ALSUntangled #75: Portable neuromodulation stimulator therapy.

Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS.

Pharmacokinetics of Atazanavir Boosted With Cobicistat in Pregnant and Postpartum Women With HIV.

Background: This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples.

Setting: A nonrandomized, open-label, parallel-group, multicenter prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children.

Methods: Intensive steady-state 24-hour pharmacokinetic profiles were performed after administration of 300 mg of atazanavir and 150 mg of cobicistat orally in fixed-dose combination once daily during the second trimester, third trimester, and postpartum.

Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV.

Objective: To evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery.

Design: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States.

Methods: Intensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800 mg of darunavir and 150 mg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum.

Pharmacokinetics of tenofovir alafenamide with and without cobicistat in pregnant and postpartum women living with HIV.

Objective: To evaluate the pharmacokinetics of tenofovir alafenamide (TAF) 10 mg with cobicistat and 25 mg without boosting in pregnant and postpartum women with HIV and to characterize TAF placental transfer and infant washout pharmacokinetics.

Design: Open-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, postpartum, delivery, and infant washout.

Methods: Pregnant women receiving TAF 10 mg with cobicistat or TAF 25 mg without boosting as part of clinical care had intensive pharmacokinetic assessments performed during the second and third trimesters, and 6-12 weeks postpartum.

Pharmacokinetics and Safety of a Raltegravir-Containing Regimen in Children Aged 4 Weeks to 2 Years Living With Human Immunodeficiency Virus and Receiving Rifampin for Tuberculosis.

Unlabelled: Pharmacological interactions limit treatment options for children living with human immunodeficiency virus (HIV) and tuberculosis (TB). We found that 12 mg/kg twice daily raltegravir chewable tablets (administered after crushing) safely achieved pharmacokinetic targets in children living with HIV aged 4 weeks to <2 years receiving concurrent rifampin to treat TB.

Clinical Trials Registration: NCT01751568.

Associations of Patient Mood, Modulators of Quality of Life, and Pharmaceuticals with Amyotrophic Lateral Sclerosis Survival Duration.

Associations of modulators of quality of life (QoL) and survival duration are assessed in the fatal motor neuron disease, Amyotrophic Lateral Sclerosis. Major categories include clinical impression of mood (CIM); physical health; patient social support; and usage of interventions, pharmaceuticals, and supplements. Associations were assessed at < 0.

Pharmacokinetics and safety of a raltegravir-containing regimen in HIV-infected children aged 2-12 years on rifampicin for tuberculosis.

Objectives: Drug-drug interactions limit current antiretroviral treatment options for HIV-infected children with tuberculosis (TB). Rifampicin (RIF) induces UDP-glucuronosyltransferase activity, accelerating the clearance of raltegravir (RAL). We sought to establish an optimal and well tolerated dose of RAL when administered with RIF to HIV and TB co-infected children.

Loss of KIBRA function activates EGFR signaling by inducing AREG.

The Hippo signaling pathway is a central regulator of organ size, tissue homeostasis, and tumorigenesis. KIBRA is a member of the WW domain-containing protein family and has recently been reported to be an upstream protein in the Hippo signaling pathway. However, the clinical significance of KIBRA deregulation and the underlying mechanisms by which KIBRA regulates breast cancer (BC) initiation and progression remain poorly understood.

The Hippo Signaling Transducer TAZ Regulates Mammary Gland Morphogenesis and Carcinogen-induced Mammary Tumorigenesis.

Hippo signaling pathway is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, apoptosis and stem cell self-renewal. TAZ (transcriptional coactivator with the PDZ-binding motif) is a key downstream effector of the mammalian Hippo pathway. Here, using a transgenic mouse model with mammary-gland-specific expression of constitutively active TAZ, we found that TAZ induction in mammary epithelial cells was associated with an increase in mammary glandular size, which probably resulted from adipocyte hypertrophy.

VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer.

Members of the mammalian Vestigial-like (VGLL) family of transcriptional cofactors activate genes in response to a wide variety of environmental cues. Recently, VGLL proteins have been proposed to regulate key signaling networks involved in cancer development and progression. However, the biological and clinical significance of VGLL dysregulation in human breast cancer pathogenesis remains unknown.

What Can a Primary Care Physician Discuss With Older Patients to Improve Advance Directive Completion Rates? A Clin-IQ.

Advance directives (ADs) provide patients with the opportunity to indicate their preferences for medical care while they still maintain the capacity to express their wishes, thus retaining autonomy. ADs increase the likelihood that patients will receive the care they desire, as their family members and physicians will better understand the level of care desired. Despite this, the AD completion rate by elderly patients continues to be low, especially for patients not facing serious illnesses.

Geriatrics Education Team Model Results in Sustained Geriatrics Training in 15 Residency and Fellowship Programs and Scholarship.

Caring for the growing elderly population will require specialty and subspecialty physicians who have not completed geriatric medicine fellowship training to participate actively in patient care. To meet this workforce demand, a sustainable approach to integrating geriatrics into specialty and subspecialty graduate medical education training is needed. This article describes the use of a geriatrics education team (GET) model to develop, implement, and sustain specialty-specific geriatrics curricula using a systematic process of team formation and needs assessment through evaluation, with a unique focus on developing curricular interventions that are meaningful to each specialty and satisfy training, scholarship, and regulatory requirements.

Elderly surgical patients: are there gaps in residency education?

Background: Geriatric education is essential to ensure the competency of residents caring for the aging population. This study assesses and correlates resident and faculty perceptions of resident geriatric-related competencies to clinical care.

Methods: A survey was sent to 40 general surgery residents and 57 faculty members.

Positioning medical students for the geriatric imperative: using geriatrics to effectively teach medicine.

Medical schools must consider innovative ways to ensure that graduates are prepared to care for the aging population. One way is to offer a geriatrics clerkship as an option for the fulfillment of a medical school's internal medicine rotation requirement. The authors' purpose was to evaluate the geriatrics clerkship's impact on internal medicine knowledge and medical student attitudes toward older adults.

One specialty at a time: achieving competency in geriatrics through an e-learning neurology clerkship module.

Background: E-learning integrated into traditional clerkships may supplement gaps in medical student training, such as geriatrics competencies.

Method: An e-module, "Neurology and Dementia: Psychosocial Aspects of Care," was offered during the M3 Neurology clerkship. OSCE scores were compared between students who did and did not complete the e-module with written examination scores as control.

Induction of cardiovascular pathology in a novel model of low-grade chronic inflammation.

Objective: Epidemiological and clinical evidence indicate that inflammatory processes play a pivotal role in a number of conditions associated with aging, including osteoporosis and cardiovascular diseases. The purpose of this study was to evaluate cardiovascular pathology and select inflammatory mediators of interest in a model of low-grade inflammation-induced osteopenia.

Methods: Slow-release pellets were subcutaneously implanted in male rats to deliver 0, 3.

Biomarker identification in human pancreatic cancer sera.

Objective: The aim of this study is to identify biomarkers in sera of pancreatic cancer patients using mass spectrometry (MS) approaches.

Methods: Sera from patients diagnosed with pancreatic adenocarcinoma and sera from normal volunteers were subjected to gel electrophoresis to resolve and quantify differences in protein levels. Protein bands that differed quantitatively were digested with trypsin, and peptides were identified by electrospray ionization (ESI) ion-trap tandem MS.

Incidence of venous thromboembolism in patients with traumatic brain injury.

Background: Traumatic brain injury (TBI) may be a risk factor for venous thromboembolism (VTE). This study was designed to review the incidence of VTE in critically injured patients with an isolated TBI using a standardized venous duplex color-flow Doppler imaging program and to compare it with the overall and high-risk trauma populations.

Methods: Trauma patients who underwent lower-extremity surveillance color-flow Doppler imaging for VTE were identified.

Objective Structured Video Examinations (OSVEs) for geriatrics education.

The Medical College of Wisconsin (MCW) and the Wisconsin Geriatric Education Center (WGEC) are committed to developing educational materials for primary care physicians in training. In response to the opportunity created by the Accreditation Council for Graduate Medical Education (ACGME) competency mandate, an MCW-led interdisciplinary working group has developed competency-linked video-based assessment tools for use in primary care residency training programs. Modeled after the Objective Structured Clinical Examinations (OSCE), used as part of the medical licensing examination process, we created geriatric-focused Objective Structured Video Examinations (OSVEs) as a strategy to infuse geriatrics into residency training.

A challenging patient, an innovative solution.

This report of the management of a 28-year-old patient over 2 and a half years illustrates how interaction between psychosocial issues and physical symptoms complicates diagnosis and management. The case also highlights the challenges inherent in a large health care system with multiple health care professionals, clinics, and available resources. A "team model" approach is outlined as a useful strategy in such cases.

A comparison of the Ranson, Glasgow, and APACHE II scoring systems to a multiple organ system score in predicting patient outcome in pancreatitis.

Background: Systems for evaluating acute pancreatitis are useful in hospitalized patients. Traditional systems of evaluation are well established but might be outdated. We propose a Multiple Organ System Score (MOSS) containing data that are more consistently collected and which are accurate in predicting patient outcome.