lineage and pangenome diversity varies geographically across Bangladesh over one year.

Cholera is a diarrhoeal disease caused by . It remains a major public health challenge in the endemic region around the Bay of Bengal. Over decadal time scales, one lineage typically dominates the others and spreads in global pandemic waves.

Ancestral Origin and Dissemination Dynamics of Reemerging Toxigenic Vibrio cholerae, Haiti.

The 2010 cholera epidemic in Haiti was thought to have ended in 2019, and the Prime Minister of Haiti declared the country cholera-free in February 2022. On September 25, 2022, cholera cases were again identified in Port-au-Prince. We compared genomic data from 42 clinical Vibrio cholerae strains from 2022 with data from 327 other strains from Haiti and 1,824 strains collected worldwide.

Population-Based Serologic Survey of Vibrio cholerae Antibody Titers before Cholera Outbreak, Haiti, 2022.

A Vibrio cholerae O1 outbreak emerged in Haiti in October 2022 after years of cholera absence. In samples from a 2021 serosurvey, we found lower circulating antibodies against V. cholerae lipopolysaccharide in children <5 years of age and no vibriocidal antibodies, suggesting high susceptibility to cholera, especially among young children.

Phage predation, disease severity and pathogen genetic diversity in cholera patients.

Despite an increasingly detailed picture of the molecular mechanisms of phage-bacterial interactions, we lack an understanding of how these interactions evolve and impact disease within patients. Here we report a year-long, nation-wide study of diarrheal disease patients in Bangladesh. Among cholera patients, we quantified (prey) and its virulent phages (predators) using metagenomics and quantitative PCR, while accounting for antibiotic exposure using quantitative mass spectrometry.

The infected and the affected: A longitudinal study of the impact of the COVID-19 pandemic on schoolchildren in Florida.

Objectives: To identify risk factors associated with symptoms of anxiety, depression, and obsessive-compulsive disorder (OCD) among children during the 1st year of the COVID-19 pandemic.

Methods: A longitudinal study with three cross-sectional timepoints [April 2020 ( = 273), October 2020 ( = 180), and April 2021 ( = 116)] was conducted at a K-12 public school in Florida. Infection and sero-positivity for SARS-CoV-2 was determined by molecular and serologic approaches.

A population-based serological survey of antibody titers in Ouest Department, Haiti in the year prior to the 2022 cholera outbreak.

After three years with no confirmed cholera cases in Haiti, an outbreak of O1 emerged in October 2022. Levels of pre-existing antibodies provide an estimate of prior immunologic exposure, reveal potentially relevant immune responses, and set a baseline for future serosurveillance. We analyzed dried blood spots collected in 2021 from a population-weighted representative cross-sectional serosurvey in two communes in the Ouest Department of Haiti.

Genome-wide association studies reveal distinct genetic correlates and increased heritability of antimicrobial resistance in under anaerobic conditions.

The antibiotic formulary is threatened by high rates of antimicrobial resistance (AMR) among enteropathogens. Enteric bacteria are exposed to anaerobic conditions within the gastrointestinal tract, yet little is known about how oxygen exposure influences AMR. The facultative anaerobe was chosen as a model to address this knowledge gap.

Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination.

Objective: Assess presence, durability, and neutralization capacity of SARS-CoV-2-specific antibodies in breastfeeding infants' stool, mother's plasma and milk following maternal vaccination.

Design: Thirty-seven mothers and 25 infants were enrolled between December 2020 and November 2021 for this prospective observational study. All mothers were vaccinated during lactation except three, which were vaccinated during pregnancy.

Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination.

Assess the presence, durability, and neutralization capacity of SARS-CoV-2-specific antibodies in breastfeeding infants' stools, mother's plasma, and human milk following maternal vaccination. Thirty-seven mothers and 25 infants were enrolled between December 2020 and November 2021 for this prospective observational study. Human milk, maternal plasma, and infants' stools were collected pre-vaccination and at periods up to 6 months following COVID-19 vaccine series initiation/completion.

Reduced mammary tumor progression in a transgenic mouse model fed an isoflavone-poor soy protein concentrate.

Dietary exposure to soy has been associated with reduced breast cancer incidence. Soy isoflavones and protein components, such as protease inhibitors and the lunasin peptide, have been indicated as potential agents reducing carcinogenesis. In this study, the effect of soy-based diets was evaluated in a transgenic mouse model of breast carcinoma, overexpressing the neu oncogene.

Effects of IL-12 gene therapy on spontaneous transgenic and transplanted breast tumors.

Cytokines are promising agents for cancer therapy due to their activity at low concentrations. We used a naked IL-12 DNA expression vector to achieve long-term systemic cytokine expression to inhibit breast tumor growth in MMTVneu transgenic and transplanted models. Constant low levels of IL-12 produced by this protocol provided effective tumor growth inhibition of both tumor models without adverse effects.

Establishment and characterization of new mammary adenocarcinoma cell lines derived from double transgenic mice expressing GFP and neu oncogene.

A new murine cell line, named GFPneu, was established from a mammary adenocarcinoma arising in double transgenic MMTVneu x CMV-GFP mice. Breast tumours develop in 100% of females after 2 months latency, as a result of the over-expression of the activated rat neu oncogene in the mammary glands. All tissues, and in particular the breast tumours, express the GFP protein.

Rescue of ATPa3-deficient murine malignant osteopetrosis by hematopoietic stem cell transplantation in utero.

Autosomal recessive osteopetrosis (ARO) is a paradigm for genetic diseases that cause severe, often irreversible, defects before birth. In ARO, osteoclasts cannot remove mineralized cartilage, bone marrow is severely reduced, and bone cannot be remodeled for growth. More than 50% of the patients show defects in the osteoclastic vacuolar-proton-pump subunit, ATP6a3.

Cell-based assay for the detection of chemically induced cellular stress by immortalized untransformed transgenic hepatocytes.

Background: Primary hepatocytes, one of the most widely used cell types for toxicological studies, have a very limited life span and must be freshly derived from mice or even humans. Attempts to use stable cell lines maintaining the enzymatic pattern of liver cells have been so far unsatisfactory. Stress proteins (heat shock proteins, HSPs) have been proposed as general markers of cellular injury and their use for environmental monitoring has been suggested.

Combined antiestrogen, antiangiogenic and anti-invasion therapy inhibits primary and metastatic tumor growth in the MMTVneu model of breast cancer.

Treatments available to women with locally advanced breast cancer are unsatisfactory, since most patients succumb to metastatic spread. Therefore, there is a need to devise novel therapeutic combinations that effectively inhibit metastatization and to test them in animal models of breast cancer showing strong similarities with their human counterpart, including the ability to give rise to metastases. With these considerations in mind, tamoxifen (TAM), 4-hydrotamoxifen (4-HT) or liposome-complexed DNA constructs coding for antiangiogenic/anti-invasion proteins (angiostatin, TIMP-2, IFN-alpha(1), sFLT-1) were individually administered to MMTVneu transgenic mice.

Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy.

The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposome-coated plasmids carrying the cDNA coding for murine and human angiostatin (CMVang and BSHang) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatment reduced melanoma growth by 50% to 90% compared to that occurring in control animals treated with liposome-coated plasmid carrying the lacZ gene or in untreated controls.

Systemic gene therapy with anti-angiogenic factors inhibits spontaneous breast tumor growth and metastasis in MMTVneu transgenic mice.

Tumor growth and metastasis are angiogenesis-dependent. The possibility of inhibiting tumor growth by interfering with the formation of new vessels has recently raised considerable interest. We previously reported that it is possible to inhibit primary tumor growth and metastasis in a transgenic model of spontaneous breast tumor, which shows many similarities to its human counterpart (including ability to metastasize) by intratumoral administration of a DNA construct carrying the murine angiostatin cDNA driven by liposomes.

Lymphoid abnormalities in CD40 ligand transgenic mice suggest the need for tight regulation in gene therapy approaches to hyper immunoglobulin M (IgM) syndrome.

Mutations in the CD40 ligand (CD40L) are responsible for human hyper immunoglobulin M (IgM) syndrome. The absence of the interaction between CD40L, expressed by T lymphocytes, and the CD40 receptor present on the surface of B cells is responsible for the inability of B cells to carry out the isotype switch from IgM to the other Ig classes. This leads to a fatal immunodeficiency for which no cure exists.

Liposome-delivered angiostatin strongly inhibits tumor growth and metastatization in a transgenic model of spontaneous breast cancer.

The possibility to inhibit tumor growth by interfering with the formation of new vessels, which most neoplasias depend on, has recently raised considerable interest. An angiogenic switch, in which proliferating cells acquire the ability to direct new vessel formation, is thought to be an early step in the natural history of solid tumors. Using a transgenic model of breast cancer, which shows many similarities to its human counterpart, including ability to metastasize, we targeted angiostatin production to an early stage of tumor formation.

Retrovirus-mediated IL-4 gene therapy in spontaneous adenocarcinomas from MMTV-neu transgenic mice.

Gene therapy approaches to the treatment of experimental cancer are usually based on established neoplastic cell lines which are manipulated in vitro and subsequently transplanted in host animals. However, the relevance of these artificial models to the biology and therapy of human tumors is uncertain. We have previously validated an experimental model based on MMTV-neu transgenic mice in which breast tumors arise spontaneously in 100% of animals and have many features in common with their human counterpart, including the involvement of the neu oncogene and the ability to metastatize.

A transgenic mouse model for the detection of cellular stress induced by toxic inorganic compounds.

Transgenic mice for genotoxicity testing have been developed, although no such models have been produced for the evaluation of toxic, nongenotoxic chemical compounds. We have developed a transgenic mouse model for the analysis of toxic inorganic compounds. We engineered a mouse lineage with the human growth hormone (hGH) gene under the control of the human hsp70 promoter, in which a plasma-detectable hGH response can be elicited by exposure to heat shock.

pH-dependent effects of lidocaine on defibrillation energy requirements in dogs.

Lidocaine increases the energy required for ventricular defibrillation in dogs. Because sodium channel-blocking agents that are weak bases have pH-dependent electrophysiologic effects, we investigated the pH dependence of lidocaine (pKa, 7.9) on internal defibrillation energy requirements in 28 dogs with atrial spring and left ventricular patch electrodes.

Evaluation of antiarrhythmic drugs on defibrillation energy requirements in dogs. Sodium channel block and action potential prolongation.

Antiarrhythmic drugs have been reported to produce variable effects on defibrillation energy requirements. However, the relation between the in vitro electrophysiologic effects of these agents and the changes in defibrillation energy requirements have not been systematically examined. Therefore, we evaluated the effects of the sodium channel blocking drugs lidocaine and procainamide, the action potential prolonging drugs N-acetyl procainamide and clofilium, and the potassium current blocker cesium in acute canine models with the same internal spring and epicardial patch electrodes used in humans for ventricular defibrillation testing.