Consumption of endemic arbovirus mosquito vectors by bats in the southeastern United States.

Mosquitoes affect human health and well-being globally through their roles as disease-causing pathogen vectors. Utilizing genetic techniques, we conducted a large-scale dietary study of three bat species common to the southeastern U.S.A., Lasiurus seminolus (Seminole bat), Nycticeius humeralis (evening bat), and Myotis austroriparius (southeastern myotis). Through next-generation sequencing of a 180 bp portion of cytochrome oxidase subunit I (COI) of mitochondrial DNA from 180 bat guano samples, we documented consumption of 17 species of mosquitoes by bats, including six endemic arbovirus vectors. Culex quinquefasciatus, Culex coronator, Culiseta melanura, Culex salinarius, Culex erraticus, and Coquillettidia perturbans were consumed by 51.3%, 43.7%, 27.2%, 22.8%, 18.0%, and 12.7% of bats sampled, respectively. Consumption of two of these mosquito species was explained by spatial variables reflecting the prevalence of mosquito larval habitat, five were explained by bat traits (bat mass, bat species), and two were explained by these factors plus temporal variables (maximum daily temperature, time since sunset, date), making it challenging to offer specific guidance on how best to promote bats as a means of reducing arbovirus vector species. Our results show that common bat species of the southeastern U.S.A. consume endemic, but not exotic, arbovirus mosquito vectors. Future studies are needed to understand the impact of bat consumption on mosquito numbers and public health.

Detection of Hemodynamic Status Using an Analytic Based on an Electrocardiogram Lead Waveform.

OBJECTIVES: Delayed identification of hemodynamic deterioration remains a persistent issue for in-hospital patient care. Clinicians continue to rely on vital signs associated with tachycardia and hypotension to identify hemodynamically unstable patients. A novel, noninvasive technology, the Analytic for Hemodynamic Instability (AHI), uses only the continuous electrocardiogram (ECG) signal from a typical hospital multiparameter telemetry monitor to monitor hemodynamics. The intent of this study was to determine if AHI is able to predict hemodynamic instability without the need for continuous direct measurement of blood pressure. DESIGN: Retrospective cohort study. SETTING: Single quaternary care academic health system in Michigan. PATIENTS: Hospitalized adult patients between November 2019 and February 2020 undergoing continuous ECG and intra-arterial blood pressure monitoring in an intensive care setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One million two hundred fifty-two thousand seven hundred forty-two 5-minute windows of the analytic output were analyzed from 597 consecutive adult patients. AHI outputs were compared with vital sign indications of hemodynamic instability (heart rate > 100 beats/min, systolic blood pressure < 90 mm Hg, and shock index of > 1) in the same window. The observed sensitivity and specificity of AHI were 96.9% and 79.0%, respectively, with an area under the curve (AUC) of 0.90 for heart rate and systolic blood pressure. For the shock index analysis, AHI's sensitivity was 72.0% and specificity was 80.3% with an AUC of 0.81. CONCLUSIONS: The AHI-derived hemodynamic status appropriately detected the various gold standard indications of hemodynamic instability (hypotension, tachycardia and hypotension, and shock index > 1). AHI may provide continuous dynamic hemodynamic monitoring capabilities in patients who traditionally have intermittent static vital sign measurements.

Characteristics and outcomes of patients with COVID-19 at a district general hospital in Surrey, UK.

BACKGROUND: This retrospective cohort study aims to define the clinical findings and outcomes of every patient admitted to a district general hospital in Surrey with COVID-19 in March 2020, providing a snapshot of the first wave of infection in the UK. This study is the first detailed insight into the impact of frailty markers on patient outcomes and provides the infection rate among healthcare workers. METHODS: Data were obtained from medical records. Outcome measures were level of oxygen therapy, discharge and death. Patients were followed up until 21 April 2020. RESULTS: 108 patients were included. 34 (31%) died in hospital or were discharged for palliative care. 43% of patients aged over 65 died. The commonest comorbidities were hypertension (49; 45%) and diabetes (25; 23%). Patients who died were older (mean difference ±SEM, 13.76±3.12 years; p<0.0001) with a higher NEWS2 score (median 6, IQR 2.5-7.5 vs median 2, IQR 2-6) and worse renal function (median differences: urea 2.7 mmol/L, p<0.01; creatinine 4 µmol/L, p<0.05; eGFR 14 mL/min, p<0.05) on admission compared with survivors. Frailty markers were identified as risk factors for death. Clinical Frailty Scale (CFS) was higher in patients over 65 who died than in survivors (median 5, IQR 4-6 vs 3.5, IQR 2-5; p<0.01). Troponin and creatine kinase levels were higher in patients who died than in those who recovered (p<0.0001). Lymphopenia was common (median 0.8, IQR 0.6-1.2; p<0.005). Every patient with heart failure died (8). 26 (24%) were treated with continuous positive airway pressure (CPAP; median 3 days, IQR 2-7.3) and 9 (8%) were intubated (median 14 days, IQR 7-21). All patients who died after discharge (4; 6%) were care home residents. 276 of 699 hospital staff tested were positive for COVID-19. CONCLUSIONS: This study identifies older patients with frailty as being particularly vulnerable and reinforces government policy to protect this group at all costs.

Identification and functional characterization of protein kinase A-catalyzed phosphorylation of potassium channel Kv1.2 at serine 449.

Vascular smooth muscle Kv1 delayed rectifier K+ channels (KDR) containing Kv1.2 control membrane potential and thereby regulate contractility. Vasodilatory agonists acting via protein kinase A (PKA) enhance vascule smooth muscle Kv1 activity, but the molecular basis of this regulation is uncertain. We characterized the role of a C-terminal phosphorylation site, Ser-449, in Kv1.2 expressed in HEK 293 cells by biochemical and electrophysiological methods. We found that 1) in vitro phosphorylation of Kv1.2 occurred exclusively at serine residues, 2) one major phosphopeptide that co-migrated with 449pSASTISK was generated by proteolysis of in vitro phosphorylated Kv1.2, 3) the peptide 445KKSRSASTISK exhibited stoichiometric phosphorylation by PKA in vitro, 4) matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectroscopy (MS) and MS/MS confirmed in vitro Ser-449 phosphorylation by PKA, 5) in situ phosphorylation at Ser-449 was detected in HEK 293 cells by MALDI-TOF MS followed by MS/MS. MIDAS (multiple reaction monitoring-initiated detection and sequencing) analysis revealed additional phosphorylated residues, Ser-440 and Ser-441, 6) in vitro 32P incorporation was significantly reduced in Kv1.2-S449A, Kv1.2-S449D, and Kv1.2-S440A/S441A/S449A mutant channels, but Kv1.2-S440A/S441A was identical to wild-type Kv1.2 (Kv1.2-WT), and 7) bath applied 8-Br-cAMP or dialysis with PKA catalytic subunit (cPKA) increased Kv1.2-WT but not Kv1.2-S449A current amplitude. cPKA increased Kv1.2-WT current in inside-out patches. Rp-CPT-cAMPS reduced Kv1.2-WT current, blocked the increase due to 8-Br-cAMP, but had no effect on Kv1.2-S449A. cPKA increased current due to double mutant Kv1.2-S440A/S441A but had no effect on Kv1.2-S449D or Kv1.2-S440A/S441A/S449A. We conclude that Ser-449 in Kv1.2 is a site of PKA phosphorylation and a potential molecular mechanism for Kv1-containing KDR channel modulation by agonists via PKA activation.