction medium with a defined chemical formulation. The initial glucose level and medium-change frequency were varied. Our results showed that essential amino acid uptake increased with time during hMSCs chondrogenesis for all initial glucose levels and medium-change frequencies. Essential amino acid uptake rates were initial glucose-level independent. The DNA-normalized glycosaminoglycans and hydroxyproline content of chondrogenic aggregates correlated with cumulative uptake of leucine, valine, and tryptophan regardless of initial glucose levels and medium-change frequencies. Collectively, our results show that amino acid uptake rates during in vitro chondrogenesis were insufficient to produce a tissue with an ECM content similar to that of human neonatal cartilage or adult cartilage. Furthermore, this deficiency was likely related to the downregulation of some key amino acid transporters in the cells. Such deficiency could be partially improved by increasing the amino acid availability in the chondrogenic medium by changing culture conditions.

Effect of Intrapersonal and Interpersonal Behavior Change Strategies on Physical Activity Among Older Adults: A Randomized Clinical Trial.

Importance: Despite guidelines that recommend physical activity (PA), little is known about which types of behavior change strategies (BCSs) effectively promote sustained increases in PA in older adults who are insufficiently active. Objective: To determine whether intrapersonal BCSs (eg, goal setting) or interpersonal BCSs (eg, peer-to-peer sharing or learning) combined with the Otago Exercise Program (17 strength and balance exercises and a walking program that are learned and individually tailored, with instruction to perform 3 times per week at home or location of choice) and a wearable PA monitor help older adults sustain increases in their PA. Design, Setting, and Participants: This 2 × 2 factorial randomized clinical trial (Community-Based Intervention Effects on Older Adults' Physical Activity) of community-dwelling older adults 70 years or older with PA levels below minimum national PA guidelines was conducted in urban community centers. Dates of enrollment were from November 17, 2017, to June 15, 2021, with final follow-up assessments completed on September 2, 2022. Interventions: Participants were randomized to intrapersonal (eg, goal setting) BCSs, interpersonal (eg, problem-solving with peer-to-peer sharing and learning) BCSs, intrapersonal and interpersonal BCSs, or an attention control group. All interventions included a PA monitor and 8 weekly small-group meetings with discussion, practice, and instructions to implement the exercise program and relevant BCSs independently between meetings and after the intervention. Main Outcomes and Measures: The primary outcome was daily minutes of objectively measured total PA (light, moderate, or vigorous intensities) averaged over 7 to 10 days, measured at baseline and after the intervention at 1 week, 6 months, and 12 months. Results: Among 309 participants (mean [SD] age, 77.4 [5.0] years; 240 women [77.7%]), 305 (98.7%) completed the intervention, and 302 (97.7%) had complete data. Participants receiving PA interventions with interpersonal BCS components exhibited greater increases in total PA than did those who did not at 1 week (204 vs 177 PA minutes per day; adjusted difference, 27.1 [95% CI, 17.2-37.0]; P < .001), 6 months (195 vs 175 PA minutes per day; adjusted difference, 20.8 [95% CI, 10.0-31.6]; P < .001), and 12 months (195 vs 168 PA minutes per day; adjusted difference, 27.5 [95% CI, 16.2-38.8]; P < .001) after the intervention. Compared with participants who did not receive interventions with intrapersonal BCS components, participants who received intrapersonal BCSs exhibited no significant changes in total PA at 1 week (192 vs 190 PA minutes per day; adjusted difference, 1.8 [95% CI, -8.6 to 12.2]; P = .73), 6 months (183 vs 187 PA minutes per day; adjusted difference, -3.9 [95% CI, -15.0 to 7.1]; P = .49), or 12 months (177 vs 186 PA minutes per day; adjusted difference, -8.8 [95% CI, -20.5 to 2.9]; P = .14) after the intervention. Interactions between intrapersonal and interpersonal BCSs were not significant. Conclusions and Relevance: In this randomized clinical trial, older adults with low levels of PA who received interpersonal BCSs, the exercise program, and a PA monitor exhibited significant increases in their PA for up to 12 months after the intervention. Intrapersonal BCSs elicited no significant PA changes and did not interact with interpersonal BCSs. Our findings suggest that because effects of a PA intervention on sustained increases in older adults' PA were augmented with interpersonal but not intrapersonal BCSs, approaches to disseminating and implementing the intervention should be considered. Trial Registration: ClinicalTrials.gov Identifier: NCT03326141.

Estimation of the transmission delays in the basal ganglia of the macaque monkey and subsequent predictions about oscillatory activity under dopamine depletion.

The timescales of the dynamics of a system depend on the combination of the timescales of its components and of its transmission delays between components. Here, we combine experimental stimulation data from 10 studies in macaque monkeys that reveal the timing of excitatory and inhibitory events in the basal ganglia circuit, to estimate its set of transmission delays. In doing so, we reveal possible inconsistencies in the existing data, calling for replications, and we propose two possible sets of transmission delays. We then integrate these delays in a model of the primate basal ganglia that does not rely on direct and indirect pathways' segregation and show that extrastriatal dopaminergic depletion in the external part of the globus pallidus and in the subthalamic nucleus is sufficient to generate ß-band oscillations (in the high part, 20-35 Hz, of the band). More specifically, we show that D2 and D5 dopamine receptors in these nuclei play opposing roles in the emergence of these oscillations, thereby explaining how completely deactivating D5 receptors in the subthalamic nucleus can, paradoxically, cancel oscillations.

Circadian Disruption across Lifespan Impairs Glucose Homeostasis and Insulin Sensitivity in Adult Mice.

Circadian rhythm disruption is associated with impaired glucose homeostasis and type 2 diabetes. For example, night shift work is associated with an increased risk of gestational diabetes. However, the effects of chronic circadian disruption since early life on adult metabolic health trajectory remain unknown. Here, using the "Short Day" (SD) mouse model, in which an 8 h/8 h light/dark (LD) cycle was used to disrupt mouse circadian rhythms across the lifespan, we investigated glucose homeostasis in adult mice. Adult SD mice were fully entrained into the 8 h/8 h LD cycle, and control mice were entrained into the 12 h/12 h LD cycle. Under a normal chow diet, female and male SD mice displayed a normal body weight trajectory. However, female but not male SD mice under a normal chow diet displayed glucose intolerance and insulin resistance, which are associated with impaired insulin signaling/AKT in the skeletal muscle and liver. Under high-fat diet (HFD) challenges, male but not female SD mice demonstrated increased body weight gain compared to controls. Both male and female SD mice developed glucose intolerance under HFD. Taken together, these results demonstrate that environmental disruption of circadian rhythms contributes to obesity in a sexually dimorphic manner but increases the risk of glucose intolerance and insulin resistance in both males and females.

A genus in the bacterial phylum Aquificota appears to be endemic to Aotearoa-New Zealand.

Allopatric speciation has been difficult to examine among microorganisms, with prior reports of endemism restricted to sub-genus level taxa. Previous microbial community analysis via 16S rRNA gene sequencing of 925 geothermal springs from the Taupo Volcanic Zone (TVZ), Aotearoa-New Zealand, revealed widespread distribution and abundance of a single bacterial genus across 686 of these ecosystems (pH 1.2-9.6 and 17.4-99.8 °C). Here, we present evidence to suggest that this genus, Venenivibrio (phylum Aquificota), is endemic to Aotearoa-New Zealand. A specific environmental niche that increases habitat isolation was identified, with maximal read abundance of Venenivibrio occurring at pH 4-6, 50-70 °C, and low oxidation-reduction potentials. This was further highlighted by genomic and culture-based analyses of the only characterised species for the genus, Venenivibrio stagnispumantis CP.B2T, which confirmed a chemolithoautotrophic metabolism dependent on hydrogen oxidation. While similarity between Venenivibrio populations illustrated that dispersal is not limited across the TVZ, extensive amplicon, metagenomic, and phylogenomic analyses of global microbial communities from DNA sequence databases indicates Venenivibrio is geographically restricted to the Aotearoa-New Zealand archipelago. We conclude that geographic isolation, complemented by physicochemical constraints, has resulted in the establishment of an endemic bacterial genus.

Geospatial analysis of Plasmodium falciparum serological indicators: school versus community sampling in a low-transmission malaria setting.

BACKGROUND: Due to low numbers of active infections and persons presenting to health facilities for malaria treatment, case-based surveillance is inefficient for understanding the remaining disease burden in low malaria transmission settings. Serological data through the detection of IgG antibodies from previous malaria parasite exposure can fill this gap by providing a nuanced picture of where sustained transmission remains. Study enrollment at sites of gathering provides a potential approach to spatially estimate malaria exposure and could preclude the need for more intensive community-based sampling. METHODS: This study compared spatial estimates of malaria exposure from cross-sectional school- and community-based sampling in Haiti. A total of 52,405 blood samples were collected from 2012 to 2017. Multiplex bead assays (MBAs) tested IgG against P. falciparum liver stage antigen-1 (LSA-1), apical membrane antigen 1 (AMA1), and merozoite surface protein 1 (MSP1). Predictive geospatial models of seropositivity adjusted for environmental covariates, and results were compared using correlations by coordinate points and communes across Haiti. RESULTS: Consistent directional associations were observed between seroprevalence and environmental covariates for elevation (negative), air temperature (negative), and travel time to urban centers (positive). Spearman's rank correlation for predicted seroprevalence at coordinate points was lowest for LSA-1 (ρ = 0.10, 95% CI: 0.09-0.11), but improved for AMA1 (ρ = 0.36, 95% CI: 0.35-0.37) and MSP1 (ρ = 0.48, 95% CI: 0.47-0.49). CONCLUSIONS: In settings approaching P. falciparum elimination, case-based prevalence data does not provide a resolution of ongoing malaria transmission in the population. Immunogenic antigen targets (e.g., AMA1, MSP1) that give higher population rates of seropositivity provide moderate correlation to gold standard community sampling designs and are a feasible approach to discern foci of residual P. falciparum transmission in an area.

Blinded Intraoperative Quantitative Indocyanine Green Metrics Associate With Intestinal Margin Acceptance in Colorectal Surgery.

BACKGROUND: Indocyanine green is a useful tool in colorectal surgery. Quantitative values may enhance and standardize its application. OBJECTIVE: To determine whether quantitative indocyanine green metrics correlate with standard subjective indocyanine green perfusion assessment in acceptance or rejection of anastomotic margins. DESIGN: Prospective single-arm, single-institution cohort study. Surgeons viewed subjective indocyanine green images but were blinded to quantitative indocyanine green metrics. SETTING: Tertiary academic center. PATIENTS: Adults undergoing planned intestinal resection. MAIN OUTCOME MEASURES: Accepted perfusion and rejected perfusion of the intestinal margin were defined by the absence or presence of ischemia by subjective indocyanine green and gross inspection. The primary outcomes included quantitative indocyanine green values, maximum fluorescence, and time-to-maximum fluorescence in accepted compared to rejected perfusion. Secondary outcomes included maximum fluorescence and time-to-maximum fluorescence values in anastomotic leak. RESULTS: There were 89 perfusion assessments comprising 156 intestinal segments. Nine segments were subjectively assessed to have poor perfusion by visual inspection and subjective indocyanine green. Maximum fluorescence (% intensity) exhibited higher intensity in accepted perfusion (accepted perfusion 161% [82%-351%] vs rejected perfusion 63% [10%-76%]; p = 0.03). Similarly, time-to-maximum fluorescence (seconds) was earlier in accepted perfusion compared to rejected perfusion (10 seconds [1-40] vs 120 seconds [90-120]; p < 0.01). Increased BMI was associated with higher maximum fluorescence. Anastomotic leak did not correlate with maximum fluorescence or time-to-maximum fluorescence. LIMITATIONS: Small cohort study, not powered to measure the association between quantitative indocyanine green metrics and anastomotic leak. CONCLUSIONS: We demonstrated that blinded quantitative values reliably correlate with subjective indocyanine green perfusion assessment. Time-to-maximum intensity is an important metric in perfusion evaluation. Quantitative indocyanine green metrics may enhance intraoperative intestinal perfusion assessment. Future studies may attempt to correlate quantitative indocyanine green values with anastomotic leak. See Video Abstract . LAS MTRICAS CUANTITATIVAS INTRAOPERATORIAS CIEGAS DEL VERDE DE INDOCIANINA SE ASOCIAN CON LA ACEPTACIN DEL MARGEN INTESTINAL EN LA CIRUGA COLORRECTAL: ANTECEDENTES:El verde de indocianina es una herramienta útil en la cirugía colorrectal. Los valores cuantitativos pueden mejorar y estandarizar su aplicación.OBJETIVO:Determinar si las métricas cuantitativas de verde de indocianina se correlacionan con la evaluación subjetiva estándar de perfusión de verde de indocianina en la aceptación o rechazo de los márgenes anastomóticos.DISEÑO:Estudio de cohorte prospectivo de un solo brazo y de una sola institución. Los cirujanos vieron imágenes subjetivas de verde de indocianina, pero no conocían las métricas cuantitativas de verde de indocianina.AJUSTE:Centro académico terciario.PACIENTES:Adultos sometidos a resección intestinal planificada.PRINCIPALES MEDIDAS DE RESULTADO:La perfusión aceptada y la perfusión rechazada del margen intestinal se definieron por la ausencia o presencia de isquemia mediante verde de indocianina subjetiva y la inspección macroscópica. Los resultados primarios fueron los valores cuantitativos de verde de indocianina, la fluorescencia máxima y el tiempo hasta la fluorescencia máxima en la perfusión aceptada en comparación con la rechazada. Los resultados secundarios incluyeron la fluorescencia máxima y el tiempo hasta alcanzar los valores máximos de fluorescencia en la fuga anastomótica.RESULTADOS:Se realizaron 89 evaluaciones de perfusión, comprendiendo 156 segmentos intestinales. Se evaluó subjetivamente que 9 segmentos tenían mala perfusión mediante inspección visual y verde de indocianina subjetiva. La fluorescencia máxima (% de intensidad) mostró una mayor intensidad en la perfusión aceptada [Perfusión aceptada 161% (82-351) vs Perfusión rechazada 63% (10-76); p = 0,03]. De manera similar, el tiempo hasta la fluorescencia máxima (segundos) fue más temprano en la perfusión aceptada en comparación con la rechazada [10 s (1-40) frente a 120 s (90-120); p < 0,01]. Aumento del índice de masa corporal asociado con una fluorescencia máxima más alta. La fuga anastomótica no se correlacionó con la fluorescencia máxima ni con el tiempo hasta la fluorescencia máxima.LIMITACIONES:Estudio de cohorte pequeño, sin poder para medir la asociación entre las mediciones cuantitativas del verde de indocianina y la fuga anastomótica.CONCLUSIÓN:Demostramos que los valores cuantitativos ciegos se correlacionan de manera confiable con la evaluación subjetiva de la perfusión de verde de indocianina. El tiempo hasta la intensidad máxima es una métrica importante en la evaluación de la perfusión. Las métricas cuantitativas de verde de indocianina pueden mejorar la evaluación de la perfusión intestinal intraoperatoria. Los estudios futuros pueden intentar correlacionar los valores cuantitativos de verde de indocianina con la fuga anastomótica. (Traducción-Dr. Yolanda Colorado).

Vertical sleeve gastrectomy improves glucose-insulin homeostasis by enhancing ß-cell function and survival via FGF15/19.

Vertical sleeve gastrectomy (VSG) restores glucose homeostasis in obese mice and humans. In addition, the increased fibroblast growth factor (FGF)15/19 circulating level postsurgery has been implicated in this effect. However, the impact of FGF15/19 on pancreatic islets remains unclear. Using a diet-induced obese mice model, we demonstrate that VSG attenuates insulin hypersecretion in isolated pancreatic islets, likely due to morphological alterations in the endocrine pancreas such as reduction in islet, ß-cell, and α-cell mass. In addition, VSG relieves gene expression of endoplasmic reticulum (ER) stress and inflammation markers in islets from obese mice. Incubation of INS-1E ß-cells with serum from obese mice induced dysfunction and cell death, whereas these conditions were not induced with serum from obese mice submitted to VSG, implicating the involvement of a humoral factor. Indeed, VSG increased FGF15 circulating levels in obese mice, as well as the expression of FGF receptor 1 (Fgfr1) and its coreceptor ß-klotho (Klb), both in pancreatic islets from VSG mice and in INS-1E cells treated with the serum from these mice. Moreover, exposing INS-1E cells to an FGFR inhibitor abolished the effects of VSG serum on insulin secretion and cell death. Also, recombinant FGF19 prevents INS-1E cells from dysfunction and death induced by serum from obese mice. These findings indicate that the amelioration of glucose-insulin homeostasis promoted by VSG is mediated, at least in part, by FGF15/19. Therefore, approaches promoting FGF15/19 release or action may restore pancreatic islet function in obesity.NEW & NOTEWORTHY Vertical sleeve gastrectomy (VSG) decreases insulin secretion, endoplasmic reticulum (ER) stress, and inflammation in pancreatic islets from obese mice. In addition, VSG increased fibroblast growth factor (FGF)15 circulating levels in obese mice, as well as the expression of FGF receptor 1 (Fgfr1) and its coreceptor ß-klotho (Klb), both in pancreatic islets from VSG mice and in INS-1E ß-cells treated with the serum from these mice. Serum from operated mice protects INS-1E cells from dysfunction and apoptosis, which was mediated by FGF15/19.

Associations Between Psychosocial Needs, Carbohydrate-Counting Behavior, and App Satisfaction: A Randomized Crossover App Trial on 92 Adults With Diabetes.

To examine whether psychosocial needs in diabetes care are associated with carbohydrate counting and if carbohydrate counting is associated with satisfaction with diabetes applications' usability, a randomized crossover trial of 92 adults with type 1 or 2 diabetes requiring insulin therapy tested two top-rated diabetes applications, mySugr and OnTrack Diabetes. Survey responses on demographics, psychosocial needs (perceived competence, autonomy, and connectivity), carbohydrate-counting frequency, and application satisfaction were modeled using mixed-effect linear regressions to test associations. Participants ranged between 19 and 74 years old (mean, 54 years) and predominantly had type 2 diabetes (70%). Among the three tested domains of psychosocial needs, only competence-not autonomy or connectivity-was found to be associated with carbohydrate-counting frequency. No association between carbohydrate-counting behavior and application satisfaction was found. In conclusion, perceived competence in diabetes care is an important factor in carbohydrate counting; clinicians may improve adherence to carbohydrate counting with strategies designed to improve perceived competence. Carbohydrate-counting behavior is complex; its impact on patient satisfaction of diabetes application usability is multifactorial and warrants consideration of patient demographics such as sex as well as application features for automated carbohydrate counting.

Technical Assistance Received by Older Adults to Use Commercially Available Physical Activity Monitors (Ready Steady 3.0 Trial): Ad-Hoc Descriptive Longitudinal Study.

Background: Despite evidence that regular physical activity (PA) among older adults confers numerous health and functional benefits, PA participation rates are low. Using commercially available wearable PA monitors (PAMs) is one way to augment PA promotion efforts. However, while expert recommendations exist for the specific information needed at the beginning of PAM ownership and the general ongoing need for structures that support as-needed technical troubleshooting, information is lacking about the type, frequency, and modes of assistance needed during initial and long-term ownership. Objective: This paper describes problems reported and technical assistance received by older adults who used PAMs during the 18 months they participated in a community-based PA trial: Ready Steady 3.0 (RS3). Methods: This was an ad-hoc longitudinal analysis of process variables representing technical problems reported and assistance received by 113 RS3 study participants in the 18 months after their orientation to PAMs. Variables included date of contact, problem(s) reported, mode of technical assistance, and whether the equipment was replaced. The descriptive analysis included frequencies and incidence rates of distinct contacts, types of problems, and technical assistance modes. Results: On average, participants were aged 77 (SD 5.2) years. Most identified as female (n=87, 77%), reported experience using smartphones (n=92, 81.4%), and used the PAM between 2 and 18 months. Eighty-two participants (72.6%) reported between 1 to 9 problems with using PAMs, resulting in a total of 150 technical assistance contacts with a mean of 1.3 (SD 1.3) contacts. The incidence rate of new, distinct contacts for technical assistance was 99 per 100 persons per year from 2018 to 2021. The most common problems were wearing the PAM (n=43, 28.7%), reading its display (n=23, 15.3%), logging into its app (n=20, 13.3%), charging it (n=18, 12%), and synchronizing it to the app (n=16, 10.7%). The modalities of technical assistance were in person (n=53, 35.3%), by telephone (n=51, 34%), by email (n=25, 16.7%), and by postal mail (n=21, 14%). Conclusions: In general, the results of this study show that after receiving orientation to PAMs, problems such as uncomfortable wristbands, difficulty using the PAM or its related app, and obtaining or interpreting relevant personal data were occasionally reported by participants in RS3. Trained staff helped participants troubleshoot and solve these technical problems primarily in person or by phone. Results also underscore the importance of involving older adults in the design, usability testing, and supportive material development processes to prevent technical problems for the initial and ongoing use of PAMs. Clinicians and researchers should further assess technical assistance needed by older adults, accounting for variations in PAM models and wear time, while investigating additional assistance strategies, such as proactive support, short GIF videos, and video calls.

Visual Search Strategies of Elite Fencers: An Exploratory Study in Ecological Competitive Situation.

This study investigates the visual activity of fencers in conditions resembling official competitions. Previous research in experimental conditions has shown that experts focus on specific areas of the torso and the armed arm to control movement initiation. Eight right-handed fencers (epee: two males, one female; foil: one male; sabre: two males, two females) participated in a simulated competition, wearing an eye tracker during one bout. The findings showed that the main fixation in foil and sabre is the upper torso, while in epee, it is the lower torso. In epee and sabre, the upper torso is viewed about 50% of the time, with three other areas also observed, while in foil, the fixation is totally directed to the upper torso. Additionally, two new areas of interest were identified: the score machine and an area involving fixations other than the opponent. The study found no direct link between visual activity and performance. The visual search strategy varies among weapons, with foil using a gaze anchor or foveal spot and epee and sabre utilizing a visual pivot due to the discipline's inherent rules. The study also emphasizes that competition-like conditions can disrupt visual activity with external stimuli, possibly affecting performance.

Dietary intake of preformed vitamin A and provitamin A carotenoids are not associated with serum retinol and carotenoid concentrations among children 36-59 months of age in rural Burkina Faso: a cross-sectional study.

PURPOSE: This study aimed to assess the association between dietary intake of preformed vitamin A (VA) and pro-VA carotenoids and serum retinol and carotenoid concentrations among 36-59-month-old children in a rural area in Burkina Faso. METHODS: Two community-based cross-sectional studies were conducted in a rural area of Burkina Faso and included 115 children aged 36-59 months. Dietary intake of preformed VA and pro-VA was assessed directly by 24-h dietary recall. Serum retinol and carotenoid (α- and ß-carotene, and ß-cryptoxanthin) concentrations were measured. The associations between serum retinol and carotenoid concentrations and their respective dietary intake were assessed by multiple linear regression. RESULTS: Geometric mean [95% CI] adjusted serum retinol concentration in children was 0.86 [0.81; 0.92] µmol/L. The prevalence of low adjusted serum retinol concentration (< 0.7 µmol/L) was 26.8%. Geometric mean [95% CI] serum carotenoid concentrations were: α-carotene (0.03 [0.02; 0.03] µmol/L), ß-carotene (0.14 [0.12; 0.16] µmol/L), and ß-cryptoxanthin (0.17 [0.15; 0.21] µmol/L). Dietary intakes of α- and ß-carotene and adjusted serum retinol and α-carotene concentrations were significantly higher during the rainy season. In multiple linear regressions, no associations were found between dietary intakes of preformed VA and pro-VA carotenoids and serum retinol and carotenoid concentrations in children aged 36-59 months in Burkina Faso. There was no effect of season on the associations between preformed VA and pro-VA carotenoids intake and serum retinol and carotenoid concentrations. CONCLUSIONS: This study shows that dietary intakes of preformed VA and pro-VA carotenoids based on 24-h dietary recall method cannot be used as proxy of serum retinol and carotenoid concentrations in this population. TRIAL REGISTRATION: The study was registered retrospectively (22 March 2018) as a clinical trial with the Pan African Clinical Trials Registry (Cochrane South Africa; PACTR201803002999356).

Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study.

BACKGROUND & AIMS: We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. METHODS: We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46. RESULTS: A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P = .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. CONCLUSIONS: Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression.

Temporal dynamics of geothermal microbial communities in Aotearoa-New Zealand.

Microbial biogeography studies, in particular for geothermal-associated habitats, have focused on spatial patterns and/or individual sites, which have limited ability to describe the dynamics of ecosystem behaviour. Here, we report the first comprehensive temporal study of bacterial and archaeal communities from an extensive range of geothermal features in Aotearoa-New Zealand. One hundred and fifteen water column samples from 31 geothermal ecosystems were taken over a 34-month period to ascertain microbial community stability (control sites), community response to both natural and anthropogenic disturbances in the local environment (disturbed sites) and temporal variation in spring diversity across different pH values (pH 3, 5, 7, 9) all at a similar temperature of 60-70°C (pH sites). Identical methodologies were employed to measure microbial diversity via 16S rRNA gene amplicon sequencing, along with 44 physicochemical parameters from each feature, to ensure confidence in comparing samples across timeframes. Our results indicated temperature and associated groundwater physicochemistry were the most likely parameters to vary stochastically in these geothermal features, with community abundances rather than composition more readily affected by a changing environment. However, variation in pH (pH ±1) had a more significant effect on community structure than temperature (±20°C), with alpha diversity failing to adequately measure temporal microbial disparity in geothermal features outside of circumneutral conditions. While a substantial physicochemical disturbance was required to shift community structures at the phylum level, geothermal ecosystems were resilient at this broad taxonomic rank and returned to a pre-disturbed state if environmental conditions re-established. These findings highlight the diverse controls between different microbial communities within the same habitat-type, expanding our understanding of temporal dynamics in extreme ecosystems.