Accessory lacrimal gland secretion mimicking seidel positivity following complex cataract surgery: Case report.

Purpose: To describe the presentation of lacrimal gland secretions mimicking a positive Seidel test following combined complex cataract surgery and endocyclophotocoagulation (ECP). Observation: The patient presented with a posterior subcapsular cataract (PSC) most likely secondary to chronic steroid use for a history of chemical burns from a firework injury in 2019. This injury resulted in symblepharon formation and limbal stem cell deficiency. He also developed glaucoma secondary to steroid response and angle structure damage. On postoperative day 1 (POD 1) after combined cataract surgery and ECP, the patient's paracentesis was Seidel positive and aqueous suppression was started. On postoperative week 1 (POW 1), the paracentesis was Seidel negative; however, it was noted at this visit that there were 3 pinpoint areas in the superotemporal conjunctiva that were Seidel positive. Digital pressure did not worsen the leak. Ultrasound biomicroscopy (UBM) was performed at POW 2.5 and showed lacrimal gland ducts in the superotemporal conjunctiva. Given this, it is likely that the "Seidel positive" finding was not due to aqueous humor leakage, but secretions from lacrimal gland tissue that may have been dragged more anteriorly due to conjunctiva scarring, thus producing a false positive Seidel sign. Conclusion & importance: This case highlights a false positive Seidel sign in the context of an eye with a complex ocular history and recent surgery. Clinicians should recognize that a false positive Seidel sign is possible if normal lacrimal gland anatomy has been disturbed.

TRPM2 and CaMKII Signaling Drives Excessive GABAergic Synaptic Inhibition Following Ischemia.

Excitotoxicity and the concurrent loss of inhibition are well-defined mechanisms driving acute elevation in excitatory/inhibitory (E/I) balance and neuronal cell death following an ischemic insult to the brain. Despite the high prevalence of long-term disability in survivors of global cerebral ischemia (GCI) as a consequence of cardiac arrest, it remains unclear whether E/I imbalance persists beyond the acute phase and negatively affects functional recovery. We previously demonstrated sustained impairment of long-term potentiation (LTP) in hippocampal CA1 neurons correlating with deficits in learning and memory tasks in a murine model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Here, we use CA/CPR and an in vitro ischemia model to elucidate mechanisms by which E/I imbalance contributes to ongoing hippocampal dysfunction in male mice. We reveal increased postsynaptic GABAA receptor (GABAAR) clustering and function in the CA1 region of the hippocampus that reduces the E/I ratio. Importantly, reduced GABAAR clustering observed in the first 24 h rebounds to an elevation of GABAergic clustering by 3 d postischemia. This increase in GABAergic inhibition required activation of the Ca2+-permeable ion channel transient receptor potential melastatin-2 (TRPM2), previously implicated in persistent LTP and memory deficits following CA/CPR. Furthermore, we find Ca2+-signaling, likely downstream of TRPM2 activation, upregulates Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, thereby driving the elevation of postsynaptic inhibitory function. Thus, we propose a novel mechanism by which inhibitory synaptic strength is upregulated in the context of ischemia and identify TRPM2 and CaMKII as potential pharmacological targets to restore perturbed synaptic plasticity and ameliorate cognitive function.

Apathy in persons living with HIV disease: A systematic narrative review.

BACKGROUND: Apathy was identified as a feature of HIV early in the epidemic; however, there are no systematic reviews of the diverse literature on the sociodemographic and clinical correlates of apathy in HIV disease. METHODS: The current study adopted a hybrid systematic-narrative review methodology in which we used PRISMA guidelines to identify, summarize, and critique peer-reviewed, empirical studies of apathy in HIV disease in the era of combination antiretroviral therapy. RESULTS: A total of 34 studies of apathy in persons living with HIV (PLWH) were identified. Findings across these studies showed that apathy was reliably related to the structure of grey and white matter pathways commonly implicated in apathy, poorer everyday functioning, education, and other neuropsychiatric symptoms (e.g., depression). Apathy was not reliably associated with age, sex, race/ethnicity, cognition, and clinical markers of HIV disease. LIMITATIONS: The current review does not provide rigorous quantitative estimates of clinical correlates of apathy, and the exclusion criteria of non-English and non-peer reviewed publications introduces risk of bias and Type I error. CONCLUSIONS: Apathy occurs at higher rates in PLWH and is linked to neuroanatomical differences, as well as negative outcomes for everyday functions, aspects of neurocognition, and neuropsychiatric symptoms. As such, apathy is an important component to consider in the clinical assessment, diagnosis, and management of neurocognitive disorders in PLWH. Future work is needed to replicate existing findings with larger sample sizes and longitudinal designs, examine apathy as a multi-dimensional construct, and develop evidence-based treatments for apathy in PLWH.

The Relationship Between Apathy and Cognitive Impairment Among Hispanic/Latin Americans: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses Systematic Review.

OBJECTIVES: The primary aim was to evaluate apathy assessment measures in relation to cognitive impairment among Hispanic/Latin Americans. METHODS: A systematic review on the relationship between apathy and cognitive impairment among Hispanic/Latin Americans across normal aging and neurocognitive disorders was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and using APA PsycInfo, Embase, and PubMed databases. Inclusion criteria required (1) a sample of English or Spanish-speaking adults ages 18 years and older, (2) with measures of apathy, (3) assessment of cognitive functioning or diagnosis of neurocognitive disorder, (4) with at least 18.5% Hispanic/Latin American represented in the sample. RESULTS: Only 14 papers met criteria to be included in this review. Of the 12 cross-sectional studies, 9 demonstrated significant associations between increased apathy and cognitive impairment, 1 demonstrated a descriptive difference between apathy and cognitive status (ie, no hypothesis test conducted), while 2 demonstrated null effects. These cross-sectional studies consisted of community and clinic samples of participants across North and South America. Two longitudinal studies conducted in North America demonstrated non-significant associations of apathy with cognitive status. CONCLUSIONS: The Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) apathy subscales were the most used measures for apathy in this review (85.7% of included studies). However, validity evidence from a review of apathy measures has warranted caution against the use of the NPI outside the context of screening for apathy. This potential measurement bias with Hispanic/Latin Americans apathy research limits conclusions drawn from the present review.

A resource of induced pluripotent stem cell (iPSC) lines including clinical, genomic, and cellular data from genetically isolated families with mood and psychotic disorders.

Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inadequate animal models for human psychiatric conditions. Human-derived induced pluripotent stem cells (iPSCs) provide a renewable cellular reagent that can be differentiated into living, disease-relevant cells and 3D brain organoids carrying the full complement of genetic variants present in the donor germline. Experimental studies of iPSC-derived cells allow functional characterization of risk alleles, establishment of causal relationships between genes and neurobiology, and screening for novel therapeutics. Here we report the creation and availability of an iPSC resource comprising clinical, genomic, and cellular data obtained from genetically isolated families with BD and related conditions. Results from the first 324 study participants, 61 of whom have validated pluripotent clones, show enrichment of rare single nucleotide variants and CNVs overlapping many known risk genes and pathogenic CNVs. This growing iPSC resource is available to scientists pursuing functional genomic studies of BD and related conditions.

Distinct mechanisms drive sequential internalization and degradation of GABAARs during global ischemia and reperfusion injury.

Synaptic inhibition is critical for controlling neuronal excitability and function. During global cerebral ischemia (GCI), inhibitory synapses are rapidly eliminated, causing hyper-excitability which contributes to cell-death and the pathophysiology of disease. Sequential disassembly of inhibitory synapses begins within minutes of ischemia onset: GABAARs are rapidly trafficked away from the synapse, the gephyrin scaffold is removed, followed by loss of the presynaptic terminal. GABAARs are endocytosed during GCI, but how this process accompanies synapse disassembly remains unclear. Here, we define the precise trafficking itinerary of GABAARs during the initial stages of GCI, placing them in the context of rapid synapse elimination. Ischemia-induced GABAAR internalization quickly follows their initial dispersal from the synapse, and is controlled by PP1α signaling. During reperfusion injury, GABAARs are then trafficked to lysosomes for degradation, leading to permanent removal of synaptic GABAARs and contributing to the profound reduction in synaptic inhibition observed hours following ischemia onset.

Multiple Chronic Conditions and Disability among Vietnamese Older Adults: Results from the Vietnamese Aging and Care Survey (VACS).

Using data from Vietnamese-origin older immigrants/refugees in the Houston, Texas area, we assessed their overall health, chronic conditions, disability, depressive symptoms, and cognitive impairment, and examined the association between their chronic conditions and disability by comorbidity clusters. The mean age of the sample was 76 years old. The majority were married in fair/poor health with several chronic conditions and disabilities and lived with families in low-income households. Hypertension and arthritis were the most common health conditions, but cognitive impairment had the most significant impact on their disability. They experienced similar health conditions to other older Americans but had higher rates of depressive symptoms and cognitive impairment possibly due to cultural factors that may have delayed mental health treatment. Culturally and linguistically tailored services created by policymakers, healthcare professionals, and local social service agencies are recommended for the well-being of immigrants/refugees who migrated to the U.S. for a better life.

Identification of a Noxo1 inhibitor by addition of a polyethylene glycol chain.

Reactive oxygen species (ROS) are a heterogeneous group of highly reactive ions and molecules derived from molecular oxygen (O2) which can cause DNA damage and lead to skin cancer. NADPH oxidase 1 (Nox1) is a major producer of ROS in the skin upon exposure to ultraviolet light. Functionally, Nox1 forms a holoenzyme complex that generates two superoxide molecules and reduces NADPH. The signaling activation occurs when the organizer subunit Noxo1 translocates to the plasma membrane bringing a cytochrome p450, through interaction with Cyba. We propose to design inhibitors that prevent Cyba-Noxo1 binding as a topical application to reduce UV-generated ROS in human skin cells. Design started from an apocynin backbone structure to generate a small molecule to serve as an anchor point. The initial compound was then modified by addition of a polyethylene glycol linked biotin. Both inhibitors were found to be non-toxic in human keratinocyte cells. Further in vitro experiments using isothermal calorimetric binding quantification showed the modified biotinylated compound bound Noxo1 peptide with a KD of 2 nM. Both using isothermal calorimetric binding and MALDI (TOF) MS showed that binding of a Cyba peptide to Noxo1 was blocked. In vivo experiments were performed using donated skin explants with topical application of the two inhibitors. Experiments show that ultraviolet light exposure of with the lead compound was able to reduce the amount of cyclobutene pyrimidine dimers in DNA, a molecule known to lead to carcinogenesis. Further synthesis showed that the polyethylene glycol but not the biotin was essential for inhibition.

miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity.

Activity-dependent protein synthesis is crucial for many long-lasting forms of synaptic plasticity. However, our understanding of the translational mechanisms controlling inhibitory synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABAARs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the precise mechanisms controlling gephyrin translation during this process remain unknown. Here, we identify miR153 as a novel regulator of Gphn mRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting GABAergic synaptic structure and function. We find that iLTP induction downregulates miR153, reversing its translational suppression of Gphn mRNA and allowing for increased de novo gephyrin protein synthesis and synaptic clustering during iLTP. Finally, we find that reduced miR153 expression during iLTP is driven by an excitation-transcription coupling pathway involving calcineurin, NFAT and HDACs, which also controls the miRNA-dependent upregulation of GABAARs. Overall, this work delineates a miRNA-dependent post-transcriptional mechanism that controls the expression of the key synaptic scaffold, gephyrin, and may converge with parallel miRNA pathways to coordinate gene upregulation to maintain inhibitory synaptic plasticity.

Selection pressure on the rhizosphere microbiome can alter nitrogen use efficiency and seed yield in Brassica rapa.

Microbial experimental systems provide a platform to observe how networks of groups emerge to impact plant development. We applied selection pressure for microbiome enhancement of Brassica rapa biomass to examine adaptive bacterial group dynamics under soil nitrogen limitation. In the 9th and final generation of the experiment, selection pressure enhanced B. rapa seed yield and nitrogen use efficiency compared to our control treatment, with no effect between the random selection and control treatments. Aboveground biomass increased for both the high biomass selection and random selection plants. Soil bacterial diversity declined under high B. rapa biomass selection, suggesting a possible ecological filtering mechanism to remove bacterial taxa. Distinct sub-groups of interactions emerged among bacterial phyla such as Proteobacteria and Bacteroidetes in response to selection. Extended Local Similarity Analysis and NetShift indicated greater connectivity of the bacterial community, with more edges, shorter path lengths, and altered modularity through the course of selection for enhanced plant biomass. In contrast, bacterial communities under random selection and no selection showed less complex interaction profiles of bacterial taxa. These results suggest that group-level bacterial interactions could be modified to collectively shift microbiome functions impacting the growth of the host plant under soil nitrogen limitation.

Understanding Questions and Concerns Regarding COVID-19 and the COVID-19 Vaccine Among Populations Presenting at a COVID-19 Vaccine Clinic Hub: A Qualitative Study.

BACKGROUND: Skepticism among the public surrounding the COVID-19 vaccine is still prevalent despite vaccine-positive communication and many Americans having already received the vaccine. Side effects of the vaccine, as well as its expeditious research and development, are among the top concerns among those hesitant to receive the coronavirus vaccine. Moreover, there is additional concern regarding the association between comorbidities and severity of illness due to the coronavirus pandemic. OBJECTIVE: We aimed to describe the pandemic- and vaccine-related concerns of South Texas residents who attended the UT Health San Antonio School of Nursing's vaccine clinic with the goal of better understanding vaccine-related misconceptions and hesitancy for subsequent vaccination campaigns and boosters. METHODS: An electronic survey accessible via a QR code on printed flyers was distributed throughout the waiting areas and post-vaccine observation rooms within the COVID-19 vaccine clinic at UT Health San Antonio School of Nursing from April 5 to 16, 2021. The survey contained a primary open-ended question designed to obtain information on concerns of the clinic attendees regarding the COVID-19 pandemic and COVID-19 vaccine. A thematic analysis was performed on the qualitative data to identify major themes to better understand concerns of vaccine clinic visitors. RESULTS: During the 11-day period, 510 attendees received vaccinations through the vaccination clinic and completed the survey. Five areas of concern were identified by the 277 attendees: immunity, future vaccinations, vaccine symptoms and safety, protocol post-vaccination, and child vaccinations. Post-hoc sentiment analysis showed that responses were generally neutral or negative. CONCLUSION: This study provides a perspective regarding questions and concerns of South Texas residents regarding the COVID-19 pandemic, the vaccine, and their general health status within a vaccinated population. Vaccine recipients were found to still have questions even after receiving the vaccine, suggesting that eliminating uncertainty surrounding the COVID-19 vaccine is not necessary to motivate individuals to receive the vaccine. Instead, addressing concerns through public health messaging could be a useful strategy to address vaccine-related concerns and increase subsequent vaccine uptake in future vaccination campaigns and boosters.

Evidence for the reliability and validity of a Spanish translation of the Medication Management Ability Assessment administered via tele-assessment.

We translated the Medication Management Ability Assessment (MMAA) from English to Spanish for use via tele-assessment and examined its reliability and validity. Following International Test Commission Guidelines for Translating and Adapting Tests, we used translation/back-translation and a small focus group (n = 6) to adapt a Spanish version of the MMAA. Eighty-six Spanish-speaking adults completed the adapted MMAA via tele-assessment at baseline and at a two-week follow-up visit. Participants also completed several self-report and performance-based cognitive and functional measures. The internal consistency of the MMAA was excellent (standardized Cronbach's α = 0.90). Performance-based functional assessments (PBFAs) and objective cognition were positively associated with the MMAA at small to medium effect sizes. Self-report measures of daily function and cognition, measures of health literacy, and estimates of premorbid intellectual functioning were not significantly associated with MMAA performance. The test-retest reliability of the MMAA was good (CCC = 0.73, 95% CI [0.62, 0.81]; rs = 0.37, p < 0.001) and demonstrated a small practice effect (Cohen's d = 0.36, p = 0.001). Preliminary evidence for the construct validity of a Spanish-language MMAA administered via tele-assessment further expands the potential clinical utility of PBFAs in culturally diverse, Spanish-speaking populations.

Stepwise disassembly of GABAergic synapses during pathogenic excitotoxicity.

GABAergic synaptic inhibition controls neuronal firing, excitability, and synaptic plasticity to regulate neuronal circuits. Following an acute excitotoxic insult, inhibitory synapses are eliminated, reducing synaptic inhibition, elevating circuit excitability, and contributing to the pathophysiology of brain injuries. However, mechanisms that drive inhibitory synapse disassembly and elimination are undefined. We find that inhibitory synapses are disassembled in a sequential manner following excitotoxicity: GABAARs undergo rapid nanoscale rearrangement and are dispersed from the synapse along with presynaptic active zone components, followed by the gradual removal of the gephyrin scaffold, prior to complete elimination of the presynaptic terminal. GABAAR nanoscale reorganization and synaptic declustering depends on calcineurin signaling, whereas disassembly of gephyrin relies on calpain activation, and blockade of both enzymes preserves inhibitory synapses after excitotoxic insult. Thus, inhibitory synapse disassembly occurs rapidly, with nanoscale precision, in a stepwise manner and most likely represents a critical step in the progression of hyperexcitability following excitotoxicity.

Self-report depression screening measures for older Hispanic/Latin American adults: A PRISMA systematic review.

BACKGROUND: Assessing depression symptoms in Hispanic/Latin American (H/Ls) older adults, a group at high risk for depression, is nuanced due to the influence of cultural characteristics in symptom expression and manifestation. Little is known about the psychometric properties of available measures when used with this population. METHODS: We conducted a two-stage systematic review of available depression assessment tools. We first identified self-report measures designed for use with adults. We then identified studies where at least one of such measures was used with older H/Ls that reported psychometric properties for the measure(s) used. RESULTS: Only 3 measures were identified for use with older H/Ls: the BDI, GDS, and CES-D. However, few data were found to support the validity of the BDI, and the CES-D was not consistently valid across cultural groups. The GDS was found appropriate, though its performance varied based on race/ethnicity, nationality, and cutoff scores. The CES-D and GDS also demonstrated varying psychometric properties based on study setting (research versus clinical) and target population (inpatient psychiatric patients versus community-dwelling individuals). LIMITATIONS: The number of articles that met criteria for inclusion in our review was small, and there was variation among samples of the few studies included. CONCLUSIONS: Currently available self-report depression screening measures have acceptable applicability among older H/Ls, but their utility may vary based on their intended use. Modified cutoff scores may be beneficial in maximizing the utility of these measures when given to diverse older adults.

Differential item functioning of the Beck Anxiety Inventory in a rural, multi-ethnic cohort.

BACKGROUND: Evaluating measurement bias is vital to ensure equivalent assessment across diverse groups. One approach for evaluating test bias, differential item functioning (DIF), assesses item-level bias across specified groups by comparing item-level responses between groups that have the same overall score. Previous DIF studies of the Beck Anxiety Inventory (BAI) have only assessed bias across age, sex, and disease duration in monolingual samples. We expand this literature through DIF analysis of the BAI across age, sex, education, ethnicity, cognitive status, and test language. METHODS: BAI data from a sample (n = 527, mean age=61.4 ± 12.7, mean education=10.9 ± 4.3, 69.3% female, 41.9% Hispanic/Latin American) from rural communities in West Texas, USA were analyzed. Item response theory (IRT) / logistic ordinal regression DIF was conducted across dichotomized demographic grouping factors. The Mann-Whitney U test and Hedge's g standardized mean differences were calculated before and after adjusting for the impact of DIF. RESULTS: Significant DIF was demonstrated in 10/21 items. An adverse impact of DIF was not identified when demographics were assessed individually. Adverse DIF was identified for only one participant (1/527, 0.2%) when all demographics were aggregated. LIMITATIONS: These results might not be generalizable to a sample with broader racial representation, more severe cognitive impairment, and higher levels of anxiety. CONCLUSIONS: Minimal item-level bias was identified across demographic factors considered. These results support prior evidence that the BAI is valid for assessing anxiety across age and sex while contributing new evidence of its clinical relevance across education, ethnicity, cognitive status, and English/Spanish test language.

Advances in novel antibiotics to treat multidrug-resistant gram-negative bacterial infections.

Antimicrobial resistance is a growing threat to public health and an increasingly common problem for acute care physicians to confront. Several novel antibiotics have been approved in the past decade to combat these infections; however, physicians may be unfamiliar with how to appropriately utilize them. The purpose of this review is to evaluate novel antibiotics active against resistant gram-negative bacteria and highlight clinical information regarding their use in the acute care setting. This review focuses on novel antibiotics useful in the treatment of infections caused by resistant gram-negative organisms that may be seen in the acute care setting. These novel antibiotics include ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilistatin/relebactam, cefiderocol, plazomicin, eravacycline, and omadacycline. Acute care physicians should be familiar with these novel antibiotics so they can utilize them appropriately.

Reduced alternative insulin dosing in hyperkalemia: A meta-analysis of effects on hypoglycemia and potassium reduction.

STUDY OBJECTIVE: Recent studies have identified that reduced alternative intravenous insulin doses, such as 5 units or 0.1 units/kg, may reduce the risk of hypoglycemia compared to standard doses of 10 units in patients treated for hyperkalemia. However, some studies suggest that these alternative doses may reduce the ability to lower serum potassium. This study was performed to determine the impact of alternative insulin dosing on hypoglycemia and potassium reduction in patients with hyperkalemia. DESIGN: Meta-analysis. DATA SOURCE: PubMed/MEDLINE, CENTRAL, Ovid, and ClinicalTrials.gov were searched from inception through November 2020. PATIENTS: Patients treated with standard (10 units) or alternative (<10 units) insulin dosing strategies for hyperkalemia. Only studies that evaluated hypoglycemia (serum glucose <70 mg/dl), severe hypoglycemia (serum glucose <50 mg/dl), and potassium reduction post-treatment were included in the meta-analysis. All articles were assessed for bias using the Cochrane Risk of Bias Assessment Tool and Newcastle-Ottawa scales for randomized prospective trials and retrospective trials, respectively. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Ten retrospective cohort studies (n = 3437) were included and had low- or moderate-risk of bias. Alternative insulin dosing strategies included 5 units, 0.1 units/kg, and <10 units. Alternative dosing had lower pooled odds of hypoglycemia (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.43-0.69, I2  = 8%) and severe hypoglycemia (OR 0.41, 95% CI 0.27-0.64, I2  = 0%). No difference in potassium reduction was detected (mean difference -0.02 mmol/L, 95% CI -0.11-0.07, I2  = 53%). CONCLUSIONS: Alternative insulin dosing strategies for hyperkalemia management resulted in less hypoglycemia and severe hypoglycemia without compromising potassium reduction compared to standard dose. Prospective studies are needed to confirm these findings.

Simulated sleep apnea alters hydrogen sulfide regulation of blood flow and pressure.

In sleep apnea, airway obstruction causes intermittent hypoxia (IH). In animal studies, IH-dependent hypertension is associated with loss of vasodilator hydrogen sulfide (H2S), and increased H2S activation of sympathetic nervous system (SNS) activity in the carotid body. We previously reported that inhibiting cystathionine γ-lyase (CSE) to prevent H2S synthesis augments vascular resistance in control rats. The goal of this study was to evaluate the contribution of IH-induced changes in CSE signaling to increased blood pressure and vascular resistance. We hypothesized that chronic IH exposure eliminates CSE regulation of blood pressure (BP) and vascular resistance. In rats instrumented with venous catheters, arterial telemeters, and flow probes on the main mesenteric artery, the CSE inhibitor dl-propargylglycine (PAG, 50 mg/kg/day i.v. for 5 days) increased BP in Sham rats but decreased BP in IH rats [in mmHg, Sham (n = 11): 114 ± 4 to 131 ± 6; IH (n = 8): 131 ± 8 to 115 ± 7 mmHg, P < 0.05]. PAG treatment increased mesenteric vascular resistance in Sham rats but decreased it in IH rats (day 5/day 1: Sham: 1.50 ± 0.07; IH: 0.85 ± 0.19, P < 0.05). Administration of the ganglionic blocker hexamethonium (to evaluate SNS activity) decreased mesenteric resistance in PAG-treated Sham rats more than in saline-treated Sham rats or PAG-treated IH rats. CSE immunoreactivity in IH carotid bodies compared with those from Sham rats. However, CSE staining in small mesenteric arteries was less in arteries from IH than in Sham rats but not different in larger arteries (inner diameter > 200 µm). These results suggest endogenous H2S regulates blood pressure and vascular resistance, but this control is lost after IH exposure with decreased CSE expression in resistance size arteries. IH exposure concurrently increases carotid body CSE expression and relative SNS control of blood pressure, suggesting both vascular and carotid body H2S generation contribute to blood pressure regulation.NEW & NOTEWORTHY These results suggest that CSE's protective role in the vasculature is impaired by simulated sleep apnea, which also upregulates CSE in the carotid body. Thus, this enzyme system can exert both pro- and antihypertensive effects and may contribute to elevated SNS outflow in sleep apnea.

A Randomized, Crossover Pilot Study of a Novel Web-Based/Mobile Platform for Collaborative Small Group Practice in Therapeutic Reasoning.

BACKGROUND AND PURPOSE: Therapeutic reasoning-the mental process of making judgments and decisions about treatment-is developed through acquisition of knowledge and application in actual or simulated experiences. Health professions education frequently uses collaborative small group work to practice therapeutic reasoning. This pilot study compared the impact of a web-based/mobile tool for collaborative case work and discussion to usual practice on student perceptions and performance on questions designed to test therapeutic knowledge and reasoning. METHODS: In a therapeutics course that includes case-based workshops, student teams of 3 to 4 were randomly assigned to usual workshop preparation (group SOAP sheet) or preparation using the Practice Improvement using Virtual Online Training (PIVOT) platform. PIVOT was also used in the workshop to review the case and student responses. The next week, groups crossed over to the other condition. Students rated favorability with the preparatory and in-workshop experiences and provided comments about the PIVOT platform via a survey. Student performance on examination items related to the 2 workshop topics was compared. RESULTS: One hundred and eleven students (94%) completed post-workshop surveys after both workshops. The majority of students (57%) preferred using the PIVOT platform for workshop collaboration. Favorability ratings for the in-workshop experience did not change significantly from first to second study week, regardless of sequence of exposure. There was no relationship between examination item scores and the workshop platform the students were exposed to for that content (P = .29). Student responses highlighted the efficiency of working independently before collaborating as a group and the ability to see other students' thought processes as valuable aspects of PIVOT. Students expressed frustration with the PIVOT user interface and the lack of anonymity when discussing their answers in the workshop. CONCLUSION: A web-based/mobile platform for student team collaboration on therapeutic reasoning cases discussed in small group settings yielded favorable ratings, examination performance comparable to standard approaches, and was preferred by a majority of students. During the rapid shift to substantial online learning for the COVID-19 pandemic, virtual collaboration tools like PIVOT may help health professions teachers to better support groups working virtually on scaffolded therapeutic reasoning tasks.