Campylobacteriosis Outbreak Linked to Municipal Water, Nebraska, USA, 2021.

In September 2021, eight campylobacteriosis cases were identified in a town in Nebraska, USA. We assessed potential exposures for a case-control analysis. We conducted whole-genome sequencing on Campylobacter isolates from patients' stool specimens.

Elucidation of the GSK3α Structure Informs the Design of Novel, Paralog-Selective Inhibitors.

Glycogen synthase kinase 3 (GSK3) remains a therapeutic target of interest for diverse clinical indications. However, one hurdle in the development of small molecule GSK3 inhibitors has been safety concerns related to pan-inhibition of both GSK3 paralogs, leading to activation of the Wnt/β-catenin pathway and potential for aberrant cell proliferation. Development of GSK3α or GSK3β paralog-selective inhibitors that could offer an improved safety profile has been reported but further advancement has been hampered by the lack of structural information for GSK3α.

Longitudinal EEG model detects antisense oligonucleotide treatment effect and increased UBE3A in Angelman syndrome.

Angelman syndrome is a neurodevelopmental disorder caused by deficiency of the maternally inherited gene in neurons. Antisense oligonucleotide therapies are under development to reinstate UBE3A protein production. Non-invasive biomarkers to detect target engagement and treatment response are needed to support clinical trials.

Aedes aegypti Identified in York, Nebraska, Through Routine Arboviral Surveillance-August-October 2019.

On August 27, 2019, Aedes aegypti mosquitoes were identified in a neighborhood located in York, NE, through routine arboviral surveillance. Expanded surveillance using traps and morphologic identification revealed 118 adult Ae. aegypti throughout the adjacent neighborhood, including identification from larval sampling.

Multistate Mumps Outbreak Originating from Asymptomatic Transmission at a Nebraska Wedding - Six States, August-October 2019.

In August 2019, 30 attendees at a Nebraska wedding developed mumps after being exposed to one asymptomatic index patient who was fully vaccinated according to Advisory Committee on Immunization Practices (ACIP) recommendations (1), resulting in a multistate outbreak. A public health investigation and response revealed epidemiologic links that extended from the index patient through secondary, tertiary, and quaternary patients and culminated in a measles-mumps-rubella (MMR) booster vaccination campaign in the local community where approximately half of the patients resided.

Successive Norovirus Outbreaks at an Event Center - Nebraska, October-November, 2017.

In October 2017, the Nebraska Department of Health and Human Services (NDHHS) was notified by a local health department of a gastrointestinal illness outbreak among attendees of a wedding reception at facility A, an event center. Shortly thereafter, state and local public health officials began receiving reports of similar gastrointestinal illness among attendees of subsequent facility A events. An investigation was initiated to identify cases, establish the cause, assess possible transmission routes, and provide control recommendations.

Centers for Disease Control and Prevention's Temporary Epidemiology Field Assignee program: Supporting state and local preparedness in the wake of Ebola.

Objectives: The Centers for Disease Control and Prevention launched the Temporary Epidemiology Field Assignee (TEFA) Program to help state and local jurisdictions respond to the risk of Ebola virus importation during the 2014-2016 Ebola Outbreak in West Africa. We describe steps taken to launch the 2-year program, its outcomes and lessons learned.

Methods: State and local health departments submitted proposals for a TEFA to strengthen local capacity in four key public health preparedness areas: 1) epidemiology and surveillance, 2) health systems preparedness, 3) health communications, and 4) incident management.

Campylobacteriosis Outbreak Associated with Contaminated Municipal Water Supply - Nebraska, 2017.

In March 2017, the Nebraska Department of Health and Human Services (NDHHS) and the Southwest Nebraska Public Health Department were notified of an apparent cluster of Campylobacter jejuni infections in city A and initiated an investigation. Overall, 39 cases were investigated, including six confirmed and 33 probable. Untreated, unboiled city A tap water (i.

REDCap for Biocontainment Worker Symptom Monitoring.

The Ebola epidemic of 2014 demonstrated that outbreaks of high-consequence infectious diseases, even in remote parts of the world, can affect communities anywhere in the developed world and that every healthcare facility must be prepared to identify, isolate, and provide care for infected patients. The Nebraska Biocontainment Unit (NBU), located at Nebraska Medicine in Omaha, Nebraska, cared for 3 American citizens exposed in West Africa and confirmed with Ebola virus disease (EVD). Symptom monitoring of healthcare workers caring for these patients was implemented, which included twice daily contact to document the absence or presence of signs of fever or illness.

Changing Antimicrobial Resistance Trends in Kathmandu, Nepal: A 23-Year Retrospective Analysis of Bacteraemia.

A comprehensive longitudinal understanding of the changing epidemiology of the agents causing bacteraemia and their AMR profiles in key locations is crucial for assessing the progression and magnitude of the global AMR crisis. We performed a retrospective analysis of routine microbiological data from April 1992 to December 2014, studying the time trends of non- associated bacteraemia at a single Kathmandu healthcare facility. The distribution of aetiological agents, their antimicrobial susceptibility profiles, and the hospital ward of isolation were assessed.

TREM2-activating antibodies abrogate the negative pleiotropic effects of the Alzheimer's disease variant on murine myeloid cell function.

Triggering receptor expressed on myeloid cells 2 (TREM2) is an orphan immune receptor expressed on cells of myeloid lineage such as macrophages and microglia. The rare variant R47H TREM2 is associated with an increased risk for Alzheimer's disease, supporting the hypothesis that TREM2 loss of function may exacerbate disease progression. However, a complete knockout of the gene in different genetic models of neurodegenerative diseases has been reported to result in both protective and deleterious effects on disease-related end points and myeloid cell function.

A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital.

Background: Salmonella serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A), the causative agents of enteric fever, have been routinely isolated organisms from the blood of febrile patients in the Kathmandu Valley since the early 1990s.

Pseudomonas aeruginosa Outbreak in a Neonatal Intensive Care Unit Attributed to Hospital Tap Water.

OBJECTIVE To investigate an outbreak of Pseudomonas aeruginosa infections and colonization in a neonatal intensive care unit. DESIGN Infection control assessment, environmental evaluation, and case-control study. SETTING Newly built community-based hospital, 28-bed neonatal intensive care unit.

Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial.

Background: Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever.

Methods: We did an open-label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2-13 years) and adult (aged 14-45 years) with criteria for suspected enteric fever (body temperature ≥38·0°C for ≥4 days without a focus of infection).

Notes from the Field: Acute Mercury Poisoning After Home Gold and Silver Smelting--Iowa, 2014.

In March 2014, a man, aged 59 years, who lived alone and had been using different smelting techniques viewed on the Internet to recover gold and silver from computer components, was evaluated at a local emergency department for shortness of breath, tremors, anorexia, and generalized weakness. During the smelting processes, he had used hydrogen peroxide, nitric acid, muriatic acid, and sulfuric acid purchased from local stores or Internet retailers. For protection, he wore a military gas mask of unknown type.

Variation at HLA-DRB1 is associated with resistance to enteric fever.

Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C(1). We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.

Prolactin/Stat5 and androgen R1881 coactivate carboxypeptidase-D gene in breast cancer cells.

Plasma membrane-bound carboxypeptidase-D (CPD) cleaves C-terminal arginine from extracellular substrates. In the cell, arginine is converted to nitric oxide (NO). We have reported that up-regulation of CPD mRNA/protein levels by 17β-estradiol and prolactin (PRL) in breast cancer cells, and by testosterone in prostate cancer cells, increased NO production and cell survival.

Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial.

Background: Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A.

Methodology And Principal Findings: Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day) in a single dose or ofloxacin (20 mg/kg/day) in two divided doses for 7 days.

Progestin-inducible EDD E3 ubiquitin ligase binds to α4 phosphoprotein to regulate ubiquitination and degradation of protein phosphatase PP2Ac.

Mammalian α4 phosphoprotein binds to the protein phosphatase 2A catalytic subunit (PP2Ac) to regulate PP2A activity, and to poly(A)-binding protein (PABP) and progestin-inducible EDD E3 ubiquitin ligase. This study showed induction of the EDD protein by progesterone, 17β-estradiol and prolactin in breast cancer cells. Co-immunoprecipitation analyses, using lysates of COS-1 cells transfected with α4-deletion constructs, showed the α4 N-terminus binding to endogenous PP2Ac and PABP, and the C-terminus to EDD.

Aetiologies of central nervous system infections in adults in Kathmandu, Nepal: a prospective hospital-based study.

We conducted a prospective hospital based study from February 2009-April 2011 to identify the possible pathogens of central nervous system (CNS) infections in adults admitted to a tertiary referral hospital (Patan Hospital) in Kathmandu, Nepal. The pathogens of CNS infections were confirmed in cerebrospinal fluid (CSF) using molecular diagnostics, culture (bacteria) and serology. 87 patients were recruited for the study and the etiological diagnosis was established in 38% (n = 33).

Evaluation of an electricity-free, culture-based approach for detecting typhoidal Salmonella bacteremia during enteric fever in a high burden, resource-limited setting.

Background: In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture.

The microbiological and clinical characteristics of invasive salmonella in gallbladders from cholecystectomy patients in kathmandu, Nepal.

Gallbladder carriage of invasive Salmonella is considered fundamental in sustaining typhoid fever transmission. Bile and tissue was obtained from 1,377 individuals undergoing cholecystectomy in Kathmandu to investigate the prevalence, characteristics and relevance of invasive Salmonella in the gallbladder in an endemic area. Twenty percent of bile samples contained a Gram-negative organism, with Salmonella Typhi and Salmonella Paratyphi A isolated from 24 and 22 individuals, respectively.

Combined high-resolution genotyping and geospatial analysis reveals modes of endemic urban typhoid fever transmission.

Typhoid is a systemic infection caused by Salmonella Typhi and Salmonella Paratyphi A, human-restricted bacteria that are transmitted faeco-orally. Salmonella Typhi and S. Paratyphi A are clonal, and their limited genetic diversity has precluded the identification of long-term transmission networks in areas with a high disease burden.

A TRPC5-regulated calcium signaling pathway controls dendrite patterning in the mammalian brain.

Transient receptor potential (TRP) channels have been implicated as sensors of diverse stimuli in mature neurons. However, developmental roles for TRP channels in the establishment of neuronal connectivity remain largely unexplored. Here, we identify an essential function for TRPC5, a member of the canonical TRP subfamily, in the regulation of dendrite patterning in the mammalian brain.