Conectar
by Jeanette Alcaraz, Charlotte Keyse, Charles Hall, David W. Walker, David P. Doupé, Rebecca I. Clark
Inflammaging is considered a driver of age-associated pathology across tissues. Similarly, intestinal permeability is a feature of ageing and underlies a range of inflammatory and age-related diseases. Increased intestinal permeability has been described as both a cause and a consequence of inflammation. Both intestinal permeability and inflammation are closely associated with microbial dysbiosis, epithelial dysplasia and mortality but dissecting the complex interplay between these phenotypes remains challenging. Here we genetically induce intestinal immune activation in Drosophila and stratify animals by their intestinal barrier status using the Smurf assay. We demonstrate that intestinal barrier failure has a distinct impact on the microbiota. Further, immune activation, both within the intestine and systemically, drives intestinal barrier failure and mortality even in the absence of the microbiota. Importantly, immune-induced intestinal barrier failure takes time to develop and is closely associated with the onset of mortality. Our work adds to building evidence that the impact of intestinal permeability on the microbiota and on animal health needs to be considered independently of its relationship with inflammation.by John Paul G. Kolcun, Ricky M. Ditzel Jr, Bradley L. Kolb, Ricardo B. V. Fontes, P. B. Raksin
Study designRetrospective chart review.
ObjectiveDescribe safety/feasibility of implementing a novel clinical protocol for acute spinal cord injury (SCI) management.
Summary of background dataSpinal cord perfusion pressure (SCPP) has emerged as a promising target for the medical management of SCI patients. We report our early experience implementing a pragmatic SCPP-driven clinical protocol to supplant conventional mean arterial pressure (MAP) monitoring in the setting of acute SCI.
MethodsWe retrospectively reviewed charts of all SCI patients managed by our SCPP protocol since its adoption at two clinical sites as of 2/1/2023. The SCPP protocol was applied for all adult SCI patients of any injury grade, at any injury level with cord tissue involvement. Intrathecal pressure (ITP) was transduced by lumbar drain (LD). MAP was determined from invasive blood pressure recordings. SCPP was calculated as the difference between MAP and ITP, with an SCPP goal of >65mmHg.
ResultsEighteen patients have been treated since our SCPP protocol was adopted. Patients were predominately male (77.8%); the average age was 52.0 ± 16.2 years. Most injuries involved the cervical segment (72.2%), all of which were manifest clinically as central cord syndrome. The most common presenting injury severity was ASIA Impairment Scale D (44.4%).All patients underwent surgical intervention. There were no complications related to surgery, LD placement, or LD maintenance/ITP transduction during hospitalization. The SCPP protocol was continued for an average 5.2 ± 1.8 days. Eight patients required vasopressor support (44.4%) during that period, for an average 3.1 ± 2.1 days. Five patients underwent therapeutic CSF drainage to augment SCPP (27.8%). All patients maintained an average SCPP above goal for the duration of monitoring.
ConclusionsThis study further establishes the safety and feasibility of monitoring SCPP via LD measurement of ITP in acute SCI patients treated by clinical protocol at two clinical sites. There were no complications related to LD placement/maintenance or SCPP monitoring.
by Hao Ma, Fred M. Tatum, Robert E. Briggs, Rohana P. Dassanayake, Tasia M. Kendrick, Eduardo Casas
Pasteurella multocida is a pathogen that causes bovine respiratory disease, and the development of an effective vaccine is important for improving animal health. Live-attenuated vaccines induce a long-lasting immune response with minimal side effects. The objective of this study was to evaluate potential live vaccine candidates from three P. multocida mutants produced by separately disrupting the genes of filamentous hemagglutinin 2 (fhaB2), hydrogenase-1 operon (hyaE), and n-acylneuraminate-9-phosphatase (nanP) of a serogroup 3 strain (P1062, WT) by clinical testing and transcriptome analysis. Challenge with WT and the three mutants conferred protection against P. multocida, with less lung lesions (4.7–6.2%) compared to 22.4% in the sham group. Transcriptome analysis identified 807 differentially expressed protein-coding transcripts (DETs) in the blood and 6473 DETs in the liver compared to the sham, WT, and each of the mutants. In total, 15 and 64 differentially expressed microRNAs (DEmiRNAs) and 12 and 74 differentially expressed long non-coding RNAs (DElncRNAs) were identified in blood and liver, respectively. The DEmiRNAs were not significantly associated with the DETs within each comparison. DElncRNAs were associated with 12 and 170 DETs in blood and liver respectively. The greatest number of unique DETs were found between hyaE and sham groups in the liver, which agreed with the low colonization rate in the nares and palatine tonsils. For the DETs between sham and WT the under-enriched gene ontology terms in blood were all included in the liver for the DETs identified by WT vs. sham, nanP vs. sham, and hyaE vs. sham, and were related to the signaling pathway, stimulus, and sensory perceptions in biological processes with the molecular function of olfactory receptor activity. The number of identified DETs, decreased percentage of lung lesions, and colonization rates indicate that fhaB2 could be a promising vaccine candidate.by Fezile Wagner, Unathi Kolanisi, Ryan G. Wagner, Lerato P. Makuapane, Mxolisi Masango, Francesc Xavier Gómez-Olivé
The COVID-19 pandemic exacerbated hunger levels in South Africa, with an increase from 10% pre-pandemic to 23% during the pandemic. Pre-pandemic national and global research identified university students to be more vulnerable to hunger compared to the general population. This elevated risk is commonly associated with prevalent financial mismanagement in this group. However, research investigating the prevalence of hunger during the pandemic among this at-risk group is limited. This cross-sectional study aimed to assess the prevalence and determinants of hunger among students at a South African university during the COVID-19 lockdown, with particular focus on the effect of returning home. An online, self-administered survey produced a sample of 596 students. The Household Hunger Scale (HHS) was used to assess hunger. Most students (84%) who resided in on- or off-campus residences before the lockdown returned home during the lockdown. The weighted prevalence of hunger during lockdown was 16.4% (95%CI 13.6%, 19.6%). Bivariate analyses found living alone to be significantly associated with hunger, while multivariate analyses found that first-generation students (adjusted odds ratio (aOR) = 1.78; 95%CI: 1.04, 3.07, p = 0.015), financial aid recipients (aOR = 2.69; 95%CI: 1.47, 4.91, p = 0.001), and those experiencing financial stress/worry (aOR = 3.38; 95%CI: 1.85, 6.18, pby Prabhnoor Tuli, Abhay P. Kolte, Rajashri A. Kolte, Vrushali N. Lathiya, Vinisha A. Bajaj, Shahabe Saquib Abullais, Manea M. Alahmari
ObjectivesIn order to treat MAGRD in the maxillary anterior region, the VISTA approach was evaluated and compared with and without A-PRF.
Materials and methodsA split mouth RCT was designed with 216 MAGRD that were assigned to VISTA alone and VISTA with A-PRF. The complete root coverage (CRC) and gingival thickness (GT) were measured using CBCT at baseline and 12 months post-operatively, while the clinical parameters of probing depth (PD), clinical attachment level (CAL), width of keratinized gingival (WKG), gingival recession depth (GRD), and gingival recession width (GRW) were recorded at baseline, 6 months, and 12 months.
ResultsFrom baseline to 12 months, there was a significant decrease in the mean values of GRD and GRW with an increase in WKG. CBCT scans showed a significant increase in GT mean values. According to these results, the Test group’s CRC was higher (95.92%) than the Control groups (85.02%).
ConclusionsIn contrast to the Control group, the Test group demonstrated superior MAGRD resolution in achieving a decrease in GRD and GRW as well as a higher increase in WKG and GT. These findings resulted into a substantially more CRC for the Test group.
Trial registrationRegistration no. CTRI/2022/09/045845.Registered on: 26/09/2022
by Erica Qureshi, Quynh Doan, Jessica Moe, Steven P. Miller, Garth Meckler, Brett Burstein, Jehannine (J9) Austin
ObjectivesEmergency department (ED) to community (ED2C) programs, which redirect patients from the pediatric ED to community healthcare professionals represent a promising strategy to reduce the impact of non-urgent visits on the pediatric ED. Given an ED2C program’s potential impact on various care professionals, we completed a qualitative study to explore key informants’ attitudes and perceptions of pediatric ED2C programs.
MethodsWe conducted one-on-one semi-structured interviews with key informants in British Columbia, Canada. Participants included: pediatric ED staff – triage nurses and physicians; community professionals – pediatricians and family physicians; and health system leaders responsible for pediatric and emergency care in British Columbia. Interviews were recorded, transcribed verbatim, de-identified, and analyzed using reflexive thematic analysis within an interpretive description framework. A visual model was developed to depict key themes in attitudes and perceptions towards pediatric ED2C programs.
ResultsWe interviewed 24 participants: 6 community professionals, 11 pediatric ED professionals, and 7 healthcare leaders. Participants viewed the ED2C program as a valuable solution to address pediatric system strain provided that systemic barriers are addressed, and both emergency and community settings are equipped with adequate training and resources. Participants emphasized the need for clear guidelines on eligibility and operations to build confidence and enhance program effectiveness.
ConclusionsOur findings suggest there is support for ED2C programs as a means to reduce the impact of non-urgent pediatric ED visits and strengthen community-based care. Successful implementation will require coordinated planning, resource investment, and clear operational frameworks.
by Caitlin D. October, Dzunisani P. Baloyi, Lario Viljoen, Rene Raad, Dillon T. Wademan, Megan Palmer, Juli Switala, Michaile G. Anthony, Karen Du Preez, Petra De Koker, Anneke C. Hesseling, Bronwyne Coetzee, Graeme Hoddinott
Children who are hospitalised for tuberculosis (TB) experience challenges that put them at risk of developing emotional, behavioural, and social difficulties. In this methodological paper, we showcase the development of a narrative intervention toolkit with key components of the resulting version 1.0 tool. The study design was participatory and pragmatic, with researchers working with the routine staff of TB hospital wards, children admitted and their caregivers, to iteratively understand and improve children’s experiences of hospitalisation. The project included three phases: (1) a situational analysis to map children and healthcare providers’ perspectives on priorities and potential intervention components, (2) co-development of a beta-version of the intervention, and (3) piloting and incremental refinement toward a version 1.0 of the intervention. The intervention toolkit combined a series of activities alongside the story of ‘Courageous Curly’ to facilitate children’s engagement with their own experiences of hospitalisation, including psychosocial and treatment challenges, captured, and described throughout data collection. We found that dividing the story into short chapters facilitated children’s engagement with the section of story that is being told on a specific day. Each chapter of the story follows/mimics a different stage children can expect during their treatment journey while hospitalised for TB care. Implementation and evaluation of such interventions can mitigate the psychosocial impact of TB in children and inform policies to improve their overall TB care.by Claire A. MacGeorge, Matthew Henry, Hannah A. Ford, Lacy Malloch, Emily Fratesi, Shannon Cabaniss, Jaime Baldner, Melody Greer, Kristin Gaffney, Milan Bimali, Preetha Abraham, Linda Y. Fu, P. Songthip Ounpraseuth, Christine B. Turley
BackgroundAttention-deficit/hyperactivity Disorder (ADHD) is the most common neurobehavioral condition of childhood and can be controlled with stimulant medication. Evidence-based guidelines endorse use of standardized ADHD symptom reports to facilitate medication titration to therapeutic dosage. Children living in under-resourced areas experience barriers to receiving this recommended evidence-based care. The Remote ADHD Monitoring Program (RAMP) uses a text-based platform to relay symptom reports from caregivers and teachers to healthcare providers. This pilot study is a feasibility study examining intervention uptake. It compares the submission of structured symptom reports in those children enrolled in RAMP compared to usual care as well as utilization of the RAMP platform by providers.
MethodsThis paper describes the protocol to evaluate the feasibility of deploying RAMP in practices serving rural or underserved children. We will recruit 36 dyads from 4 practices in 2 separate states. Each dyad will include a caregiver and their child aged 5–11 years with a diagnosis of ADHD who is starting or reinitiating stimulants. Dyads will be randomized 1:1 to receive the RAMP intervention or usual care with attention controls. Our primary outcome is number of symptom reports (paper assessments in control arm and RAMP reports in intervention arm) per participant that are completed by caregivers and teachers and returned to providers. Our secondary outcome is proportion of submitted RAMP reports that are reviewed by providers.
DiscussionAs telehealth use increases, it is critical that we improve access to high quality care for children with chronic conditions. Leveraging technology may be a meaningful approach to improve efficiency in optimizing medication management. This pilot study tests a text-based platform designed to improve communication between the caregivers and teachers of children with ADHD and health care providers. If successful, a future trial will examine the effectiveness of the RAMP intervention on improvement in symptoms.
Trial registrationClinicalTrials.gov NCT06743425.
by Carly E. Hawkins, Thomas P. Hahn, Jessica L. Malisch, Gail L. Patricelli
Males in socially monogamous species can achieve reproductive success through multiple tactics– by defending paternity within the social nest and siring extra-pair offspring, or both. Previous studies have found that sperm morphology may differentially affect fertilization success in extra-pair compared to within-pair matings; therefore, we explored whether sperm morphological traits can predict the probability of success within components of reproductive success. Here, we measured sperm component traits (head length and flagellum length) and derived traits (total length and flagellum:head ratio) in free-living Mountain White-crowned Sparrows (Zonotrichia leucophrys oriantha) and examined how these morphological traits relate to extra-pair and within-pair reproductive components of reproductive success. We found no evidence for correlations between sperm morphology and total seasonal reproductive success. However, we did find that sperm morphology appeared to be associated with whether a male was successful at acquiring extra-pair offspring or defending his own paternity within his nest: males that achieved extra-pair success had longer flagella and longer total length of sperm cells compared to males that did not sire outside of their social nest. In contrast, males that successfully defended all paternity within their social nest tended to have shorter heads and larger flagellum:head ratios compared to males that lost paternity in their social nest. While these patterns suggest that different sperm traits may be linked to success in different components of reproductive success, they should be interpreted with caution given the exploratory nature of this study and limited sample size, and further investigation is warranted.by Nadeen Ibrahim, Shaifer Jones, Katherine Rich, Lisandra Alvarez, Carolina Price, Natalie Kil, Frederick L. Altice, Jaimie P. Meyer
BackgroundPeople who inject drugs (PWID) experience high risk for HIV and HCV infection, which can be mitigated by harm reduction strategies, including syringe service programs (SSP). Understanding individuals’ patterns of substance use and SSP utilization is important for optimizing harm reduction strategies and disease prevention for PWID.
MethodsWe evaluated demographic characteristics and service utilization from the New Haven Syringe Services Program (NHSSP), a low-threshold service delivery site in New Haven, Connecticut that provides fully integrated harm reduction and primary healthcare services to PWID. Site-specific data were extracted from the e2ctprevention database, managed by the Connecticut Department of Public Health, and EvaluationWeb from January 2017 to October 2023. We conducted a descriptive analysis of basic demographic and social characteristics of SSP clients, transaction characteristics, and service utilization. Statistical analyses were conducted using STATA v 16.1 and IBM SPSS Statistics (v 29.0.2.0).
ResultsAmong 1,189 unique individuals utilizing SSP during the observation period, most (65.2%) identified as men and white (73.3%), consistent with SSP clients regionally and nationally. The mean age of clients was 41 years (SD = 9.8); approximately half of participants were unstably housed and 80% were unemployed at intake. From June 2020 to October 2023, there were 7,238 transactions, which increased throughout the COVID-19 pandemic period. During this period, the program dispensed 1,860,621 syringes, in addition to other materials, including overdose education and naloxone distribution (OEND), and provided patient education on safer injecting techniques and wound care.
ConclusionIn this first comprehensive analysis of a large SSP since its inception and through the COVID-19 pandemic, we described important client characteristics and utilization of an array of syringe services from an integrated SSP. Findings suggest the SSP attracts a high volume of clients, provides on-demand services, and reaches a wide range of clients. Future research is needed to evaluate the impact of the program’s home-delivery service and increased outreach efforts. Despite limitations, the program’s success demonstrates the SSP can serve as a model for other harm reduction programs nationally.
by Joseph E. Rubin, Florence Huby, Roshan P. Madalagama, Shyamali de Alwis, Melinda Wyshynski, Rasika Jinadasa
The ability to prepare sterilized media is a critical capability of any microbiology lab. Diagnostic labs in low-resource settings, which lack autoclave facilities, are therefore severely limited in their ability to perform basic assays such as bacterial culture or biochemical tests. This investigation aimed to validate the use of a commercially available pressure cooker as an autoclave substitute to produce agar plates. First, a Geobacillus stearothermophilus biological indicator was used to confirm adequate sterilization. Next, the colony morphology of several important bacterial species were compared on MacConkey and 5% sheep’s blood agar plates prepared using the pressure cooker with those made in an autoclave. Finally, disc diffusion susceptibility testing was performed to determine whether the sterilization method impacts the inhibitory zone diameters. Overall, the morphology of colonies was similar on media prepared in both ways; key phenotypic characteristics (lactose fermentation, colour, shape, hemolysis and smell) were the same. Kirby-Bauer disc diffusion test results were nearly identical. These findings indicate that a commercially available pressure cooker may be suitable to prepare media in low-resource laboratories.
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