Primary α and secondary ß relaxation dynamics of meta-toluidine in the liquid state investigated by broadband dielectric spectroscopy.

We report a broadband dielectric spectroscopic (BDS) study on the clustering fragile glass-former meta-toluidine (m-TOL) from 187 K up to 289 K over a wide frequency range of 10-3-109 Hz with focus on the primary α relaxation and the secondary ß relaxation above the glass temperature Tg. The broadband dielectric spectra were fitted by using the Havriliak-Negami (HN) and Cole-Cole (CC) models. The ß process disappearing at Tß,disap = 1.12Tg exhibits non-Arrhenius dependence fitted by the Vogel-Fulcher-Tamman-Hesse equation with T0ßVFTH in accord with the characteristic differential scanning calorimetry (DSC) limiting temperature of the glassy state. The essential feature of the α process consists in the distinct changes of its spectral shape parameter ßHN marked by the characteristic BDS temperatures TB1ßHN and TB2ßHN. The primary α relaxation times were fitted over the entire temperature and frequency range by several current three-parameter up to six-parameter dynamic models. This analysis reveals that the crossover temperatures of the idealized mode coupling theory model (TcMCT), the extended free volume model (T0EFV), and the two-order parameter (TOP) model (Tmc) are close to TB1ßHN, which provides a consistent physical rationalization for the first change of the shape parameter. In addition, the other two characteristic TOP temperatures T0TOP and TA are coinciding with the thermodynamic Kauzmann temperature TK and the second change of the shape parameter at around TB2ßHN, respectively. These can be related to the onset of the liquid-like domains in the glassy state or the disappearance of the solid-like domains in the normal liquid state.

A whole cell biocatalyst for double oxidation of cyclooctane.

A novel whole cell cascade for double oxidation of cyclooctane to cyclooctanone was developed. The one-pot oxidation cascade requires only a minimum of reaction components: resting E. coli cells in aqueous buffered medium (=catalyst), the target substrate and oxygen as environmental friendly oxidant. Conversion of cyclooctane was catalysed with high efficiency (50% yield) and excellent selectivity (>94%) to cyclooctanone. The reported oxidation cascade represents a novel whole cell system for double oxidation of non-activated alkanes including an integrated cofactor regeneration. Notably, two alcohol dehydrogenases from Lactobacillus brevis and from Rhodococcus erythropolis with opposite cofactor selectivities and one monooxygenase P450 BM3 were produced in a coexpression system in one single host. The system represents the most efficient route with a TTN of up to 24363 being a promising process in terms of sustainability as well.

Two-spinon and orbital excitations of the spin-Peierls system TiOCl.

We combine high-resolution resonant inelastic x-ray scattering with cluster calculations utilizing a recently derived effective magnetic scattering operator to analyze the polarization, excitation energy, and momentum-dependent excitation spectrum of the low-dimensional quantum magnet TiOCl in the range expected for orbital and magnetic excitations (0-2.5 eV). Ti 3d orbital excitations yield complete information on the temperature-dependent crystal-field splitting. In the spin-Peierls phase we observe a dispersive two-spinon excitation and estimate the inter- and intradimer magnetic exchange coupling from a comparison to cluster calculations.

Provider barriers to the uptake of isoniazid preventive therapy among people living with HIV in Ethiopia.

SETTING: Sixty-seven government health facilities providing tuberculosis (TB) and human immunodeficiency virus (HIV) services across Ethiopia. OBJECTIVE: To examine clinician barriers to implementing isoniazid preventive therapy (IPT) among people living with HIV. DESIGN: A cross-sectional study to evaluate the provider-related factors associated with high IPT coverage at the facility level. RESULTS: On bivariate analysis, the odds of high IPT implementation were lower when clinicians felt patients were negatively affected by the side effects of IPT (OR 0.18, 95%CI 0.04-0.81) and perceived that IPT increased multidrug-resistant TB (MDR-TB) rates (OR 0.66, 95%CI 0.44-0.98). The presence of IPT guidelines on site (OR 2.93, 95%CI 1.10-7.77) and TB-HIV training (OR 3.08, 95%CI 1.11-8.53) had a positive relationship with high IPT uptake. In the multivariate model, clinician's perception that active TB was difficult to rule out had a negative association with a high IPT rate (OR 0.93; 95%CI 0.90-0.95). CONCLUSIONS: Clinician impression that ruling out active TB among HIV patients is difficult was found to be a significant barrier to IPT uptake. Continued advancement of IPT relies greatly on improving the ability of providers to determine IPT eligibility and more confidently care for patients on IPT. Improved clinician support and training as well as development of new TB diagnostic technologies could impact IPT utilization among providers.

A stable latent reservoir for HIV-1 in resting CD4(+) T lymphocytes in infected children.

HIV-1 persists in a latent state in resting CD4(+) T lymphocytes of infected adults despite prolonged highly active antiretroviral therapy (HAART). To determine whether a latent reservoir for HIV-1 exists in infected children, we performed a quantitative viral culture assay on highly purified resting CD4(+) T cells from 21 children with perinatally acquired infection. Replication-competent HIV-1 was recovered from all 18 children from whom sufficient cells were obtained. The frequency of latently infected resting CD4(+) T cells directly correlated with plasma virus levels, suggesting that in children with ongoing viral replication, most latently infected cells are in the labile preintegration state of latency. However, in each of 7 children who had suppression of viral replication to undetectable levels for 1-3 years on HAART, latent replication-competent HIV-1 persisted with little decay, owing to a stable reservoir of infected cells in the postintegration stage of latency. Drug-resistance mutations generated by previous nonsuppressive regimens persisted in this compartment despite more than 1 year of fully suppressive HAART, rendering untenable the idea of recycling drugs that were part of failed regimens. Thus the latent reservoir for HIV-1 in resting CD4(+) T cells will be a major obstacle to HIV-1 eradication in children.

Factors promoting and inhibiting sustained impact of a mental health task-shifting program for HIV providers in Ethiopia.

BACKGROUND: Task-shifting mental health into general medical care requires more than brief provider training. Generalists need long-term support to master new skills and changes to work context are required to sustain change in the face of competing priorities. We examined program and context factors promoting sustainability of a mental health task-shifting training for hospital-based HIV providers in Ethiopia. METHODS: Convergent mixed-methods quasi-experimental study. Sustained impact was measured by trained/not-trained provider differences in case detection and management 16 months following the end of formal support. Factors related to sustainability were examined through interviews with trained providers. RESULTS: Extent of sustained impact: Trained providers demonstrated modest but better agreement with standardized screeners (greater sensitivity with similar specificity). They were more likely to request that patients with mental health problems return to see them v. making a referral. Factors promoting sustainability (reported in semi-structured interviews): provider belief that the treatments they had learned were effective. New interactions with on-site mental health staff were a source of ongoing learning and encouragement. Factors diminishing sustainability: providers feelings of isolation when mental health partners left for work elsewhere, failure to incorporate mental health indicators into administrative data, to re-stock staff education materials, and to build formal mechanisms for generalist-mental health staff interaction. CONCLUSIONS: An intervention seen as feasible and effective, and promotion of relationships across professional lines, helped generalists sustain new skills. Failure to address key system context issues made use of the skills unsustainable as external supports ended.

Dielectric properties of complex magnetic field induced states in PbCuSO4(OH)2.

Spin spirals, which coexist with collinear spin order in linarite PbCuSO4(OH)2, indicate electrical polarisation textures of spin-multipolar phases. We derive experimental evidence by a detailed investigation of the magnetic-field dependent dielectric and electric polarization properties at low temperatures. Linarite exhibits a quasi-one-dimensional frustrated S = ½ spin chain, which forms 3D spin-spiral order in zero magnetic field for T < 2.85 K. Recently, due to the monoclinic lattice of linarite with CuO2 ribbon chains, complex magnetic field induced states were found. These spin-multipolar phases, which compete with spin-density waves at low magnetic fields, exist in close vicinity to the transition from the spin spiral into field induced spin polarized state. Via antisymmetric Dzyaloshinskii-Moriya interaction spin-driven ferroelectricity develops in the spin-spirals state. Via electric polarization measurements this allows to prove the transitions into complex magnetic field induced phases. Thorough analyses of the temperature and magnetic field dependent dielectric properties of a naturally grown single crystalline sample provide a detailed (T,H) phase diagrams for the three different crystallographic directions.

Tuberculosis along the continuum of HIV care in a cohort of adolescents living with HIV in Ethiopia.

SETTING: Eight health facilities in Ethiopia. OBJECTIVE: To determine tuberculosis (TB) incidence rates and associated factors among adolescents living with the human immunodeficiency virus (ALHIV). DESIGN: This was a retrospective cohort study. Adolescents enrolled in HIV care between January 2005 and 31 December 2013 constituted the study population. The main outcome variable was TB diagnosis during follow-up. Baseline World Health Organization (WHO) clinical stage, CD4 count, previous history of TB and use of isoniazid preventive therapy (IPT) were the main independent variables. We estimated TB incidence rates as incident cases per 100 person-years of observation (PYO). Cox regression analysis was used to control for confounders. RESULTS: Of the 1221 adolescents screened, 1072 were studied; 60.1% were girls. TB incidence rate was 16.32 per 100 PYO during pre-antiretroviral therapy (pre-ART) follow-up but declined to 2.25 per 100 PYO after initiation of ART. Advanced WHO clinical stage (adjusted hazard ratio [aHR] 2.71, 95%CI 1.69-4.33) and CD4 count <350 cells/µl (aHR 2.28, 95%CI 1.10-4.81) predicted TB incidence in the pre-ART cohort. IPT use was associated with a significant reduction in TB incidence in the ART cohort, but not in the pre-ART group. CONCLUSION: Although TB was a significant problem in ALHIV, timely administration of ART and IPT had a significant protective effect.

The utility of verbal autopsies for identifying HIV-1-related deaths in Haitian children.

OBJECTIVE: To determine whether deaths among Haitian infants born to HIV-1-seronegative women could be distinguished from deaths among children born to HIV-1-seropositive women using the verbal autopsy technique. METHODS: Mothers of 315 Haitian children who died were interviewed about events leading to the child's death. Three physicians independently reviewed interview data and determined the probable cause of death without knowledge of maternal HIV-1 status or hospital records. The underlying causes of death assigned to the infants were analyzed to determine whether maternal HIV status could be predicted. RESULTS: There was good agreement among the physicians (kappa = 0.62) and 90% agreement between hospital records and the verbal autopsy diagnosis. Compared with children born to HIV-1-seronegative women, deaths in children born to HIV-1-seropositive mothers were more likely to be ascribed to a presumptive diagnosis of AIDS (37 versus 21%; P = 0.01). The sensitivity and specificity of verbal autopsies for identifying deaths associated with maternal HIV-1 infection ranged from 37 to 59% and from 69 to 79%, respectively, depending on the classification system used. The predictive positive value of a death believed to be consistent with pediatric HIV-1 infection was 26-30% and the predictive negative value was 85-90%. CONCLUSION: Verbal autopsies may be useful for distinguishing certain causes of death, but have limited utility for distinguishing deaths associated with maternal HIV-1 infection from deaths among children born to HIV-1-seronegative women.

HIV-1 in Haitian women 1982-1988. The Cite Soleil/JHU AIDS Project Team.

Pregnant Haitian women (n = 4,474) residing in a periurban slum were interviewed to identify risk factors for sexually transmitted diseases and sera were tested to identify antibodies to HIV-1 and syphilis. The seroprevalence rates for antibodies to HIV-1 increased from 8.9% in 1986 to 9.9% in 1987 and 10.3% in 1988. Sera obtained in 1982 from 533 mothers of young infants in the same community revealed that 7.8% were HIV-1 seropositive. Of women pregnant for the first time in 1986-1988, 6.6% were HIV-1 seropositive and 6.0% had a positive VDRL. The highest seropositivity rates (greater than 15%) were noted in women 20 to 29 years of age with a history of two or more sexual partners in the year prior to pregnancy. Factors independently associated with HIV-1 seropositivity in pregnant women by logistic regression analysis included being unmarried, age 20-29 years, having had more than one sex partner in the year prior to pregnancy, a positive serologic test for syphilis, and smoking. A dose-response effect was noted in the association between HIV-1 seropositivity and smoking. The association between smoking and HIV-1 infections could be confounded by unrecognized behavioral factors or due to a biologic effect of smoking. The continuing high HIV-1 seropositivity rates in pregnant women indicate that current preventive measures are insufficient and increased control efforts are urgently needed.

Prevalence of HIV-1 DNA and p24 antigen in breast milk and correlation with maternal factors.

Breast milk specimens from human immunodeficiency virus type 1 (HIV-1)-seropositive and HIV-1-seronegative women were examined for the presence of HIV-1 p24 antigen by the antigen capture method and for viral DNA using the polymerase chain reaction. HIV-1 DNA was present in 70% of milk specimens collected from 47 HIV-seropositive women 0-4 days after delivery and in approximately 50% of specimens collected 6 and 12 months postpartum. p24 antigen, present in 24% of milk specimens collected from 37 seropositive women within the first 4 days postpartum, was not detected in any of the subsequent specimens. The presence of HIV-1 DNA or p24 antigen in milk was not significantly associated with maternal CD4 lymphocyte count, beta 2-microglobulin level, or fulfillment of the AIDS clinical case definition. Although the correlation of either HIV-1 proviral DNA or p24 antigen with the presence of infectious virus is not known, these data indicate the need for additional studies examining the role of breastfeeding in maternal-infant transmission of HIV-1.

Bacillus Calmette-Guérin complications in children born to HIV-1-infected women with a review of the literature.

OBJECTIVE: To compare the risk of complications following Bacillus Calmette-Guérin (BCG) vaccination among children by maternal and infant HIV-1 infection status as part of an investigation of an outbreak of BCG complications. METHODS: A nonconcurrent cohort study of BCG complications among 125 infants born to HIV-1 seropositive and 166 infants born to HIV-1 seronegative mothers was conducted in Cité Soleil, Haiti. Infants were examined at regular intervals until 15 months of age, and complications from BCG were documented. An investigation of BCG vaccination practices was conducted. RESULTS: Mild or moderate complications occurred among 16 of 166 (9.6%) infants born to HIV-1 seronegative mothers compared with 4 of 13 HIV-1-infected infants (30.8%, P = .04) and 10 of 75 (13.3%, P = .39) uninfected infants born to HIV-1-infected mothers. No serious complications were noted. The outbreak of complications was associated with administration of 2.0 to 2.5 times the recommended dose of BCG vaccine. CONCLUSIONS: This and five other cohort studies indicate that there may be a small increased risk of complications following BCG vaccination among HIV-1-infected children, but the reactions are usually mild and the risk does not outweigh the benefits of BCG vaccination in populations at high risk of tuberculosis during infancy and childhood.

Pediatric acquired immunodeficiency syndrome: special considerations for developing nations.

PIP: WHO estimates the existence of 1 million AIDS cases and over 500,000 AIDS deaths over the past 10 years. An estimated 9-11 million people are infected, including 3 million women and 500,000 infants and children. 80% of infected women and children live in sub-Saharan Africa. Their numbers are expected to continue to rise. HIV-1 will probably lead to the death of 3 million or more women and 2.7 million children over the next decade, and will become the leading cause of death for men and women aged 15-49 in major North, Central, and South American, West European, and sub-Saharan African cities. Accordingly, pediatric AIDS threatens much of what has been achieved in improving developing country child survival over the past 20 years. Concerted efforts must be made on an international scale to prevent and control the growing pandemic. This paper discusses the magnitude of HIV-1 infection and AIDS, maternal-infant transmission, breast-feeding, blood transfusion, diagnosis, clinical features and medical management, impact on child survival, and prevention and control.^ieng

Bancroftian filariasis in Haiti: preliminary characterization of the immunological responsiveness of microfilaremic individuals.

Patent infections with the lymphatic filariae, Wuchereria bancrofti and Brugia malayi, are associated with suppressed in vitro cellular responsiveness to filarial antigens. In studies of bancroftian filariasis in Haiti, a significant number of microfilaremic individuals can be characterized as "responders" to filarial antigens. Cells from 37/74 untreated microfilaremic subjects responded to B. pahangi antigen (stimulation ratio greater than 2) as detected by in vitro blastogenesis. A comparison of responders to nonresponders revealed a significant difference in mean B. pahangi reactivity (15,822 vs. 4,538 cpm, P less than 0.001), but no significant differences with respect to age, microfilaremia, PPD or PHA reactivity, or B. pahangi-specific antibody levels. Subtle differences may exist between these groups with respect to recognition of specific antigens on Western blots.

Breastmilk, breastfeeding, and transmission of viruses to the neonate.

The benefits of breast milk have been well delineated, and breastfeeding should be encouraged whenever possible. However, the potential transmission of HIV-1, HTLV-1, and possibly HTLV-II warrant the recommendation that women in industrialized countries who are infected with these viruses not breastfeed their infants. These recommendations reflect what is currently known about the risks of viral transmission through breastfeeding; ongoing and future studies may provide additional data, enabling a better definition of the precise risks and factors associated with the transmission of viruses through breastfeeding.

HIV-related knowledge and risk behaviors of street youth in Belo Horizonte, Brazil. The Street Youth Study Group.

Individual interviews were conducted with 379 youth who work and/or live on the streets of a large Brazilian city to assess HIV-related knowledge, sources of information, risk behaviors, and prevention beliefs and strategies. Respondents demonstrated high levels of factual knowledge about HIV transmission (84% correct) coupled with high levels of misconceptions about casual transmission (53% correct) and intermediate levels of knowledge about prevention (64% correct). Only 54% of the respondents had heard about AIDS recently, and 37.5% said they talked to someone about AIDS. The most common sources of information about HIV/AIDS were the mass-media and friends. Over half the sample reported taking precautions to reduce their risk of HIV infection; however, the proportion of youth taking effective precautions was low. Among the 247 youth (65% of the sample) who had initiated sexual activity, lifetime condom use was reported by 18%, and condom use at last intercourse by 10%. Youth with higher levels of knowledge were more likely to report behavior changes to avoid HIV infection. These findings underscore the urgent need for prevention programs tailored to street youth in developing countries.

Cultural feasibility studies in preparation for clinical trials to reduce maternal-infant HIV transmission in Haiti.

A cultural feasibility study is defined as one that investigates scientific as well as ethical, behavioral, and social issues in the design of clinical trials. The value of such a broadly defined assessment is illustrated through the presentation of two case studies conducted to prepare for clinical trials to reduce maternal-infant HIV transmission on Cité Soleil, Haiti. The first study addressed issues surrounding a trial of breast-feeding and exclusive bottle-feeding among HIV seropositive mothers. The second study focused on the implementation of a double-blind trial of HIV immune globulin and standard immune globulin to be administered to infants of seropositive mothers shortly after birth. Both cases used focus group interviews with mothers and in-depth interviews with key informants to investigate AIDS-related beliefs, acceptability of trial participation, risks to subjects, and community reactions and repercussions to the trial. Findings point to the difficulties posed by attempts to conduct trial involving complex research designs in socially disadvantaged populations. Recommendations highlight the need to consider the community-wide impact of a trial, and the need to undertake extensive educational preparation of participants to ensure informed consent and adherence to protocols.

PIP: Cultural feasibility studies use ethnographic methods to explore ethical, behavioral, and social issues inherent in the design of proposed clinical trials. This approach was applied in advance of clinical trials aimed at reducing maternal-infant HIV transmission in Cite Soleil, Haiti. The first focused on conditions that would be necessary to conduct a trial of breast feeding versus exclusive bottle feeding by HIV-positive mothers; the second investigated the feasibility of a double-blind trial of administration of a high- titer antibody preparation--HIV immune globulin (HIVIG)--to infants of seropositive mothers shortly after birth. Study methods included focus group discussions with mothers and in-depth interviews with key informants about AIDS-related beliefs, acceptability of trial participation, risks to subjects, and community repercussions. Concerns identified included the potential negative effect on breast feeding promotion efforts in Haiti, the scarcity of economic means to sustain safe bottle feeding, the risk of being labeled HIV-positive by virtue of study participation, the potential for the HIVIG trial to reinforce the misconception that a vaccine effective against AIDS exists, and problems explaining the concept of a double-blind study and accepting random assignment to treatment and control groups. As a result of these studies, it was decided to conduct the infant feeding study in a community with higher rates of exclusive bottle feeding and lower infant mortality than exist in Cite Soleil. The HIVIG trial could be conducted, but only after extensive community education to ensure informed consent. An objective assessment of subject comprehension was developed for this purpose.

Selenium deficiency and cardiomyopathy in acquired immunodeficiency syndrome.

Selenium deficiency is common in patients with human immunodeficiency virus infection and may contribute to the development of cardiomyopathy. A 5-year-old boy with congenital human immunodeficiency virus infection developed cardiomyopathy. Evaluation for reversible causes of cardiomyopathy was notable for the diagnosis of selenium deficiency. Cardiac function improved on selenium supplementation. The role of selenium in cardiac dysfunction and the need for nutritional evaluation and supplementation of malnourished patients with acquired immunodeficiency syndrome is discussed.

Parasitic infections of the central nervous system in children. Part II: Disseminated infections.

In the second segment of this three-part review of parasitic infections of the central nervous system in children, we consider parasitic infections which typically involve various tissues and organs in addition to the brain and spinal cord. Parasites capable of dissemination in immunocompetent hosts are discussed first, and, as in Part I, organisms are grouped according to their predominant geographic location. This is followed by a discussion of the unique aspects of toxoplasmosis, strongyloidiasis and infection with microsporidia in immunocompromised patients, with an emphasis on the central nervous system.

Parasitic infections of the central nervous system in children. Part III: Space-occupying lesions.

In the last part of this three-part review of parasitic infections of the central nervous system in children, we consider parasites which due to their size, distribution, or the nature of the host response, tend to cause focal lesions in the brain and spinal cord and therefore present as space-occupying lesions which occasionally mimic malignant tumors. As in Parts I and II, infections are grouped according to their predominant geographic area. Such infections include cysticercosis, one of the more common and important infections of the central nervous system.