Analysis of Orientia tsutsugamushi promoter activity.

Orientia tsutsugamushi is an obligate intracellular bacterium that causes scrub typhus, a potentially fatal rickettsiosis, and for which no genetic tools exist. Critical to addressing this technical gap is to identify promoters for driving expression of antibiotic resistance and fluorescence reporter genes in O. tsutsugamushi.

Digitalization of contact tracing: balancing data privacy with public health benefit.

The COVID-19 pandemic has brought the long-standing public health practice of contact tracing into the public spotlight. While contact tracing and case investigation have been carefully designed to protect privacy, the huge volume of tracing which is being carried out as part of the pandemic response in the United States is highlighting potential concerns around privacy, legality, and equity. Contact tracing during the pandemic has gained particular attention for the new use of digital technologies-both on the consumer side in the form of Exposure Notification applications, and for public health agencies as digital case management software systems enable massive scaling of operations.

Altered effective connectivity of the reward network during an incentive-processing task in adults with alcohol use disorder.

Background: Abnormalities of reward sensitivity and impulsivity are known to be correlated with each other and alcohol use disorder (AUD) risk, but the underlying aberrant neural circuitry involved is not clearly defined. We sought to extend the current knowledge of AUD pathophysiology by studying incentive processing in persons with AUD using functional neuroimaging data.

Methods: We utilized functional MRI data from the Human Connectome Project Database obtained during performance of a number-guessing incentive-processing task with win, loss, and neutral feedback conditions in 78 participants with either DSM-IV alcohol abuse or dependence (combined as the AUD group) and 78 age- and sex-matched control (CON) participants.

An in vitro pharmacodynamic spiking study of befovacimab, a tissue factor pathway inhibitor monoclonal antibody, in blood samples from patients with severe FVIII deficiency.

Introduction: Tissue factor pathway inhibitor (TFPI) is an endogenous protein that inhibits the extrinsic (tissue factor) pathway and negatively regulates thrombin production during coagulation. Inhibiting TFPI may become a useful target for haemophilia drug development to allow greater thrombin generation without use of the intrinsic (contact) pathway.

Aims: The in vitro effects of befovacimab, a humanized TFPI neutralizing antibody, were studied in whole blood and plasma samples from patients with severe FVIII deficiency.

Evaluation of the Olweus Bullying Prevention Program in US Urban Middle Schools Using a Multiple Baseline Experimental Design.

We evaluated the impact of the Olweus Bullying Prevention Program (OBPP) in an 8-year study in urban middle schools that served primarily African American students living in low-income areas. Participants included 2755 students and 242 teachers. We evaluated the OBPP with a multiple-baseline experimental design where the order and intervention start time was randomly assigned for each school.

Gene Expression Differences Between Young Adults Based on Trauma History and Post-traumatic Stress Disorder.

The purpose of this study was to identify gene expression differences associated with post-traumatic stress disorder (PTSD) and trauma exposure (TE) in a three-group study design comprised of those with and without trauma exposure and PTSD. We conducted gene expression and gene network analyses in a sample ( = 45) composed of female subjects of European Ancestry (EA) with PTSD, TE without PTSD, and controls. We identified 283 genes differentially expressed between PTSD-TE groups.

Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis.

[Figure: see text].

Schemes for Drug-Induced Treatment of Osteonecrosis of Jaws with Particular Emphasis on the Influence of Vitamin D on Therapeutic Effects.

Drugs that inhibit bone resorption are prescribed most often by orthopedists, hematologists, or oncologists. Dental practice rarely draws attention to their importance and the effects they carry. The problem concerns mainly older people owing to oncological problems or postmenopausal consequences, but everyone can be at risk.

Restoring the DREAM Complex Inhibits the Proliferation of High-Risk HPV Positive Human Cells.

High-risk (HR) human papillomaviruses are known causative agents in 5% of human cancers including cervical, ano-genital and head and neck carcinomas. In part, HR-HPV causes cancer by targeting host-cell tumor suppressors including retinoblastoma protein (pRb) and RB-like proteins p107 and p130. HR-HPV E7 uses a LxCxE motif to bind RB proteins, impairing their ability to control cell-cycle dependent transcription.

Child lead exposure near abandoned lead acid battery recycling sites in a residential community in Bangladesh: Risk factors and the impact of soil remediation on blood lead levels.

Lead is a potent neurotoxin that is particularly detrimental to children's cognitive development. Batteries account for at least 80% of global lead use and unsafe battery recycling is a major contributor to childhood lead poisoning. Our objectives were to assess the intensity and nature of child lead exposure at abandoned, informal used lead acid battery (ULAB) recycling sites in Kathgora, Savar, Bangladesh, as well as to assess the feasibility and effectiveness of a soil remediation effort to reduce exposure.

A Review of Bleeding Risk with Impella-supported High-risk Percutaneous Coronary Intervention.

Complex, high-risk percutaneous coronary intervention (HR-PCI) is increasingly being performed, often with mechanical circulatory support (MCS), though to date, there are limited randomised data on the efficacy of MCS for HR-PCI. The majority of MCS is provided by intra-aortic balloon pumps, but increasingly Impella® (Abiomed, Danvers, MA, USA) heart pumps are being used. While the Impella pumps provide greater increases in cardiac output, these devices require large bore access, which has been associated with an increased risk of bleeding and vascular complications.

Human Papillomavirus 16 (HPV16) E2 Repression of TWIST1 Transcription Is a Potential Mediator of HPV16 Cancer Outcomes.

Human papillomaviruses (HPVs) are causative agents in around 5% of all cancers, including cervical and oropharyngeal. A feature of HPV cancers is their better clinical outcome compared with non-HPV anatomical counterparts. In turn, the presence of E2 predicts a better clinical outcome in HPV-positive cancers; the reason(s) for the better outcome of E2-positive patients is not fully understood.

Functional inhibition or genetic deletion of acid sphingomyelinase bacteriostatically inhibits Anaplasma phagocytophilum infection in vivo.

Anaplasma phagocytophilum infects neutrophils to cause granulocytic anaplasmosis. It poorly infects mice deficient in acid sphingomyelinase (ASM), a lysosomal enzyme critical for cholesterol efflux, and wild-type mice treated with desipramine that functionally inhibits ASM. Whether inhibition or genetic deletion of ASM is bacteriostatic or bactericidal for A.

The role of noninvasive biomarkers in diagnosis and risk stratification in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronically elevated liver enzymes. Diagnosis and risk stratification of NAFLD remains clinically challenge as patients with NAFLD are either asymptomatic or have nonspecific presenting complaints and may have normal liver enzymes. Nonalcoholic steatohepatitis (NASH), the clinically aggressive variant of NAFLD, is also difficult to differentiate noninvasively, and a liver biopsy is required to definitively diagnose NASH.

Neuroretinal-Derived Caveolin-1 Promotes Endotoxin-Induced Inflammation in the Murine Retina.

Purpose: The immune-privileged environment and complex organization of retinal tissue support the retina's essential role in visual function, yet confound inquiries into cell-specific inflammatory effects that lead to dysfunction and degeneration. Caveolin-1 (Cav1) is an integral membrane protein expressed in several retinal cell types and is implicated in immune regulation. However, whether Cav1 promotes or inhibits inflammatory processes in the retina (as well as in other tissues) remains unclear.

Werner Syndrome Protein (WRN) Regulates Cell Proliferation and the Human Papillomavirus 16 Life Cycle during Epithelial Differentiation.

Human papillomaviruses recruit a host of DNA damage response factors to their viral genome to facilitate homologous recombination replication in association with the viral replication factors E1 and E2. We previously demonstrated that SIRT1 deacetylation of WRN promotes recruitment of WRN to E1-E2 replicating DNA and that WRN regulates both the levels and fidelity of E1-E2 replication. The deacetylation of WRN by SIRT1 results in an active protein able to complex with replicating DNA, but a protein that is less stable.

Factors Associated With the Need for Pharmacological Management of Neonatal Opioid Withdrawal Syndrome.

Background: Neonatal opioid withdrawal syndrome (NOWS) is a significant and growing health problem that affects more than 23,000 infants annually, with an estimated hospital cost of more than $720 million.

Purpose: The purpose of this study was to examine factors associated with the need to initiate medication for the treatment of NOWS.

Methods: A retrospective review of medical records was conducted of 204 infants born to mothers who used opioids during pregnancy from April 2011 to September 2017.

Activating the DNA Damage Response and Suppressing Innate Immunity: Human Papillomaviruses Walk the Line.

Activation of the DNA damage response (DDR) by external agents can result in DNA fragments entering the cytoplasm and activating innate immune signaling pathways, including the stimulator of interferon genes (STING) pathway. The consequences of this activation can result in alterations in the cell cycle including the induction of cellular senescence, as well as boost the adaptive immune response following interferon production. Human papillomaviruses (HPV) are the causative agents in a host of human cancers including cervical and oropharyngeal; HPV are responsible for around 5% of all cancers.

The Evolving Design of NIH-Funded Cardio-Oncology Studies to Address Cancer Treatment-Related Cardiovascular Toxicity.

Cardiovascular (CV) toxicity from cancer therapy is a significant and growing concern. Conventional oncology clinical trial designs focused singularly on cancer treatment efficacy have not provided sufficient information on both CV risk factors and outcomes. Similarly, traditional CV trials evaluating standard interventions typically exclude cancer patients, particularly those actively receiving cancer therapy.

Vaya Con Dios: The Influence of Religious Constructs on Stressors around the Migration Process and U.S. Lived Experiences among Latina/o Immigrants.

This qualitative study explores the role of religious practices on the migration process and the U.S. lived experiences of Latina/o immigrants.

The Relationship between Estrogen-Related Signaling and Human Papillomavirus Positive Cancers.

High risk-human papillomaviruses (HPVs) are known carcinogens. Numerous reports have linked the steroid hormone estrogen, and the expression of estrogen receptors (ERs), to HPV-related cancers, although the exact nature of the interactions remains to be fully elucidated. Here we will focus on estrogen signaling and describe both pro and potentially anti-cancer effects of this hormone in HPV-positive cancers.

Lumefantrine, an antimalarial drug, reverses radiation and temozolomide resistance in glioblastoma.

Glioblastoma multiforme (GBM) is an aggressive cancer without currently effective therapies. Radiation and temozolomide (radio/TMZ) resistance are major contributors to cancer recurrence and failed GBM therapy. Heat shock proteins (HSPs), through regulation of extracellular matrix (ECM) remodeling and epithelial mesenchymal transition (EMT), provide mechanistic pathways contributing to the development of GBM and radio/TMZ-resistant GBM.

Leadership Development for Future Medical School Deans: Outcomes of the AAMC Council of Deans Fellowship Program.

Purpose: To determine the outcomes of the Association of American Medical Colleges (AAMC) Council of Deans (COD) Fellowship Program with respect to participants' achieving the goals of becoming a medical school dean and developing leadership skills, and to ascertain fellows' views about the program's value, beneficial aspects, and areas for improvement.

Method: The 37 COD fellows from 2002 to 2016 were invited to participate in a 2017 survey addressing demographics, training, current leadership position, and value of the program. The survey also included 3 open-ended questions.