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espanolObjetivos. Argentina ha informado de altos niveles de farmacorresistencia transmitida (TDR), en mujeres embarazadas infectadas por el VIH por secuenciacion poblacional. Nuestro objetivo fue describir, en pacientes con TDR, el porcentaje de cuasiespecies que albergan mutaciones de resistencia (RAM) y la carga mutacional (ML). Pacientes y metodos. Estudio retrospectivo en una cohorte de 40 mujeres embarazadas VIH positivas naive, cuyas muestras pretratamiento habian sido genotipificadas por TRUGENE (periodo 2008-2014). Las muestras se genotipificaron por secuenciacion ultraprofunda y se calculo la ML considerando la carga viral multiplicada por la frecuencia de las cuasiespecies que albergan RAMs. Resultados. La TDR para ITINN, ITIAN e IP fue del 17,5% (n=7 pacientes), 10% (n=4), 12,5% (n=5) respectivamente. Las RAMs ITINN predominantes fueron K103N (n=4; 10%) y G190A/E/ S (n=3; 7,5%). Para los ITINN, el 78% de los RAM estaban presentes en >93,5% de la poblacion viral y la ML fue >1000 copias/ml (c/mL) para el 89%, con una mediana (IQR) de 8330 c/ml (7738-29796). Se describieron los siguientes RAM de ITIAN (% de cuasiespecies, ML): T215I (99,7%, 11014 c/ml); D67G (1,28%, 502 c/ml); M41L (79,8%, 88578 c/mL) y M184I (1,02%, 173 c/mL). Las IP-RAMs mas frecuentes fueron I85V, M46I, I50V y L90M (n=2, 5% cada una). Para los IP, las cuasiespecies con RAMs fueron Conclusion. Los ITINN-RAMs son predominantes dentro de la poblacion viral, por lo general superan el umbral de 1000 c/mL, que indicaria un riesgo potencial mas alto de transmision perinatal. Por el contrario, las mutaciones de IP aparecen principalmente como variantes minoritarias, con un riesgo menor de transmision. Para ITIAN, las cuasiespecies que albergan RAM y los valores de ML fueron variables. EnglishObjective. Argentina has reported high levels of transmitted drug resistance (TDR), in HIV-infected pregnant women by population sequencing. We aimed to describe, in patients with TDR, the percentage of quasispecies harboring resistance mutations (RAMs) and mutational load (ML). Patients and Methods. Retrospective study in a cohort of 40 naive HIV-infected pregnant women, whose pretreatment samples had been genotyped by TRUGENE (period 2008-2014). Samples were re-sequenced with Ultra-deep Sequencing and ML was calculated considering baseline HIV-1 RNA load multiplied by the frequency of quasispecies harboring RAMs. Results. TDR for NNRTIs, NRTIs and PIs was 17.5% (n=7 patients), 10% (n=4), 12.5% (n=5) respectively. Predominant NNRTI RAMs were K103N (n=4; 10%) and G190A/E/S (n=3; 7.5%). For NNRTIs, 78% of RAMs were present in >93.5% of viral population and ML was >1000 copies/mL (c/mL) for 89%, with a median (IQR) of 8330 c/ml (7738-29796). The following NRTI RAMs were described (per patient: % of quasispecies, ML): T215I (99.7%, 11014 c/ml); D67G (1.28%, 502 c/mL); M41L (79.8%, 88578 c/mL) and M184I (1.02%, 173 c/mL). Most frequent PI-RAMs were I85V, M46I, I50V and L90M (n=2, 5% each). For PIs, quasispecies with RAMs were Conclusion. NNRTI-RAMs are predominant within the viral population, usually exceeding the threshold of 1000 c/mL, indicating potential higher risk of perinatal transmission. Conversely, PI mutations appear mostly as minority variants, with potential lower risk of transmission. Among NRTI, quasispecies harboring RAMs and ML values were variable.

Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

The Dominican Republic (DR) has the second-highest prevalence of HIV infection in the Caribbean, but viral suppression and treatment adherence are not well understood. We conducted a cross-sectional study among people living with HIV/AIDS(PLWHA) to fill in the knowledge gap. Questionnaire was used to collect demographic data, antiretroviral therapy (ART) adherence, and barriers and facilitators to HIV care. Viral load and other clinical information were extracted through chart reviews. Descriptive analyzes and logistic regression were conducted to explore factors associated with non-viral suppression and imperfect ART adherence. Of 193 PLWHA 83.9% were virally suppressed. Those that were non-virally suppressed were more likely of being male (odds ratio [OR]: 2.55, 95% confidence interval [CI]: 1.17-5.58) and less likely of being unemployed (OR: 0.28, 95% CI: 0.08-0.96). However, being male (OR: 0.78, 95% CI:0.40-1.53) and unemployed (OR: 0.28, 95% CI:0. 08-1.21) were less likely to report imperfect adherence. Tailored interventions are needed to improve adherence and viral suppression in DR.

A 60-year-old HIV-1 infected woman on antiretroviral therapy (emtricitabine/tenofovir, and ritonavir-boosted atazanavir) developed Hodgkin’s lymphoma. The patient initiated ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and presented with neutropenia and severe hypokalemia. Hypokalemia was considered as part of a proximal tubular renal dysfunction, and other causes of hypokalemia were excluded. Due to suspicion of drug-–drug interactions between antiretrovirals and vinblastine, ritonavir-boosted atazanavir was switched to dolutegravir and the patient continued emtricitabine/tenofovir. In the subsequent ABVD cycles, no neutropenia or hypokalemia were observed. Vinblastine is metabolized by the hepatic P450 cytochrome isoenzyme CYP3A4, therefore, concomitant administration with protease inhibitors may increase plasma levels of vinblastine. Vinblastine is also a substrate and inhibitor of multidrug resistance-associated protein 2 (MRP2) transporter in the proximal renal tubule. Inhibition of this renal transporter could increase tenofovir renal toxicity. Our hypothesis is that the hypokalemia could be a result of a tenofovir-mediated tubular damage triggered by the increased vinblastine serum levels secondary to a CYP3A4 inhibition by ritonavir. To the best of our knowledge, this is the first report of severe hypokalemia and proximal tubular renal dysfunction as a result of a possible drug–drug interaction between vinblastine, tenofovir and ritonavir-boosted atazanavir.

Bodily attractiveness is an important component of mate value. Musculature—a crucial component of men’s bodily attractiveness—provides women with probabilistic information regarding a potential mate’s quality. Overall musculature is comprised of several muscle groups, each of which varies in information value; different muscles should be weighted differently by attractiveness-assessment adaptations as a result. In the current study, women and men (N = 1,742) reported size preferences for 14 major muscle groups. Women’s reported preferences provided only partial support for our hypotheses that women will prefer muscles that most reliably differentiate between potential mates to be larger; men tended to prefer larger upper-body muscles. We discuss possible interpretations of these mixed findings. Ultimately, our findings suggest that attractiveness-assessment adaptations are sensitive to the information contained within specific muscle groups and they highlight the potential for additional research on the nuances of bodily attractiveness assessment., The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Government of Chile (FONDECYT REGULAR 1170513).

Prosocial third-party punishment (3PP) is a punitive behavior against antisocial individuals, which might explain extended cooperativeness in humans. 3PP shows sexual dimorphism, being more frequent in men than in women. We studied whether sexually dimorphic features related to sexual hormones during development (facial dimorphism and 2D:4D) influence the tendency to engage in 3PP in a sample of 511 women and 328 men. After playing a Prisoner’s Dilemma, participants had to decide whether to penalize the defection of a third player who had exploited his/her counterpart’s cooperation. In line with previous studies, we observe that men are more prone to engage in 3PP than women. We find that this sex difference is due to cooperative men being more likely to punish than cooperative women. In addition, men with higher facial masculinity are less likely to engage in 3PP, whereas no features influence 3PP in women. We discuss the possibility that sex differences in the motivations and fitness implications underlying 3PP might be driving the observed results, Funding from the Spanish Ministry for Science and Innovation (grant ECO2015-66281-P) and from Chilean FONDECYT (Grant No. 1170513) are gratefully acknowledged

Current evidence proposes diet quality as a modifiable risk factor for mental or emotional impairments. However, additional studies are required to investigate the effect of dietary patterns and weight loss on improving psychological symptoms. The aim of this investigation was to evaluate the effect of energy-restriction, prescribed to overweight and obese participants, on anxiety and depression symptoms, as well as the potential predictive value of some baseline psychological features on weight loss. Overweight and obese participants (n = 305) were randomly assigned for 16 weeks to two hypocaloric diets with different macronutrient distribution: a moderately high-protein (MHP) diet and a low-fat (LF) diet. Anthropometrical, clinical, psychological, and lifestyle characteristics were assessed at baseline and at the end of the intervention. The nutritional intervention evidenced that weight loss has a beneficial effect on trait anxiety score in women (&beta, = 0.24, p = 0.03), depression score in all population (&beta, = 0.15, p = 0.02), particularly in women (&beta, = 0.22, p = 0.03) and in subjects who followed the LF diet (&beta, = 0.22, p = 0.04). Moreover, weight loss could be predicted by anxiety status at baseline, mainly in women and in those who were prescribed a LF diet. This trial suggests that weight loss triggers an improvement in psychological traits, and that anxiety symptoms could predict those volunteers that benefit most from a balanced calorie-restricted intervention, which will contribute to individualized precision nutrition.

Determining the status of HER2-neu amplification and overexpression in breast cancer is crucial for prognosis but mostly for treatment purposes. Standard techniques include the determination of IHC in combination with in situ hybridization techniques to confirm a HER2-neu amplification in case of IHC2+ using either a core-needle biopsy or a surgical specimen. qPCR has been also demonstrated to be able to determine HER2 status, mostly in core biopsies or in surgical specimens. Fine-needle aspiration is a reliable, quicker and less invasive technique that is widely used for diagnosis of invasive breast cancer. In this study, we assessed the performance of qPCR in invasive breast carcinomas to determine HER2-neu status by using fine-needle aspiration samples and comparing to standard IHC and FISH. From a total of 154 samples from patients who had nodular breast lesions and attended the 1-day-stop clinic at the Gustave Roussy from March 2013 to October 2014, qPCR was able to determine the HER2 status in a mean of 3.7 days (SD 3.1). The overall concordance with standard HER2-testing was very high: 97% (95% CI 0.94 to 0.99); sensitivity was 96% (0.87–1), specificity 98% (0.95–1) and positive and negative predictive values 88% (0.75–1) and 99% (0.98–1), respectively. In conclusion, our study demonstrates that qPCR performed using fine-needle aspiration samples from a primary tumour is a reliable and fast method to determine HER2/neu status in patients with early breast cancer.

Background: Prior studies have suggested that physicians and residents may not have sufficient knowledge to appropriately interpret urine drug tests (UDTs) in patients who are prescribed opioids or using illicit substances. Therefore, the aim of this study was to survey psychiatry residents and fellows about their confidence and knowledge in interpreting UDTs in patients with chronic pain or receiving office-based opioid treatment. Methods: All psychiatry residency and fellowship program directors in the New England states were approached to recruit their trainees to participate in an anonymous online survey including a 7-item knowledge test. Results: A total of 93 residents and fellows completed the survey. Only a minority (24.7%) reported any prior training in UDT interpretation. A majority (62.6%) felt confident about interpreting UDTs. The mean total score for the knowledge test was 3.5 (SD =1.1, range: 1–6). There were no significant differences in total score by confidence in UDT interpretation (3.7 vs. 3.4, t = −1.17, nonsignificant [NS]), nor by prior training in UDT interpretation (3.8 vs. 3.5, t = −1.22, NS). Conclusions: Psychiatry residents and fellows infrequently receive training in UDT interpretation, score poorly on the knowledge test, and their confidence in UDT interpretation does not reflect their knowledge. Future research should evaluate educational interventions that improve UDT interpretation among psychiatry residents and fellows.

Background Patients may spike urine samples with buprenorphine during office-based opioid treatment to simulate adherence to prescribed buprenorphine, potentially to conceal diversion of medications. However, routine immunoassay screens do not detect instances of spiking, as these would simply result in a positive result. The aim of this study was to report on the experience of using quantitative urine testing for buprenorphine and norbuprenorphine to facilitate the identification of urine spiking. Methods This is a retrospective chart review of 168 consecutive patients enrolled in outpatient buprenorphine treatment at an urban academic medical setting between May 2013 and August 2014. All urine samples submitted were subjected to quantitative urine toxicology testing for buprenorphine and norbuprenorphine. Norbuprenorphine-to-buprenorphine ratio of less than 0.02 were further examined for possible spiking. Demographic and clinical variables were also extracted from medical records. Clinical and demographic variables of those who did and did not spike their urines were compared. Statistically significant variables from the univariate testing were entered as predictors of spiking in a regression analysis. Results A total of 168 patients were included, submitting a total of 2275 urine samples. Patients provided on average 13.6 (SD = 9.9) samples, and were in treatment for an average 153.1 days (SD = 142.2). In total, 8 samples (0.35%) from 8 patients (4.8%) were deemed to be spiked. All of the samples suspected of spiking contained buprenorphine levels greater than 2000 ng/mL, with a mean norbuprenorphine level of 11.9 ng/mL. Spiked samples were submitted by 6 patients (75.0%) during the intensive outpatient (IOP) phase of treatment, 2 patients (25.0%) during the weekly phase, and none from the monthly phase. Regression analysis indicated that history of intravenous drug use and submission of cocaine-positive urine samples at baseline were significant predictors of urine spiking. Conclusions Even though only a small number of patients were identified to have spiked their urine samples, quantitative testing may help identify urine spiking during office-based opioid treatment with buprenorphine.

The use of alternative medicines, including herbs, is common among HIV-positive patients, even in those on antiretroviral treatment. Equisetum arvense, known as "horsetail," is mainly used for its diuretic properties. There are limited data about the pharmacological properties of this compound and the potential drug-herb interactions. The authors report 2 cases in which a possible drug-herb interaction may have led to virological breakthrough in patients who were maintained on the same regimen for many years, including lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV) and emtricitabine (FTC)/tenofovir (TDF)/EFV, respectively. Therefore, a drug-herb interaction may be expected when these agents are taken concurrently. Until additional data are available, the authors advise clinicians to avoid this combination when possible.

Profound changes occur in the maternal circulation during pregnancy. Routine measures of arterial function – central systolic pressure (CSP) and augmentation index (AIx) – decline during normal human pregnancy. The objectives of this study were twofold: (1) explore wave reflection indices besides CSP and AIx that are not routinely reported, if at all, during normal human pregnancy; and (2) compare wave reflection indices and global arterial compliance (gAC) obtained from carotid artery pressure waveforms (CAPW) as a surrogate for aortic pressure waveforms (AOPW) versus AOPW synthesized from radial artery pressure waveforms (RAPW) using a generalized transfer function. To our knowledge, a comparison of these two methods has not been previously evaluated in the context of pregnancy. Ten healthy women with normal singleton pregnancies were studied using applanation tonometry (SphygmoCor) at pre‐conception, and then during 10–12 and 33–35 gestational weeks. CSP and AIx declined, and gAC increased during pregnancy as previously reported. As a consequence of the rise in gAC, the return of reflected waves of lesser magnitude from peripheral reflection sites to the aorta was delayed that, in turn, reduced systolic duration of reflected waves, augmentation index, central systolic pressure, LV wasted energy due to reflected waves, and increased brachial‐central pulse pressure. For several wave reflection indices, those derived from CAPW as a surrogate for AOPW versus RAPW using a generalized transfer function registered greater gestational increases of arterial compliance. This discordance may reflect imprecision of the generalized transfer function for some waveform parameters, though potential divergence of carotid artery and aortic pressure waveforms during pregnancy cannot be excluded.

Antiphospholipid antibody syndrome is a non-inflammatory autoimmune disease characterized by recurrent thrombotic events and/or obstetric complications associated with the presence of circulating antiphospholipid antibodies (anticardiolipin antibodies, anti-β2 glycoprotein-i antibodies, and/or lupus anticoagulant. Antiphospholipid antibodies are a heterogeneous group of autoantibodies associated with recurrent miscarriage, stillbirth, fetal growth restriction and premature birth. The diversity of the features of the proposed placental antiphospholipid antibodies fingerprint suggests that several disease processes may occur in the placentae of women with antiphospholipid antibody syndrome in the form of immune responses: inflammatory events, complement activation, angiogenic imbalance and, less commonly, thrombosis and infarction. Because of the disparity between clinical and laboratory criteria, and the impact on perinatal outcome in patients starting treatment, we reviewed the aspects of antiphospholipid antibody syndrome related to obstetric complications and seronegative antiphospholipid antibody syndrome, and their treatment in obstetrics.

Here we present a survey including 52 drug-naive recently HIV-1-infected subjects from Buenos Aires City and province (79%) and 3 other regions in Argentina (21%). Recent infections were established from previous negative serology (32/52), indeterminate Western blot (12/52), or acute retroviral syndrome after high-risk HIV exposure (8/52) within 9 months before genotyping (median time, 4.2 months). Genotyping was performed from plasma by sequencing both protease and reverse transcriptase. Phylogenetic analysis combined with bootscanning resulted in 21 subtype B sequences and 31 B/F recombinants (RecBF). On protease, minor resistance-related mutations were found in both subtype B and RecBF with low frequencies. The substitution L89M, recently suggested as a resistance-related mutation in some subtype F viruses, was observed in 1 RecBF. On reverse transcriptase, major resistance-related mutations were found in 4 of 52 (7.7%) patients from different health centers: M41L (subtype B) and K103N+/-P225H (1 RecBF and 2 subtype B). The greater than 5% resistance threshold found indicates a need for sentinel resistance surveillances calling for an update in the current resistance testing guidelines in Argentina.

Background X chromosome inactivation is the transcriptional silencing of one X chromosome in the somatic cells of female mammals. In eutherian mammals (e.g. humans) one of the two X chromosomes is randomly chosen for silencing, with about 15% (usually in younger evolutionary strata of the X chromosome) of genes escaping this silencing. In contrast, in the distantly related marsupial mammals the paternally derived X is silenced, although not as completely as the eutherian X. A chromosome wide examination of X inactivation, using RNA-seq, was recently undertaken in grey short-tailed opossum (Monodelphis domestica) brain and extraembryonic tissues. However, no such study has been conduced in Australian marsupials, which diverged from their American cousins ~80 million years ago, leaving a large gap in our understanding of marsupial X inactivation. Results We used RNA-seq data from blood or liver of a family (mother, father and daughter) of tammar wallabies (Macropus eugenii), which in conjunction with available genome sequence from the mother and father, permitted genotyping of 42 expressed heterozygous SNPs on the daughter’s X. These 42 SNPs represented 34 X loci, of which 68% (23 of the 34) were confirmed as inactivated on the paternally derived X in the daughter’s liver; the remaining 11 X loci escaped inactivation. Seven of the wallaby loci sampled were part of the old X evolutionary stratum, of which three escaped inactivation. Three loci were classified as part of the newer X stratum, of which two escaped inactivation. A meta-analysis of previously published opossum X inactivation data revealed that 5 of 52 genes in the old X stratum escaped inactivation. Conclusions We demonstrate that chromosome wide inactivation of the paternal X is common to an Australian marsupial representative, but that there is more escape from inactivation than reported for opossum (32% v 14%). We also provide evidence that, unlike the human X chromosome, the location of loci within the oldest evolutionary stratum on the marsupial X does not correlate with their probability of escape from inactivation. Electronic supplementary material The online version of this article (doi:10.1186/s12862-014-0267-z) contains supplementary material, which is available to authorized users.

Recent research has explored the relationship between facial masculinity, human male behaviour and males' perceived features (i.e. attractiveness). The methods of measurement of facial masculinity employed in the literature are quite diverse. In the present paper, we use several methods of measuring facial masculinity to study the effect of this feature on risk attitudes and trustworthiness. We employ two strategic interactions to measure these two traits, a first-price auction and a trust game. We find that facial width-to-height ratio is the best predictor of trustworthiness, and that measures of masculinity which use Geometric Morphometrics are the best suited to link masculinity and bidding behaviour. However, we observe that the link between masculinity and bidding in the first-price auction might be driven by competitiveness and not by risk aversion only. Finally, we test the relationship between facial measures of masculinity and perceived masculinity. As a conclusion, we suggest that researchers in the field should measure masculinity using one of these methods in order to obtain comparable results. We also encourage researchers to revise the existing literature on this topic following these measurement methods.

To describe characteristics of mother-child binomium (MCB), antiretroviral (ARV) prophylaxis, time trends, and variables associated with vertical transmission of HIV-1 in a population assisted by a tertiary public hospital in Argentina.Prospective descriptive study undertaken by the Hospital Cosme Argerich s Vertical Transmission Working Group, Buenos Aires city, Argentina 1998-2008. Periods 1998-2003 vs. 2004-2008 were compared and variables associated with vertical transmission identified.Of 357 MCB, 21.0% of the mothers had HCV coinfection and 68.0% CD4500/µL. During pregnancy, 75.0% received ARV: zidovudine (17.8%), zidovudinelamivudine (19.8%), zidovudine-lamivudine-nevirapine (41.9%), and zidovudinelamivudine-protease inhibitor (11.4%); 74.0% had viral load (VL) peripartum1 000 copies/mL. Caesarean delivery: 58.0%. Intrapartum zidovudine: 83.4%; 98.0% of infants received prophylaxis; zidovudine monotherapy was the most frequently used (73.0%). Of neonates, 15.4% had low birthweight and 6.7% were premature. The global vertical transmission was 3.3% (10/302). Comparing both periods, an increase in triple ARV and VL1 000 copies/mL in peripartum and a decrease in the absence of maternal/neonatal prophylaxis and overall VT was observed. The vertical transmission for 2004-2008 was 1.3% vs. 6.3% in Buenos Aires city (official statistics). Absence of maternal/intrapartum prophylaxis and prematurity were associated with vertical transmission (P0.01 and P = 0.01, respectively).A decline in overall vertical transmission between the two periods was observed attributable to increased coverage of maternal/neonatal ARV administration and increased use of triple therapy. The absence of maternal/intrapartum prophylaxis was the main factor associated with vertical transmission, emphasizing the need to improve accessibility of MCB to the local public health system.

Objectives: The purpose of this study was to examine the effect of a community-based nutrition education program on the nutritional knowledge, hemoglobin levels, and nutritional status of Nicaraguan adolescent girls and the nutritional knowledge of their mothers. Theory: Self-care deficit nursing theory was used in this study. Design: This longitudinal study used a mixed quantitative/qualitative design to study the effect of the nutrition education program. Sample: The nonprobability sample consisted of 182 adolescent girls and 67 of their mothers. The setting for the study was a community (barrio) in Managua, Nicaragua. Intervention/Measurement: A team of nurse and nutrition researchers created the nutrition education program designed to improve girls' and mother's nutrition-related self-care operations. Data collection was carried out for 4 years for girls and 2 years for mothers in Managua, Nicaragua, using questionnaires, a HemoCue, and anthropometric measures. Results and Conclusion: The findings of this study were that girls' and mothers' nutritional knowledge scores significantly improved in most cases after participation in the nutrition intervention program. Girls' hemoglobin levels did not significantly improve and their nutritional status findings were mixed. Girls and mothers described what dietary changes girls made and why.

Background: In BMS Study 045, once-daily (QD) atazanavir/ritonavir (ATV/RTV) demonstrated comparable efficacy and safety to twice-daily (BID) lopinavir/ritonavir (LPV/RTV) over 48 weeks in treatment-experienced patients. Results of extended follow-up to 96 weeks are presented. Methods: BMS Study 045 was an open-label, randomized, multi-national trial of HIV-infected patients with virologic failure on two or more prior HAART regimens designed to evaluate the efficacy and safety of ATV/RTV (300/100 mg) QD and LPV/RTV (400/ 100 mg) BID, each with tenofovir (300 mg) QD and one nucleoside reverse transcriptase inhibitor. The primary efficacy measure was the time-averaged difference (TAD) in reduction in HIV RNA from baseline. Secondary objectives included evaluation of safety and plasma lipid levels through week 96. Results: Over 96 weeks, the ATV/RTV regimen demonstrated similar virologic efficacy to the LPV/RTV regimen. Mean reductions from baseline in HIV RNA were -2.29 and -2.08 log 10 copies/ml, respectively [TAD (97.5% confidence interval): 0.14 log 10 copies/ml (-0.13, 0.41)]. The LPV/RTV regimen resulted in significant increases in total cholesterol (+9%) and fasting triglycerides (+30%) in comparison with the ATV/ RTV regimen, which demonstrated decreases in these parameters [-7 and -2%, respectively, (P < 0.0001)]. Grade 2-4 diarrhoea occurred less frequently in ATV/ RTV patients (3%) in comparison with LPV/RTV patients (13%) (P < 0.01). Grade 3-4 elevations in bilirubin were more common in ATV/RTV patients (53%) than LPV/RTV patients (< 1%) (P < 0.0001), with no resulting discontinuations. Conclusions: Regimens containing once-daily ATV/RTV demonstrated comparable efficacy and safety, with significant reductions in total cholesterol and fasting triglycerides and improved gastrointestinal-tolerability in comparison with twice-daily regimens containing LPV/RTV over 96 weeks in treatment-experienced patients.

Numerous factors are known to affect the plasma metabolism of HDL, including lipoprotein receptors, lipid transfer protein, lipolytic enzymes and HDL apolipoproteins. In order to better define the role of HDL apolipoproteins in determining plasma HDL concentrations, the aims of the present study were: a) to compare the in vivo rate of plasma turnover of HDL apolipoproteins [i.e., apolipoprotein A-I (apoA-I), apoC-I, apoC-III, and apoE], and b) to investigate to what extent these metabolic parameters are related to plasma HDL levels. We thus studied 16 individuals with HDL cholesterol levels ranging from 0.56-1.66 mmol/l and HDL apoA-I levels ranging from 89-149 mg/dl. Plasma kinetics of HDL apolipoproteins were investigated using a primed constant (12 h) infusion of deuterated leucine. Plasma HDL apolipoprotein levels were 41.8 +/- 1.5, 9.7 +/- 0.5, 4.9 +/- 0.5, and 0.7 +/- 0.1 micromol/l for apoA-I, apoC-I, apoC-III and apoE. Plasma transport rates (TRs) were 388.6 +/- 24.7, 131.5 +/- 12.5, 66.5 +/- 9.1, and 31.4 +/- 3.3 nmol.kg-1.day-1; and residence times (RTs) were 5.1 +/- 0.4, 3.7 +/- 0.3, 3.6 +/- 0.3, and 1.1 +/- 0.1 days, respectively. HDL cholesterol and apoA-I levels were significantly correlated with HDL apoA-I RT (r = 0.69 and r = 0.56), and were not significantly correlated with HDL apoA-I TR. In contrast, HDL apoC-I, apoC-III, and apoB levels were all positively related to their TRs and not their RTs. HDL apoC-III TR was positively correlated with levels of HDL apoC-III (r = 0.73, P0.01), and with those of HDL cholesterol and apoA-I (r = 0.54 and r = 0.53, P0.05, respectively). HDL apoC-III TR was in turn related to HDL apoA-I RT (r = 0.51, P0.05). Together, these results provide in vivo evidence for a link between the metabolism of HDL apoC-III and apoA-I, and suggest a role for apoC-III in the regulation of plasma HDL levels.

ApoC-I has several different lipid-regulating functions including, inhibition of receptor-mediated uptake of plasma triglyceride-rich lipoproteins, inhibition of cholesteryl ester transfer activity, and mediation of tissue fatty acid uptake. Since little is known about the rate of production and catabolism of plasma apoC-I in humans, the present study was undertaken to determine the plasma kinetics of VLDL and HDL apoC-I using a primed constant (12 h) intravenous infusion of deuterium-labeled leucine. Data were obtained for 14 subjects: normolipidemics (NL, n = 4), hypertriglyceridemics (HTG, n = 4) and combined hyperlipidemics (CHL, n = 6). Plasma VLDL triglyceride (TG) levels were 0.59 +/- 0.03, 4.32 +/- 0.77 (P < 0.01 vs. NL), and 2.20 +/- 0.39 mmol/l (P < 0.01 vs. NL), and plasma LDL cholesterol (LDL-C) levels were 2.34 +/- 0.22, 2.48 +/- 0.26, and 5.35 +/- 0.48 mmol/l (P < 0.01 vs. NL), respectively. HTG and CHL had significantly (P < 0.05) increased levels of total plasma apoC-I (12.5 +/- 1.2 and 12.4 +/- 1.3 mg/dl, respectively) versus NL (7.9 +/- 0.6 mg/dl), due to significantly (P < 0.01) elevated levels of VLDL apoC-I (5.8 +/- 0.8 and 4.5 +/- 0.8 vs. 0.3 +/- 0.1 mg/dl). HTG and CHL also had increased rates of VLDL apoC-I transport (i.e., production) versus NL: 2.29 +/- 0.34 and 3.04 +/- 0.53 versus 0.24 +/- 0.11 mg/kg.day (P < 0.01), with no significant change in VLDL apoC-I residence times (RT): 1.16 +/- 0.12 versus 0.69 +/- 0.06 versus 0.74 +/- 0.17. Although HDL apoC-I concentrations were not significantly lower in HTG and CHL versus NL, HDL apoC-I rates of transport were inversely related to plasma and VLDL-TG levels (r = -0.63 and -0.62, respectively, P < 0.05). Our results demonstrate that increased levels of plasma and VLDL apoC-I in hypertriglyceridemic subjects (with or without elevated LDL-C levels) are associated with increased levels of plasma VLDL apoC-I production.

Background The important triacylglycerol-lowering capacity of n-3 fatty acids is counterbalanced by their inherent sensitivity to oxidation. Inconsistent results about the latter have been reported in hypertriglyceridemic individuals. After incorporation into cell membranes, n-3 fatty acids may alter membrane-related functions. In view of the distinct composition of hypertriglyceridemic membranes and the prooxidant status in this condition, it can be surmised that cell enrichment with the oxidizable n-3 fatty acids will be associated with an increased hemolytic process. Objective We sought to evaluate the effect of fish oil consumption on n-3 fatty acid incorporation into erythrocyte membranes and subsequent ex vivo oxidative-stress-induced hemolysis in normotriglyceridemic and hypertriglyceridemic subjects. Design Sixteen normotriglyceridemic and 12 hypertriglyceridemic subjects were given 6 g fish oil/d for 8 wk. Blood samples were collected before and 4 and 8 wk after treatment. Resistance to 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced hemolysis was assayed in fresh erythrocyte suspensions, and erythrocyte samples were stored at -70 degrees C for later analysis of cholesterol, hemoglobin, fatty acids, vitamin E, and glutathione peroxidase activity. Results Fish oil supplementation induced n-3 fatty acid incorporation in normotriglyceridemic and hypertriglyceridemic erythrocyte membranes without decreasing their resistance to AAPH. n-3 Fatty acids significantly protected normotriglyceridemic but not hypertriglyceridemic erythrocytes against hemolysis. In normotriglyceridemic subjects only, the higher resistance to hemolysis correlated with changes in cell vitamin E. Conclusion Although they exhibit a high susceptibility to oxidation, n-3 fatty acids may preserve membrane integrity and represent an added benefit in the treatment of hypertriglyceridemic patients.