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Abstract Background Community Health Workers locally known as Village Health Workers (VHW) in Lesotho are key members of the primary health workforce, and has been playing a significant role in building primary health systems in many countries and they can fill significant gaps in human resources as low and middle income countries work towards universal health coverage in the era of Sustainable Development Goals (SDGs). The 2014 Lesotho health reform restructured the VHW program to compensate, professionalize, and integrate VHWs into primary care services. We sought to document the ways in which the VHW program changed as a result of the health reform and the perceived impact of those changes. Methods In 2018, we conducted a qualitative research study with an inductive content analysis approach in the four pilot health reform districts of Lesotho. We conducted 26 in-depth interviews with health workers practicing in the community and in primary health facilities, as well as district health authorities, and Ministry of Health officials. Results We found that the Lesotho health reform program was observed that it helped to professionalize the VHW program by introducing clear roles and responsibilities, regular monitoring, and supervision. The initiation of performance-based payment of VHWs and regular monitoring and reporting was thought contribute to overall improvement; in performance, strengthened links between communities and facilities, and promoted uptake of services. Conclusion The Lesotho Health Reform program was felt to be highly effective in re-structuring the VHW program in Lesotho, suggesting that when VHWs are well-incentivized, monitored, and supervised they can better fulfil their essential role as the backbone of the primary health workforce.

Abstract Background Pediatric depression is a global concern that has fueled efforts for enhanced detection and treatment engagement. As one example, the US Preventive Services Task Force recommends depression screening for adolescents ages 12–18 years. While many health systems have implemented components of depression screening protocols, there is limited evidence of effective follow-up for pediatric depression. A key barrier is timely team communication and coordination across clinicians and staff within and across service areas for prompt service linkage. However, team effectiveness interventions have been shown to improve team processes and outcomes and can be applied in healthcare settings. Methods This project aims to refine and test a team communication training implementation strategy to improve implementation of an existing pediatric depression screening protocol in a large pediatric healthcare system. The team will be defined as part of the study but is expected to include medical assistants, nurses, physicians, and behavioral health clinicians within and across departments. The implementation strategy will target team mechanisms at the team-level (i.e., intra-organizational alignment and implementation climate) and team member-level (i.e., communication, coordination, psychological safety, and shared cognition). First, the project will use mixed methods to refine the team training strategy to fit the organizational context and workflows. Next, a hybrid type 3 implementation-effectiveness pilot trial will assess the initial effectiveness of the team communication training (implementation strategy) paired with the current universal depression screening protocol (clinical intervention) on implementation outcomes (i.e., feasibility, acceptability, appropriateness, workflow efficiency) and clinical/services outcomes (increased frequency of needed screening and reduced time to service linkage). Finally, the study will assess mechanisms at the team and team member levels that may affect implementation outcomes. Discussion Team communication training is hypothesized to lead to improved, efficient, and effective decision-making to increase the compliance with depression screening and timely service linkage. Findings are expected to yield better understanding and examples of how to optimize team communication to improve efficiency and effectiveness in the pediatric depression screening-to-treatment cascade. This should also culminate in improved implementation outcomes including patient engagement critical to address the youth mental health crisis. Trial registration NCT06527196. Trial Sponsor: University of California San Diego.

ObjectiveTranscranial direct current stimulation (tDCS), a non-invasive, painless method of applying direct current electrical stimulation to specific areas of the brain, is an effective method for enhancing attention and post-stroke fatigue, as shown by behavioral improvements in post-stroke populations. While behavioral evidence supports this method, there is a paucity of physiological data corroboration of this improvement. The current study is designed to investigate if a single session of tDCS will improve attention and fatigue as shown by relevant physiological methods in persons with post-stroke aphasia.MethodsTen participants (5 male; mean age: 62.8) engaged in two identically structured data collection sessions with at least a 3-day wash-out period between them. Sessions started with a sustained attention task with simultaneous electroencephalography (EEG) and pupillometry data collection, followed by an attention training program with simultaneous active or sham tDCS. Following tDCS, participants repeated the sustained attention task with simultaneous EEG and pupillometry data collection. Participants received active tDCS during one session, and sham tDCS during the other, with the order randomized.ResultsNo differences between conditions were found for either behavioral results from the sustained attention task (i.e., reaction time of correct responses; n = 9 p = 0.39) or EEG measured attention state data for any of the four attention states: no attention (n = 10, p = 0.83), distracted attention (n = 10, p = 0.20), moderate attention (n = 10, p = 0.95), or high attention (n = 10, p = 0.62). Pupil dilation was significantly greater in the post-active tDCS stimulation condition than in either pre-training condition (n = 10, p

Glucocorticosteroids remain the most common pharmaceutical approach for the treatment of equine asthma but can be associated with significant side effects, including respiratory microbiome alterations. The goal of the study was to assess the impact of 2% lidocaine nebulization, a projected alternative treatment of equine asthma, on the healthy equine respiratory microbiota. A prospective, randomized, controlled, blinded, 2-way crossover study was performed, to assess the effect of 1 mg/kg 2% lidocaine (7 treatments over 4 days) on the equine respiratory microbiota compared to control horses (saline and no treatment). Clinical assessments and respiratory samples, including nasal wash, endoscopic tracheal aspirate and bronchoalveolar lavage fluid, were obtained at each sample collection timepoint. The profile of the respiratory bacterial microbiota was evaluated using 16S amplicon sequencing, and clinical data compared using related samples analyses, based on data normality. The treatment did not affect the clinical data or alter the tracheal and nasal microbiota in healthy horses. However, time explained 12.6% of microbiota variation among samples. A significant difference in bacterial composition was observed between nasal and tracheal samples, showing the greatest relative abundance of Actinobacteria and Firmicutes, respectively. Bacterial DNA from bronchoalveolar lavage fluid did not amplify with generic primers targeting the V4 variable region of the prokaryotic small subunit ribosomal RNA gene, despite attempting multiple DNA extraction methods and PCR protocols, and after excluding PCR inhibition. This observation indicates that bronchoalveolar lavage fluid of healthy horses has a low bacterial load.

Hepatitis C (HCV) disproportionately affects people who inject drugs (PWID). Despite availability of safe and effective treatment, HCV treatment access and uptake among PWID in low- and middle-income countries (LMICs) has been limited. Understanding the lived experiences of PWID in these settings who have undergone treatment provides the opportunity to gain insight into how to implement treatment programs that meet the needs of this population. Using Rhodes' Risk Environment Framework to guide our work, we conducted semi-structured interviews with 35 PWID who received HCV treatment in methadone clinics and drop-in-centers (DICs) in Nairobi and coastal Kenya supported by peer case managers from August to September 2019. Translated and transcribed interviews were analyzed thematically. Three overarching themes emerged in our thematic analysis: 1) Financial constraints as a barrier to HCV treatment, 2) HCV-related stigma, and 3) HCV treatment impacts on health and risk behaviors. These data signal unique challenges faced by PWID seeking HCV treatment in this LMIC setting and highlight the importance of interventions to reduce barriers to treatment. In order for positive treatment outcomes to be sustained, HCV treatment programs must address the barriers patients face at multiple levels and implement system-level changes.

Abstract Background The minority of people with an eating disorder receive treatment. Little is known about predictors of receiving treatment. Methods Using data from the Growing Up Today Study we identified correlates of receiving treatment for an eating disorder among the 1237 U.S. women who answered questions on treatment history in 2013 and reported meeting criteria for subthreshold eating disorder in ≥ 1 year between 1996 and 2013. Logistic regression models using generalized estimating equations were used to estimate the relative odds of receiving treatment. Results Approximately 11% of the women reported receiving treatment for an eating disorder. Independent of type of eating disorder, those who had received a diagnosis of depression or anxiety were more likely (odds ratio (OR) = 3.05 95% confidence interval (CI) 1.87–4.97) to receive treatment for an eating disorder. Women with obesity were approximately 85% less likely to receive treatment (OR = 0.13, 95% CI 0.04–0.46) regardless of their type of eating disorder or history of depression of anxiety diagnosis. Conclusions Most women meeting criteria for an eating disorder do not receive treatment. Women with BED or obesity are the least likely to receive treatment.

It has been demonstrated that helminths are capable of critically impacting the fitness of their hosts. This has typically been shown experimentally through the administration of anthelmintic drugs but are rarely performed on a landscape or host population scale. Here, the anthelmintic fenbendazole (FBZ) was mixed in a supplemental feed and provided to a free-ranging population of Northern bobwhite quail (Colinus virginianus). Abundances of Northern bobwhite and two nematode parasites commonly found infecting Northern bobwhite were monitored and compared to a neighboring untreated population. The Northern bobwhite population receiving the medicated feed grew substantially from 2019 to 2022, while the neighboring site had no change in abundance. The treated population was also substantially greater than the untreated population in 2021 and 2022. Additionally, the treated Northern bobwhite population had substantially lower abundances of the two nematodes. This research provides evidence of the ability of helminth populations to have a negative impact on Northern bobwhite populations and presents a method for reducing helminth abundance in those populations on a landscape scale.

Digestive health is an overlooked but vital component of the success of Western honey bee (Apis mellifera) colonies. Viral, bacterial, fungal, and protozoal infections can inhibit nutrient uptake and waste elimination by the honey bee digestive tract. Active management requires monitoring honey bee health on an individual and colony basis, providing adequate nutrition, and controlling for other pests and diseases. One organism that has gained recent attention is Malpighamoeba mellificae. This publication describes how to detect M. mellificae in A. mellifera colonies.

Atmospheric hydrogen concentrations have been increasing in recent decades. Hydrogen is radiatively inert, but it is chemically reactive and exerts an indirect radiative forcing through chemistry that perturbs the concentrations of key species within the troposphere, including ozone. Using the atmospheric version of the United Kingdom Earth System Model, we analyse the impact of 10% increased surface concentrations of hydrogen on ozone production and loss. We also analyse the impact of this hydrogen in atmospheres with lower anthropogenic emissions of nitrogen oxides (80% and 30% of present-day anthropogenic surface emissions), as this is a likely outcome of the transition from fossil fuels towards cleaner technologies. In each case, we also assess the changes in hydroxyl radical concentration and hence methane lifetime and calculate the net impact on the hydrogen tropospheric global warming potential (GWP). We find that the hydrogen tropospheric GWP100 will change relatively little with decreases in surface anthropogenic NOx emissions (9.4 and 9.1 for our present day and 30% anthropogenic emissions, respectively). The current estimate for hydrogen GWP100 can therefore be applied to future scenarios of differing NOx, although this conclusion may be impacted by future changes in emissions of other reactive species.

Summary:. Onycholysis secondary to nail bed scarring can be a challenging problem for hand surgeons, given the relatively few techniques available for nail bed lengthening. Here, we present the case of a patient with upper extremity onycholysis, secondary to porphyria cutanea tarda. We used a technique first described by Lemperle et al in 2003 to successfully lengthen the nail bed and improve the appearance of the nail plate. This involved full-thickness excision of a crescent-shaped wedge of the distal nail bed in all five right sided digits in a single operation. We found this technique to be simple and effective, meeting our patient’s goals after just one excision.

Abstract The dependence of Cryptosporidium parasites on host cell metabolites suggests that the development of nutritional interventions to limit parasite proliferation should be feasible. Based on this concept, we are testing dietary interventions to affect the enterocytes’ metabolism in a manner that limits intracellular multiplication of the parasite. We hypothesize that changes in the metabolic pathways encoded by the gastro-intestinal tract microbiota may restrict parasite proliferation. To identify taxonomic and metabolic features of the microbiota associated with severity of cryptosporidiosis, as determined by estimating oocyst output, we characterized the fecal microbiota from mice experimentally infected with Cryptosporidium parvum. To eliminate the confounding effect of the interaction between co-housed mice, as well as facilitate the identification of microbiota markers associated with severity of cryptosporidiosis, fecal microbiota from individually caged mice were analyzed. Variation partitioning analysis applied to 16S sequence data from 25 mice belonging to four experiments shows that experiment was by far the biggest source of microbiota variation. Severity of cryptosporidiosis explained a smaller, though significant, fraction of microbiota variation. Notably, this effect was significant in the pre-patent phase of the infection, before mice excreted oocysts. These results are consistent with the pre-patent intestinal microbiota having a modest, but measurable, effect on cryptosporidiosis.

Introduction Neonatal mortality is a global public health challenge. Guatemala has the fifth highest neonatal mortality rate in Latin America, and Indigenous communities are particularly impacted. This study aims to understand factors driving neonatal mortality rates among Maya Kaqchikel communities.Methods We used sequential explanatory mixed methods. The quantitative phase was a secondary analysis of 2014–2016 data from the Global Maternal and Newborn Health Registry from Chimaltenango, Guatemala. Multivariate logistic regression models identified factors associated with perinatal and late neonatal mortality. A number of 33 in-depth interviews were conducted with mothers, traditional Maya midwives and local healthcare professionals to explain quantitative findings.Results Of 33 759 observations, 351 were lost to follow-up. There were 32 559 live births, 670 stillbirths (20/1000 births), 1265 (38/1000 births) perinatal deaths and 409 (12/1000 live births) late neonatal deaths. Factors identified to have statistically significant associations with a higher risk of perinatal or late neonatal mortality include lack of maternal education, maternal height

Objective: Buprenorphine is an evidence-based treatment for opioid use disorder that is underused in the emergency department (ED). In this study we evaluated changes in emergency physician knowledge, confidence, and self-efficacy regarding buprenorphine prescribing and working with patients who use drugs after implementation of an ED buprenorphine quality improvement (QI) initiative. Methods: An anonymous, online survey was administered to emergency physicians staffing four EDs in New England in 2019 and 2020 before and after an ED QI initiative. Survey questions included novel and previously validated questions to assess confidence, knowledge, self-efficacy, and attitudes about buprenorphine and working with patients who use drugs. Confidence, self-efficacy, and attitude responses were assessed on a Likert scale. Participants received a gift card for survey completion. We analyzed pre- and post- survey responses descriptively and compared them using t-tests. Using logistic regression we evaluated the factors associated with buprenorphine prescribing. Results: Of 95 emergency physicians, 56 (58.9% response rate) completed the pre-intervention survey and 60 (63.2%) completed the post-survey. There was an increase in the number of X-waivered adult emergency physicians and ED buprenorphine prescribing after program implementation. Physician confidence increased from a mean of 3.4 (SD 0.8) to 3.9 (SD 0.7; scale 1–5, p

Abstract Individuals seeking support or inspiration for eating disorder recovery may turn to pro-recovery content on social media sites such as TikTok. While research has thus far treated pro-recovery social media as a fairly homogeneous space, many pro-recovery hashtags single out particular eating disorder diagnoses. This exploratory study used codebook thematic analysis of 241 popular pro-recovery videos on TikTok to compare the presentation of eating disorders and eating disorder recovery across five different diagnosis-specific hashtags: #anarecovery, #arfidrecovery, #bedrecovery, #miarecovery, and #orthorexiarecovery. These hashtags refer to the following eating disorder diagnoses respectively: anorexia nervosa, avoidant restrictive food intake disorder, binge eating disorder, bulimia nervosa, and orthorexia nervosa. Our analysis generated the following qualitative themes across the entire dataset: (1) centrality of food to eating disorders and recovery, (2) what eating disorders look and feel like, (3) recovery as a process, (4) getting and giving help, and (5) negotiating diet culture in recovery. To supplement our qualitative findings and facilitate cross-diagnostic comparisons, we also conducted one-way ANOVAs and chi-square tests to probe for statistically significant differences in audience engagement and code prevalence across the different hashtags. Our results indicate that there are clear differences in how recovery is envisioned on TikTok based on which diagnostic hashtags are employed. Such variations in how different eating disorders are imagined on popular social media demand further investigation and clinical consideration.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Objective To retrospectively analyse routinely collected data on the drivers and barriers to retention in chronic care for patients with hypertension in the Kono District of Sierra Leone.Design Convergent mixed-methods study.Setting Koidu Government Hospital, a secondary-level hospital in Kono District.Participants We conducted a descriptive analysis of key variables for 1628 patients with hypertension attending the non-communicable disease (NCD) clinic between February 2018 and August 2019 and qualitative interviews with 21 patients and 7 staff to assess factors shaping patients’ retention in care at the clinic.Outcomes Three mutually exclusive outcomes were defined for the study period: adherence to the treatment protocol (attending >80% of scheduled visits); loss-to-follow-up (LTFU) (consecutive 6 months of missed appointments) and engaged in (but not fully adherent) with treatment (

Salmon is the most commonly consumed finfish in the United States of America (USA), and the mislabeling of salmon is a widespread problem. Washington State is a global supplier of wild-caught Pacific salmon and local salmon mislabeling results in substantial economic, ecological, and cultural impacts. Previous studies in Washington State identified high levels of mislabeled salmon in both markets and restaurants, resulting in local legislation being passed that requires proper labeling of salmon products, including identifying it as wild-caught or farm-raised. To investigate whether recent legislative efforts reduced salmon fraud rates, we acquired and genetically barcoded salmon samples from 67 grocery stores and 52 sushi restaurants in Seattle, Washington. DNA from each salmon sample was isolated and the cytochrome c oxidase gene was sequenced to identify the fish species. Our study, conducted from 2022-2023, revealed 18% of salmon samples from both grocery stores and sushi restaurants were mislabeled. While most samples were acquired during the fall months when wild salmon is in season, we still observed a high salmon mislabeling rate. Unlike grocery stores, Seattle sushi restaurants often sold farmed salmon mislabeled as wild salmon. Specifically, substitutions of vendor-claimed wild salmon with farmed salmon occurred in 32.3% of sushi restaurant samples compared to 0% of grocery store samples. Additionally, occurrences of wild salmon being substituted with another salmon species (wild or farmed) occurred in 38.7% of sushi restaurant samples compared to 11.1% of grocery store samples. All salmon substitutions in sushi restaurants harmed the customer financially as they were given a cheaper market-priced fish. In grocery stores, however, we did not detect significant economic loss to customers due to salmon mislabeling. Taken together, it is important to continue to develop and enforce legislation in Washington State that prevents salmon fraud and promotes ecologically sustainable fishing practices.

We present the localization and host galaxy of FRB 20190208A, a repeating source of fast radio bursts (FRBs) discovered using CHIME/FRB. As part of the Pinpointing REpeating ChIme Sources with EVN dishes repeater localization program on the European VLBI Network (EVN), we monitored FRB 20190208A for 65.6 hr at ∼1.4 GHz and detected a single burst, which led to its very long baseline interferometry localization with 260 mas uncertainty (2 σ ). Follow-up optical observations with the MMT Observatory ( i ≳ 25.7 mag (AB)) found no visible host at the FRB position. Subsequent deeper observations with the Gran Telescopio Canarias, however, revealed an extremely faint galaxy ( r = 27.32 ± 0.16 mag), very likely (99.95%) associated with FRB 20190208A. Given the dispersion measure of the FRB (∼580 pc cm ^−3 ), even the most conservative redshift estimate ( ${z}_{\max }\sim 0.83$ ) implies that this is the lowest-luminosity FRB host to date (≲10 ^8 L _⊙ ), even less luminous than the dwarf host of FRB 20121102A. We investigate how localization precision and the depth of optical imaging affect host association and discuss the implications of such a low-luminosity dwarf galaxy. Unlike the other repeaters with low-luminosity hosts, FRB 20190208A has a modest Faraday rotation measure of a few tens of rad m ^−2 , and EVN plus Very Large Array observations reveal no associated compact persistent radio source. We also monitored FRB 20190208A for 40.4 hr over 2 yr as part of the Extragalactic Coherent Light from Astrophysical Transients repeating FRB monitoring campaign on the Nançay Radio Telescope and detected one burst. Our results demonstrate that, in some cases, the robust association of an FRB with a host galaxy will require both high localization precision and deep optical follow-up.

Animal behavior is a useful way to evaluate the environment and can be a predictive tool to assess not only the effects of treatments in a laboratory setting, but also the status of ecological habitats. As invasive species of crayfish encroach on territories of native species, the social behaviors and interactions can be informative for ecological studies. For a wider and more impactful effect, training community scientists using a scoring system to record the social interactions of crayfish that includes both the level of aggression and intensity would provide useable data to monitor the environment. Amateur scientists with little training were fairly reliable in their average scoring of the crayfish and the maximum behavior score with an expert as well as among themselves. However, the number of interactions was not as a reliable metric to compare with the expert or just among the amateurs.

Abstract Dysregulation of cellular metabolism is a hallmark of breast cancer progression and is associated with metastasis and therapeutic resistance. Here, we show that the breast tumor suppressor gene SIM2 promotes mitochondrial oxidative phosphorylation (OXPHOS) using breast cancer cell line models. Mechanistically, we found that SIM2s functions not as a transcription factor but localizes to mitochondria and directly interacts with the mitochondrial respiratory chain (MRC) to facilitate functional supercomplex (SC) formation. Loss of SIM2s expression disrupts SC formation through destabilization of MRC Complex III, leading to inhibition of electron transport, although Complex I (CI) activity is retained. A metabolomic analysis showed that knockout of SIM2s leads to a compensatory increase in ATP production through glycolysis and accelerated glutamine-driven TCA cycle production of NADH, creating a favorable environment for high cell proliferation. Our findings indicate that SIM2s is a novel stabilizing factor required for SC assembly, providing insight into the impact of the MRC on metabolic adaptation and breast cancer progression.

The cooperative activity of two proximal metal ions is well-known to exhibit highly efficient and synergistic catalytic activities in living organisms. Owing to this knowledge, tandem Cu–Zn systems have been widely used to catalyze a diversity of chemical transformations. This report describes the use of CuI and zinc dust as a sustainable tandem catalyst for the preparation of propargylamines via a three-component coupling reaction under neat conditions. This reaction proceeds at low temperature, and produces good yields with a number of aliphatic and aromatic aldehydes. The reactivity of a number of amines and alkynes has also been explored under these reaction conditions, resulting in 33 fully characterized compounds prepared in the process. Among the ketones tested during this study, only cyclohexanone was able to produce the expected product in a decent yield. The catalytic system reported here represents one of the sustainable approaches to the preparation of propargylamines, as it involves the use of naturally abundant metals as a tandem catalyst, at a low temperature and under neat conditions.

Introduction: The recreational use of fentanyl in combination with xylazine (i.e., “tranq-dope”) represents a rapidly emerging public health threat characterized by significant toxicity and mortality. This study quantified the interactions between these drugs on lethality and examined the effectiveness of potential rescue medications to prevent a lethal overdose.Methods: Male and female mice were administered acute doses of fentanyl, xylazine, or their combination via intraperitoneal injection, and lethality was determined 0.5, 1.0, 1.5, 2.0, and 24 h after administration. Both fentanyl and xylazine produced dose-dependent increases in lethality when administered alone.Results: A nonlethal dose of fentanyl (56 mg/kg) produced an approximately 5-fold decrease in the estimated LD50 for xylazine (i.e., the dose estimated to produce lethality in 50% of the population). Notably, a nonlethal dose of xylazine (100 mg/kg) produced an approximately 100-fold decrease in the estimated LD50 for fentanyl. Both drug combinations produced a synergistic interaction as determined via isobolographic analysis. The opioid receptor antagonist, naloxone (3 mg/kg), but not the alpha-2 adrenergic receptor antagonist, yohimbine (3 mg/kg), significantly decreased the lethality of a fentanyl-xylazine combination. Lethality was rapid, with death occurring within 10 min after a high dose combination and generally within 30 min at lower dose combinations. Males were more sensitive to the lethal effects of fentanyl-xylazine combinations under some conditions suggesting biologically relevant sex differences in sensitivity to fentanyl-xylazine lethality.Discussion: These data provide the first quantification of the lethal effects of “tranq-dope” and suggest that rapid administration of naloxone may be effective at preventing death following overdose.

Oxyspirura petrowi is a heteroxenous nematode that infects the harderian gland and other ocular tissues in birds. High-intensity infections often cause damage to the infected tissues. Due to the nature of the infection sites, treatment of O. petrowi in these hosts can be difficult. Fenbendazole (FBZ) is a common anthelmintic used to treat birds for helminth infections; however, little information exists as to the efficacy of the drug on O. petrowi infections. The present study aims to estimate lethal concentrations of FBZ to O. petrowi. Adult O. petrowi were maintained in vitro and exposed to doses of 5, 50, 100, and 200 µM concentrations of FBZ and included both negative and vehicle controls. Exposure lasted 7.5 days and lethality was determined for each treatment. Negative and vehicle controls did not differ, and both had 75% survival at the end of the treatment period. The percentage survivorship in ascending order of concentration, corrected for the controls, was 66.67%, 44.44%, 33.33%, and 0%. LC10, LC50, and LC90 estimates were 7.5 ± 0.26, 49.1 ± 1.69, and 163.2 ± 5.63 µM, respectively. In the context of known pharmacokinetics of FBZ in birds, a single oral dose of FBZ can achieve exposure levels that are lethal to O. petrowi, but the drug does not stay in the system long enough. Thus, treatment of O. petrowi infections will require multiple oral doses over several days.

The resting membrane potential enables neurons to rapidly initiate and conduct electrical signals. K2p channels are key in maintaining this membrane potential and electrical excitability. They direct the resting membrane potential toward the K+ equilibrium potential. Doxapram is a known blocker for a subset of K2p channels that are pH sensitive. We assessed the effects of 0.1 and 5 mM doxapram on the neural activity within the propodite-dactylopodite (PD) proprioceptive sensory organ in the walking legs of blue crabs (Callinectes sapidus). Results indicate that 0.1 mM doxapram enhances excitation, while the higher concentration 5 mM may over-excite the neurons and promote a sustained absolute refractory period until the compound is removed. The effect of 5 mM doxapram mimics the effect of 40 mM K+ exposure. Verapamil, another known K2p channel blocker as well as an L-type Ca2+ channel blocker, reduces neural activity at both 0.1 and 5 mM. Verapamil may block stretch activated channels in sensory endings, in addition to reducing the amplitude of the compound action potential with whole nerve preparations. These findings are notable as they demonstrate that doxapram has acute effects on neurons of crustaceans, suggesting a targeted K2p channel. The actions of verapamil are complex due to the potential of affecting multiple ion channels in this preparation. Crustacean neurons can aid in understanding the mechanisms of action of various pharmacological agents as more information is gained.

There is a genetic component to the risk of severe COVID-19, but the genetic effects are difficult to separate from social constructs that covary with genetic ancestry. To address this, the authors identify determinants of COVID-19 severity using admixture mapping, viral phylodynamics, and host immune and metagenomic sequencing.

Streptococcus pneumoniae is capable of randomly switching their genomic DNA methylation pattern between six distinct bacterial subpopulations (A-F) via recombination of a type 1 restriction-modification locus, spnIII. These pneumococcal subpopulations exhibit phenotypic changes which favor carriage or invasive disease. In particular, the spnIIIB allele has been associated with increased nasopharyngeal carriage and the downregulation of the luxS gene. The LuxS/AI-2 QS system represent a universal language for bacteria and has been linked to virulence and biofilm formation in S. pneumoniae. In this work, we have explored the link between spnIII alleles, the luxS gene and virulence in two clinical pneumococcal isolates from the blood and cerebrospinal fluid (CSF) of one pediatric meningitis patient. The blood and CSF strains showed different virulence profiles in mice. Analysis of the spnIII system of these strains recovered from the murine nasopharynx showed that the system switched to different alleles commensurate with the initial source of the isolate. Of note, the blood strain showed high expression of spnIIIB allele, previously linked with less LuxS protein production. Importantly, strains with deleted luxS displayed different phenotypic profiles compared to the wildtype, but similar to the strains recovered from the nasopharynx of infected mice. This study used clinically relevant S. pneumoniae strains to demonstrate that the regulatory network between luxS and the type 1 restriction-modification system play a key role in infections and may support different adaptation to specific host niches.

Acanthamoeba species, Naegleria fowleri, and Balamuthia mandrillaris are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.0. Herein, we report the activity of the compounds against the trophozoite stage of each of the three amoebae, ranging from nanomolar to low micromolar potency. The most potent compounds that were identified from this screening effort were: 2d (A. castellanii EC50: 0.92 ± 0.3 μM; and N. fowleri EC50: 0.43 ± 0.13 μM), 1c and 2b (N. fowleri EC50s:

Understanding the interactions between SARS-CoV-2 and host cell machinery may reveal new targets to treat COVID-19. We focused on an interaction between the SARS-CoV-2 ORF3A accessory protein and the CLIC-like chloride channel-1 (CLCC1). We found that ORF3A partially co-localized with CLCC1 and that ORF3A and CLCC1 could be co-immunoprecipitated. Since CLCC1 plays a role in the unfolded protein response (UPR), we hypothesized that ORF3A may also play a role in the UPR. Indeed, ORF3A expression triggered a transcriptional UPR that was similar to knockdown of CLCC1. ORF3A expression in 293T cells induced cell death and this was rescued by the chemical chaperone taurodeoxycholic acid (TUDCA). Cells with CLCC1 knockdown were partially protected from ORF3A-mediated cell death. CLCC1 knockdown upregulated several of the homeostatic UPR targets induced by ORF3A expression, including HSPA6 and spliced XBP1, and these were not further upregulated by ORF3A. Our data suggest a model where CLCC1 silencing triggers a homeostatic UPR that prevents cell death due to ORF3A expression.

The changes that prostate cancer (PCa) induces in its microenvironment are not fully understood. Here the authors use single-cell RNA-seq and organoids to characterise how the microenvironment responds to PCa, and also identify tumour-associated epithelial cell states and club cells.

ABSTRACTFemale scientists and researchers with diverse cultural backgrounds, especially of the Global South, are underrepresented in scientific systems. This is also the case for land use science and even for research teams researching in Global South countries. To assess trends in gender parity, ethnic diversity and intersectionality in this field, we conducted a meta-analysis based on systematic literature review that included 316,390 peer-reviewed journal articles. We found that 27% of all authors between 2000–2021 represented women. Ethnicity representation was biased towards White researchers (62%) followed by Asian (30%), Hispanic (6%) and Black (2%) researchers. Intersection of inequalities further underrepresented Black and Hispanic women when author positions were considered, giving Black women 0.6% chance of becoming first authors in land use science in comparison to 19.3% chance of White women. Supportive actions to empower women are needed to reduce intersectional inequalities and to achieve the sustainable development goals.

ABSTRACT The Toxoplasma inner membrane complex (IMC) is a unique organelle that plays critical roles in parasite motility, invasion, egress, and replication. The IMC is delineated into the apical, body, and basal regions, defined by proteins that localize to these distinct subcompartments. The IMC can be further segregated by proteins that localize specifically to the maternal IMC, the daughter bud IMC, or both. While the function of the maternal IMC has been better characterized, the precise roles of most daughter IMC components remain poorly understood. Here, we demonstrate that the daughter protein IMC29 plays an important role in parasite replication. We show that Δimc29 parasites exhibit severe replication defects, resulting in substantial growth defects and loss of virulence. Deletion analyses revealed that IMC29 localization is largely dependent on the N-terminal half of the protein containing four predicted coiled-coil domains while IMC29 function requires a short C-terminal helical region. Using proximity labeling, we identify eight novel IMC proteins enriched in daughter buds, significantly expanding the daughter IMC proteome. We additionally report four novel proteins with unique localizations to the interface between two parasites or to the outer face of the IMC, exposing new subregions of the organelle. Together, this work establishes IMC29 as an important early daughter bud component of replication and uncovers an array of new IMC proteins that provides important insights into this organelle. IMPORTANCE The inner membrane complex (IMC) is a conserved structure across the Apicomplexa phylum, which includes obligate intracellular parasites that cause toxoplasmosis, malaria, and cryptosporidiosis. The IMC is critical for the parasite to maintain its intracellular lifestyle, particularly in providing a scaffold for daughter bud formation during parasite replication. While many IMC proteins in the later stages of division have been identified, components of the early stages of division remain unknown. Here, we focus on the early daughter protein IMC29, demonstrating that it is crucial for faithful parasite replication and identifying specific regions of the protein that are important for its localization and function. We additionally use proximity labeling to reveal a suite of daughter-enriched IMC proteins, which represent promising candidates to further explore this IMC subcompartment.

BackgroundLesotho is one of the 30 countries with the highest tuberculosis incidence rates in the world, estimated at 650 per 100,000 population. Tuberculosis case detection is extremely low, particularly with the rapid spread of COVID-19, dropping from an estimated 51% in 2020 to 33% in 2021. The aim of this study is to understand the barriers to tuberculosis diagnosis and treatment completion.MethodsWe used a convergent mixed methods study design. We collected data on the number of clients reporting symptoms upon tuberculosis screening, their sputum test results, the number of clients diagnosed, and the number of clients who started treatment from one district hospital and one health center in Berea district, Lesotho. We conducted in-depth interviews and focus group discussions with 53 health workers and patients. We used a content analysis approach to analyze qualitative data and integrated quantitative and qualitative findings in a joint display.FindingsDuring March-August, 2019, 218 clients at the hospital and 292 clients at the health center reported tuberculosis symptoms. The full diagnostic testing process was completed for 66% of clients at the hospital and 68% at the health center. Among clients who initiated tuberculosis treatment, 68% (61/90) at the hospital and 74% (32/43) at the health center completed treatment. The main barriers to testing and treatment completion were challenges at sample collection, lack of decentralized diagnostic services, and socioeconomic factors such as food insecurity and high patient movement to search for jobs.ConclusionsTuberculosis diagnosis could be improved through the effective decentralization of laboratory services at the health facility level, and treatment completion could be improved by providing food and other forms of social support to patients.

Leishmaniasis is a group of vector-borne, parasitic diseases caused by over 20 species of the protozoan Leishmania spp. The three major disease classifications, cutaneous, visceral, and mucocutaneous, have a range of clinical manifestations from self-healing skin lesions to hepatosplenomegaly and mucosal membrane damage to fatality. As a neglected tropical disease, leishmaniasis represents a major international health challenge, with nearly 350 million people living at risk of infection a year. The current chemotherapeutics used to treat leishmaniasis have harsh side effects, prolonged and costly treatment regimens, as well as emerging drug resistance, and are predominantly used for the treatment of visceral leishmaniasis. There is an undeniable need for the identification and development of novel chemotherapeutics targeting cutaneous leishmaniasis (CL), largely ignored by concerted drug development efforts. CL is mostly non-lethal and the most common presentation of this disease, with nearly 1 million new cases reported annually. Recognizing this unaddressed need, substantial yet fragmented progress in early drug discovery efforts for CL has occurred in the past 15 years and was outlined in this review. However, further work needs to be carried out to advance early discovery candidates towards the clinic. Importantly, there is a paucity of investment in the translation and development of therapies for CL, limiting the emergence of viable solutions to deal with this serious and complex international health problem.

Proprioception of all animals is important in being able to have coordinated locomotion. Stretch activated ion channels (SACs) transduce the mechanical force into electrical signals in the proprioceptive sensory endings. The types of SACs vary among sensory neurons in animals as defined by pharmacological, physiological and molecular identification. The chordotonal organs within insects and crustaceans offer a unique ability to investigate proprioceptive function. The effects of the extracellular environment on neuronal activity, as well as the function of associated SACs are easily accessible and viable in minimal saline for ease in experimentation. The effect of extracellular [Ca2+] on membrane properties which affect voltage-sensitivity of ion channels, threshold of action potentials and SACs can be readily addressed in the chordotonal organ in crab limbs. It is of interest to understand how low extracellular [Ca2+] enhances neural activity considering the SACs in the sensory endings could possibly be Ca2+ channels and that all neural activity is blocked with Mn2+. It is suggested that axonal excitability might be affected independent from the SAC activity due to potential presence of calcium activated potassium channels (K(Ca)) and the ability of Ca2+ to block voltage gated Na+ channels in the axons. Separating the role of Ca2+ on the function of the SACs and the excitability of the axons in the nerves associated with chordotonal organs is addressed. These experiments may aid in understanding the mechanisms of neuronal hyperexcitability during hypocalcemia within mammals.

ABSTRACT Leishmaniasis, a category I neglected tropical disease, is a group of diseases caused by the protozoan parasite Leishmania species with a wide range of clinical manifestations. Current treatment options can be highly toxic and expensive, with drug relapse and the emergence of resistance. Bacteriocins, antimicrobial peptides ribosomally produced by bacteria, are a relatively new avenue for potential antiprotozoal drugs. Particular interest has been focused on enterocin AS-48, with previously proven efficacy against protozoan species, including Leishmania spp. Sequential characterization of enterocin AS-48 has illustrated that antibacterial bioactivity is preserved in linearized, truncated forms; however, minimal domains of AS-48 bacteriocins have not yet been explored against protozoans. Using rational design techniques to improve membrane penetration activity, we designed peptide libraries using the minimal bioactive domain of AS-48 homologs. Stepwise changes to the charge (z), hydrophobicity (H), and hydrophobic dipole moment (μH) were achieved through lysine and tryptophan substitutions and the inversion of residues within the helical wheel, respectively. A total of 480 synthetic peptide variants were assessed for antileishmanial activity against Leishmania donovani. One hundred seventy-two peptide variants exhibited 50% inhibitory concentration (IC50) values below 20 μM against axenic amastigotes, with 60 peptide variants in the nanomolar range. Nine peptide variants exhibited potent activity against intracellular amastigotes with observed IC50 values of

Abstract Background Treatment guidelines for generalized anxiety disorder (GAD) are based on a relatively small number of randomized controlled trials and do not consider patient-centered perceptions of treatment helpfulness. We investigated the prevalence and predictors of patient-reported treatment helpfulness for DSM-5 GAD and its two main treatment pathways: encounter-level treatment helpfulness and persistence in help-seeking after prior unhelpful treatment. Methods Data came from community epidemiologic surveys in 23 countries in the WHO World Mental Health surveys. DSM-5 GAD was assessed with the fully structured WHO Composite International Diagnostic Interview Version 3.0. Respondents with a history of GAD were asked whether they ever received treatment and, if so, whether they ever considered this treatment helpful. Number of professionals seen before obtaining helpful treatment was also assessed. Parallel survival models estimated probability and predictors of a given treatment being perceived as helpful and of persisting in help-seeking after prior unhelpful treatment. Results The overall prevalence rate of GAD was 4.5%, with lower prevalence in low/middle-income countries (2.8%) than high-income countries (5.3%); 34.6% of respondents with lifetime GAD reported ever obtaining treatment for their GAD, with lower proportions in low/middle-income countries (19.2%) than high-income countries (38.4%); 3) 70% of those who received treatment perceived the treatment to be helpful, with prevalence comparable in low/middle-income countries and high-income countries. Survival analysis suggested that virtually all patients would have obtained helpful treatment if they had persisted in help-seeking with up to 10 professionals. However, we estimated that only 29.7% of patients would have persisted that long. Obtaining helpful treatment at the person-level was associated with treatment type, comorbid panic/agoraphobia, and childhood adversities, but most of these predictors were important because they predicted persistence rather than encounter-level treatment helpfulness. Conclusions The majority of individuals with GAD do not receive treatment. Most of those who receive treatment regard it as helpful, but receiving helpful treatment typically requires persistence in help-seeking. Future research should focus on ensuring that helpfulness is included as part of the evaluation. Clinicians need to emphasize the importance of persistence to patients beginning treatment.

Flying pigeons (Columbia livia) are extensively studied for their physical endurance and superior sense of orientation. The extreme physical endurance of which these birds are capable creates a unique opportunity to investigate the possible impact of long-distance flying on the taxonomy and metabolic function of the gut microbiota. This project was enabled by access to two groups of pigeons raised by the same breeder in the same conditions, except that one group was trained in long-distance flying and participated in multiple races covering a total distance of over 2600 km over a 9-week period. In contrast, the second group did not fly. The fecal microbiota was analyzed using 16S amplicon sequencing, and the taxonomy and metabolic function were inferred from this sequence data. Based on phylogenetic distance and metabolic function, flying and non-flying pigeons were found to harbor distinct bacterial microbiota. The microbiota taxonomy varied extensively between the birds, whereas the inferred metabolic potential was relatively stable. Age was not a significant determinant of the fecal microbiota profile. In flying birds, the metabolic pathways annotated with biosynthesis were enriched, representing 60% of the 20 metabolic pathways that were most closely associated with flying.

Abstract The hippocampus, particularly its ventral domain, can promote negative affective states (i.e. stress and anxiety) that play an integral role in the development and persistence of alcohol use disorder (AUD). The ventral hippocampus (vHC) receives strong excitatory input from the basolateral amygdala (BLA) and the BLA-vHC projection bidirectionally modulates anxiety-like behaviors. However, no studies have examined the effects of chronic alcohol on the BLA-vHC circuit. In the present study, we used ex vivo electrophysiology in conjunction with optogenetic approaches to examine the effects of chronic intermittent ethanol exposure (CIE), a well-established rodent model of AUD, on the BLA-vHC projection and putative intrinsic vHC synaptic plasticity. We discovered prominent BLA innervation in the subicular region of the vHC (vSub). CIE led to an overall increase in the excitatory/inhibitory balance, an increase in AMPA/NMDA ratios but no change in paired-pulse ratios, consistent with a postsynaptic increase in excitability in the BLA-vSub circuit. CIE treatment also led to an increase in intrinsic network excitability in the vSub. Overall, our findings suggest a hyperexcitable state in BLA-vSub specific inputs as well as intrinsic inputs to vSub pyramidal neurons which may contribute to the negative affective behaviors associated with CIE.

Verbal insults go against a universal moral imperative not to inflict harm on others, and they also pose a threat to one's face or reputation. As such, these “verbal slaps in the face” provide a unique opportunity to explore the interface between language and emotion. We used electroencephalography (EEG) and skin conductance (SC) recordings to compare the short-term impact of verbal insults such as “Linda is an idiot” or “Paula is horrible” to that of more positive evaluations (e.g., “Linda is an angel”, “Paula is impressive”) and neutral factual descriptions (e.g., “Linda is a student”), examining how responses to these various speech acts adapt as a function of massive repetition. By using either the participant's or somebody else's name, we also explored how statement impact depended on who was being evaluated. Multilevel ERP analysis with three predesignated latency ranges revealed an early insult effect in P2 amplitude that was highly robust over repetition and also did not depend on who the insult was about. This P2 effect points to a very rapid and stable capture of emotional attention, plausibly triggered by the retrieval of evaluative word meaning from long-term memory. Insults also elicited a larger late positive potential (LPP), again regardless of who the insult was about, but this later effect did not withstand repetition. Skin conductance responses showed that insults did not lead to more arousal than compliments did. In all, our findings suggest that in a standard psycholinguistic comprehension experiment without real interaction between speakers, insults deliver lexical “mini-slaps in the face,” such that the strongly negative evaluative words involved (e.g., “idiot”) automatically grab attention during lexical retrieval, regardless of how often that retrieval occurs.

Background:. The use of local anesthesia in nasal surgery has gained popularity as a cost-effective and safe alternative. With the potential benefit of reconstruction without using general anesthesia, the goal of the study was to evaluate the patient-reported experience in addition to surgical outcomes and perioperative complications. Methods:. A mixed-methods study was completed with retrospective chart review and patient-reported outcome questionnaire. The primary outcome measures were demographics, oncologic and surgical details, and postoperative complications. Secondary outcome measures were aesthetic outcomes and procedure tolerance, which were gathered from the FACE-Q questionnaire. Results:. Of the 22 patients who met inclusion criteria, nine patients (41%) had forehead flaps performed and 13 patients (59%) had multilayer reconstruction with local flaps and cartilage grafts. The average number of surgeries performed, including revisions, was 2.3 ± 0.2. The overall complication rate for reconstructions and revisions was 20%, most of these were minor complications. The overall subjective rating of patient’s appearance was excellent with an average score of 83.9 (± 17.3) out of 100. There was minimal appearance distress as a product of the surgery with an average score of 84.9 (±18.8). On a scale of one to five, patients reported an average of 4.3 for convenience, 3.8 for efficiency of setup and procedure, and 3.4 out of 5 for comfortability with having an operation performed on their face wide awake. Conclusion:. Our study demonstrated that complex nasal reconstruction performed under local anesthetic in a minor procedure setting is a feasible and safe option with good patient-reported outcomes.

Abstract COVID‐19 has halted research around the globe and forced researchers out of their laboratories. Non‐emergency medical appointments were canceled. Ongoing clinical trials were challenged to create new modes of operation while public pressure mounted to find therapeutic options against COVID‐19. Yet, the inability to conduct research during COVID‐19 was overcome with cooperation, resource sharing, and compassion, which provides important lessons on how to improve health related research as we enter a new normal.

Background: Prevalence rates of smokeless tobacco (SLT) use among firefighters are remarkably high and substantially higher than similar occupational groups and the general U.S. population. The purpose of this study was to explore the perspectives of fire service personnel regarding cancer and its associations with tobacco and SLT use. Methods: This descriptive study used a qualitative approach. Key informant interviews were conducted in 39 career firefighters and fire service administration from across the U.S. Discussion were recorded, transcribed verbatim and transferred to NVivo software for narrative analysis. Topics explored included cancer perceptions, attitudes and beliefs, and cultural factors related to SLT use behaviors. Results: Major themes that emerged among fire service personnel included concerns about cancer and its risk factors including firefighting tasks, such as fire overhaul operations, and from their lifestyle behaviors, such as alcohol and tobacco use. Firefighters also suggested a number of reasons for their increased SLT use, such as fire department tobacco-free policy and fire service culture. Conclusion: The current study provides a rich foundation for future research, prevention, and intervention efforts for the fire service and research communities regarding tobacco and SLT use and cancer risk. Additional research on firefighters' cancer beliefs deserves future research in order to improve messaging about the risks of cancer due to firefighting.

Summary: Metabolites are crucial for bidirectional communication between host and microbiome. We describe a protocol for the isolation of organic and aqueous metabolites from mucosal scrapes and feces from mouse and human samples. Although some of the most reactive organic compounds may be lost, this approach generates a functionally reproducible metabolic extract containing both host and microbial compounds appropriate for quantitative mass spectrometry and functional characterization. Our mass spectrometry approach identifies low-abundant and difficult to identify microbially derived metabolites.For complete details on the use and execution of this protocol, please refer to Bell et al. (2021) and Das et al. (2020).

Streptococcus pneumoniae is the leading cause of bacterial paediatric meningitis after the neonatal period worldwide, but the bacterial factors and pathophysiology that drive pneumococcal meningitis are not fully understood. In this work, we have identified differences in raffinose utilization by S. pneumoniae isolates of identical serotype and sequence type from the blood and cerebrospinal fluid (CSF) of a single pediatric patient with meningitis. The blood isolate displayed defective raffinose metabolism, reduced transcription of the raffinose utilization pathway genes, and an inability to grow in vitro when raffinose was the sole carbon source. The fitness of these strains was then assessed using a murine intranasal infection model. Compared with the CSF isolate, mice infected with the blood isolate displayed higher bacterial numbers in the nose, but this strain was unable to invade the ears of infected mice. A premature stop codon was identified in the aga gene in the raffinose locus, suggesting that this protein likely displays impaired alpha-galactosidase activity. These closely related strains were assessed by Illumina sequencing, which did not identify any single nucleotide polymorphisms (SNPs) between the two strains. However, these wider genomic analyses identified the presence of an alternative alpha-galactosidase gene that appeared to display altered sequence coverage between the strains, which may account for the observed differences in raffinose metabolic capacity. Together, these studies support previous findings that raffinose utilization capacity contributes to disease progression, and provide insight into a possible alternative means by which perturbation of this pathway may influence the behavior of pneumococci in the host environment, particularly in meningitis.

This article examines how individuals proximate to online body justice communities utilized and experienced social media during COVID-19. The majority of research during the pandemic has been quantitative and survey-based; it has also tended to center (dis)information spread or mental health concerns. Our qualitative interviews with 44 individuals offer nuanced insights into what social media meant to people during quarantine, how they used it, and how they reflected on their experience of it. Five major themes emerged through reflexive, thematic analysis of the interview data: changed temporal rhythms, influx of toxic content, resource building, additive and subtractive actions, and algorithmic awareness. Some participants described social media as an increasingly harmful influence in their lives during the pandemic due to compulsive usage and exposure to “toxic content” like misinformation, weight stigma, and homophobia. At the same time, participants noted how social media positively enabled social connection, education, and activation around social justice. Across both of these extremes, many elaborated on the intensive, self-reflective labor of cultivating their accounts so that they mirrored their identities and the kinds of experiences they wanted to have online while preventing the infiltration of unwanted content. In addition to offering new insights into social media usage in body justice communities during COVID-19, our data suggest alternative ways of understanding how individuals manage their experience of social media, curate their social media feeds through additive and subtractive actions, and frequently reflect on how their choices interact with platform algorithms.

Endoparasitism is a major cause of morbidity and mortality in alpacas (Lama pacos), with growing emergence of anthelmintic resistance. The purpose of the study was to correlate nematode worm burden and selected host phenotypic characteristics, such as age and weight, with the composition of the intestinal microbiota of adult alpacas. Fecal samples were collected per rectum from 102 healthy adult (2.1-11.2 years) alpacas at 3 separate timepoints (pre- and post-treatment with 8.8 mg/kg oral Levamisole HCL, and 4.6 months later) at a single farm. The profile of the fecal bacterial microbiota was characterized using 16S amplicon sequencing. Serial clinical exams and fecal egg counts were compared using related-samples analyses. The fecal microbiota of identically managed, healthy alpacas was characterized by a high level of temporal stability, as both α and β-diversity significantly correlated between sampling timepoints. Pairwise β-diversity between samples collected at each timepoint was low, ranging from 0.16-0.21 UniFrac distance units. The intensity of strongylid nematode infection (including Haemonchus, Ostertagia, Trichostrongylus) was only significantly correlated with microbiota composition in samples collected 14 days after treatment with levamisole. Analysis of similarity revealed no clustering of microbiota from anthelmintic responders or non-responders. Alpaca age explained the largest proportion of fecal microbiota variation and was the only consistently significant predictor of fecal microbiota taxonomic composition, by impacting the ratio of relative Bacteroidetes and Firmicutes abundance. Firmicutes, mostly Clostridiales, was the most abundant taxon across all collections.

Lesotho has one of the highest tuberculosis (TB) incidence rates in the world, estimated at 654/100,000 population. However, TB detection remains low, with only 51% of people with TB being diagnosed and treated. The aim of this study was to evaluate implementation of TB screening and identify drivers of suboptimal TB screening in Lesotho. We used a convergent mixed methods study design. We collected data on the number of health facility visits and the number of clients screened for TB during March-August, 2019 from one district hospital and one health center. We conducted interviews and focus group discussions with patients and health workers to elucidate the mechanisms associated with suboptimal screening. Out of an estimated 70,393 visitors to the two health facilities, only 22% of hospital visitors and 48% of health center visitors were asked about TB symptoms. Only 2% of those screened at each facility said that they had TB symptoms, comprising a total of 510 people. Lack of training on tuberculosis screening, overall staff shortages, barriers faced by patients in accessing care, and health care worker mistrust of tuberculosis screening procedures were identified as drivers of suboptimal TB screening. TB screening could be improved by ensuring the availability of well-trained, incentivized, and dedicated screeners at health facilities, and by providing TB screening services in community settings.