Vicarious excretion of 99mTc-pyrophosphate in the gallbladder.

Vicarious excretion of tracer and contrast media is a known phenomenon and is not fully understood [1,2]. We report a case of unexpected vicarious excretion of 99mTc-pyrophosphate in the gallbladder seen on a scan performed to evaluate suspected cardiac amyloidosis, which is the first report of this phenomenon to the best of our knowledge.

Discovery and Synthesis of Hydroxy-l-Proline Blockers of the Neutral Amino Acid Transporters SLC1A4 (ASCT1) and SLC1A5 (ASCT2).

As a conformationally restricted amino acid, hydroxy-l-proline is a versatile scaffold for the synthesis of diverse multi-functionalized pyrrolidines for probing the ligand binding sites of biological targets. With the goal to develop new inhibitors of the widely expressed amino acid transporters SLC1A4 and SLC1A5 (also known as ASCT1 and ASCT2), we synthesized and functionally screened synthetic hydroxy-l-proline derivatives using electrophysiological and radiolabeled uptake methods against amino acid transporters from the SLC1, SLC7, and SLC38 solute carrier families. We have discovered a novel class of alkoxy hydroxy-pyrrolidine carboxylic acids (AHPCs) that act as selective high-affinity inhibitors of the SLC1 family neutral amino acid transporters SLC1A4 and SLC1A5. AHPCs were computationally docked into a homology model and assessed with respect to predicted molecular orientation and functional activity. The series of hydroxyproline analogs identified here represent promising new agents to pharmacologically modulate SLC1A4 and SLC1A5 amino acid exchangers which are implicated in numerous pathophysiological processes such as cancer and neurological diseases.

Generation and characterization of a knock-in mouse model for spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM).

Solute carrier family 1 member 4 (SLC1A4), also referred to as Alanine/Serine/Cysteine/Threonine-preferring Transporter 1 (ASCT1), is a sodium-dependent neutral amino acid transporter. It is expressed in many tissues, including the brain, where it is expressed primarily on astrocytes and plays key roles in neuronal differentiation and development, maintaining neurotransmitter homeostasis, and N-methyl-D-aspartate neurotransmission, through regulation of L- and D-serine. Mutations in SLC1A4 are associated with the rare autosomal recessive neurodevelopmental disorder spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM, OMIM 616657). Psychomotor development and speech are significantly impaired in these patients, and many develop seizures. We generated and characterized a knock-in mouse model for the most common mutant allele, which results in a single amino acid change (p.Glu256Lys, or E256K). Homozygous mutants had increased D-serine uptake in the brain, microcephaly, and thin corpus callosum and cortex layer 1. While p.E256K homozygotes showed some significant differences in exploratory behavior relative to wildtype mice, their performance in assays for motor coordination, endurance, learning, and memory was normal, and they showed no significant differences in long-term potentiation. Taken together, these results indicate that the impact of the p.E256K mutation on cognition and motor function is minimal in mice, but other aspects of SLC1A4 function in the brain are conserved. Mice homozygous for p.E256K may be a good model for understanding the developmental basis of the corpus callosum and microcephaly phenotypes observed in SPATCCM patients and assessing whether they are rescued by serine supplementation.

Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints.

Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that <25% PrP suppression is sufficient to extend survival and delay symptoms in a prophylactic paradigm. Rise in both neuroinflammation and neuronal injury markers can be reversed by a single dose of PrP-lowering ASO administered after the detection of pathological change. Chronic ASO-mediated suppression of PrP beginning at any time up to early signs of neuropathology confers benefit similar to constitutive heterozygous PrP knockout. Remarkably, even after emergence of frank symptoms including weight loss, a single treatment prolongs survival by months in a subset of animals. These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general, as a promising path forward against prion disease.

Reduced Expression of the PP2A Methylesterase, PME-1, or the PP2A Methyltransferase, LCMT-1, Alters Sensitivity to Beta-Amyloid-Induced Cognitive and Electrophysiological Impairments in Mice.

Beta-amyloid (Aß) is thought to play a critical role in Alzheimer's disease (AD), and application of soluble oligomeric forms of Aß produces AD-like impairments in cognition and synaptic plasticity in experimental systems. We found previously that transgenic overexpression of the PP2A methylesterase, PME-1, or the PP2A methyltransferase, LCMT-1, altered the sensitivity of mice to Aß-induced impairments, suggesting that PME-1 inhibition may be an effective approach for preventing or treating these impairments. To explore this possibility, we examined the behavioral and electrophysiological effects of acutely applied synthetic Aß oligomers in male and female mice heterozygous for either a PME-1 KO or an LCMT-1 gene-trap mutation. We found that heterozygous PME-1 KO mice were resistant to Aß-induced impairments in cognition and synaptic plasticity, whereas LCMT-1 gene-trap mice showed increased sensitivity to Aß-induced impairments. The heterozygous PME-1 KO mice produced normal levels of endogenous Aß and exhibited normal electrophysiological responses to picomolar concentrations of Aß, suggesting that reduced PME-1 expression in these animals protects against Aß-induced impairments without impacting normal physiological Aß functions. Together, these data provide additional support for roles for PME-1 and LCMT-1 in regulating sensitivity to Aß-induced impairments, and suggest that inhibition of PME-1 may constitute a viable therapeutic approach for selectively protecting against the pathologic actions of Aß in AD.SIGNIFICANCE STATEMENT Elevated levels of ß-amyloid (Aß) in the brain are thought to contribute to the cognitive impairments observed in Alzheimer's disease patients. Here we show that genetically reducing endogenous levels of the PP2A methylesterase, PME-1, prevents the cognitive and electrophysiological impairments caused by acute exposure to pathologic concentrations of Aß without impairing normal physiological Aß function or endogenous Aß production. Conversely, reducing endogenous levels of the PP2A methyltransferase, LCMT-1, increases sensitivity to Aß-induced impairments. These data offer additional insights into the molecular factors that control sensitivity to Aß-induced impairments, and suggest that inhibiting PME-1 may constitute a viable therapeutic avenue for preventing Aß-related impairments in Alzheimer's disease.

Rapid Screening of Aedes aegypti Mosquitoes for Susceptibility to Insecticides as Part of Zika Emergency Response, Puerto Rico.

In response to the 2016 Zika outbreak, Aedes aegypti mosquitoes from 38 locations across Puerto Rico were screened using Centers for Disease Control and Prevention bottle bioassays for sensitivity to insecticides used for mosquito control. All populations were resistant to pyrethroids. Naled, an organophosphate, was the most effective insecticide, killing all mosquitoes tested.

Octopamine neuromodulation regulates Gr32a-linked aggression and courtship pathways in Drosophila males.

Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-Fru(M) neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway.

Validation of the Intensive Care Unit Early Warning Dashboard: Quality Improvement Utilizing a Retrospective Case-Control Evaluation.

INTRODUCTION: Risk stratification with the Modified Early Warning System (MEWS) or electronic cardiac arrest trigger (eCART) has been utilized with ward patients to preemptively identify high-risk patients who might benefit from enhanced monitoring, including early intensive care unit (ICU) transfer. In-hospital mortality from cardiac arrest is ∼80%, making preventative interventions an important focus area. ICUs have lower patient to nurse ratios than wards, resulting in less emphasis on the development of ICU early warning systems. MATERIALS AND METHODS: Our institution developed an early warning dashboard (EWD) identifying patients who may benefit from earlier interventions. Using the adverse outcomes of cardiac arrest, ICU mortality, and ICU readmissions, a retrospective case-control study was performed using three demographic items (age, diabetes, and morbid obesity) and 24 EWD measured items, including vital signs, laboratory values, ventilator information, and other clinical information, to validate the EWD. RESULTS: Ten statistically significant areas were identified for cardiac arrest and 13 for ICU death. Identified items included heart rate, dialysis, leukocytosis, and lactate. The ICU readmission outcome was compared to controls from both ICU patients and ward patients, and statistical significance was identified for respiratory rate >30. DISCUSSION: With several statistically significant data elements, the EWD parameters have been incorporated into advanced clinical decision algorithms to identify at-risk ICU patients. CONCLUSION: Earlier identification and treatment of organ failure in the ICU improve outcomes and the EWD can serve as a safety measure for both at-risk in-house patients and also extend critical care expertise through telemedicine to smaller hospitals.

Single mutation to a sex pheromone receptor provides adaptive specificity between closely related moth species.

Sex pheromone communication, acting as a prezygotic barrier to mating, is believed to have contributed to the speciation of moths and butterflies in the order Lepidoptera. Five decades after the discovery of the first moth sex pheromone, little is known about the molecular mechanisms that underlie the evolution of pheromone communication between closely related species. Although Asian and European corn borers (ACB and ECB) can be interbred in the laboratory, they are behaviorally isolated from mating naturally by their responses to subtly different sex pheromone isomers, (E)-12- and (Z)-12-tetradecenyl acetate and (E)-11- and (Z)-11-tetradecenyl acetate (ACB: E12, Z12; ECB; E11, Z11). Male moth olfactory systems respond specifically to the pheromone blend produced by their conspecific females. In vitro, ECB(Z) odorant receptor 3 (OR3), a sex pheromone receptor expressed in male antennae, responds strongly to E11 but also generally to the Z11, E12, and Z12 pheromones. In contrast, we show that ACB OR3, a gene that has been subjected to positive selection (ω = 2.9), responds preferentially to the ACB E12 and Z12 pheromones. In Ostrinia species the amino acid residue corresponding to position 148 in transmembrane domain 3 of OR3 is alanine (A), except for ACB OR3 that has a threonine (T) in this position. Mutation of this residue from A to T alters the pheromone recognition pattern by selectively reducing the E11 response ∼14-fold. These results suggest that discrete mutations that narrow the specificity of more broadly responsive sex pheromone receptors may provide a mechanism that contributes to speciation.

The central cavity in trimeric glutamate transporters restricts ligand diffusion.

A prominent aqueous cavity is formed by the junction of three identical subunits in the excitatory amino acid transporter (EAAT) family. To investigate the effect of this structure on the interaction of ligands with the transporter, we recorded currents in voltage-clamped Xenopus oocytes expressing EAATs and used concentration jumps to measure binding and unbinding rates of a high-affinity aspartate analog that competitively blocks transport (ß-2-fluorenyl-aspartylamide; 2-FAA). The binding rates of the blocker were approximately one order of magnitude slower than l-Glu and were not significantly different for EAAT1, EAAT2, or EAAT3, but 2-FAA exhibited higher affinity for the neuronal transporter EAAT3 as a result of a slower dissociation rate. Unexpectedly, the rate of recovery from block was increased by l-Glu in a saturable and concentration-dependent manner, ruling out a first-order mechanism and suggesting that following unbinding, there is a significant probability of ligand rebinding to the same or neighboring subunits within a trimer. Consistent with such a mechanism, coexpression of wild-type subunits with mutant (R447C) subunits that do not bind glutamate or 2-FAA also increased the unblocking rate. The data suggest that electrostatic and steric factors result in an effective dissociation rate that is approximately sevenfold slower than the microscopic subunit unbinding rate. The quaternary structure, which has been conserved through evolution, is expected to increase the transporters' capture efficiency by increasing the probability that following unbinding, a ligand will rebind as opposed to being lost to diffusion.

Widespread Reactive Lymphatic and Splenic FDG Avidity After mRNA COVID Vaccination.

ABSTRACT: A 75-year-old woman with history of metastatic lung adenocarcinoma in remission develops new widespread FDG-avid lymphadenopathy in the neck, chest, abdomen, and pelvis on surveillance PET/CT, as well as intense FDG uptake in the spleen, without evidence of local recurrence. Short-term follow-up PET demonstrates near-complete resolution of FDG-avid lymphatic and splenic FDG avidity without interval change in management. Further history reveals that the patient received her fifth dose of COVID mRNA vaccine 6 days before the abnormal PET. Although unilateral axillary adenopathy after COVID vaccination is well-recognized, this widespread symmetric lymphatic and splenic FDG avidity is a significantly rarer phenomenon.

Novel Internal Medicine Residency Ultrasound Curriculum Led by Critical Care and Emergency Medicine Staff.

INTRODUCTION: Point-of-care ultrasound (POCUS) is an integral aspect of critical care and emergency medicine curriculums throughout the country, but it has been slow to integrate into internal medicine residency programs. POCUS has many benefits for internal medicine providers, guiding diagnostic decisions and aiding in procedures. Additionally, POCUS is a convenient and portable resource specifically for internal medicine providers in the military when practicing in deployed or critical care settings. Critical care and emergency medicine clinicians are excellent resources to lead these courses. We sought to develop a new POCUS curriculum for internal medicine residents within the Naval Medical Center Portsmouth Internal Medicine Residency program with the support of emergency medicine and critical care medicine staff to lead and oversee the training. The project's aim was to increase internal medicine resident confidence with POCUS by 20% and proficiency with POCUS as evidenced by pretest and posttest analysis by 10%. MATERIALS AND METHODS: The program consisted of a 2-day, 9-hour, introductory course, combining lecture with hands-on scanning taught by emergency medicine physicians who had completed emergency ultrasound fellowship-level training. This was followed by a longitudinal component of hands-on scanning throughout the academic year built into the residents' schedules. Emergency and critical care medicine ultrasound staff reviewed all studies for quality assurance (QA). The residents were given both precourse and post-course knowledge tests and confidence surveys, which utilized a 5-point Likert scale. The knowledge assessments were analyzed with a paired t-test, and the Likert scale data were analyzed using the Wilcoxon signed-rank test. The Naval Medical Center Portsmouth Institutional Review Board deemed this project nonhuman subjects' research. RESULTS: Twenty participants were enrolled, with 10 (50%) of those enrolled completing all course requirements. The average precourse knowledge assessment score was 76.60%, and postcourse assessment score was 80.95% (+4.35%, P = .33). The confidence survey scores were initially 73.33% and improved to 77.67% (+4.34%, P = .74). CONCLUSIONS: A curriculum comprised of a 9-hour workshop followed by a longitudinal hands-on experience can provide improvement in internal medicine resident POCUS knowledge and confidence. This model emphasizes the benefit of emergency and critical care cooperation for ultrasound training and provides an emphasis on medicine-relevant scans and longitudinal training.

Generation and characterization of a knock-in mouse model for Spastic Tetraplegia, Thin Corpus Callosum, and Progressive Microcephaly (SPATCCM).

SLC1A4 (solute carrier family 1 member 4, also referred to as ASCT1, Alanine/Serine/Cysteine/Threonine-preferring Transporter 1) is a sodium-dependent neutral amino acid transporter. It is highly expressed in many tissues, including the brain, where it is expressed primarily on astrocytes and plays key roles in neuronal differentiation and development, maintaining neurotransmitter homeostasis, and N-methyl-D-aspartate (NMDA) neurotransmission, through regulation of L- and D-serine. Mutations in SLC1A4 are associated with the rare autosomal recessive neurodevelopmental disorder spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM, OMIM 616657). Psychomotor development and speech are significantly impaired in these patients, and many develop seizures. We generated and characterized a knock-in mouse model for the most common mutant allele, which results in a single amino acid change (p.Glu256Lys, or E256K). Homozygous mutants had increased D-serine uptake in the brain, microcephaly, and thin corpus callosum and cortex layer 1. While p.E256K homozygotes showed some significant differences in exploratory behavior relative to wildtype mice, their performance in assays for motor coordination, endurance, learning, and memory was normal, and they showed no significant differences in long-term potentiation. Taken together, these results indicate that some aspects of SLC1A4 function in brain development are conserved between mice and humans, but the impact of the p.E256K mutation on cognition and motor function is minimal in mice.

Chlorinated ethene source remediation: lessons learned.

Chlorinated solvents such as trichloroethene (TCE) and tetrachloroethene (PCE) are widespread groundwater contaminants often released as dense nonaqueous phase liquids (DNAPLs). These contaminants are difficult to remediate, particularly their source zones. This review summarizes the progress made in improving DNAPL source zone remediation over the past decade, and is structured to highlight the important practical lessons learned for improving DNAPL source zone remediation. Experience has shown that complete restoration is rare, and alternative metrics such as mass discharge are often useful for assessing the performance of partial restoration efforts. Experience also has shown that different technologies are needed for different times and locations, and that deliberately combining technologies may improve overall remedy performance. Several injection-based technologies are capable of removing a large fraction of the total contaminant mass, and reducing groundwater concentrations and mass discharge by 1 to 2 orders of magnitude. Thermal treatment can remove even more mass, but even these technologies generally leave some contamination in place. Research on better delivery techniques and characterization technologies will likely improve treatment, but managers should anticipate that source treatment will leave some contamination in place that will require future management.

Upscaled modeling of complex DNAPL dissolution.

A straightforward, upscaled DNAPL mass dissolution model is developed using relatively simple input consisting of characteristic dimensions and saturations of a DNAPL accumulation. Multiple accumulations are aggregated into a single source zone volume. Physically, the dissolution process is a combination of flow through the mass (advective component) and flow around the mass (dispersive component). The contribution of each component is based on initial characteristic length scales and the average initial saturation. Changes over time with the depletion of mass are captured with a changing relative permeability and a power law relationship for the fraction of initial mass remaining. The utility of the upscaled process model is demonstrated with data from three studies: numerical simulation of multiple pools, two-dimensional test cell experiments with mixed architecture and with heterogeneous soil, and a controlled field study of multicomponent DNAPL release and depletion. Use of the model successfully reproduced the observed multistage mass discharge in each study and illuminated the governing processes. The power law exponent was relatively constant for the various conditions and relative permeability changes were integral to the success. The numerical and experimental studies were run to complete mass depletion which the upscaled model matched. The input parameters are minimal and are found in typical DNAPL source zone characterization data.

Malaria Rapid Diagnostic Tests: Literary Review and Recommendation for a Quality Assurance, Quality Control Algorithm.

Malaria rapid diagnostic tests (RDTs) have had an enormous global impact which contributed to the World Health Organization paradigm shift from empiric treatment to obtaining a parasitological diagnosis prior to treatment. Microscopy, the classic standard, requires significant expertise, equipment, electricity, and reagents. Alternatively, RDT's lower complexity allows utilization in austere environments while achieving similar sensitivities and specificities. Worldwide, there are over 200 different RDT brands that utilize three antigens: Plasmodium histidine-rich protein 2 (PfHRP-2), Plasmodium lactate dehydrogenase (pLDH), and Plasmodium aldolase (pALDO). pfHRP-2 is produced exclusively by Plasmodium falciparum and is very Pf sensitive, but an alternative antigen or antigen combination is required for regions like Asia with significant Plasmodium vivax prevalence. RDT sensitivity also decreases with low parasitemia (<100 parasites/uL), genetic variability, and prozone effect. Thus, proper RDT selection and understanding of test limitations are essential. The Center for Disease Control recommends confirming RDT results by microscopy, but this is challenging, due to the utilization of clinical laboratory standards, like the College of American Pathologists (CAP) and the Clinical Lab Improvement Act (CLIA), and limited recourses. Our focus is to provide quality assurance and quality control strategies for resource-constrained environments and provide education on RDT limitations.

Leucine Carboxyl Methyltransferase 1 Overexpression Protects Against Cognitive and Electrophysiological Impairments in Tg2576 APP Transgenic Mice.

BACKGROUND: The serine/threonine protein phosphatase, PP2A, is thought to play a central role in the molecular pathogenesis of Alzheimer's disease (AD), and the activity and substrate specificity of PP2A is regulated, in part, through methylation and demethylation of its catalytic subunit. Previously, we found that transgenic overexpression of the PP2A methyltransferase, LCMT-1, or the PP2A methylesterase, PME-1, altered the sensitivity of mice to impairments caused by acute exposure to synthetic oligomeric amyloid-ß (Aß). OBJECTIVE: Here we sought to test the possibility that these molecules also controlled sensitivity to impairments caused by chronically elevated levels of Aß produced in vivo. METHODS: To do this, we examined the effects of transgenic LCMT-1, or PME-1 overexpression on cognitive and electrophysiological impairments caused by chronic overexpression of mutant human APP in Tg2576 mice. RESULTS: We found that LCMT-1 overexpression prevented impairments in short-term spatial memory and synaptic plasticity in Tg2576 mice, without altering APP expression or soluble Aß levels. While the magnitude of the effects of PME-1 overexpression in Tg2576 mice was small and potentially confounded by the emergence of non-cognitive impairments, Tg2576 mice that overexpressed PME-1 showed a trend toward earlier onset and/or increased severity of cognitive and electrophysiological impairments. CONCLUSION: These data suggest that the PP2A methyltransferase, LCMT-1, and the PP2A methylesterase, PME-1, may participate in the molecular pathogenesis of AD by regulating sensitivity to the pathogenic effects of chronically elevated levels of Aß.

Supplemental Ascorbate Diminishes DNA Damage Yet Depletes Glutathione and Increases Acute Liver Failure in a Mouse Model of Hepatic Antioxidant System Disruption.

Cellular oxidants are primarily managed by the thioredoxin reductase-1 (TrxR1)- and glutathione reductase (Gsr)-driven antioxidant systems. In mice having hepatocyte-specific co-disruption of TrxR1 and Gsr (TrxR1/Gsr-null livers), methionine catabolism sustains hepatic levels of reduced glutathione (GSH). Although most mice with TrxR1/Gsr-null livers exhibit long-term survival, ~25% die from spontaneous liver failure between 4- and 7-weeks of age. Here we tested whether liver failure was ameliorated by ascorbate supplementation. Following ascorbate, dehydroascorbate, or mock treatment, we assessed survival, liver histology, or hepatic redox markers including GSH and GSSG, redox enzyme activities, and oxidative damage markers. Unexpectedly, rather than providing protection, ascorbate (5 mg/mL, drinking water) increased the death-rate to 43%. In adults, ascorbate (4 mg/g × 3 days i.p.) caused hepatocyte necrosis and loss of hepatic GSH in TrxR1/Gsr-null livers but not in wildtype controls. Dehydroascorbate (0.3 mg/g i.p.) also depleted hepatic GSH in TrxR1/Gsr-null livers, whereas GSH levels were not significantly affected by either treatment in wildtype livers. Curiously, however, despite depleting GSH, ascorbate treatment diminished basal DNA damage and oxidative stress markers in TrxR1/Gsr-null livers. This suggests that, although ascorbate supplementation can prevent oxidative damage, it also can deplete GSH and compromise already stressed livers.

Incursion and establishment of the Old World arbovirus vector Aedes (Fredwardsius) vittatus (Bigot, 1861) in the Americas.

Routine biosurveillance efforts at the Naval Station Guantanamo Bay, Cuba, on 18 June 2019, detected two unusual mosquitos in a CO2-baited CDC light trap. Morphological and molecular analysis confirmed the presence of Aedes (Fredwardsius) vittatus (Bigot, 1861) - the first record of the Old World dengue, chikungunya, Zika and yellow fever virus vector into the Americas - and provides evidence for its establishment in Cuba. Newly submitted GenBank sequences from Dominican Republic further evidence its establishment in the Caribbean, and a median-joining network analysis using mitochondrial COI gene sequences clearly supports multiple introductions of Ae. vittatus into the Caribbean from the Indian subcontinent. It was determined that many Ae. vittatus COI barcode sequences in GenBank are currently misidentified as Aedes (Fredwardsius) cogilli Edwards, 1922.

Sepsis Management in Prolonged Field Care: 28 October 2020.

This Role 1 prolonged field care (PFC) guideline is intended for use in the austere environment when evacuation to higher level of care is not immediately possible. A provider must first be an expert in Tactical Combat Casualty Care (TCCC). The intent of this guideline is to provide a functional, evidence-based and experience-based solution to those individuals who must manage patients suspected of having or diagnosed with sepsis in an austere environment. Emphasis is placed on the basics of diagnosis and treatment using the tools most familiar to a Role 1 provider. Ideal hospital techniques are adapted to meet the limitations of austere environments while still maintaining the highest standards of care possible. Sepsis and septic shock are medical emergencies. Patients suspected of having either of these conditions should be immediately evacuated out of the austere environment to higher echelons of care. These patients are often complex, requiring 24-hour monitoring, critical care skills, and a great deal of resources to treat. Obtaining evacuation is the highest treatment priority for these patients. This Clinical Practice Guideline (CPG) uses the minimum, better, best paradigm familiar to PFC and gives medics of varying capabilities and resources options for treatment.