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Context: Recommendations for heat illness prevention provided by sports medicine associations do not always account for sex differences, specific age populations, regional environmental conditions, equipment worn during activity, or the athlete's size or preexisting level of fitness. Objective: To evaluate the rate of exertional heat illness (EHI) among collegiate football athletes and to monitor environmental conditions during American football practice for a 3-month period. Design: Epidemiologic study in which we reviewed the occurrence rates of EHI and wet bulb globe temperature readings during a 3-month period of American collegiate football practice sessions. Setting: Five universities in the southeastern region of the United States. Patients or Other Participants: Collegiate football players at the 5 universities. Main Outcome Measure(s): Wet bulb globe temperatures were recorded from August through October 2003, at the beginning, middle, and end of each practice session. The EHIs were identified and recorded, and athlete-exposures (AEs) were calculated. Results: A total of 139 EHIs and 33 196 AEs were reported (EHI rate = 4.19/1000 AEs). The highest incidence of EHIs was in August (88%, EHI rate = 8.95/1000 AEs) and consisted of 70% heat cramps (6.13/1000 AEs), 23% heat exhaustion (2.06/ 1000 AEs), and 7% heat syncope (0.58/1000 AEs). No cases of heat stroke or hyponatremia were identified. The highest risk of EHI occurred during the first 3 weeks of the study; mean wet bulb globe temperature declined significantly as the study continued ( P < .001). Temperatures in the final 5 weeks of the study were significantly cooler than in the first 5 weeks ( P < .05). Conclusions: Heat cramps were the most common EHI and occurred most often during the first 3 weeks of practice. Athletic trainers should take all necessary preventive measures to reduce the risk of EHI. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To identify the causes of mortality in children with vertically transmitted human immunodeficiency virus (HIV) infection and to study age-related mortality trends. METHODS: In the multicenter P(2)C(2) HIV Study, 816 children born to HIV-infected mothers were followed for a median of 3.6 years. Two hundred five study participants with HIV infection were enrolled at a median age of 23 months; 611 were enrolled either prenatally or in the neonatal period before their HIV infection status was known. There were 121 deaths in study patients. The cause of death for all patients, its relationship to HIV infection, and pulmonary or cardiac involvement were determined. Age trends in disease-specific mortality were summarized for the HIV-related deaths. RESULTS: Ninety-three children died of HIV-related conditions. Infection was the most prevalent cause of death for children under 6 years of age with 32.3% caused by pulmonary infection and another 16.9% caused by nonpulmonary infection. The frequency of pulmonary disease as the underlying cause of death decreased significantly with increasing age: 5/9 (55.6%) by age 1, 1/12 (8.3%) after age 10 years. The frequency of chronic cardiac disease as the underlying cause increased with age-0% by age 1 year, 3/12 (25.0%) after age 10 years, as did the frequency of wasting syndrome with disseminated Mycobacterium avium complex-0% by age 1 year, 6/12 (50.0%) after age 10 years. CONCLUSIONS: Children with HIV who survive longer are less likely to die of pulmonary disease or infection and more likely to die of cardiac causes or with wasting syndrome.pediatric acquired immunodeficiency syndrome, mortality, human immunodeficiency virus. [ABSTRACT FROM AUTHOR]

To determine the impact of the AIDS Clinical Trials Group (ACTG) Protocol 076 results on the subsequent use of zidovudine during pregnancy and the transmission rate of human immunodeficiency virus (HIV) in a cohort of mother-infant pairs (Women and Infants Transmission Study), a retrospective analysis was done. Transmission rates were calculated by simple proportion for infants with at least 6 months of follow-up, stratified by date of birth (n = 453 born on or before 1 March 1994; n = 103 born after 1 March 1994). Transmission rates decreased from 19% to 8% (P = .005, Fisher's exact test). Zidovudine use increased during pregnancy (22% vs. 89%) and in newborns (1% vs. 79%). Both cohorts were similar with respect to maternal immunosuppression, mode of delivery, and demographics. In summary, in a perinatal HIV observational study, the release of results of ACTG Protocol 076 was associated with an increase in zidovudine use during pregnancy and a concomitant decline in HIV transmission from mothers to infants. [ABSTRACT FROM AUTHOR]

Lithium and sodium metal batteries continue to occupy the forefront of battery research. Their exceptionally high energy density and nominal voltages are highly attractive for cutting-edge energy storage applications. Anode-free metal batteries are also coming into the research spotlight offering improved safety and even higher energy densities than conventional metal batteries. However, uneven metal nucleation and growth which leads to dendrites continues to limit the commercialisation of conventional and anode-free metal batteries alike. This review connects models and theories from well-established fields in metallurgy and electrodeposition to both conventional and anode-free metal batteries. These highly applicable models and theories explain the driving forces of uneven metal growth and can inform future experiment design. Finally, the models and theories that are most relevant to each anode-related cell component are identified. Keeping these specific models and theories in mind will assist with rational design for these components., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Advances in medical treatments in recent years have contributed to an overall decline in HIV-related opportunistic infections and deaths in youth; however, mortality and morbidity rates in perinatally and nonperinatally infected adolescents and young adults (AYA) living with HIV remain relatively high today., Objective: The goal of this project was to assess the use, utility, and cost-effectiveness of PlusCare, a digital app for HIV case management in AYA living with HIV. The app supports routine case management tasks, such as scheduling follow-up visits, sharing documents for review and signature, laboratory test results, and between-visit communications (eg, encouraging messages)., Methods: We conducted a single-group mixed methods pre-post study with HIV case management programs in 2 large urban hospitals in the Boston metro area. Case management staff (case managers [CMs], N=20) and AYA living with HIV participants (N=45) took part in the study with access to PlusCare for up to 15 and 12 months, respectively., Results: The CMs and AYA living with HIV reported mean System Usability Scale scores of 51 (SD 7.9) and 63 (SD 10.6), respectively. Although marginally significant, total charges billed at 1 of the 2 sites compared with the 12 months before app use (including emergency, inpatient, and outpatient charges) decreased by 41% (P=.046). We also observed slight increases in AYA living with HIV self-reported self-efficacy in chronic disease management and quality of life (Health-Related Quality of Life-4) from baseline to the 12-month follow-up (P=.02 and P=.03, respectively) and increased self-efficacy from the 6- to 12-month follow-up (P=.02). There was no significant change in HIV viral suppression, appointment adherence, or medication adherence in this small-sample pilot study., Conclusions: Although perceived usability was low, qualitative feedback from CMs and use patterns suggested that direct messaging and timely, remote, and secure sharing of laboratory results and documents (including electronic signatures) between CMs and AYA living with HIV can be particularly useful and have potential value in supporting care coordination and promoting patient self-efficacy and quality of life., Trial Registration: ClinicalTrials.gov NCT03758066; https://clinicaltrials.gov/ct2/show/NCT03758066., (©Connie Fee, Julia Fuller, Carly E Guss, Elizabeth R Woods, Ellen R Cooper, Urmi Bhaumik, Dionne Graham, Sandra K Burchett, Olivia Dumont, Emily B Martey, Maria Narvaez, Jessica E Haberer, Dallas Swendeman, Shelagh A Mulvaney, Vikram S Kumar, Jonathan L Jackson, Y Xian Ho. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.11.2022.)

Recent studies have highlighted the potential role of 11oxygenated (keto or hydroxy) androgens in human reproductive function with 11keto androgens circulating at concentrations comparable with testosterone in women and children. However, the intrinsic androgenic bioactivities of 11 keto and hydroxy androgens are not fully characterized. We therefore investigated the full androgen dose-response curves using complementary in vitro yeast and mammalian (HEK293) host cell bioassays of 11 keto and hydroxy derivatives of the potent androgens, testosterone (T) and dihydrotestosterone (DHT), compared with their parent non-11 oxygenated steroids together with the pro-androgen precursor (androstenedione (A 4 )) and metabolites (androstanedione, androsterone). For potent androgens, the mammalian HEK293 host cell bioassay was 22-138 times more sensitive than the yeast host cell bioassay. In both androgen bioassays, 11keto derivatives displayed androgenic bioactivity but significantly lower molar potency than their parent non-keto steroids. By contrast, the 11hydroxy derivatives had minimal or no androgenic bioactivity. In both bioassays 5α-reduction increased androgenic potency. These findings confirm that that 11keto androgens may contribute directly to androgen status in women, children, and other conditions apart from healthy eugonadal men whereas 11hydroxy androgens have negligible androgenic potency although it cannot be excluded that they may be converted to more potent androgens in vivo., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to describe maternal characteristics and clinical outcomes of infants born to mothers with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests during pregnancy at an urban, safety-net hospital in Boston., Study Design: We abstracted electronic chart data from 75 pregnant women with positive SARS-CoV-2 tests at any stage of gestation until 72 hours after birth who delivered consecutively between March 31 and August 6, 2020 at our center. We collected clinical data on maternal and infant characteristics, including testing, signs, and symptoms of coronavirus disease 2019 (COVID-19), delivery outcomes, newborn care practices (skin-to-skin care, location of care, and breastfeeding) and 30-day postdischarge infant emergency room visits and readmissions. We described categorical characteristics as percentages for this case series., Results: Among 75 pregnant women, 47 (63%) were Hispanic, 10 (13%) had hypertension, 23 (30%) had prepregnancy obesity, and 57 (76%) had symptomatic SARS-CoV-2 infection. Regarding birth outcomes, 32 (41%) had cesarean delivery and 14 (19%) had preterm birth. Among 75 infants, 5 (7%) had positive SARS-CoV-2 polymerase chain reaction tests in the first week of life, all of whom were born to Hispanic mothers with symptomatic SARS-CoV-2 infection and had clinical courses consistent with gestational age. Six (8%) infants visited the emergency department within 30 days of discharge; one was admitted with a non-COVID-19 diagnosis., Conclusion: At our urban, safety-net hospital among pregnant women with positive SARS-CoV-2 tests, 41% had a cesarean delivery and 19% had a preterm birth. Seven percent of infants had one or more positive SARS-CoV-2 tests and all infants had clinical courses expected for gestational age., Key Points: · Among 75 pregnant women with SARS-CoV-2 positive testing at our center, five infants (7%) had one or more SARS-CoV-2 positive tests in the first week of life.. · Infants with positive SARS-CoV-2 tests had clinical courses expected for gestational age.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Massachusetts began newborn screening (NBS) for severe combined immunodeficiency (SCID) using measurement of T-cell receptor excision circles (TRECs) from dried blood spots., Objective: We describe developments and outcomes from the first 10 years of this program (February 1, 2009, to January 31, 2019)., Methods: TREC values, diagnostic, and outcome data from all patients screened for SCID were evaluated., Results: NBS of 720,038 infants prompted immunologic evaluation of 237 (0.03%). Of 237, 9 were diagnosed with SCID/leaky SCID (4% of referrals vs 0.001% general population). Another 7 were diagnosed with other combined immunodeficiencies, and 3 with athymia. SCID/leaky SCID incidence was approximately 1 in 80,000, whereas approximately 1 in 51,000 had severe T-cell lymphopenia for which definitive treatment was indicated. All patients with SCID/leaky SCID underwent hematopoietic cell transplant or gene therapy with 100% survival. One patient with athymia underwent successful thymus transplant. No known cases of SCID were missed. Compared with outcomes from the 10 years before SCID NBS, survival trended higher (9 of 9 vs 4 of 7), likely due to a lower rate of infection before treatment., Conclusions: Our data support a single NBS testing-and-referral algorithm for all gestational ages. Despite lower median TREC values in premature infants, the majority for all ages are well above the TREC cutoff and the algorithm, which selects urgent (undetectable TREC) and repeatedly abnormal TREC values, minimizes referral. We also found that low naïve T-cell percentage is associated with a higher risk of SCID/CID, demonstrating the utility of memory/naïve T-cell phenotyping as part of follow-up flow cytometry., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Androgens remain abused performance-enhancing drugs in sports. Technologies based on mass spectrometry can detect all forms of androgens but fail if the androgen represents a novel structure. A bioassay detects androgens based on function rather than structure. To date, there has been limited adoption of cell-based in vitro bioassays as a screening tool for nontargeted androgen detection because they require expert personnel and specialized equipment to perform. We now describe the development of a cell-free version of an androgen in vitro bioassay. Stage 1 involved in vitro transcription/translation reactions (IVTT) using a DNA template encoding an enhancer/androgen response element (ARE) regulatory region upstream of a minimal promoter that drives expression of a reporter protein. The assay detected testosterone across the concentration range of 106.7 to 0.0144 ng/ml (3.7 × 10 -7 to 5 × 10 -11 M), with an EC 50 of 6.63 ng/ml (23 nM). To reduce complexity, Stages 2-4 of development included just in vitro transcription (IVT) reactions, whereby the output was an RNA molecule. Stage 2 involved directly labelling the RNA molecule with fluorophore-labelled nucleotide triphosphates, Stage 3 involved reverse transcription-polymerase chain reaction (PCR) of the RNA molecule, and Stage 4 utilized an RNA aptamer, Mango II, as its RNA output. The Stage 4 product detected testosterone across the range of 106.7-0.0001 ng/ml (3.7 × 10 -7 to 5 × 10 -13 M), with an EC 50 of 0.04 ng/ml (0.155 nM). Further to this, we show that the Stage 4 product can detect other androgenic molecules. Relative to cell-based bioassays, the Stage 4 product is easy to perform and could be developed into a routine, high-throughput, nontargeted androgen screen., (© 2021 John Wiley & Sons, Ltd.)

Androgens, both steroidal and nonsteroidal in nature, are among the most commonly misused substances in competitive sports. Their recognized anabolic and performance enhancing effects through short- and long-term physiological adaptations make them popular. Androgens exist as natural steroids, or are chemically synthesized as anabolic androgenic steroids (AAS) or selective androgen receptor modulators (SARMs). In order to effectively detect misuse of androgens, targeted strategies are used. These targeted strategies rely heavily on mass spectrometry, and detection requires prior knowledge of the targeted structure and its metabolites. Although exquisitely sensitive, such approaches may fail to detect novel structures that are developed and marketed. A nontargeted approach to androgen detection involves the use of cell-based in vitro bioassays. Both yeast and mammalian cell androgen bioassays demonstrate a clear ability to detect AAS and SARMS, and if paired with high resolution mass spectrometry can putatively identify novel structures. In vitro cell bioassays are successfully used to characterize designer molecules and to detect exogenous androgens in biological samples. It is important to continue to develop new and effective detection approaches to prevent misuse of designer androgens, and in vitro bioassays represent a potential solution to nontargeted detection strategies., (© 2021 John Wiley & Sons, Ltd.)

Objective: To develop best-practice recommendations using thermal indices to determine work-to-rest ratios and facilitate further implementation of environmental monitoring for heat safety in secondary school athletics in the United States., Data Sources: A narrative review of the current literature on environmental monitoring for heat safety during athletics was conducted by content experts. A list of action-oriented recommendations was established from the narrative review and further refined using the Delphi method., Conclusions: Assessment of wet bulb globe temperature at the site of activity and throughout the duration of the event is recommended to assist clinicians and administrators in making appropriate decisions regarding the duration and frequency of activity and rest periods. Activity-modification guidelines should be predetermined and approved by stakeholders and should outline specific actions to be followed, such as the work-to-rest ratio, frequency and timing of hydration breaks, and adjustment of total exercise duration, equipment, and clothing. Furthermore, integration of exertional heat illness injury data with environmental condition characteristics is critical for the development of evidence-based heat safety guidelines for secondary school athletics. Athletic trainers play an essential role in conducting prospective injury data collection, recording onsite wet bulb globe temperature levels, and implementing recommendations to protect the health and safety of athletes., (© by the National Athletic Trainers' Association, Inc.)

Pediatric human immunodeficiency virus post-exposure prophylaxis is frequently indicated, but delays in medication receipt are common. Using plan-do-study-act cycles, we developed a multidisciplinary collaboration to reduce critical process delays in our pediatric emergency department. Interruptions decreased from a median 1 per month pre-intervention to zero per month during the intervention., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to describe the natural history of individuals with congenital HIV who develop JC virus (JCV) infection of the central nervous system (CNS)., Methods: We retrospectively evaluated individuals with congenital HIV who met criteria for progressive multifocal leukoencephalopathy (PML) or JCV granule cell neuronopathy (JCV GCN) at three major healthcare centres in the northeast USA. Data on adherence to combined antiretroviral therapy (cART), neurologic symptoms, serum markers of immunity and HIV infection, cerebrospinal fluid (CSF) analyses, radiographic features, modified Rankin Scale (mRS) scores and survival were collected from the electronic medical record up to a censoring date of 1 August 2020., Results: Among 10 adults with congenitally acquired HIV, nine were diagnosed with definitive PML and one was diagnosed with probable JCV GCN. Individuals presented at the time of their PML or JCV GCN diagnosis with a mean mRS of 2.0 (standard deviation 1.0). A premorbid mRS was documented for six patients and was zero in all cases. The most common risk factor was confirmed cART nonadherence in nine individuals. Five individuals with PML and one with JCV GCN died, with a latency from symptom onset to death of approximately 3 months for three individuals, and approximately 2 years for the remaining two., Conclusion: Youth-adulthood transition is a high-risk point for dropping off from medical care. The study of this timepoint in people living with HIV could help inform effective care in these individuals., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this observational study was to determine the optimal timing of interleukin-6 receptor inhibitor (IL6ri) administration for coronavirus disease 2019 (COVID-19)., Methods: Patients with COVID-19 were given an IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients with lower oxygen requirements. Patients were divided into two groups: those requiring ≤45% fraction of inspired oxygen (FiO 2 ) (termed stage IIB) and those requiring >45% FiO 2 (termed stage III) at the time of IL6ri administration. The main outcomes were all-cause mortality, discharge alive from hospital, and extubation., Results: A total of 255 COVID-19 patients were treated with IL6ri (149 stage IIB and 106 stage III). Patients treated in stage IIB had lower mortality than those treated in stage III (adjusted hazard ratio (aHR) 0.24, 95% confidence interval (CI) 0.08-0.74). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR 1.43, 95% CI 1.06-1.93) and were less likely to be intubated (aHR 0.43, 95% CI 0.24-0.79)., Conclusions: IL6ri administration prior to >45% FiO 2 requirement was associated with improved COVID-19 outcomes. This can guide clinical management pending results from randomized controlled trials., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Context: Interscholastic heat policies for football have not been evidence based. Therefore, their effectiveness in mitigating exertional heat illness has not been assessed., Objective: To discuss the development of the Georgia High School Association heat policy and assess the effectiveness of revised guidelines., Design: Descriptive epidemiology study., Setting: Georgia high schools., Patients or Other Participants: Interscholastic football players in grades 9 through 12., Main Outcome Measure(s): Heat syncope and heat exhaustion (HS/HE) illness rates (IRs) were calculated per 1000 athlete-exposures (AEs), and relative risk (RR) was calculated as a ratio of postpolicy (POST) IR divided by prepolicy (PRE) IR., Results: A total of 214 HS/HE cases (172 PRE, 42 POST) and 341 348 AEs (178 230 PRE, 163 118 POST) were identified. During the first 5 days of the PRE period, approximately 50% of HS/HE illnesses occurred; HS/HE IRs doubled when practice sessions increased from 2 to 2.5 hours and tripled for practices ≥3 hours. The HS/HE IRs in the PRE period increased from 0.44/1000 AEs for wet-bulb globe temperatures (WBGTs) of <82°F (<27.8°C) to >2.0/1000 AEs for WBGTs from 87°F (30.6°C) to 89.9°F (32.2°C). The RRs comparing PRE and POST policy periods were 0.29 for WBGTs of <82.0°F (<27.80°C), 0.65 for WBGTs from 82.0°F (27.8°C) to 86.9°F (30.5°C), and 0.23 for WBGTs from 87.0°F (30.6°C) to 89.9°F (32.2°C). No HS/HE illnesses occurred in the POST period for WBGTs at >90°F (>32.3°C)., Conclusions: Results from the PRE period guided the Georgia High School Association to revise its heat and humidity policy to include a mandated 5-day acclimatization period when no practices may exceed 2 hours and the use of WBGT-based activity-modification categories. The new policy reduced HS/HE IRs by 35% to 100%, depending on the WBGT category. Our results may be generalizable to other states with hot and humid climates similar to that of Georgia., (© by the National Athletic Trainers' Association, Inc.)

Both athletes and the general population use nutritional supplements. Athletes often turn to supplements hoping that consuming the supplement will help them be more competitive and healthy, while the general population hopes to improve body image or vitality. While many supplements contain ingredients that may have useful properties, there are supplements that are contaminated with compounds that are banned for use in sport or have been deliberately adulterated to fortify a supplement with an ingredient that will produce the advertised effect. In the present study, we have used yeast cell and mammalian cell androgen bioassays to characterize the androgenic bioactivity of 112 sports supplements available from the Australian market, either over the counter or via the Internet. All 112 products did not declare an androgen on the label as an included ingredient. Our findings show that six out of 112 supplements had strong androgenic bioactivity in the yeast cell bioassay, indicating products spiked or contaminated with androgens. The mammalian cell bioassay confirmed the strong androgenic bioactivity of five out of six positive supplements. Supplement 6 was metabolized to weaker androgenic bioactivity in the mammalian cells. Further to this, Supplement 6 was positive in a yeast cell progestin bioassay. Together, these findings highlight that nutritional supplements, taken without medical supervision, could expose or predispose users to the adverse consequences of androgen abuse. The findings reinforce the need to increase awareness of the dangers of nutritional supplements and highlight the challenges that clinicians face in the fast-growing market of nutritional supplements.

On August 1, 2001, Korey Stringer, a Pro Bowl offensive tackle for the Minnesota Vikings, became the first and to date the only professional American football player to die from exertional heat stroke (EHS). The death helped raise awareness of the dangers of exertional heat illnesses in athletes and prompted the development of heat safety policies at the professional, collegiate, and interscholastic levels. Despite the public awareness of this death, no published study has examined in detail the circumstances surrounding Stringer's fatal EHS. Using the well-documented details of the case, our study shows that Stringer's fatal EHS was the result of a combination of physiological limitations, organizational and treatment failings, and extreme environmental conditions. The COMfort FormulA (COMFA) energy budget model was used to assess the relative importance of several extrinsic factors on Stringer's EHS, including weather conditions, clothing insulation, and activity levels. We found that Stringer's high-intensity training in relation to the oppressive environmental conditions was the most prominent factor in producing dangerous, uncompensable heat stress conditions and that the full football uniform played a smaller role in influencing Stringer's energy budget. The extreme energy budget levels that led to the fatal EHS would have been avoided according to our modeling through a combination of reduced intensity and lower clothing insulation. Finally, a long delay in providing medical treatment made the EHS fatal. These results highlight the importance of modern heat safety guidelines that provide controls on extrinsic factors, such as the adjustment of duration and intensity of training along with protective equipment modifications based on environmental conditions and the presence of an emergency action plan focused on rapid recognition and immediate on-site aggressive cooling of EHS cases.

Sport supplements containing steroids never approved for therapeutic use have the potential for abuse by athletes. Most are marketed online and may contain undisclosed steroids yet are readily available despite lacking toxicological or pharmacological evaluation. In this study, 18 supplements purchased online underwent organic solvent extraction to isolate any steroids they contained. From the 18 supplements, 19 steroids were identified and for each, its intrinsic androgenic potency was determined by a yeast cell (Saccharomyces cerevisiae) androgen bioassay and its potential androgenic potency was determined by a liver (HuH7) cell androgen bioassay. The yeast bioassay showed that of the 19 steroids tested, 6 demonstrated strong intrinsic bioactivity, with 4 metabolically activated to even stronger androgens. Moreover, 4 steroids with moderate and 1 with intrinsically weak androgenic bioactivity were activated to more potent androgens. Finally, 8 steroids were metabolically inactivated or deactivated into weaker androgens. Our results show that Internet-sourced sport supplements may contain intrinsically strong androgens, or precursors that can be metabolized to them. These potentially potent pharmacologically active steroids are being used without regulatory control or consumer awareness of their potential adverse effects. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

We report our experience with 2 infants with in utero HIV-1 infection who began very early combination antiretroviral therapy within 4 hours of birth. Further neonatal studies of antiretroviral pharmacokinetics (PKs), safety, efficacy and treatment strategies are critically needed for the development of more potent regimens for use in HIV-infected infants.

Context: Knowledge about the specific environmental and practice risks to participants in American intercollegiate football during preseason practices is limited. Identifying risks may mitigate occurrences of exertional heat illness (EHI)., Objective: To evaluate the associations among preseason practice day, session number, and wet bulb globe temperature (WBGT) and the incidence of EHI., Design: Descriptive epidemiology study., Setting: Sixty colleges and universities representing 5 geographic regions of the United States., Patients or Other Participants: National Collegiate Athletic Association football players., Main Outcome Measure(s): Data related to preseason practice day, session number, and WBGT. We measured WBGT every 15 minutes during the practice sessions and used the mean WBGT from each session in the analysis. We recorded the incidence of EHIs and calculated the athlete-exposures (AEs)., Results: A total of 553 EHI cases and 365 810 AEs were reported for an overall EHI rate of 1.52/1000 AEs (95% confidence interval [CI] = 1.42, 1.68). Approximately 74% (n = 407) of the reported EHI cases were exertional heat cramps (incidence rate = 1.14/1000 AEs; 95% CI = 1.03, 1.25), and about 26% (n = 146) were a combination of exertional heat syncope and heat exhaustion (incidence rate = 0.40/1000 AEs; 95% CI = 0.35, 0.48). The highest rate of EHI occurred during the first 14 days of the preseason period, and the greatest risk was during the first 7 days. The risk of EHI increased substantially when the WBGT was 82.0°F (27.8°C) or greater., Conclusions: We found an increased rate of EHI during the first 14 days of practice, especially during the first 7 days. When the WBGT was greater than 82.0°F (27.8°C), the rate of EHI increased. Sports medicine personnel should take all necessary preventive measures to reduce the EHI risk during the first 14 days of practice and when the environmental conditions are greater than 82.0°F (27.8°C) WBGT.

Objective: To determine whether the restriction of young sibling (<13 years) visitation in the neonatal intensive care unit (NICU) during the respiratory syncytial virus (RSV) season was associated with a reduction in the rate of RSV infection among NICU patients., Study Design: A retrospective chart review of all RSV positive infants from the 2001-2010 RSV seasons. The 2001-2006 RSV seasons (group 1) contained 639 admissions and the 2007-2010 (group 2, with sibling restriction) contained 461 admissions. Groups were compared by using the Fisher's Exact Test., Results: There was a reduction of RSV positive infants from 6.7% in Group 1 to 1.7% in Group 2 (P<0.0001). There was a reduction of symptomatic infants from the number of infants with symptomatic RSV infection from 23/639 infants with young sibling visitation to 2/461 (P<0.001)., Conclusion: Exclusion of young sibling visitors <13 years of age during RSV season was associated with a significant reduction in the number of RSV positive infants in the NICU.

Predicting the response of fine roots to increased atmospheric CO₂ concentration has important implications for carbon (C) and nutrient cycling in forest ecosystems. Root architecture is known to play an important role in how trees acquire soil resources in changing environments. However, the effects of elevated CO₂ on the fine-root architecture of trees remain unclear. We investigated the architectural response of fine roots exposed to 14 yr of CO₂ enrichment and 6 yr of nitrogen (N) fertilization in a Pinus taeda (loblolly pine) forest. Root traits reflecting geometry, topology and uptake function were measured on intact fine-root branches removed from soil monoliths and the litter layer. CO₂ enrichment resulted in the development of a fine-root pool that was less dichotomous and more exploratory under N-limited conditions. The per cent mycorrhizal colonization did not differ among treatments, suggesting that root growth and acclimation to elevated CO₂ were quantitatively more important than increased mycorrhizal associations. Our findings emphasize the importance of architectural plasticity in response to environmental change and suggest that changes in root architecture may allow trees to effectively exploit larger volumes of soil, thereby pre-empting progressive nutrient limitations., (© 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.)

Root systems serve important roles in carbon (C) storage and resource acquisition required for the increased photosynthesis expected in CO2-enriched atmospheres. For these reasons, understanding the changes in size, distribution and tissue chemistry of roots is central to predicting the ability of forests to capture anthropogenic CO2. We sampled 8000 cm(3) soil monoliths in a pine forest exposed to 14 years of free-air-CO2-enrichment and 6 years of nitrogen (N) fertilization to determine changes in root length, biomass, tissue C : N and mycorrhizal colonization. CO2 fumigation led to greater root length (98%) in unfertilized plots, but root biomass increases under elevated CO2 were only found for roots <1 mm in diameter in unfertilized plots (59%). Neither fine root [C] nor [N] was significantly affected by increased CO2. There was significantly less root biomass in N-fertilized plots (19%), but fine root [N] and [C] both increased under N fertilization (29 and 2%, respectively). Mycorrhizal root tip biomass responded positively to CO2 fumigation in unfertilized plots, but was unaffected by CO2 under N fertilization. Changes in fine root [N] and [C] call for further study of the effects of N fertilization on fine root function. Here, we show that the stimulation of pine roots by elevated CO2 persisted after 14 years of fumigation, and that trees did not rely exclusively on increased mycorrhizal associations to acquire greater amounts of required N in CO2-enriched plots. Stimulation of root systems by CO2 enrichment was seen primarily for fine root length rather than biomass. This observation indicates that studies measuring only biomass might overlook shifts in root systems that better reflect treatment effects on the potential for soil resource uptake. These results suggest an increase in fine root exploration as a primary means for acquiring additional soil resources under elevated CO2., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Large-scale, long-term FACE (Free-Air CO2 enrichment) experiments indicate that increases in atmospheric CO2 concentrations will influence forest C cycling in unpredictable ways. It has been recently suggested that responses of mycorrhizal fungi could determine whether forest net primary productivity (NPP) is increased by elevated CO2 over long time periods and if forests soils will function as sources or sinks of C in the future. We studied the dynamic responses of ectomycorrhizae to N fertilization and atmospheric CO2 enrichment at the Duke FACE experiment using minirhizotrons over a 6 year period (2005-2010). Stimulation of mycorrhizal production by elevated CO2 was observed during only 1 (2007) of 6 years. This increased the standing crop of mycorrhizal tips during 2007 and 2008; during 2008, significantly higher mortality returned standing crop to ambient levels for the remainder of the experiment. It is therefore unlikely that increased production of mycorrhizal tips can explain the lack of progressive nitrogen limitations and associated increases in N uptake observed in CO2 -enriched plots at this site. Fertilization generally decreased tree reliance on mycorrhizae as tip production declined with the addition of nitrogen as has been shown in many other studies. Annual NPP of mycorrhizal tips was greatest during years with warm January temperatures and during years with cool spring temperatures. A 2 °C increase in average late spring temperatures (May and June) decreased annual production of mycorrhizal root tip length by 50%. This has important implications for ecosystem function in a warmer world in addition to potential for forest soils to sequester atmospheric C., (© 2013 John Wiley & Sons Ltd.)

Root systems are important for global models of below-ground carbon and nutrient cycling. Notoriously difficult sampling methods and the fractal distribution of root diameters in the soil make data being used in these models especially susceptible to error resulting from under-sampling. We applied the concept of species accumulation curves to root data to quantify the extent of under-sampling inherent to minirhizotron and soil coring sampling for both root uptake and carbon content studies. Based on differences in sample size alone, minirhizotron sampling missed approximately one third of the root diameters observed by soil core sampling. Sample volumes needed to encounter 90% of root diameters averaged 2481 cm(3) for uptake studies and 5878 cm(3) for root carbon content studies. These results show that small sample volumes encounter a non-representative sample of the overall root pool, and provide future guidelines for determining optimal sample volumes in root studies., (© 2013 John Wiley & Sons Ltd/CNRS.)

Androgens are the class of sex steroids responsible for male sexual characteristics, including increased muscle mass and decreased fat mass. Illicit use of androgen doping can be an attractive option for those looking to enhance sporting performance and/or physical appearance. The use of in vitro bioassays to detect androgens, especially designer or proandrogens, is becoming increasingly important in combating androgen doping associated with nutritional supplements. The nutritional sports supplement market has grown rapidly throughout the past decade. Many of these supplements contain androgens, designer androgens or proandrogens. Many designer or proandrogens cannot be detected by the standard highly-sensitive screening methods such as gas chromatography-mass spectrometry because their chemical structure is unknown. However, in vitro androgen bioassays can detect designer and proandrogens as these assays are not reliant on knowing the chemical structure but instead are based on androgen receptor activation. For these reasons, it may be advantageous to use routine androgen bioassay screening of nutraceutical samples to help curb the increasing problem of androgen doping.

Objectives: The aim of this study was to investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in human immunodeficiency virus (HIV)-negative children., Background: ART reduces vertical HIV transmission. Long-term cardiotoxicity after in utero exposure to ART is unknown in children but has occurred in young animals., Methods: Using a prospective multisite cohort study design, echocardiograms taken between birth and 24 months were compared in 2 groups of HIV-negative infants of HIV-positive mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART-)., Results: Mean left ventricular (LV) mass z-scores were consistently lower in ART+ girls than in ART- girls: differences in mean z-scores were -0.46 at birth (p = 0.005), -1.02 at 6 months (p < 0.001), -0.74 at 12 months (p < 0.001), and -0.79 at 24 months (p < 0.001). Corresponding differences in z-scores for boys were smaller: 0.13 at 1 month (p = 0.42), -0.44 at 6 months (p = 0.01), -0.15 at 12 months (p = 0.37), and -0.21 at 24 months (p = 0.21). Septal wall thickness and LV dimension were smaller than expected in ART+ infants, but LV contractility was consistently about 1 SD higher at all ages (p < 0.001). In ART+ infants, LV fractional shortening was higher than in ART- infants; girls showed a greater difference., Conclusions: Fetal exposure to ART is associated with reduced LV mass, LV dimension, and septal wall thickness z-scores and increased LV fractional shortening and contractility up to age 2 years. These effects are more pronounced in girls than in boys. Fetal ART exposure may impair myocardial growth while improving depressed LV function., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Severe combined immunodeficiency (SCID) is a Primary Immune Deficiency that is under consideration for population-based newborn screening (NBS) by many NBS programs, and has recently been recommended for inclusion in the US uniform panel of newborn screening conditions. A marker of SCID, the T cell receptor excision circle (TREC), is detectable in the newborn dried blood spot using a unique molecular assay as a primary screen. The New England Newborn Screening Program developed and validated a multiplex TREC assay in which both the TREC analyte and an internal control are acquired from a single punch and run in the same reaction. Massachusetts then implemented a statewide pilot SCID NBS program. The authors describe the rationale for a pilot SCID NBS program, a comprehensive strategy for successful implementation, the screening test algorithm, the screening follow-up algorithm and preliminary experience based on statewide screening in the first year. The Massachusetts experience demonstrates that SCID NBS is a program that can be implemented on a population basis with reasonable rates of false positives.

This short paper is a personal account of the development of techniques to enhance the bioavailability of a series of poorly soluble drugs by particle size reduction to the nanometer size range. This is a nanotechnological approach which has come of age and has had a practical impact on drug delivery. The drug is in effect the nanosystem., (Copyright 2009 Elsevier B.V. All rights reserved.)

Objectives: The difficulties diagnosing infants and children with HIV infection have been cited as barriers to increasing the number of children receiving antiretroviral therapy worldwide., Design: We implemented routine HIV antibody counseling and testing for pediatric patients hospitalized at the University Teaching Hospital, a national reference center, in Lusaka, Zambia. We also introduced HIV DNA polymerase chain reaction (PCR) testing for early infant diagnosis., Methods: Caregivers/parents of children admitted to the hospital wards were routinely offered HIV counseling and testing for their children. HIV antibody positive (HIV+) children <18 months of age were tested with PCR for HIV DNA., Results: From January 1, 2006, to June 30, 2007, among 15,670 children with unknown HIV status, 13,239 (84.5%) received counseling and 11,571 (87.4%) of those counseled were tested. Overall, 3373 (29.2%) of those tested were seropositive. Seropositivity was associated with younger age: 69.6% of those testing HIV antibody positive were <18 months of age. The proportion of counseled children who were tested increased each quarter from 76.0% in January to March 2006 to 88.2% in April to June 2007 (P < 0.001). From April 2006 to June 2007, 1276 PCR tests were done; 806 (63.2%) were positive. The rate of PCR positivity increased with age from 22% in children <6 weeks of age to 61% at 3-6 months and to 85% at 12-18 months (P < 0.001)., Conclusions: Routine counseling and antibody testing of pediatric inpatients can identify large numbers of HIV-seropositive children in high prevalence settings. The high rate of HIV infection in hospitalized infants and young children also underscores the urgent need for early infant diagnostic capacity in high prevalence settings.

Postural control assessments are commonly administered to athletes as part of a pre-season screening. Establishing a baseline level of function permits the clinician to compare post-injury results to normal functioning during the return to play decision-making process. In the athletic setting, follow-up tests may be completed on the sideline immediately following injury. We sought to examine the effect of commonly administered external ankle joint support on postural control using the balance error scoring system (BESS) and the NeuroCom sensory organization test (SOT). Nineteen volunteers free from balance issues completed three sessions with varied ankle support: bilateral prophylactic ankle taping, laced bracing device, or barefoot. Each session included an initial balance assessment on the BESS and SOT, a 20 min treadmill walk, and post-walk balance test. Fewer errors, indicating improved balance, were committed on the BESS during the barefoot condition than the braced ankle condition (p=0.044) at the pre-walk assessment. During the post-walk assessment, fewer errors were committed during the barefoot condition compared to the braced ankle condition (p=0.034) and the taped ankle condition (p=0.037). All ankle support conditions showed similar improvements in balance between the pre and post-walk assessments on the BESS (p<0.001) and SOT composite balance score (p=0.009). These findings indicate that ankle support devices may influence postural control on the BESS, but not on the NeuroCom SOT. Clinicians using the BESS as a balance assessment device at multiple time points should be consistent in the application of ankle support devices.

There is increasing concern about pharmaceuticals entering surface waters and the impacts these compounds may have on aquatic organisms. Many contaminants, including pharmaceuticals, are not completely removed by wastewater treatment. Discharge of effluent into surface waters results in chronic low-concentration exposure of aquatic organisms to these compounds, with unknown impacts. Exposure of virulent bacteria in wastewater to antibiotic residues may also induce resistance, which could threaten human health. The purpose of this study was to provide information on pharmaceutical threats to the environment. A preliminary risk assessment database for common pharmaceuticals was created and put into a web-accessible database named "Pharmaceuticals in the Environment, Information for Assessing Risk" (PEIAR) to help others evaluate potential risks of pharmaceutical contaminants in the environment. Information from PEIAR was used to prioritize compounds that may threaten the environment, with a focus on marine and estuarine environments. The pharmaceuticals were ranked using five different combinations of physical-chemical and toxicological data, which emphasized different risks. The results of the ranking methods differed in the compounds identified as high risk; however, drugs from the central nervous system, cardiovascular, and anti-infective classes were heavily represented within the top 100 drugs in all rankings. Anti-infectives may pose the greatest overall risk based upon our results using a combination of factors that measure environmental transport, fate, and aquatic toxicity. The dataset is also useful for highlighting information that is still needed to assuredly assess risk.

Objectives: Identify endocrine differences between human immunodeficiency virus- (HIV) infected versus uninfected children and evaluate associations of growth and body composition with endocrine measures., Study Design: Nested case-control study in 21 HIV-infected and 46 age- and sex-matched uninfected children in the Women and Infant Transmission Study. Plasma specimens from children between 2.5 to 7.0 years of age, taken during 3-4 visits, were tested for insulin-like growth factor binding protein-3 (IGFBP-3), cortisol, dehydroepiandrosterone (DHEA), growth hormone and thyroid studies. Longitudinal mixed and generalized estimating equation models compared group means and examined effects of endocrine measures on growth and body composition, respectively., Results: HIV-infected children had lower IGFBP-3 than uninfected children (1.96 +/- 0.09 mg/L versus 2.34 +/- 0.06 mg/L, P < 0.001). In infected but not in uninfected children, IGFBP-3 values and DHEA:cortisol ratios were associated with weight- and body mass index-for-age z scores ([WAZ] P = 0.019, <.001 respectively, and [BMZ] P = 0.029, 0.038). DHEA concentration was associated with height-for-age z score (P = 0.049)., Conclusions: In these HIV-infected children compared with their uninfected counterparts, IGFBP-3 concentration was different between groups. Infected children had multiple endocrine associations with growth and body composition not found in their uninfected peers. We hypothesize that in HIV-infected children, growth hormone resistance and shunting of precursors from adrenal androgen to cortisol production contributes to altered body composition and stunting.

To determine if HIV-1 resistance testing of the blood predicts mutants in the genital secretions of ZDV-treated pregnant women, ZDV resistance mutations were assessed by an oligonucleotide ligation assay. ZDV resistance was detected in viral sequences from blood (16/48; 33%) and cervical secretions (6/24; 25%) collected during 57 pregnancies. The genotype of 11/69 (16%) resistance codons was discordant between blood and cervical virus of pregnant women near term. However, in only 1 (1.8%) of 57 pregnancies evaluated was resistant virus limited to the cervical secretions. ZDV-resistant virus is rarely limited to the female genital tract.

Objective: We evaluated morbidity and mortality during the first 2 years of life among children born to human immunodeficiency virus-(HIV) type 1-infected women enrolled in the Women and Infants Transmission Study (WITS) during an 11-year period (1990-2001)., Design and Methods: As part of WITS, evaluations were performed at birth and at 1, 2, 4, 6, 9, 12, 18 and 24 months of age. Growth, hospitalization and the incidence of clinical disease were assessed regularly., Results: Data regarding 1118 children born to HIV-infected women (955 HIV-uninfected children and 163 HIV-infected children) were analyzed. Fewer changes in the caretaker of the child and fewer in utero exposures to drugs, tobacco and alcohol occurred in the latter periods of the study (all P values for time trend analyses <0.01). The percentages of HIV-uninfected children with poor weight gain (44 of 767; 5.7%), short stature (32 of 703; 4.5%) and wasting (27 of 792; 3.4%) were higher than expected for the general population. Two or more changes in caretaker were associated with all growth deficiencies except wasting, and fetal exposure to tobacco was associated with height abnormalities. Anemia was common and was associated with receipt of zidovudine prophylaxis. Morbidity and mortality decreased during the study period. For the uninfected children, a decrease in class A events (Kaplan-Meier rates: group 1, 22.3%; group 2, 6.8%; group 3, 4.2%; P < 0.001) and class C events and death (Kaplan- Meier event rates: group 1, 2.0%; group 2, 1.7%; group 3, 0.2%; P = 0.062) during the first 2 years of life account for the differences in the curves over time., Conclusions: During an 11-year period, morbidity and mortality during the first 24 months of life decreased substantially for children born to HIV-infected women.

The challenges associated with synthesizing porous materials mean that new classes of zeolites (zeotypes)-such as aluminosilicate zeolites and zeolite analogues-together with new methods of preparing known zeotypes, continue to be of great importance. Normally these materials are prepared hydrothermally with water as the solvent in a sealed autoclave under autogenous pressure. The reaction mixture usually includes an organic template or 'structure-directing agent' that guides the synthesis pathway towards particular structures. Here we report the preparation of aluminophosphate zeolite analogues by using ionic liquids and eutectic mixtures. An imidazolium-based ionic liquid acts as both solvent and template, leading to four zeotype frameworks under different experimental conditions. The structural characteristics of the materials can be traced back to the solvent chemistry used. Because of the vanishingly low vapour pressure of ionic liquids, synthesis takes place at ambient pressure, eliminating safety concerns associated with high hydrothermal pressures. The ionic liquid can also be recycled for further use. A choline chloride/urea eutectic mixture is also used in the preparation of a new zeotype framework.

Poorly-water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. The use of media milling technology to formulate poorly-water-soluble drugs as nanocrystalline particles offers the opportunity to address many of the deficiencies associated with this class of molecules. NanoCrystal Technology is an attrition process wherein large micron size drug crystals are media milled in a water-based stabilizer solution. The process generates physically stable dispersions consisting of nanometer-sized drug crystals. Nanocrystalline particles are a suitable delivery system for all commonly used routes of administration, i.e. oral, injectable (IV, SC, and IM) and topical applications. In addition, aqueous dispersions of nanoparticles can be post-processed into tablets, capsules, fast-melts and lyophilized for sterile product applications. The technology has been successfully incorporated into all phases of the drug development cycle from identification of new chemical entities to refurbishing marketed products for improving their performance and value.

Context: The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989., Objective: To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level., Design: Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000., Main Outcome Measure: HIV-1 status of the infant., Results: HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively., Conclusion: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.

Background: Early infection of the thymus, an organ central to the ontogeny of the immune system, has been proposed as a cause of rapid progression in pediatric HIV disease., Objective: To test the hypothesis that small thymic volume is associated with rapid disease progression in HIV-infected children., Design: Three pediatric radiologists established criteria for rating the size of the thymic profile on chest radiographs. All available baseline chest radiographs were reviewed in a random sequence, with radiologists blinded to study subjects' clinical status. A consensus was reached on whether the thymus was normal or small for age., Setting: A prospective multicenter study of the natural history of HIV-1 infection in children, the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted Human Immunodeficiency Virus Infection (P2C2) Study., Patients: Fifty-eight HIV-infected children and 38 control children (uninfected but born to HIV-infected women) for whom chest radiographs in the first year of life were available., Main Outcome Measure: Rapid progression of HIV disease, defined as CDC Clinical Category C (severely symptomatic) or Immunologic Category 3 (severe immunosuppression) by 1 year of age., Results: The mean age at the time of chest radiography was 3.5 months. Ten (17%) HIV-infected children had reduced thymic profile size, whereas no controls did (P = 0.006). Of the 58 (59%) HIV-infected children 34 were classified as rapid progressors, and 9 (26%) of them had reduced thymus size, compared with 1 (4%) of the non-rapid progressor children [odds ratio, 8.28; 95% confidence interval (CI), 1.0, 70.5; P = 0.035]. Baseline mean CD4+ count was 1642 (95% CI 1322 to 2009) cells/microl for those with normal thymus and 740 (95% CI 380 to 1275) cells/microl for those with reduced thymus (P = 0.007)., Conclusion: Early thymic involution is associated with rapidly progressive disease in HIV-infected children.

Background: Nonoccupational human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) for adults has been described, although the Centers for Disease Control and Prevention, Atlanta, Ga, offer no specific recommendations. There is limited information about its use in children and adolescents., Objective: To describe the current practices of physicians in pediatric infectious disease (PID) and pediatric emergency medicine (PEM) departments regarding nonoccupational HIV PEP for children and adolescents., Design: Survey., Participants: Directors of all PID and PEM departments with fellowship programs in the United States and Canada between July and November 1998., Main Outcome Measures: General questions regarding HIV PEP and questions concerning 2 scenarios (5-year-old with a needlestick injury and a 15-year-old after sexual assault)., Results: The return rate was 67 (78%) of 86 for PID and 36 (75%) of 48 for PEM physicians. Fewer than 20% of physicians reported institutional policies for nonoccupational HIV PEP; 33% had ever initiated nonoccupational HIV PEP. In both scenarios, PID physicians were more likely than PEM physicians to recommend or offer HIV PEP in the first 24 hours after the incident (55 [83%] of 66 vs 20 [56%] of 36 for needlestick injuries [odds ratio, 4.0; 95% confidence interval, 1.6-10.1] and 47 [72%] of 65 vs 16 [50%] of 32 for sexual assault [odds ratio, 2.6; 95% confidence interval, 1.1-6.3]). Seven different antiretroviral agents in single, dual, or triple drug regimens administered for 2 to 12 weeks were suggested., Conclusions: Although few physicians reported institutional policies, and only one third had ever initiated HIV PEP, many would offer or recommend HIV PEP for children and adolescents within 24 hours after possible HIV exposure. A wide variation of regimens have been suggested. There is a need for a national consensus for nonoccupational HIV PEP.

Trends in the vertical transmission rate of HIV and evolving antiretroviral usage between 1990 and 1998 within the Women and Infants Transmission Study were evaluated. A decline in mother-infant transmission was temporally associated with advances in therapy, especially when regimens including a protease inhibitor were included in the analysis.