The FAST in screening for at-risk drinking among middle-aged women

Objective: There is a need for brief methods to screen for at-risk drinking. The FAST is a two-stepped structured questionnaire. In the FAST-1, one question categorizes into three groups: low-risk drinking, potential at-risk drinking or at-risk drinking. In the FAST-2, those with potential at-risk drinking are asked three additional questions. The aim was to study its effectiveness in screening for at-risk drinking among women and to define an optimal cut-off score.

Method: The FAST was validated against the Timeline Followback (TLFB) utilizing data from a health check of a group of 40-year old women (response rate 69.2%; n = 907/1311). The TLFB-based definition of at-risk drinking was consuming ≥140 grams of alcohol weekly (6.1% reported at-risk drinking).

Results and conclusions: Of all women, 54.5% could be correctly classified either as having low-risk or at-risk drinking with the FAST-1. The optimal cut-off score was ≥2 (sensitivity 0.82, specificity 0.86) which is lower than has previously been reported. Only those with a FAST-1 score of one needed further evaluation with the FAST-2. A FAST-2 score of ≥1 resulted in a positive screen for at-risk drinking. The FAST seems to be a valid and feasible method in screening for at-risk drinking among middle-aged women.     

Cellular Pharmacology and Potency of HIV-1 Nucleoside Analogs in Primary Human Macrophages

Understanding the cellular pharmacology of antiretroviral agents in macrophages and subsequent correlation with antiviral potency provides a sentinel foundation for definition of the dynamics between antiretroviral agents and viral reservoirs across multiple cell types, with the goal of eradication of HIV-1 from these cells. Various clinically relevant nucleoside antiviral agents, and the integrase inhibitor raltegravir, were selected for this study. The intracellular concentrations of the active metabolites of the nucleoside analogs were found to be 5- to 140-fold lower in macrophages than in lymphocytes, and their antiviral potency was significantly lower in macrophages constitutively activated with macrophage colony-stimulating factor (M-CSF) during acute infection than in resting macrophages (EC₅₀, 0.4 to 9.42 μM versus 0.03 to 0.4 μM, respectively). Although tenofovir-treated cells displayed significantly lower intracellular drug levels than cells treated with its prodrug, tenofovir disoproxil fumarate, the levels of tenofovir-diphosphate for tenofovir-treated cells were similar in lymphocytes and macrophages. Raltegravir also displayed significantly lower intracellular concentrations in macrophages than in lymphocytes, independent of the activation state, but had similar potencies in resting and activated macrophages. These data underscore the importance of delivering adequate levels of drug to macrophages to reduce and eradicate HIV-1 infection.     

Time in Parenting Activities in Dual‐Earner Families at the Transition to Parenthood

Time parenting was compared for new mothers and fathers in a sample of 182 dual‐earner families. Parenting domains included positive engagement, responsibility, routine child care, and accessibility. Time diaries captured parents' time use over a 24‐hour workday and nonworkday when infants were age 3 and 9 months. Parents were highly involved with their infants. Mothers were more involved than fathers in positive engagement and routine child care on days and at each assessment, and allocated more available time on workdays to these domains than fathers, with one exception. Fathers and mothers allocated similar shares of available workday time to positive engagement at 9 months. Greater equity in responsibility and accessibility was found; mothers spent more, and a greater share of, parenting time in responsibility than fathers on the 9‐month workday only, and were more accessible on the 3‐month workday only. Implications for parents in today's diverse families are discussed.     

Nocturnal Body Movements and Hypoxemia in Middle-Aged Females After Lower Abdominal Surgery Under General Anesthesia: A Study With the Static-Charge-Sensitive Bed (SCSB)

Objective. The aim of this study was to evaluate the feasibility of the static-charge-sensitive-bed (SCSB) combined with pulse oximetry (SpO₂) for postoperative monitoring and to determine variables which could be used for evaluating the quality of postoperative sleep and breathing. Methods. The frequency of body movements and the perioperative breathing abnormalities were assessed using the SCSB and pulse oximeter in 15 female ASA-class I–II patients undergoing elective lower abdominal surgery under general anesthesia. Anesthesia and control of postoperative pain followed standard practice. The patients were monitored during one preoperative and three consecutive postoperative nights. Movements were analyzed according to their duration and time interval. The effect of opioids was evaluated by measuring arterial oxyhemoglobin saturation (SpO₂) with pulse oximetry for one hour before and two hours after administration of standard doses of oxycodone. Results. The total movement time per hour increased during the first postoperative night (p = 0.003). Conversely, periodic movement activity decreased significantly during the three postoperative nights (p = 0.05, p < 0.001, p = 0.007). The mean SpO₂ decreased during the first postoperative night (95.5% vs. 94.2%, p = 0.002), but returned to the preoperative level during the following nights. No episodes of apnea with significant oxygen desaturation (a decrease in SpO₂<5%) were observed. Opioid administration was associated with decreased mean SpO₂ (94.8% vs. 93.6%, p = 0.02), but did not lead to clinically significant hypoxemia (lowest observed SpO₂ 89.8%). Conclusions. Postoperative periodic movement activity was suppressed, but sleep remained fragmented with frequent body movements. In our middle-aged non-obese females (ASA I–II), no severe postoperative hypoxemia was observed during the three-nights postoperative survey. Perioperative movement monitoring with the SCSB was a valuable tool in rejecting movement artefacts of SpO₂ and in evaluating general sleep quality.     

IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe-/- mice

IgE has a key role in the pathogenesis of allergic responses through its ability to activate mast cells via the receptor FcεR1. In addition to mast cells, many cell types implicated in atherogenesis express FcεR1, but whether IgE has a role in this disease has not been determined. Here, we demonstrate that serum IgE levels are elevated in patients with myocardial infarction or unstable angina pectoris. We found that IgE and the FcεR1 subunit FcεR1α were present in human atherosclerotic lesions and that they localized particularly to macrophage-rich areas. In mice, absence of FcεR1α reduced inflammation and apoptosis in atherosclerotic plaques and reduced the burden of disease. In cultured macrophages, the presence of TLR4 was required for FcεR1 activity. IgE stimulated the interaction between FcεR1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis. These IgE activities were reduced in the absence of FcεR1 or TLR4. Furthermore, IgE activated macrophages by enhancing Na+/H+ exchanger 1 (NHE1) activity. Inactivation of NHE1 blocked IgE-induced macrophage production of inflammatory molecules and apoptosis. Cultured human aortic SMCs (HuSMCs) and ECs also exhibited IgE-induced signal transduction, cytokine expression, and apoptosis. In human atherosclerotic lesions, SMCs and ECs colocalized with IgE and TUNEL staining. This study reveals what we believe to be several previously unrecognized IgE activities that affect arterial cell biology and likely other IgE-associated pathologies in human diseases.