Universal Germline-Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision-Making.

Background: Whereas the National Comprehensive Cancer Network (NCCN) criteria restrict germline-genetic testing (GGT) to a subset of breast cancer (BC) patients, the American Society of Breast Surgeons recommends universal GGT. Although the yield of pathogenic germline variants (PGV) in unselected BC patients has been studied, the practicality and utility of incorporating universal GGT into routine cancer care in community and rural settings is understudied. This study reports real-world implementation of universal GGT for patients with breast cancer and genetics-informed, treatment decision-making in a rural, community practice with limited resources.

Should we routinely add CRP to clozapine titrations? - Learning from three cases.

Objectives: An international guideline recently provided certain personalized schedules for titrating clozapine in adult inpatients by considering: 1) DNA ancestry group, 2) sexsmoking subgroup, and 3) presence/absence of clozapine poor metabolizer (PM) status. Measuring CRP levels at baseline and during the first 4 weeks is recommended. Titrations too fast for the metabolism of specific patients can lead to clozapine-induced inflammations and CRP elevations.

Assessing Breast Cancer Risks to Improve Care for an Increased-Risk Population within Eastern North Carolina.

The average lifetime risk of breast cancer for an American woman is 12.5%, but individual risks vary significantly. Risk modeling is a standard of care for breast cancer screening and prevention with recommended tools to stratify individual risks based on age, family history, breast density, and a host of other known risk factors.

Four cases of myocarditis in US hospitals possibly associated with clozapine poor metabolism and a comparison with prior published cases.

Objectives: Clozapine-induced myocarditis may be a hypersensitivity reaction due to titration that was too rapid for a patient's clozapine metabolism. Obesity, infections, and inhibitors (e.g.

High Doses of Drugs Extensively Metabolized by CYP3A4 Were Needed to Reach Therapeutic Concentrations in Two Patients Taking Inducers.

Introduction: In the last 20 years of clinical practice, the senior author has identified these 2 rare cases in which the patients needed extremely high doses of drugs metabolized by CYP3A4 to reach and maintain serum therapeutic concentrations.

Methods: The high metabolic ability of these 2 patients was demonstrated by the low concentration-to-dose ratios (C/D ratios) of several drugs metabolized by CYP3A4.

Results: Case 1 was characterized by a history of high carbamazepine doses (up to 2,000mg/day) and needed 170 mg/day of diazepam in 2 days to cooperate with dental cleaning.

Congenital intravascular abdominal aortic band initially thought to be a metallic foreign body: Characterization using microanatomical CT reconstruction technique.

We present a patient with the initial misdiagnosis of a metallic foreign body in the abdominal aorta. Computed tomographic angiography utilizing microanatomical reconstruction technique revealed the structure to instead be a partially calcified abdominal aortic congenital fibrous band. Most congenital fibrous bands spanning the aortic lumen are proximal within the aorta and are thought to be supportive structures of the aortic valve leaflets.

A retrospective analysis of the association between providing nicotine replacement therapy at admission and motivation to quit and nicotine withdrawal symptoms during an inpatient psychiatric hospitalization.

Background: Psychiatric patients have high tobacco use prevalence, dependence, and withdrawal severity. A tobacco-free psychiatric hospitalization necessitates the management of nicotine withdrawal (NW) for tobacco using patients. NW management often requires the provision of approved nicotine replacement therapy (NRT) to patients, which may also motivate tobacco users towards cessation.

Effect of radiation and repeated sub-culturing on the transforming growth factor-β1 signaling pathway in FRTL-5 cells.

Background/aim: Fisher rat thyroid cells (FRTL-5) display increased proliferation, reduced follicularization and decreased thyroxin release with repeated sub-culturing. These changes occur earlier and more rapidly following exposure to ionizing radiation. We hypothesized that altered transforming growth factor-β1 (TGF-β1) signaling contributes to these differences.

Higher estrogen levels during pregnancy in Andean than European residents of high altitude suggest differences in aromatase activity.

Context: Uteroplacental hypoxia has been reported to lower estrogen levels in preeclampsia as the result of reduced aromatase activity.

Objective: We asked whether the chronic hypoxia of residence at high altitude in the absence of preeclampsia lowered estrogen, whether such effects differed in Andean vs European high-altitude residents, and whether such effects were related to uterine artery diameter or blood flow.

Design, Setting, And Participants: Studies at weeks 20 and 36 of pregnancy were conducted in 108 healthy Bolivian low- (400 m, n = 53) or high-altitude (3600 m, n = 55) residents of European (n = 28 low and 26 high altitude) or Andean (n = 25 low and 29 high altitude) ancestry.

Pregnancy increases myometrial artery myogenic tone via NOS- or COX-independent mechanisms.

Myogenic tone (MT) is a primary modulator of blood flow in the resistance vasculature of the brain, kidney, skeletal muscle, and perhaps in other high-flow organs such as the pregnant uterus. MT is known to be regulated by endothelium-derived factors, including products of the nitric oxide synthase (NOS) and/or the cyclooxygenase (COX) pathways. We asked whether pregnancy influenced MT in myometrial arteries (MA), and if so, whether such an effect could be attributed to alterations in NOS and/or COX.

Diabetes and adverse mental health among African Americans.

This article reviews the connection between diabetes and adverse mental health among African Americans. Concern about safe insulin prescribing and administration is raised, and the importance of integrated physical and mental health care in the prevention and control of diabetes is highlighted.

Capsaicin pre-treatment provides neurovascular protection against neonatal hypoxic-ischemic brain injury in rats.

Capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, has recently been shown to provide neuroprotection against brain injury in experimental adult models of cerebral ischemia. Accordingly, in this study, we investigated the way in which capsaicin-mediated TRPV1 modulation could attenuate damage in an experimental hypoxic-ischemic (HI) neonatal brain injury model. The Rice-Vannucci method was used in 10-day-old rat pups by performing unilateral carotid artery ligation followed by 2 h of hypoxia (8% O2 at 37°C).

Humans at high altitude: hypoxia and fetal growth.

High-altitude studies offer insight into the evolutionary processes and physiological mechanisms affecting the early phases of the human lifespan. Chronic hypoxia slows fetal growth and reduces the pregnancy-associated rise in uterine artery (UA) blood flow. Multigenerational vs.

Roles of cytosolic Ca2+ concentration and myofilament Ca2+ sensitization in age-dependent cerebrovascular myogenic tone.

In light of evidence that immature arteries contain a higher proportion of noncontractile smooth muscle cells than found in fully differentiated mature arteries, the present study explored the hypothesis that age-related differences in the smooth muscle phenotype contribute to age-related differences in contractility. Because Ca(2+) handling differs markedly between contractile and noncontractile smooth muscle, the present study specifically tested the hypothesis that the relative contributions of Ca(2+) influx and myofilament sensitization to myogenic tone are upregulated, whereas Ca(2+) release is downregulated, in immature [14 days postnatal (P14)] compared with mature (6 mo old) rat middle cerebral arteries (MCAs). Myofilament Ca(2+) sensitivity measured in β-escin-permeabilized arteries increased with pressure in P14 but not adult MCAs.

Factors impacting the selection of antidepressant treatment in patients with major depressive disorder at risk for nonadherence.

Treatment with the newer generation antidepressants is considered generally effective for most patients with major depressive disorder when taken in accordance with treatment guidelines. However, multiple clinical studies have demonstrated that rates of patient adherence to antidepressants are inadequate, specifically with regard to long-term maintenance treatment. Tolerability issues associated with antidepressants can increase the risk for patient nonadherence and result in subsequent relapse of depressive symptoms.

Postnatal maturation attenuates pressure-evoked myogenic tone and stretch-induced increases in Ca2+ in rat cerebral arteries.

Although postnatal maturation potently modulates agonist-induced cerebrovascular contractility, its effects on the mechanisms mediating cerebrovascular myogenic tone remain poorly understood. Because the regulation of calcium influx and myofilament calcium sensitivity change markedly during early postnatal life, the present study tested the general hypothesis that early postnatal maturation increases the pressure sensitivity of cerebrovascular myogenic tone via age-dependent enhancement of pressure-induced calcium mobilization and myofilament calcium sensitivity. Pressure-induced myogenic tone and changes in artery wall intracellular calcium concentrations ([Ca(2+)](i)) were measured simultaneously in endothelium-denuded, fura-2-loaded middle cerebral arteries (MCA) from pup [postnatal day 14 (P14)] and adult (6-mo-old) Sprague-Dawley rats.

Diagnosis and management of anxiety disorders.

Major anxiety disorders are more prevalent in women than in men. Although the tendency toward anxiety disorders appears familial, other factors such as environmental influences can play a role in the risk for anxiety. This clinical review focuses on the pathophysiologic basis for anxiety disorders.

Venlafaxine XR demonstrates higher rates of sustained remission compared to fluoxetine, paroxetine or placebo.

The combined serotonin-norepinephrine reuptake inhibitor, venlafaxine XR, has demonstrated significant response and remission in patients diagnosed with depression when measured with the Hamilton Depression Rating Scale (HAM-D). This pooled analysis of data from five studies compared the sustained remission of depressive symptoms in patients treated with venlafaxine XR, the selective serotonin reuptake inhibitors (SSRIs) fluoxetine or paroxetine, or placebo. Data from 1391 subjects enrolled in five active and placebo-controlled studies who met the DSM-III-R or DSM-IV criteria for major depressive disorder were analysed.

Long-term management of major depressive disorder: are differences among antidepressant treatments meaningful?

Recurrent depression poses a problem for up to 80% of patients with major depressive disorder (MDD) during their lifetime. Therefore, the optimal treatment goal established by the American Psychiatric Association and the Agency for Health Care Policy and Research is remission and virtual elimination of symptoms. Patients who have a high risk of recurrence often require maintenance therapy and long-term treatment.