Study protocol: a pragmatic, cluster-randomized controlled trial to evaluate the effect of implementation of the Truenat platform/MTB assays at primary health care clinics in Mozambique and Tanzania (TB-CAPT CORE).

BACKGROUND: In 2020, the WHO-approved Molbio Truenat platform and MTB assays to detect Mycobacterium tuberculosis complex (MTB) and resistance to rifampicin directly on sputum specimens. This primary health care center-based trial in Mozambique and Tanzania investigates the effect of Truenat platform/MTB assays (intervention arm) combined with rapid communication of results compared to standard of care on TB diagnosis and treatment initiation for microbiologically confirmed TB at 7 days from enrolment. METHODS: The Tuberculosis Close the Gap, Increase Access, and Provide Adequate Therapy (TB-CAPT) CORE trial employs a pragmatic cluster randomized controlled design to evaluate the impact of a streamlined strategy for delivery of Truenat platform/MTB assays testing at primary health centers. Twenty-nine centers equipped with TB microscopy units were selected to participate in the trial. Among them, fifteen health centers were randomized to the intervention arm (which involves onsite molecular testing using Truenat platform/MTB assays, process process optimization to enable same-day TB diagnosis and treatment initiation, and feedback on Molbio platform performance) or the control arm (which follows routine care, including on-site sputum smear microscopy and the referral of sputum samples to off-site Xpert testing sites). The primary outcome of the study is the absolute number and proportion of participants with TB microbiological confirmation starting TB treatment within 7 days of their first visit. Secondary outcomes include time to bacteriological confirmation, health outcomes up to 60 days from first visit, as well as user preferences, direct cost, and productivity analyses. ETHICS AND DISSEMINATION: TB-CAPT CORE trial has been approved by regulatory and ethical committees in Mozambique and Tanzania, as well as by each partner organization. Consent is informed and voluntary, and confidentiality of participants is maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals. TRIAL REGISTRATION: US National Institutes of Health's ClinicalTrials.gov, NCT04568954. Registered 23 September 2020.

Bilateral blindness after starting highly active antiretroviral treatment in a patient with HIV infection and cryptococcal meningitis.

A 26-year-old HIV-seropositive Caucasian man with cryptococcal meningitis developed permanent bilateral blindness shortly after starting highly active antiretroviral treatment. The blindness may have been a consequence of an immune reactivation inflammatory syndrome caused by this treatment.

Embryo survival, uterine fluids and tubal SEM in progesterone-asynchronized rabbits.

Survival of embryos exposed to several concentrations of uterine proteins and changes in tubal morphology in rabbits given low preovulatory doses of progesterone (P4) that had previously not affected ovulation or fertilization, but caused severe embryo mortality, were studied. In experiment 1, 332 morulae were cultured for 24 h in a control medium containing < 0.5 to > 3.0 mg x mL(-1) of Day 3 uterine fluid proteins. There was no difference in blastocyst development nor implantation to Day 12 following transfer of the blastocysts to recipients, except fewer implants developed in the BSA control. In experiment 2 the oviducts and uteri of control and P4-treated does were examined by SEM for 8 days following ovulation. Secretory cells in the oviducts and to a lesser extent in the uteri were stimulated by P4 treatment for 3 to 4 days after ovulation. Morphology of ciliated cells was unaffected. The subtle changes did not fully account for P4-induced embryo mortality in vivo.

Infusion of GDNF into the cerebral spinal fluid through two different routes: effects on body weight and corticospinal neuron survival.

Survival of axotomized adult rat corticospinal neurons (CSN) is supported by glial cell line-derived neurotrophic factor (GDNF). We have evaluated the trophic effects of intrathecally applied GDNF on CSN survival and rat body weight. Body weight reduction is the major side effect of intracerebral neurotrophic factor treatment. GDNF was tested at total doses of 30, 100 and 300 microg over 7 days after axotomy via different application routes: intracerebroventricularly (i.c.v.) and cisternally (cis). Animals injected i.c.v. displayed severe body weight reduction at all doses tested but CSN rescue only at the highest dose. In contrast, cis-infusion of GDNF promoted CSN survival at all doses and only the highest dose reduced the body weight. These results show that intracisternal, but not i.c.v., GDNF infusion at low doses can promote CSN survival without negatively affecting rat body weight. This finding may have implications for the clinic use of GDNF.

GDNF is a trophic factor for adult rat corticospinal neurons and promotes their long-term survival after axotomy in vivo.

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for several neuronal populations involved in motor control. The present study evaluates the trophic actions of GDNF on corticospinal neurons, an important central nervous system motor projection into the spinal cord. Death of spinal motoneurons and corticospinal neurons is observed in the neurodegenerative disease amyotrophic lateral sclerosis. Axotomy of adult rat corticospinal neurons at internal capsule levels induces half of them to die, and the surviving population displays severe atrophy. To examine the trophic effects of GDNF on corticospinal neurons, Fast Blue-labelled corticospinal neurons were stereotaxically axotomized at internal capsule levels and GDNF was infused intracortically to lesioned corticospinal neurons at total doses of 2, 4, 10, 20, 40, 100 and 300 microg for 7 days. GDNF prevented axotomy-induced death of corticospinal neurons at doses between 2 and 40 microg and abolished or attenuated their atrophy at all doses examined. In addition, treatment with 8 microg GDNF for the first 2 weeks after axotomy resulted in the long-term survival of corticospinal neurons for 42 days. With regard to the development of treatment strategies for upper motoneuron degeneration in amyotrophic lateral sclerosis, application of GDNF via the cerebrospinal fluid may be more relevant than intracortical delivery as its diffusion within the brain parenchyma is limited. Intraventricular as well as intracisternal infusion of GDNF (300 microg over 7 days) completely prevented corticospinal neuron death. These results show that GDNF promotes the long-term survival of corticospinal neurons and has a positive effect on their size in vivo. Furthermore, the survival-promoting effect of GDNF on corticospinal neurons after delivery via cerebrospinal fluid has important clinical implications for potential treatment of the upper motoneuron degeneration seen in amyotrophic lateral sclerosis.

The case for greater Australian support for population issues.

PIP: The 1989 Report of the Joint Committee on Foreign Affairs, Defence and Trade recommended rapid growth in aid, saying that if Australia is to achieve the internationally accepted aid goal of 0.7% of GNP within 5 years, then aid should reach 0.5% of GNP by 1992. Aid presently is at 0.34% of GNP. In the 1991-92 aid budget, population activities totaled around $7 million, with $1.7 million to the United Nations Population Fund and around $1.2 million to the International Planned Parenthood Federation, the World Health Organization's Human Reproduction Program, the Population Council, and the International Union for the Scientific Study of Population. Over the last 20 years, the percentage of Third World couples participating in voluntary family planning programs has risen to 50%. It is estimated that 300 million more families wish to limit their family size and would participate if they had the means to do so. An estimated 100 million women have inadequate access to contraception. Programs such as the Australian International Development Assistance Bureau (AIDAB)'s Activities Scheme work towards widening women's options. Literacy allows access to information on family planning and health care. The Australian Human Rights Delegation to China discussed population and family planning policies within China. Family planning officials admitted the problem of female infanticide in rural and remote areas. In Sichuan Province, for every 108 boys registered at birth in 1990, only 100 girls were registered. Officials also admitted the problem of having to rely on abortion for contraception. In China assistance is needed to make available contraceptive devices to Chinese women. In 1991, the Australian bilateral and multilateral aid for family planning was less than $10 million, of a total aid budget of $1100 million. An initial population funding to the level of around $10 million, rising to $60 million per year by the end of a 4-year program, would enable Australia to be recognized as a major donor in the Asia-Pacific region.^ieng

Carcinoma anaplástico del tiroides: consideraciones clínico patológicas / Anaplastic carcinoma of the thyroid gland: pathological clinic considerations

El objetivo de la presente investigación fue pesquisar evidencias clínicas e histopatológicas que confirmaran la conversión de un carcinoma tiroideo diferenciado en uno indiferenciado. El material está constituido por 24 casos de carcinoma anaplástico. Se hizo un análisis retrospectivo de las observaciones clínicas y una revisión de las preparaciones histológicas. Los 24 casos de carcinoma anaplástico del tiroides representan el 6,5% del total de carcinomas tiroideos. Hubo 15 pacientes de sexo femenino y 9 de sexo masculino. La edad osciló entre 29 y 84 años, el promedio de 62 años. En 13 hubo bocio preexistente. Se revisó las preparaciones histológicas de 20 casos y en 14 hubo estructuras histológicas de carcinoma diferenciado; de éstos, 5 tuvieron historia de bocio. En 19 pacientes se encontró evidencias clínicas y/o histopatológicas de carcinoma diferenciado preexistente

Penicillin V and rifampin for the treatment of group A streptococcal pharyngitis: a randomized trial of 10 days penicillin vs 10 days penicillin with rifampin during the final 4 days of therapy.

To improve the bacteriologic and clinical cure rates of streptococcal pharyngitis, 79 children were randomly assigned to receive penicillin V alone for 10 days (39 patients) or penicillin for the same duration and rifampin during the last 4 days of penicillin therapy (40 patients). Eleven patients given penicillin had evidence of bacteriologic failure (including eight with relapse of clinical illness) on repeat cultures done 4 to 7 days after treatment, whereas there were no failures in children given combination therapy (P = 0.0015). All eight symptomatic children improved with penicillin-rifampin therapy and subsequent cultures were negative, whereas three asymptomatic children continued to harbor group A streptococci even after combination therapy. Antibody response by antistreptolysin O or antideoxyribonuclease B assay was seen in 50.6% of patients; the antibody responses in both groups were comparable. These results show that addition of rifampin to the penicillin regimen improves the clinical and bacteriologic cure rates in children with streptococcal pharyngitis.