Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy.

Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a lethal muscle-wasting disease that is caused by mutations in the LAMA2 gene, resulting in the loss of laminin-α2 protein. MDC1A patients exhibit severe muscle weakness from birth, are confined to a wheelchair, require ventilator assistance, and have reduced life expectancy. There are currently no effective treatments or cures for MDC1A.

Move it or lose it? A survey of the aims of treatment when using passive movements in intensive care.

Objectives: To identify the aims of treatment when physiotherapists use passive movements (PMs) for ventilated and sedated patients on intensive care in the UK.

Method: Postal questionnaires distributed to senior physiotherapists working within all National Health Service (NHS) trusts with open level 3 ICU beds. Open questionnaire items surveyed the aims of using PMs in different clinical areas (neurology, cardiology, orthopaedics/trauma, general surgery, medicine, other).

The Nurse Advocate in End-of-Life Care.

End-of-life nursing encompasses many aspects of care: pain and symptom management, culturally sensitive practices, assisting patients and their families through the death and dying process, and ethical decisionmaking. Advocacy has been identified as a key core competency for the professional nurse, yet the literature reveals relevant barriers to acquiring this skill. Challenges exist, such as limitations in nursing school curricula on the death and dying process, particularly in multicultural settings; differing policies and practices in healthcare systems; and various interpretations of end-of-life legal language.

Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission.

A mainstay of strategies to prevent HIV-1 transmission is to use antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP). Critical to the design and interpretation of PrEP prevention trials is the ability to make accurate pharmacological measurements of ART drugs in human genital and colorectal mucosal tissues, the principal route of HIV transmission. Here, we evaluated two drugs that are preferentially used for PrEP: tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC).

Circadian variation of the response of T cells to antigen.

Circadian clocks regulate many important aspects of physiology, and their disturbance leads to various medical conditions. Circadian variations have been found in immune system variables, including daily rhythms in circulating WBC numbers and serum concentration of cytokines. However, control of immune functional responses by the circadian clock has remained relatively unexplored.

Timing of antiretroviral therapy for HIV-1 infection and tuberculosis.

Background: Antiretroviral therapy (ART) is indicated during tuberculosis treatment in patients infected with human immunodeficiency virus type 1 (HIV-1), but the timing for the initiation of ART when tuberculosis is diagnosed in patients with various levels of immune compromise is not known.

Methods: We conducted an open-label, randomized study comparing earlier ART (within 2 weeks after the initiation of treatment for tuberculosis) with later ART (between 8 and 12 weeks after the initiation of treatment for tuberculosis) in HIV-1 infected patients with CD4+ T-cell counts of less than 250 per cubic millimeter and suspected tuberculosis. The primary end point was the proportion of patients who survived and did not have a new (previously undiagnosed) acquired immunodeficiency syndrome (AIDS)-defining illness at 48 weeks.

Initial viral decay to assess the relative antiretroviral potency of protease inhibitor-sparing, nonnucleoside reverse transcriptase inhibitor-sparing, and nucleoside reverse transcriptase inhibitor-sparing regimens for first-line therapy of HIV infection.

Objectives: To evaluate the effects of sex and initial antiretroviral regimen on decay of HIV-RNA and virologic outcome.

Methods: We conducted a viral dynamics substudy of A5142, a trial comparing lopinavir (LPV)/ritonavir with efavirenz (LPV/EFV) versus LPV and two nucleoside reverse transcriptase inhibitor (NRTI) (LPV) versus EFV and two NRTI (EFV) in antiretroviral (ARV)-naive individuals. HIV-RNA was measured at days 2, 10, and 14 in the substudy and at weeks 1, 4, and 8 in A5142 participants.

Multicenter breast cancer collaborative registry.

The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare.

Abacavir/lamivudine versus tenofovir DF/emtricitabine as part of combination regimens for initial treatment of HIV: final results.

Background: AIDS Clinical Trials Group A5202 compared blinded abacavir/lamivudine (ABC/3TC) to tenofovir DF/emtricitabine (TDF/FTC) with efavirenz (EFV) or atazanavir/ritonavir (ATV/r) in human immunodeficiency virus (HIV)-infected treatment-naive patients, stratified by screening HIV RNA (< or ≥ 10(5) copies/mL). Due to higher virologic failure with ABC/3TC in the high HIV RNA stratum, blinded treatment was stopped in this group, but study follow-up continued for all patients.

Methods: Primary endpoints were times to virologic failure, regimen modification, and safety event.

Pharmacokinetics and safety of single-dose tenofovir disoproxil fumarate and emtricitabine in HIV-1-infected pregnant women and their infants.

Tenofovir (TFV) is effective in preventing simian immunodeficiency virus (SIV) transmission in a macaque model, is available as the oral agent tenofovir disoproxil fumarate (TDF), and may be useful in the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). We conducted a trial of TDF and TDF-emtricitabine (FTC) in HIV-infected pregnant women and their infants. Women received a single dose of either 600 mg TDF, 900 mg TDF, or 900 mg TDF-600 mg FTC at labor onset or prior to a cesarean section.

Transgenic overexpression of the α7 integrin reduces muscle pathology and improves viability in the dy(W) mouse model of merosin-deficient congenital muscular dystrophy type 1A.

Merosin-deficient congenital muscular dystrophy 1A (MDC1A) is a devastating neuromuscular disease that results in children being confined to a wheelchair, requiring ventilator assistance to breathe and premature death. MDC1A is caused by mutations in the LAMA2 gene, which results in the partial or complete loss of laminin-211 and laminin-221, the major laminin isoforms found in the basal lamina of skeletal muscle. MDC1A patients exhibit reduced α7β1 integrin; however, it is unclear how the secondary loss of α7β1 integrin contributes to MDC1A disease progression.

Asking the right questions: developing evidence-based strategies for treating HIV in women and children.

In July 2010, the World Health Organization (WHO) issued formal revisions of its guidelines on the use of highly active antiretroviral therapy for HIV. The new guidelines greatly expand eligibility for treatment of adults and children, as well as for pregnant women seeking prophylaxis for vertical HIV transmission. WHO's new recommendations bring the guidelines closer to practices in developed countries, and its shift to earlier treatment alone will increase the number of treatment-eligible people by 50% or more.

Natural substrate concentrations can modulate the prophylactic efficacy of nucleotide HIV reverse transcriptase inhibitors.

Preexposure prophylaxis (PrEP) with antiretroviral drugs is a novel human immunodeficiency virus (HIV) prevention strategy. It is generally thought that high systemic and mucosal drug levels are sufficient for protection. We investigated whether GS7340, a next-generation tenofovir (TFV) prodrug that effectively delivers tenofovir diphosphate (TFV-DP) to lymphoid cells and tissues, could protect macaques against repeated weekly rectal simian-human immunodeficiency virus (SHIV) exposures.

Controlled mild hypothermia prolongs survival in a rat model of large scald burns.

Objectives: Early surface cooling of burns reduces pain and depth of injury and improves healing. However, there are concerns that cooling of large burns may result in hypothermia and worsen outcomes. In contrast, controlled mild hypothermia improves outcomes after cardiac arrest and traumatic brain injury.

Autophagy-dependent regulation of the DNA damage response protein ribonucleotide reductase 1.

Protein synthesis and degradation are posttranscriptional pathways used by cells to regulate protein levels. We have developed a systems biology approach to identify targets of posttranscriptional regulation and we have employed this system in Saccharomyces cerevisiae to study the DNA damage response. We present evidence that 50% to 75% of the transcripts induced by alkylation damage are regulated posttranscriptionally.

Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1.

Background: Limited data compare once-daily options for initial therapy for HIV-1.

Objective: To compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.

Design: A randomized equivalence trial accrued from September 2005 to November 2007, with median follow-up of 138 weeks.

The plaque removal efficacy of a novel power brush head.

Objective: To assess the plaque removal efficacy of an oscillating/rotating power toothbrush with novel brush head (Oral-B Precision Clean) in comparison to an American Dental Association (ADA) reference manual toothbrush.

Methods: This was a replicate-use, single-brushing, two-treatment, examiner-blind, randomized, four-period (visit) study with a crossover design. At each visit, subjects disclosed their plaque with disclosing solution for one minute, and an examiner performed a baseline (pre-brushing) plaque examination (Rustogi, et al.

Lessons learned from a fatal case of mercury intoxication.

Context: While many cases of metallic mercury poisoning have been reported, cases of metallic mercury poisoning from multiple exposure routes are rare.

Case Presentation: We report the case of a 36-year-old Latin American male who presented with rash, sore throat, fever, chills, cough, and diarrhea after chronic mercury vapor exposure and likely intravenous injection. Despite chelation treatment with meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropanesulfonic acid (DMPS), the patient's clinical course was complicated by renal failure and he passed away after 18 days.

Cross-species Functionome analysis identifies proteins associated with DNA repair, translation and aerobic respiration as conserved modulators of UV-toxicity.

Cellular responses to DNA damage can prevent mutations and death. In this study, we have used high throughput screens and developed a comparative genomic approach, termed Functionome mapping, to discover conserved responses to UVC-damage. Functionome mapping uses gene ontology (GO) information to link proteins with similar biological functions from different organisms, and we have used it to compare 303, 311 and 288 UVC-toxicity modulating proteins from Escherichia coli, Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively.

Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.

Background: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition.

Methods: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections.

Antiretroviral therapies in women after single-dose nevirapine exposure.

Background: Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus.

Methods: In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death.

An investigation of the use of passive movements in intensive care by UK physiotherapists.

Objectives: To investigate the current use of passive movements (PMs) by National Health Service (NHS) physiotherapists working with sedated and ventilated patients in critical care settings.

Design: Postal questionnaire.

Setting: All open NHS critical/intensive care units in England, Northern Ireland, Scotland and Wales.