Combinatorial quantification of distinct neural projections from retrograde tracing.

Comprehensive quantification of neuronal architectures underlying anatomical brain connectivity remains challenging. We introduce a method to identify distinct axonal projection patterns from a source to a set of target regions and the count of neurons with each pattern. A source region projecting to n targets could have 2n-1 theoretically possible projection types, although only a subset of these types typically exists. By injecting uniquely labeled retrograde tracers in k target regions (k < n), one can experimentally count the cells expressing different color combinations in the source region. The neuronal counts for different color combinations from n-choose-k experiments provide constraints for a model that is robustly solvable using evolutionary algorithms. Here, we demonstrate this method's reliability for 4 targets using simulated triple injection experiments. Furthermore, we illustrate the experimental application of this framework by quantifying the projections of male mouse primary motor cortex to the primary and secondary somatosensory and motor cortices.

Combinatorial quantification of distinct neural projections from retrograde tracing.

Comprehensive quantification of neuronal architectures underlying anatomical brain connectivity remains challenging. We introduce a method to identify the distinct axonal projection patterns from a source to a set of target regions and the count of neurons with each pattern. For a source region projecting to n targets, there are 2n - 1 theoretically possible projection types, although only a subset of these types typically exists. By injecting uniquely labeled retrograde tracers in k regions (k < n), one can experimentally count the cells expressing different combinations of colors in the source region1,2. Such an experiment can be performed for n choose k combinations. The counts of cells with different color combinations from all experiments provide constraints for a system of equations that include 2n - 1 unknown variables, each corresponding to the count of neurons for a projection pattern. Evolutionary algorithms prove to be effective at solving the resultant system of equations, thus allowing the determination of the counts of neurons with each of the possible projection patterns. Numerical analysis of simulated 4 choose 3 retrograde injection experiments using surrogate data demonstrates reliable and precise count estimates for all projection neuron types. We illustrate the experimental application of this framework by quantifying the projections of mouse primary motor cortex to four prominent targets: the primary and secondary somatosensory and motor cortices.

Casirivimab/imdevimab treatment for outpatient COVID-19 during a SARS-CoV-2 B1.617.2 (Delta) surge at a community hospital.

CONTEXT: Vaccination status has been shown to be linked to patient-centered outcomes in those with COVID-19. However, minimal data have explored the relationship between vaccination status and representation rates after receiving monoclonal antibodies (MABs) the Delta strain of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in a community setting. OBJECTIVES: The authors sought to determine if there was a difference in patient-centered outcomes between those who were vaccinated and unvaccinated after the administration of casirivimab/imdevimab for mild-to-moderate COVID-19 during the time when the Delta strain was most prevalent. METHODS: A convenience sample of consecutive adults given casirivimab/imdevimab at either an outpatient infusion center or within the emergency department (ED) were included in analysis. Patient demographics, authorized-use qualifiers from the emergency use authorization (EUA), baseline vital signs at the time of infusion, representation rates to a healthcare provider within the hospital's network, and any admissions to the hospital following infusion were all collected from the patient's electronic medical record. Vaccination status was confirmed in both the patient's electronic medical record and the Arizona State Immunization Information System (ASIIS). Analysis was conducted utilizing descriptive statistics, the Mann-Whitney U test for continuous data, and the chi-squared analysis for nominal data. RESULTS: In total, 743 patients were included in the study, with 585 being unvaccinated and 158 being vaccinated at the time of administration. Those in the vaccinated group were more likely to be older (60.0 vs. 55.0 years; p<0.001) and to have a history of diabetes (18.4% vs. 11.3%; p=0.02), hypertension (39.9% vs. 28.5%; p=0.006), immunosuppression (7.0% vs. 1.4%; p<0.001), and chronic kidney disease (7.0% vs. 3.4%; p=0.05). In the entire sample, 105 (14.1%) patients had an unexpected return visit to either the ED or urgent care at 28 days, with 17 (2.3%) requiring hospitalization. Patients who were vaccinated were more likely to represent for care after casirivimab/imdevimab infusion (20.3% vs. 12.5%; p=0.01), but no difference was noted in hospitalization rates between the two groups (18.8% vs. 15.1%; p=0.15). CONCLUSIONS: MAB therapy with casirivimab/imdevimab for the outpatient treatment of mild-to-moderate COVID-19 was associated with a low rate of hospitalization. However, those who were vaccinated were more likely to present for unexpected return care at either the ED or urgent care within 28 days of the initial infusion.

A Comparison of Inhaled Epoprostenol in Patients With Acute Respiratory Distress Syndrome and COVID-19-Associated Acute Respiratory Distress Syndrome.

Introduction Acute respiratory distress syndrome (ARDS) and coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (CARDS) are both characterized by non-cardiogenic pulmonary edema and severe hypoxemia that leads to a high percentage of patients suffering in-hospital mortality. Mechanistically, inhaled epoprostenol (iEPO) has shown a role in the treatment of ARDS and CARDS but little data are available directly comparing the two disease processes. Due to the lack of evidence of iEPO in ARDS and CARDS, the authors sought to compare the pulmonary effects of iEPO for mechanically ventilated patients with CARDS against a case match control of those with ARDS. Methods A retrospective cohort of all patients receiving iEPO between January 1, 2020, and February 22, 2022, was reviewed. Patients with ARDS were case-matched in a 2:1 allocation ratio of CARDS to ARDS by the number of medical comorbidities and age +/- 5 years. Clinical data collected included patient demographics, laboratory values, ventilator settings, length of hospitalization, and 28-day mortality. Comparisons of the effectiveness of iEPO between ARDS and CARDS were conducted using the chi-squared statistic for categorical variables and the Mann-Whitney statistic for continuous variables. Results A total of 72 patients were included in the final analysis, with 24 having ARDS and 48 CARDS. The number of medical comorbidities was no different for patients with ARDS or CARDs (p = 0.18), though the frequency of patients diagnosed with coronary artery disease (p=0.007), congestive heart failure (p=0.003), chronic obstructive pulmonary disease (p=0.004), and pulmonary hypertension (p=0.004) did vary between the two groups. A moderate but non-significant difference in pre-iEPO partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio was noted between the groups (0.74 vs 0.65; p=0.33). Following iEPO treatment, patients with ARDS showed a greater PaO2/FiO2 ratio than those with CARDS (0.87 vs 0.70; p=0.02). CARDS patients who received iEPO had a longer length of stay as compared to those with ARDS (17.5 vs 12.5 days; p=0.01). However, no difference was noted in 28-day mortality between the two groups (14 vs 34; p=0.29). Conclusion In this small sample from a single community hospital, a statistically significant improvement in the PaO2/FiO2 ratio was noted for both those with ARDS and CARDS. However, those with CARDS who were given iEPO had a longer length of stay without a significant difference in mortality as compared to those with traditional ARDS.

Multisite assessment of emergency medicine resident knowledge of evidence-based medicine as measured by the Fresno Test of Evidence-Based Medicine.

CONTEXT: Evidence-based medicine (EBM) is the application of scientific evidence while treating a patient. To date, however, there is very little evidence describing how residents in emergency medicine understand and incorporate EBM into practice. OBJECTIVES: The aim of this study was to determine EBM theoretical and quantitative knowledge in emergency medicine residents in community hospital-based training programs. METHODS: A sample of emergency medicine residents from nine hospitals was enrolled to complete a cross-sectional assessment of EBM skills from April 2021 through June 2021. Performance on the Fresno Test of Evidence-Based Medicine (FTEBM) was assessed utilizing descriptive statistics, t tests, and one-way analysis of variance. RESULTS: A total of 50.8% (124/244) of current emergency medicine residents completed the FTEBM during the study period. No significant difference on FTEBM scores was noted between the different types of medical degrees (DO vs. MD) (p=0.511), holding an advanced research degree (p=0.117), or between each postgraduate year of training (p=0.356). The mean score of those residents who rated their knowledge of EBM as average or higher was 36.0% (32.8-39.1%). The mean score of those residents who rated their programs as having an "average" or higher institutional focus on EBM was 34.9% (32.2-37.6%). CONCLUSIONS: Participating emergency medicine residents show an incomplete understanding of EBM both in theory and applied computations despite rating themselves as having an average understanding. Emergency medicine residencies would be well suited to implement a standardized EBM curriculum that focuses on longitudinal reinforcement of key concepts needed for the practicing physician.

Analysis of Smoking Behavior in Patients With Peritonsillar Abscess: A Rural Community Hospital's Experience.

Background Peritonsillar abscesses (PTA) are the most common deep space infection of the head and neck. They appear to have an association with a patient's smoking history but data showing this relationship is sparse and controversial. Currently, no data on this association exists for those who seek care at a rural community emergency department (ED). Based upon the lack of data in this setting, the authors sought to determine the incidence, treatments, and outcomes between smokers and non-smokers with a PTA at a rural community ED. Methods A retrospective chart review of all patients undergoing a soft tissue neck computed tomography (CT) scan with or without intravenous contrast was completed from September 25th, 2019 through October 4th, 2021. Patients with a previously diagnosed PTA and those diagnosed via another means (clinical, needle aspiration, etc.), or outside of the ED were excluded from the dataset. Abstracted data included demographics, treatments, and outcomes of each patient. The data were analyzed using the Mann-Whitney test for continuous data and the chi-square test for categorical data. Results During the study period, a total of 50 patients were diagnosed with a PTA via soft tissue neck CT. Of those diagnosed, the median age was 40.5 (25.5 - 53.3) years, 15 were female, 38 self-identified as white, and 27 noted a current smoking history. Smokers presented to ED earlier than non-smokers (2.0 vs 4.0 days; p=0.03), but no difference was noted in the size of PTA identified via CT (2.0 vs 1.5 cm; p=0.13). No difference among smokers and non-smokers was noted in corticosteroid therapy either administered in the ED (p = 0.53) or prescribed as an outpatient (p = 0.75), incision and drainage (p = 0.19), outpatient follow-up (p = 0.53), or resolution of the symptoms (p = 0.86). However, more patients in the non-smoking group had an unplanned return to the ED as compared to those who smoked (p=0.02). In those patients who were not discharged from the ED after initial presentation, four were admitted to the hospital and 11 were transferred to a higher level of care. Conclusion Although drawn from a limited sample from a single rural community ED, a positive smoking history was more common among patients with a PTA. While there was no statistically significant difference in the overall treatment, a difference was noted for unscheduled return visits to the ED in those without a history of smoking.

Real world utilization of Dalbavancin at a rural community emergency department.

INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSI) are frequently encountered in the emergency department and compromise more than 700,000 hospital admissions annually. Dalbavancin is a single dose long acting semi-synthetic lipogylcopepitde antibiotic with coverage against gram-positive organisms including methicillin resistant Staphylococcus aureus. Recent data from large tertiary care centers have shown a decrease in hospital admissions and repeat emergency department visits for ABSSI's but little data is available for those who practice in a rural community setting. The primary objective of this study was to describe the use of dalbavancin at a single rural emergency department. METHODS: A retrospective cohort study of all adult patients who received dalbavancin between 2019 and 2021 while in the emergency department was completed. Abstracted data included patient demographics, infection location by body region, emergency department return visits, hospital admissions, and length of stay. Analysis was conducted using descriptive statistics, the Mann-Whitney test for continuous data, and the chi-squared analysis for nominal data. RESULTS: A total of 125 patients were included in the final analysis with 35.2% being female. The median age of those treated with dalbavancin was 54 years (42.0-64.0) and the most common infection site was the lower extremities. A total of 35 patients re-presented to the emergency department following treatment with dalbavancin within 30 days and 16 were admitted to the hospital. Of those who re-presented to the emergency department, the median age was 56 (40.0-66.0) and the median re-presentation was 9 days (3-17) after dalbavancin administration. A total of 16 patients (12.8%) were subsequently admitted to the hospital with a median length of stay of 5.5 days (3.0-8.0). 30-day readmission rates were 23.9% in those who had an abnormal WBC count at initial presentation, 26.1% for those with congestive heart failure, 20.3% for those with hypertension, and 26.0% in those who had diabetes mellitus. CONCLUSION: Following the administration of dalbavancin for ABSSI at a rural emergency department, few patients are subsequently admitted within the following 30 days. To further decrease this number and alleviate the burden on emergency departments and hospitals, local treatment algorithms should be developed to minimize the risk of representation and hospitalization following administration.

Real World Utilization of Bamlanivimab at a Rural Community Hospital.

Introduction Although there were several proposed treatments for patients that were hospitalized with COVID-19, outpatient treatments for those with mild to moderate illness were limited prior to the emergency use authorization (EUA) of virus-neutralizing monoclonal antibodies. To assess the efficacy of outpatient monoclonal therapy, the investigators assessed the seven, 14, and 28-day emergency department and hospitalization rates of adult patients given bamlanivimab for the treatment of COVID-19 at a community hospital. Methods A retrospective chart review was performed of all adult patients given bamlanivimab within the emergency department or an outpatient infusion center from December 2, 2020 through January 8, 2021 for the treatment of mild to moderate COVID-19. Patients were compared to a set of controls who would have qualified for bamlanivimab treatment prior to its authorization in reverse temporal order from November 30, 2020 through August 1, 2020. Abstracted data included patient demographics, allergic reactions, emergency department presentations, and hospitalizations at seven, 14, and 28 days post-infusion due to COVID-19 and any in-hospital mortality in those admitted with a COVID-19 complication.  Results A total of 136 patients received bamlanivimab during the study period with none having an allergic reaction during infusion. In those who received bamlanivimab, 84 (61.8%) patients included were aged 65 years or older. At 28 days, there was a statistically significant reduction in emergency department visits in those who received bamlanivimab (20 vs 36 patients; p = 0.03) but not at seven days (12 vs 20 patients; p = 0.18) or 14 days (17 vs 28 patients; p = 0.11). No statistically significant difference in emergency department returns was noted in those aged 65 years or older at seven (eight vs eight patients; p = 0.70), 14 (11 vs 10 patients; p = 0.83), or 28 days (13 vs 14 patients, p = 0.46). A total of six (4.4%) patients were hospitalized at 28 days following the bamlanivimab infusion with five (83.3%) being aged 65 or older. No statistical difference was noted for decreased hospitalizations at seven (four vs five patients; p = 0.79), 14 (five vs nine patients; p = 0.32), or 28 days (six vs nine patients; p = 0.49) post-infusion. No patients suffered from in-hospital mortality after infusion with bamlanivimab. Conclusion Outpatient infusion of bamlanivimab reduced the incidence of those with mild to moderate COVID-19 requiring subsequent care through the emergency department at 28 days but not hospitalizations within this time frame. No statistical difference was noted in either emergency department visits or hospitalizations in those aged 65 or greater who were treated as an outpatient with bamlanivimab for mild to moderate COVID-19.

The mouse cortico-basal ganglia-thalamic network.

The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.

Incidence of Non-thrombotic Diagnoses Following Venous Duplex Ultrasound at a Community Emergency Department.

BACKGROUND:  When used as a diagnostic aid for diagnosing deep vein thrombosis (DVT), venous duplex ultrasound (US) may reveal non-thrombotic findings in those with acute extremity pain. The objective of this study was to determine the prevalence and predictors of non-thrombotic findings on venous duplex US at a community emergency department. METHODS: A retrospective chart review of all adult patients who presented to a community emergency department who underwent either an upper or lower extremity venous duplex US for the evaluation of DVT from June 1, 2019, to September 15, 2020. All US studies were completed by certified sonographers and interpreted by board-certified radiologists. Two trained research assistants manually abstracted patient demographics and US findings. Data were analyzed using the chi-square statistic for categorical variables and the student's independent t-test for continuous variables. Multivariate binomial regression was used to identify independent predictors of non-thrombotic results on venous duplex US. RESULTS: A total of 1,448 venous duplex US were obtained during the study period with 126 DVTs being diagnosed. A total of 1071 US had no acute abnormality and 252 had non-thrombotic findings. All non-thrombotic findings were found in the lower extremity. Of those with non-thrombotic findings, the most common diagnoses included edema (34.9%, 88/252), Baker's cyst (22.6%, 57/252), and an unspecified fluid collection (16.3%, 41/252). Patients with non-thrombotic findings were more likely to have a history of atrial fibrillation (p=0.001) or hypertension (p=0.001), be older than the age of 70 (p=0.042), or have a history of using illicit drugs (p=0.003). Females were less likely to have non-thrombotic findings. CONCLUSION: In this single-site study, non-thrombotic findings were present in 23.5% of all venous duplex US completed at a community emergency department. These findings are more common in the elderly, those with cardiovascular disorders, and those who have used illicit drugs.

Real world utilization of REGEN-COV2 at a community hospital.

INTRODUCTION: Monoclonal antibodies received an Emergency Use Authorization (EUA) from the U.S. Food & Drug Administration for the outpatient treatment of mild to moderate coronavirus disease 2019 (COVID-19). REGN-COV2, casirivimab and imdevimab, has been shown to decrease the viral load and healthcare visits of those with mild to moderate COVID-19 who are treated in the outpatient setting. OBJECTIVE: To determine 7- and 14-day emergency department (ED) and hospitalization rates of adult patients given REGN-COV2 for the outpatient treatment of COVID-19 at a community hospital. METHODS: A convenience sample of consecutive adult patients given REGN-COV2 from January 18, 2021 through March 31, 2021 for the outpatient treatment of mild to moderate COVID-19. Abstracted data included patient demographics, allergic reactions, ED presentations and hospitalizations at 7 and 14 days, and in-hospital mortality. RESULTS: A total of 68 patients with a medain age of 69 years (IQR 57-75.5) and 58.3% being female were given REGEN-COV2 during the study period. No allergic reactions were noted during infusion. Of those infused, 18% (12/68) were infused in the ED and had a median length of stay of 477 min. Following infusion, 10% (7/68) of patients re-presented to the ED and 2% (1/68) were hospitalized for COVID-19 at 14 days. In those aged 65 years or greater, 12% (5/42) of patients re-presented to the ED following infusion. Of those who re-presented to the emergency department, the median age was 72.5 years and the median time from infusion to re-presentation was 2.0 days. No patients suffered in-hospital mortality during the study period. CONCLUSION: There was a significant length of stay associated with REGN-COV2 infusion in the emergency department. Following REGN-COV2 infusion, few patients under the age of 65 re-presented to the emergency department at seven and 14 days. However, a large number of patients aged over 65 years re-presented to the ED following infusion.

Gender Differences in Language of Standardized Letter of Evaluation Narratives in Osteopathic Emergency Medicine Residency Applicants.

Background The standardized letter of evaluation (SLOE) is used by emergency medicine (EM) faculty during the interview and match process. Data has shown that female allopathic applicants score higher in communal characteristics and have a greater number of ability words in the narrative portion of the SLOE as compared to their male counterparts.  Objective To determine if there is a difference in the language used to describe male and female osteopathic applicants within the SLOE.  Methods All applicants to a three-year EM residency within a single application cycle were eligible for inclusion. Exclusion criteria included allopathic applicants, applicants without a SLOE, or applicants with a SLOE only from the interviewing program. Data collected included applicant demographics and SLOE narratives. The previously validated Linguistic Inquiry and Word Count (LIWC; Pennebaker Conglomerates, Inc., Austin, TX) product was used to analyze word counts from the narrative portion of each SLOE. Descriptive statistics and t-tests for continuous data were used.  Results Of the 577 applicants to the residency program, 318 met inclusion criteria and 33% were female. Females had a higher COMLEX-2 (590 vs 559; p=0.05) as compared to males but no difference was found for the remainder of the baseline demographics. No difference was found for the number of words in the narrative portion of the SLOE between males and females (males = 122 words; females = 127 words; p=0.53). Words within the social (p=0.006), achievement (p=0.007), and standout (p<0.001) categories were more frequent in osteopathic female applicants as compared to males. No statistical differences were detected for the other 13 categories analyzed.  Conclusion In this sample of osteopathic applicants, little linguistic difference was noted for the narrative portion of the SLOE. SLOE authors did, however, use more social, achievement, and standout words to describe females as compared to male applicants.

Impact of the COVID-19 Pandemic on Emergency Department Transfers to a Higher Level of Care.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, a reduction in emergency department (ED) visits was seen nationally according to the US Centers for Disease Control and Prevention. However, no data currently exists for the impact of ED transfers to a higher level of care during this same time period. The primary objective of the study was to determine whether the COVID-19 pandemic affected the rate of non-COVID-19 transfers from a rural community ED. METHODS: We completed a retrospective chart review of all ED patients who presented to Kingman Regional Medical Center in Kingman, Arizona, from March 1-June 31, 2019 and March 1-June 31, 2020. To ensure changes were not due to seasonal trends, we examined transfer rates from the same four-month period in 2019 and 2020. Patients were included in the study if they were transferred to an outside facility for a higher level of care not related to COVID-19. RESULTS: Between the time periods studied there was a 25.33% (P = 0.001) reduction in total ED volume and a 21.44% (P = 0.009) reduction in ED transfers to a higher level of care. No statistical difference was noted in ED transfer volume following adjustment for decreased ED volumes. Transfers for gastroenterology (45%; P = 0.021), neurosurgery (29.2%; P = 0.029), neurology (76.3%; P < 0.001), trauma (37.5%; P = 0.039), urology (41.8%; P = 0.012), and surgery (56.3%; P = 0.028) all experienced a decrease in transfer rates during the time period studied. When gender was considered, males exhibited an increased rate of transfers to psychiatric facilities (P = 0.018). CONCLUSION: Significant reductions in both ED volume and transfers have coincided with the emergence of the COVID-19 pandemic. Further research is needed to determine how the current pandemic has affected patient care.

National Institutes of Health Funding in Internal Medicine: Analysis of Physicians Receiving an R01 Grant Between 2008 and 2017.

Introduction As the world's largest funding source for biomedical research, the National Institutes of Health (NIH) supports physician-scientists with a discipline-specific R01 grant. Recently, scholarly activity disparities regarding investigator degree and gender have been highlighted in the medical literature among allopathic and osteopathic investigators of various medical backgrounds. We aimed to assess trends in internal medicine NIH R01 grants over the past decade. Methodology Internal medicine R01 funding was retrospectively obtained from a centralized online NIH database encompassing 2008 through 2017. Principal investigators (PIs) were then categorized by gender and academic degree(s). Two-way analysis of variance was used to analyze NIH grant funding trends over the time period studied. Results A total of 5,089 NIH R01s were awarded to internal medicine PIs, with an average value per grant of $469,270. Awardees were predominantly male (71.5%, 3,639/5,089). Most awards were issued to PIs with an MD degree (62.4%, 3,173/5,089), followed by PhD degree (36.3%, 1,845/5,089). DOs accounted for five awards over the time period studied (0.15%). MDs were awarded higher funding than PhDs ($466,494 and $421,576, p < 0.001), and females were awarded higher amounts than males ($462,771 and $444,868, p < 0.001). Investigators who held a second degree received more funding than PIs with a single degree ($476,693 and $439,693, p < 0.001). Conclusion In the decade under investigation, both gender and degree disparities existed within NIH R01 funding for PIs in the field of internal medicine, and osteopathic representation accounted for a paucity of R01 funding.

The seroprevalence of SARS-CoV-2 in a rural southwest community.

Context: The true prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has been difficult to determine due to limited testing, inconsistent symptom severity, and asymptomatic infections. Systematic investigation of the prevalence of SARS-CoV-2 has been limited to urban environments and large academic centers. Limited data on the seroprevalence of SARS-CoV-2 is available for those who live in a rural community setting, leaving rural practitioners to extrapolate the epidemiology of COVID-19 to a nonhomogeneous population. Objective: To determine the seroprevalence of SARS-CoV-2 in a community setting. The secondary objective of this study was to describe the difference in infection rate and reverse transcription polymerase chain reaction (RT-PCR) testing in the same rural community. Methods: A prospective convenience sample of community members and healthcare workers from the Kingman, Arizona area were tested for SARS-CoV-2-specific antibodies using a lateral flow immunoassay with the VITROS Anti-SARS-CoV-2 IgG test (Ortho-Clinical Diagnostics, Inc.) from September 28, 2020 to October 09, 2020. Upon recruitment, participants were asked to complete a demographic survey assessing socioeconomic status, comorbidities, and COVID-19 symptoms in the preceding two months. Following enrollment, a retrospective chart review was completed to determine the percentage of patients who had undergone previous SARS-CoV-RT-PCR testing. Results: A total of 566 participants were included in the final analysis: 380 (67.1%) were women, 186 (32.9%) were men, a majority (458; 80.9%) self-identified as White, and 303 (53.5%) were employed as healthcare professionals. Seroprevalence of SARS-CoV-2 was found to be 8.0% (45 of 566) across the sample and 9.9% (30 of 303) in healthcare workers. No statistical difference in seroprevalence was found between men and women, healthcare workers and other participants, amongst racial groups, by socioeconomic status, by comorbid conditions, or by education level. Among the participants, 108 (19.1%) underwent previous RT-PCR testing. Of the 45 patients who were antibody positive, 27 (60%) had received a previous RT-PCR test, with 20 (44.4%) testing positive for SARS-CoV-2. Participants with symptoms of anosmia/ageusia (p<0.001), chest congestion (p=0.047), fever (p=0.007), and shortness of breath (p=0.002) within the past two months were more likely to have antibodies to SARS-CoV-2. Conclusion: Only 8% of 566 participants in this rural community setting were found to have antibodies for SARS-CoV-2. A large minority (18; 40%) of patients testing seropositive for SARs-CoV-2 had never received a prior test, suggesting that the actual rates of infection are higher than publicly available data suggest. Further large-scale antibody testing is needed to determine the true prevalence of SARS-CoV-2 in the rural setting.

Remdesivir for the Treatment of Severe COVID-19: A Community Hospital's Experience.

Context: Following the emergence of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), researchers sought safe and effective treatment modalities. Remdesivir is currently being evaluated for clinical efficacy and safety in patients with COVID-19. Objective: To describe the clinical outcomes of COVID-19 patients following treatment with remdesivir at a community hospital. Methods: A retrospective review of medical records was conducted in August 2020 for all patients given remdesivir while hospitalized for severe COVID-19 between May 1 and August 19, 2020. A convenience sample of consecutive patients with treatment including remdesivir, antibiotics, convalescent plasma, dexamethasone, or a combination of multiple drugs was included in the analysis. Patients receiving remdesivir were administered a 5-day treatment course. Patients with a glomerular filtration rate of less than 30 mL/min, those with liver function tests 5 times the normal reference range, and those who were pregnant were excluded from treatment with remdesivir. Differences in between men and women were detected with χ2 and independent samples t tests. The degree to which presenting symptoms influenced patient outcomes was analyzed with a stepwise logistic regression. Results: Among the 76 patients who received remdesivir, the mean (95% confidence interval, CI) age was 63 years (59.8-66.2). Thirty-six (47.4%) were men and 40 (52.6%) were women. Forty-nine (64.5%) were White and 27 (35.5%) were nonWhite. The majority of patients (54; 71.1%) had at least 1 comorbid condition, with hypertension being the most common (43; 56.6%). The mean (95% CI) length of stay for patients who received remdesivir was 10.09 days (8.6-11.6) and the mean (95% CI) duration of oxygen therapy was 9.42 days (8.0-10.8). A total of 14 (18.4%) patients given remdesivir were admitted to the intensive care unit (ICU) with an mean (95% CI) length of stay of 9.29 days (5.6-13.0). Women administered remdesivir were more likely to be admitted to the ICU (11 [27.5%] vs 3 [8.3%]; P=.031). The mortality rate was 14 patients (18.4%), with no statistically significant difference observed between men (5; 13.9%) and women (9; 22.5%; P=.33). No significant difference was seen amongst sexes for duration of oxygen therapy (men, 8.0 days [6.2-9.8] vs women, 10.76 days [8.8-12.8]; P=.051) or length of stay (men, 8.61 days [6.7-10.5] vs women, 11.43 days [9.3-13.5]; P=.058). There was no statistically significant difference in pooled racial groups (White vs nonWhite) for in-hospital mortality, number admitted to the ICU, days spent in the ICU, duration of oxygen use, or length of stay. Conclusion: Remdesivir may show clinical efficacy for the treatment of severe COVID-19 in a community setting. Although this was a small-scale study with limited patients, it represents a point of reference for the use of remdesivir at other community hospitals.

Contextual fear retrieval-induced Fos expression across early development in the rat: An analysis using established nervous system nomenclature ontology.

The neural circuits underlying the acquisition, retention and retrieval of contextual fear conditioning have been well characterized in the adult animal. A growing body of work in younger rodents indicates that context-mediated fear expression may vary across development. However, it remains unclear how this expression may be defined across the full range of key developmental ages. Nor is it fully clear whether the structure of the adult context fear network generalizes to earlier ages. In this study, we compared context fear retrieval-induced behavior and neuroanatomically constrained immediate early-gene expression across infant (P19), early and late juvenile (P24 and P35), and adult (P90) male Long-Evans rats. We focused our analysis on neuroanatomically defined subregions and nuclei of the basolateral complex of the amygdala (BLA complex), dorsal and ventral portions of the hippocampus and the subregions of the medial prefrontal cortex as defined by the nomenclature of the Swanson (2004) adult rat brain atlas. Relative to controls and across all ages tested, there were greater numbers of Fos immunoreactive (Fos-ir) neurons in the posterior part of the basolateral amygdalar nuclei (BLAp) following context fear retrieval that correlated statistically with the expression of freezing. However, Fos-ir within regions having known connections with the BLA complex was differentially constrained by developmental age: early juvenile, but not adult rats exhibited an increase of context fear-dependent Fos-ir neurons in prelimbic and infralimbic areas, while adult, but not juvenile rats displayed increases in Fos-ir neurons within the ventral CA1 hippocampus. These results suggest that juvenile and adult rodents may recruit developmentally unique pathways in the acquisition and retrieval of contextual fear. This study extends prior work by providing a broader set of developmental ages and a rigorously defined neuroanatomical ontology within which the contextual fear network can be studied further.

Sexual differentiation of contextual fear responses.

Development and sex differentiation impart an organizational influence on the neuroanatomy and behavior of mammalian species. Prior studies suggest that brain regions associated with fear motivated defensive behavior undergo a protracted and sex-dependent development. Outside of adult animals, evidence for developmental sex differences in conditioned fear is sparse. Here, we examined in male and female Long-Evans rats how developmental age and sex affect the long-term retention and generalization of Pavlovian fear responses. Experiments 1 and 2 describe under increasing levels of aversive learning (three and five trials) the long-term retrieval of cued and context fear in preadolescent (P24 and P33), periadolescent (P37), and adult (P60 and P90) rats. Experiments 3 and 4 examined contextual processing under minimal aversive learning (1 trial) procedures in infant (P19, P21), preadolescent (P24), and adult (P60) rats. Here, we found that male and female rats display a divergent developmental trajectory in the expression of context-mediated freezing, such that context fear expression in males tends to increase toward adulthood, while females displayed an opposite pattern of decreasing context fear expression toward adulthood. Longer (14 d) retention intervals produced an overall heightened context fear expression relative to shorter (1 d) retention intervals an observation consistent with fear incubation. Male, but not Female rats showed increasing generalization of context fear across development. Collectively, these findings provide an initial demonstration that sexual differentiation of contextual fear conditioning emerges prior to puberty and follows a distinct developmental trajectory toward adulthood that strikingly parallels sex differences in the etiology and epidemiology of anxiety and trauma- and stressor-related disorders.

Conditioning- and time-dependent increases in context fear and generalization.

A prominent feature of fear memories and anxiety disorders is that they endure across extended periods of time. Here, we examine how the severity of the initial fear experience influences incubation, generalization, and sensitization of contextual fear memories across time. Adult rats were presented with either five, two, one, or zero shocks (1.2 mA, 2 sec) during contextual fear conditioning. Following a recent (1 d) or remote (28 d) retention interval all subjects were returned to the original training context to measure fear memory and/or to a novel context to measure the specificity of fear conditioning. Our results indicate rats that received two or five shocks show an "incubation"-like enhancement of fear between recent and remote retention intervals, while single-shocked animals show stable levels of context fear memory. Moreover, when fear was tested in a novel context, 1 and 2 shocked groups failed to freeze, whereas five shocked rats showed a time-dependent generalization of context memory. Stress enhancement of fear learning to a second round of conditioning was evident in all previously shocked animals. Based on these results, we conclude that the severity or number of foot shocks determines not only the level of fear memory, but also the time-dependent incubation of fear and its generalization across distinct contexts.