Chagas Disease Diagnostic Practices at Four Major Hospital Systems in California and Texas.

BACKGROUND: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy. METHODS: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis. RESULTS: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all testing, and the most frequently cited cardiac condition was heart failure. Fewer than 1% of tests were ordered by obstetric and gynecologic services. Fewer than half (47%) of patients had confirmatory testing performed at the Centers for Disease Control and Prevention. DISCUSSION: Four major hospitals systems in California and Texas demonstrated low overall rates of CD diagnostic testing, testing primarily among older patients with end-organ damage, and incomplete confirmatory testing. This suggests missed opportunities to diagnose CD in at-risk individuals early in the course of infection when antiparasitic treatment can reduce the risk of disease progression and prevent vertical transmission.

Corticotropin Releasing Factor (CRF) Coexpression in GABAergic, Glutamatergic, and GABA/Glutamatergic Subpopulations in the Central Extended Amygdala and Ventral Pallidum of Young Male Primates.

The central extended amygdala (CEA) and ventral pallidum (VP) are involved in diverse motivated behaviors based on rodent models. These structures are conserved, but expanded, in higher primates, including human. Corticotropin releasing factor (CRF), a canonical "stress molecule" associated with the CEA and VP circuitry across species, is dynamically regulated by stress and drugs of abuse and misuse. CRF's effects on circuits critically depend on its colocation with primary "fast" transmitters, making this crucial for understanding circuit effects. We surveyed the distribution and colocalization of CRF-, VGluT2- (vesicular glutamate transporter 2), and VGAT- (vesicular GABA transporter) mRNA in specific subregions of the CEA and VP in young male monkeys. Although CRF-containing neurons were clustered in the lateral central bed nucleus (BSTLcn), the majority were broadly dispersed throughout other CEA subregions, and the VP. CRF/VGAT-only neurons were highest in the BSTLcn, lateral central amygdala nucleus (CeLcn), and medial central amygdala nucleus (CeM) (74%, 73%, and 85%, respectively). In contrast, lower percentages of CRF/VGAT only neurons populated the sublenticular extended amygdala (SLEAc), ventrolateral bed nucleus (BSTLP), and VP (53%, 54%, 17%, respectively), which had higher complements of CRF/VGAT/VGluT2-labeled neurons (33%, 29%, 67%, respectively). Thus, the majority of CRF-neurons at the "poles" (BSTLcn and CeLcn/CeM) of the CEA are inhibitory, while the "extended" BSTLP and SLEAc subregions, and neighboring VP, have a more complex profile with admixtures of "multiplexed" excitatory CRF neurons. CRF's colocalization with its various fast transmitters is likely circuit-specific, and relevant for understanding CRF actions on specific target sites.SIGNIFICANCE STATEMENT The central extended amygdala (CEA) and ventral pallidum (VP) regulate multiple motivated behaviors through differential downstream projections. The stress neuropeptide corticotropin releasing factor (CRF) is enriched in the CEA, and is thought to "set the gain" through modulatory effects on coexpressed primary transmitters. Using protein and transcript assays in monkey, we found that CRF neurons are broadly and diffusely distributed in CEA and VP. CRF mRNA+ neurons colocalize with VGAT (GABA) and VGluT2 (glutamate) mRNAs in different proportions depending on subregion. CRF mRNA was also coexpressed in a subpopulation of VGAT/VGluT2 mRNA ("multiplexed") cells, which were most prominent in the VP and "pallidal"-like parts of the CEA. Heterogeneous CRF and fast transmitter coexpression across CEA/VP subregions implies circuit-specific effects.

The network structure of mania symptoms differs between people with and without binge eating.

OBJECTIVES: People with bipolar disorder who also report binge eating have increased psychopathology and greater impairment than those without binge eating. Whether this co-occurrence is related to binge eating as a symptom or presents differently across full-syndrome eating disorders with binge eating is unclear. METHODS: We first compared networks of 13 lifetime mania symptoms in 34,226 participants from the United Kingdom's National Institute for Health and Care Research BioResource with (n = 12,104) and without (n = 22,122) lifetime binge eating. Second, in the subsample with binge eating, we compared networks of mania symptoms in participants with lifetime anorexia nervosa binge-eating/purging (n = 825), bulimia nervosa (n = 3737), and binge-eating disorder (n = 3648). RESULTS: People with binge eating endorsed every mania symptom significantly more often than those without binge eating. Within the subsample, people with bulimia nervosa most often had the highest endorsement rate of each mania symptom. We found significant differences in network parameter statistics, including network structure (M = 0.25, p = 0.001) and global strength (S = 1.84, p = 0.002) when comparing the binge eating with no binge-eating participants. However, network structure differences were sensitive to reductions in sample size and the greater density of the latter network was explained by the large proportion of participants (34%) without mania symptoms. The structure of the anorexia nervosa binge-eating/purging network differed from the bulimia nervosa network (M = 0.66, p = 0.001), but the result was unstable. CONCLUSIONS: Our results suggest that the presence and structure of mania symptoms may be more associated with binge eating as a symptom rather than any specific binge-type eating disorder. Further research with larger sample sizes is required to confirm our findings.

Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.

OBJECTIVE: The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic. METHOD: Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self-harm ideation (n = 18,040), and self-harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes. RESULTS: Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation. DISCUSSION: Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics. PUBLIC SIGNIFICANCE: In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.

The United Kingdom Eating Disorders Genetics Initiative.

OBJECTIVE: The United Kingdom Eating Disorders Genetics Initiative (EDGI UK), part of the National Institute for Health and Care Research (NIHR) Mental Health BioResource, aims to deepen our understanding of the environmental and genetic etiology of eating disorders. EDGI UK launched in February 2020 and is partnered with the UK eating disorders charity, Beat. Multiple EDGI branches exist worldwide. This article serves the dual function of providing an in-depth description of our study protocol and of describing our initial sample including demographics, diagnoses, and physical and psychiatric comorbidities. METHOD: EDGI UK recruits via media and clinical services. Anyone living in England, at least 16 years old, with a lifetime probable or clinical eating disorder is eligible to sign up online: edgiuk.org. Participants complete online questionnaires, donate a saliva sample for genetic analysis, and consent to medical record linkage and recontact for future studies. RESULTS: As of September 2022, EDGI UK recruited 7435 survey participants: 98% female, 93.1% white, 97.8% cisgender, 65.9% heterosexual, and 52.1% have a university degree. Over half (57.8%) of these participants have returned their saliva DNA kit. The most common diagnoses are anorexia nervosa (48.3%), purging disorder (37.8%), bulimia nervosa (37.5%), binge-eating disorder (15.8%), and atypical anorexia nervosa (7.8%). CONCLUSION: EDGI UK is the largest UK eating disorders study and efforts to increase its diversity are underway. It offers a unique opportunity to accelerate eating disorder research. Researchers and participants with lived experience can collaborate on projects with unparalleled sample size. PUBLIC SIGNIFICANCE STATEMENT: Eating disorders are debilitating and costly for society but are under-researched due to underfunding. EDGI UK is one of the largest eating disorder studies worldwide with ongoing recruitment. The collected data constitute a resource for secondary analysis. We will combine data from all international EDGI branches and the NIHR BioResource to facilitate research that improves our understanding of eating disorders and their comorbidities.

Sociodemographic, mental health, and physical health factors associated with participation within re-contactable mental health cohorts: an investigation of the GLAD Study.

BACKGROUND: The Genetic Links to Anxiety and Depression (GLAD) Study is a large cohort of individuals with lifetime anxiety and/or depression, designed to facilitate re-contact of participants for mental health research. At the start of the pandemic, participants from three cohorts, including the GLAD Study, were invited to join the COVID-19 Psychiatry and Neurological Genetics (COPING) study to monitor mental and neurological health. However, previous research suggests that participation in longitudinal studies follows a systematic, rather than random, process, which can ultimately bias results. Therefore, this study assessed participation biases following the re-contact of GLAD Study participants. METHODS: In April 2020, all current GLAD Study participants (N = 36,770) were invited to the COPING study. Using logistic regression, we investigated whether sociodemographic, mental, and physical health characteristics were associated with participation in the COPING baseline survey (aim one). Subsequently, we used a zero-inflated negative binomial regression to examine whether these factors were also related to participation in the COPING follow-up surveys (aim two). RESULTS: For aim one, older age, female gender identity, non-binary or self-defined gender identities, having one or more physical health disorders, and providing a saliva kit for the GLAD Study were associated with an increased odds of completing the COPING baseline survey. In contrast, lower educational attainment, Asian or Asian British ethnic identity, Black or Black British ethnic identity, higher alcohol consumption at the GLAD sign-up survey, and current or ex-smoking were associated with a reduced odds. For aim two, older age, female gender, and saliva kit provision were associated with greater COPING follow-up survey completion. Lower educational attainment, higher alcohol consumption at the GLAD Study sign-up, ex-smoking, and self-reported attention deficit hyperactivity disorder had negative relationships. CONCLUSIONS: Participation biases surrounding sociodemographic and physical health characteristics were particularly evident when re-contacting the GLAD Study volunteers. Factors associated with participation may vary depending on study design. Researchers should examine the barriers and mechanisms underlying participation bias in order to combat these issues and address recruitment biases in future studies.

Perigenual and Subgenual Anterior Cingulate Afferents Converge on Common Pyramidal Cells in Amygdala Subregions of the Macaque.

The subgenual (sgACC) and perigenual (pgACC) anterior cingulate are important afferents of the amygdala, with different cytoarchitecture, connectivity, and function. The sgACC is associated with arousal mechanisms linked to salient cues, whereas the pgACC is engaged in conflict decision-making, including in social contexts. After placing same-size, small volume tracer injections into sgACC and pgACC of the same hemisphere in male macaques, we examined anterogradely labeled fiber distribution to understand how these different functional systems communicate in the main amygdala nuclei at both mesocopic and cellular levels. The sgACC has broad-based termination patterns. In contrast, the pgACC has a more restricted pattern, which was always nested in sgACC terminals. Terminal overlap occurred in subregions of the accessory basal and basal nuclei, which we termed "hotspots." In triple-labeling confocal studies, the majority of randomly selected CaMKIIα-positive cells (putative amygdala glutamatergic neurons) in hotspots received dual contacts from the sgACC and pgACC. The ratio of dual contacts occurred over a surprisingly narrow range, suggesting a consistent, tight balance of afferent contacts on postsynaptic neurons. Large boutons, which are associated with greater synaptic strength, were ∼3 times more frequent on sgACC versus pgACC axon terminals in hotspots, consistent with a fast "driver" function. Together, the results reveal a nested interaction in which pgACC ("conflict/social monitoring") terminals converge with the broader sgACC ("salience") terminals at both the mesoscopic and cellular level. The presynaptic organization in hotspots suggests that shifts in arousal states can rapidly and flexibly influence decision-making functions in the amygdala.SIGNIFICANCE STATEMENT The subgenual (sgACC) and perigenual cingulate (pgACC) have distinct structural and functional characteristics and are important afferent modulators of the amygdala. The sgACC is critical for arousal, whereas the pgACC mediates conflict-monitoring, including in social contexts. Using dual tracer injections in the same monkey, we found that sgACC inputs broadly project in the main amygdala nuclei, whereas pgACC inputs were more restricted and nested in zones containing sgACC terminals (hotspots). The majority of CaMKIIα + (excitatory) amygdala neurons in hotspots received converging contacts, which were tightly balanced. pgACC and sgACC afferent streams are therefore highly interdependent in these specific amygdala subregions, permitting "internal arousal" states to rapidly shape responses of amygdala neurons involved in conflict and social monitoring networks.

Assessing Student Readiness to Work with People Who Use Drugs: Development of a Multi-disciplinary Addiction Educational Survey.

BACKGROUND: As health profession schools implement addiction curricula, they need survey instruments to evaluate the impact of the educational interventions. However, existing measures do not use current non-stigmatizing language and fail to capture core concepts. OBJECTIVE: To develop a brief measure of health profession student readiness to work with people who use drugs (PWUDs) and establish its content validity. METHODS: We conducted a literature review of existing instruments and desired clinical competencies related to providing care to PWUD and used results and expert feedback to create and revise a pool of 72 items. We conducted cognitive interviews with ten pre-clinical health profession students from various US schools of nursing, pharmacy, and medicine to ensure the items were easy to understand. Finally, we used a modified Delphi process with twenty-four health professions educators and addiction experts (eight each from nursing, pharmacy, and medicine) to select items for inclusion in the final scale. We analyzed expert ratings of individual items and interdisciplinary agreement on ratings to decide how to prioritize items. We ultimately selected 12 attitudes and 12 confidence items to include in the REadiness to Discuss Use, Common Effects, and HArm Reduction Measure (REDUCE-HARM). Experts rated their overall assessment of the final scale. RESULTS: Twenty-two of twenty-four experts agreed or strongly agreed that the attitudes scale measures student attitudes that impact readiness to work with PWUDs. Twenty-three of twenty-four experts agreed or strongly agreed that the confidence scale measures student self-efficacy in competencies that impact readiness to work with PWUDs. Seven of 72 initial items and none of the 24 selected items had statistically significant differences between disciplines. CONCLUSIONS: The REDUCE-HARM instrument has strong content validity and may serve as a useful tool in evaluating addiction education. Additional research is needed to establish its reliability, construct validity, and responsiveness to change.

Brilliantia kiribatiensis, a new genus and species of Cladophorales (Chlorophyta) from the remote coral reefs of the Southern Line Islands, Pacific Ocean.

The marine green alga Brilliantia kiribatiensis gen. et sp. nov. is described from samples collected from the coral reefs of the Southern Line Islands, Republic of Kiribati, Pacific Ocean. Phylogenetic analysis of sequences of the large- and small-subunit rDNA and the rDNA internal transcribed spacer region revealed that Brilliantia is a member of the Boodleaceae (Cladophorales), containing the genera Apjohnia, Boodlea, Cladophoropsis, Chamaedoris, Phyllodictyon, and Struvea. Within this clade it formed a distinct lineage, sister to Struvea elegans, but more distantly related to the bona fide Struvea species (including the type S. plumosa). Brilliantia differs from the other genera by having a very simple architecture forming upright, unbranched, single-celled filaments attached to the substratum by a rhizoidal mat. Cell division occurs by segregative cell division only at the onset of reproduction. Based on current sample collection, B. kiribatiensis seems to be largely restricted to the Southern Line Islands, although it was also observed on neighboring islands, including Orona Atoll in the Phoenix Islands of Kiribati, and the Rangiroa and Takapoto Atolls in the Tuamotus of French Polynesia. This discovery highlights the likeliness that there is still much biodiversity yet to be discovered from these remote and pristine reefs of the central Pacific.

Comparative Performance of Latest-Generation and FDA-Cleared Serology Tests for the Diagnosis of Chagas Disease.

Confirmed diagnosis of chronic Chagas disease (CD) requires positive results by two different IgG serology tests. Variable sensitivity has been reported among tests and in different geographic regions. Inadequate specificity presents a particular challenge in low-prevalence settings such as the United States. This study provides a direct comparison of the latest-generation IgG serology assays with four previously assessed FDA-cleared tests. Seven hundred ten blood donor plasma specimens were evaluated by Wiener Lisado and Wiener v.4.0 enzyme-linked immunosorbent assays (ELISAs) and Abbott PRISM Chagas chemiluminescent assay (ChLIA). Sensitivity and specificity were assessed relative to infection status as determined by the original blood donation testing algorithm. All three latest-generation assays demonstrated 100% specificity (95% confidence interval [CI], 98.6 to 100.0). Wiener Lisado, Wiener v.4.0, and Abbott PRISM had sensitivities of 97.1% (95% CI, 95.1 to 98.4), 98.9% (95% CI, 97.4 to 99.6), and 95.5% (95% CI, 93.2 to 97.3), respectively. As with previously evaluated FDA-cleared tests, all three assays had the highest reactivity and sensitivity in samples from donors born in South America and lowest reactivity and sensitivity in specimens from those born in Mexico, with intermediate results in specimens from Central American donors. Wiener v.4.0 had the highest diagnostic sensitivity in all comparisons. Our findings suggest that the latest-generation CD serology tests could improve diagnostic sensitivity without affecting specificity.

The Role of Topical Anesthetics in the Treatment of Pediatric Facial Lacerations.

PURPOSE: Pediatric facial lacerations (PLACS) are a common emergency, often requiring a general anesthetic (GA) or sedation if infiltration of local anesthetic (LA) cannot be tolerated. Topical anesthetics are a well-established and accepted alternative to infiltrations for facial lacerations which can reduce the need for general anesthesia. We report our experience following the introduction of topical 5% cocaine w/v and 1:2000 adrenaline gel (TCA) in a single center. METHODS: A secondary data analysis of 11 months attendances with PLACS following the introduction of TCA as part of a service improvement project. RESULTS: Fifty-three patients had wounds suitable for use of TCA. Twenty-three patients were treated with TCA, 14 with TCA alone and 9 with top-up local anesthetic infiltration (TCA + LA). Fourteen patients were treated using LA alone and 16 underwent GA. No adverse reactions were recorded. CONCLUSION: Topical anesthetics are a safe and effective alternative to infiltration of local anesthetic for PLACS and can be used to avoid the additional risks posed by sedation or GA. We recommend more departments introduce a topical anesthetic for this purpose.

Implementation of a Nurse Practitioner-Led Drive-Through COVID-19 Testing Site.

Efficient strategies for testing large numbers of patients must be developed to limit the spread of coronavirus disease 2019 (COVID-19). We demonstrate that our drive-through model is an efficient method of testing large numbers of patients during a pandemic. In the drive-through, cost per patient and personal protective equipment use were significantly less than in 3 brick-and-mortar clinics providing testing. We provide an example of effective nurse practitioner leadership in a drive-through testing site and demonstrate that nurse practitioners are ideally suited to provide leadership given their adaptability, ability to function in a variety of settings, and extensive experience with care coordination and logistics.

Outbreak of Norovirus Illness Among Wildfire Evacuation Shelter Populations - Butte and Glenn Counties, California, November 2018.

The Camp Fire, California's deadliest wildfire, began November 8, 2018, and was extinguished November 25 (1). Approximately 1,100 evacuees from the fire sought emergency shelter. On November 10, acute gastroenteritis (AGE) was reported in two evacuation shelters; norovirus illness was suspected, because it is commonly detected in shelter-associated AGE outbreaks. Norovirus is highly contagious and resistant to several disinfectants. Butte County Public Health Department (BCPHD), assisted by the California Department of Public Health (CDPH), initiated active surveillance to identify cases, confirm the etiology, and assess shelter infection prevention and control (IPC) practices to guide recommendations. During November 8-30, a total of 292 patients with AGE were identified among nine evacuation shelters; norovirus was detected in 16 of 17 unique patient stool specimens. Shelter IPC assessments revealed gaps in illness surveillance, isolation practices, cleaning, disinfection, and handwashing. CDPH and BCPHD collaborated with partner agencies to implement AGE screening, institute isolation protocols and 24-hour cleaning services, and promote proper hand hygiene. During disasters with limited resources, damaged infrastructure, and involvement of multiple organizations, establishing shelter disease surveillance and IPC is difficult. However, prioritizing effective surveillance and IPC at shelter activation is necessary to prevent, identify, and contain outbreaks.

Environmental impacts and implications of tropical carrageenophyte seaweed farming.

Field-based cultivation of Kappaphycus and Eucheuma seaweeds is widespread across the tropics and is largely done to extract the polysaccharide carrageenan, which is used in commercial applications. Although such seaweed farming has been cited as a sustainable alternative livelihood to destructive fishing, there has not been a comprehensive review of its environmental impacts to assess its potential conservation benefit. We reviewed the peer-reviewed and industry gray literature to determine what is known about seaweed farming techniques and their impacts on local ecosystems, organisms, and ecosystem services. We identified 43 tropical or subtropical countries that are currently cultivating or have cultivated carrageenophytes. Ecosystem impacts of seaweed farming were measured directly in 33 publications with variable results. Placement of seaweed farms above seagrass beds led to reduced productivity and shoot density in 5 studies and reduced or altered meiofaunal abundance and diversity in 6 studies. On coral reefs, overgrowth of corals by farmed seaweed species was documented in 8 cases. Two studies showed changes to herbivorous fish communities in adjacent areas because seaweed farms changed the environment, whereas in 2 studies measures of overall abundance or diversity did not change. The impacts of seaweed farming may not be as destructive as some other human activities, but they should still be considered when establishing new farms or managing existing farm sites. Our findings are consistent with suggestions to mitigate impact on local ecosystems by shifting seaweed farms to deeper, sandy-bottom areas. However, some of these changes may adversely affect farmers and associated communities.

Impactos e Implicaciones Ambientales del Cultivo de Algas Marinas Carragenofitas Tropicales Resumen El cultivo de las algas marinas Kappaphycus y Eucheuma se encuentra distribuido extensamente en los trópicos y generalmente se realiza para extraer el polisacárido carragenano, el cual se usa en la industria comercial. Aunque se ha mencionado que dicho cultivo de algas marinas es una alternativa sustentable para la pesca destructiva como medio de subsistencia, no se ha realizado una revisión completa de sus impactos ambientales para evaluar su potencial beneficio de conservación. Analizamos la literatura gris y la revisada por pares sobre la industria para determinar qué se conoce sobre las técnicas de cultivo de algas marinas y sus impactos sobre los ecosistemas locales, organismos y servicios ambientales. Identificamos 43 países tropicales o subtropicales que actualmente cultivan o han cultivado carragenofitas. Medimos los impactos ambientales del cultivo de algas marinas de manera directa en 33 publicaciones con resultados variables. La colocación de granjas de algas marinas por encima de lechos de pasto marino derivó en una productividad reducida y en una densidad observada en cinco estudios. En seis estudios, esta colocación derivó en una reducción o alteración de la abundancia y diversidad de meiofauna. En los arrecifes de coral, se documentó en ocho casos la proliferación de corales por causa de las especies cultivadas de algas marinas. Dos estudios mostraron cambios en las comunidades de peces herbívoros de las áreas circundantes debido al cambio en el ambiente generado por los cultivos de algas marinas, mientras que, en otros dos estudios, las medidas de la abundancia o diversidad generalizadas no cambió. Los impactos del cultivo de algas marinas pueden no ser tan destructivos como otras actividades humanas, pero todavía deberían considerarse durante el establecimiento de nuevas granjas o durante el manejo de los sitios de cultivo existentes. Nuestros hallazgos van a la par de las sugerencias actuales para mitigar el impacto sobre los ecosistemas locales mediante la reubicación de las granjas de algas marinas a áreas más profundas con un lecho arenoso. Sin embargo, algunos de estos cambios podrían afectar negativamente a los cultivadores y a las comunidades asociadas.

Combination treatment for male lower urinary tract symptoms with anticholinergic and alpha-blockers.

PURPOSE OF REVIEW: Although alpha-adrenergic antagonists (α-blockers) are effective for relieving voiding lower urinary tract symptoms (LUTS) in men, storage symptoms often persist. The aim of this manuscript is to evaluate the efficacy and safety of combination therapy with α-blockers and muscarinic receptor antagonists (anticholinergics). RECENT FINDINGS: High-quality evidence confirms that the addition of an anticholinergic improves micturition diary parameters, such as daytime and nocturnal frequency and urgency incontinence episodes, as well as total and storage subset scores on the International Prostate Symptom Score. Most studies demonstrate a statistically significant improvement over α-blocker monotherapy. Both, incidence of urinary retention and study withdrawal because of treatment-related adverse events with combination therapy, are low. Urodynamic indices, such as maximum flow rate and postvoid residual volume, are also minimally impacted by combination therapy. Outcomes on validated questionnaires and quality-of-life (QoL) indices also indicate a significant improvement. SUMMARY: The addition of an anticholinergic to an α-blocker in men with storage and voiding LUTS is an effective practice in reducing both categories of symptoms. The addition of anticholinergic is associated with a low rate of urinary retention and the impact on efficient bladder emptying is minimal. Not unexpectedly, QoL is improved.

Investigating functional redundancy versus complementarity in Hawaiian herbivorous coral reef fishes.

Patterns of species resource use provide insight into the functional roles of species and thus their ecological significance within a community. The functional role of herbivorous fishes on coral reefs has been defined through a variety of methods, but from a grazing perspective, less is known about the species-specific preferences of herbivores on different groups of reef algae and the extent of dietary overlap across an herbivore community. Here, we quantified patterns of redundancy and complementarity in a highly diverse community of herbivores at a reef on Maui, Hawaii, USA. First, we tracked fish foraging behavior in situ to record bite rate and type of substrate bitten. Second, we examined gut contents of select herbivorous fishes to determine consumption at a finer scale. Finally, we placed foraging behavior in the context of resource availability to determine how fish selected substrate type. All species predominantly (73-100 %) foraged on turf algae, though there were differences among the types of macroalgae and other substrates bitten. Increased resolution via gut content analysis showed the composition of turf algae consumed by fishes differed across herbivore species. Consideration of foraging behavior by substrate availability revealed 50 % of herbivores selected for turf as opposed to other substrate types, but overall, there were variable foraging portfolios across all species. Through these three methods of investigation, we found higher complementarity among herbivorous fishes than would be revealed using a single metric. These results suggest differences across species in the herbivore "rain of bites" that graze and shape benthic community composition.

Development of novel activin-targeted therapeutics.

Soluble activin type II receptors (ActRIIA/ActRIIB), via binding to diverse TGF-ß proteins, can increase muscle and bone mass, correct anemia or protect against diet-induced obesity. While exciting, these multiple actions of soluble ActRIIA/IIB limit their therapeutic potential and highlight the need for new reagents that target specific ActRIIA/IIB ligands. Here, we modified the activin A and activin B prodomains, regions required for mature growth factor synthesis, to generate specific activin antagonists. Initially, the prodomains were fused to the Fc region of mouse IgG2A antibody and, subsequently, "fastener" residues (Lys(45), Tyr(96), His(97), and Ala(98); activin A numbering) that confer latency to other TGF-ß proteins were incorporated. For the activin A prodomain, these modifications generated a reagent that potently (IC(50) 5 nmol/l) and specifically inhibited activin A signaling in vitro, and activin A-induced muscle wasting in vivo. Interestingly, the modified activin B prodomain inhibited both activin A and B signaling in vitro (IC(50) ~2 nmol/l) and in vivo, suggesting it could serve as a general activin antagonist. Importantly, unlike soluble ActRIIA/IIB, the modified prodomains did not inhibit myostatin or GDF-11 activity. To underscore the therapeutic utility of specifically antagonising activin signaling, we demonstrate that the modified activin prodomains promote significant increases in muscle mass.

Proximal tubule-derived colony stimulating factor-1 mediates polarization of renal macrophages and dendritic cells, and recovery in acute kidney injury.

Infiltrating cells play an important role in both the development of and recovery from acute kidney injury (AKI). Macrophages and renal dendritic cells are of particular interest because they can exhibit distinctly different functional phenotypes, broadly characterized as proinflammatory (M1) or tissue reparative (M2). Resident renal macrophages and dendritic cells participate in recovery from AKI in response to either ischemia/reperfusion or a model of selective proximal tubule injury induced by diphtheria-toxin-induced apoptosis in transgenic mice expressing the human diphtheria toxin receptor on proximal tubule cells. Colony-stimulating factor-1 (CSF-1) is an important factor mediating the recovery from AKI, and CSF-1 can stimulate macrophage and dendritic cell proliferation and polarization during the recovery phase of AKI. The kidney, and specifically the proximal tubule, is a major source of intrarenal CSF-1 production in response to AKI. We induced selective deletion of proximal tubule CSF-1 to determine its role in expansion and proliferation of renal macrophages and dendritic cells and in recovery from AKI. In both models of AKI, there was decreased M2 polarization, delayed functional and structural recovery, and increased tubulointerstitial fibrosis. Thus, intrarenal CSF-1 is an important mediator of macrophage/dendritic cell polarization and recovery from AKI.