Feasibility and acceptability of conducting HIV vaccine trials in adolescents in South Africa: Going beyond willingness to participate towards implementation

Background. HIV/AIDS remains a leading cause of death in adolescents (aged 15 - 25 years), and in sub-Saharan Africa HIV-related deaths continue to rise in this age group despite a decline in both adult and paediatric populations. This is attributable in part to high adolescent infection rates and supports the urgent need for more efficacious prevention strategies. In particular, an even partially effective HIV vaccine, given prior to sexual debut, is predicted to significantly curb adolescent infection rates. While adolescents have indicated willingness to participate in HIV vaccine trials, there are concerns around safety, uptake, adherence, and ethical and logistic issues.Objectives. To initiate a national, multisite project with the aim of identifying obstacles to conducting adolescent HIV vaccine trials in South Africa (SA).Method. A simulated HIV vaccine trial was conducted in adolescents aged 12 - 17 years across five SA research sites, using the already licensed Merck human papillomavirus vaccine Gardasil as a proxy for an HIV vaccine. Adolescents were recruited at community venues and, following a vaccine discussion group, invited to participate in the trial. Consent for trial enrolment was obtained from a parent or legal guardian, and participants aged 16 - 17 years were eligible only if sexually active. Typical vaccine trial procedures were applied during the five study visits, including the administration of vaccination injections at study visits 2, 3 and 4.Results. The median age of participants was 14 years (interquartile range 13 - 15), with 81% between the ages of 12 and 15 years at enrolment. Overall, 98% of screened participants opted to receive the vaccine, 588 participants enrolled, and 524 (89%) attended the final visit.Conclusions. This trial showed that adolescents can be recruited, enrolled and retained in clinical prevention trials with parental support. While promising, these results were tempered by the coupling of sexual-risk eligibility criteria and the requirement for parental/guardian consent, which was probably a barrier to the enrolment of high-risk older adolescents. Further debate around appropriate consent approaches for such adolescents in HIV prevention studies is required

Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients

BACKGROUND: Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation. The object of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed by a comparative investigation examining TRPM3 surface expression, and cytoplasmic and mitochondrial calcium influx in CD19+ B cells, CD56bnght and CD56dim cell populations from CFS/ME patients. RESULTS: TRPM3 cell surface expression was identified for NK and B lymphocytes in healthy controls (CD56bright TRPM3 35.72 % ± 7.37; CD56dim 5.74 % ± 2.00; B lymphocytes 2.05 % ± 0.19, respectively). There was a significant reduction of TRPM3 surface expression on CD19+ B cells (1.56 ± 0.191) and CD56bright NK cells (17.37 % ± 5.34) in CFS/ME compared with healthy controls. Anti-CD21 and anti-IgM conjugated biotin was cross-linked with streptavidin,and subsequently treatment with thapsigargin. This showed a significant reduction in cytoplasmic calcium ion concentration in CD19+ B lymphocytes. CD56bright NK cells also had a significant decrease in cytoplasmic calcium in the presence of 2-APB and thapsigargin in CFS/ME patients. CONCLUSIONS: The results from this preliminary investigation identify, for the first time, TRPM3 surface expression on both NK and B lymphocytes in healthy controls. We also report for the first time, significant reduction in TRPM3 cell surface expression in NK and B lymphocytes, as well as decreased intracellular calcium within specific conditions in CFS/ME patients. This warrants further examination of these pathways to elucidate whether TRPM3 and impaired calcium mobilisation has a role in CFS/ME.

A Literature Review of Dietitians’ Knowledge Attitudes and Opinions towards Dietary Supplements.

Background: Since the late 1990’s, public interest and use of dietary supplements has dramatically increased despite the evidence supporting the use of dietary supplements being largely inconclusive, NHS Choices [1]. Various reports indicate that the public have insufficient knowledge of dietary supplements to enable them to use them safely and effectively, Miller and Russell [2]. With the lack of public knowledge of dietary supplements already recognised, dietitians play a critical role in offering impartial advice based on the best available evidence to support the public in making informed decisions in the use of dietary supplements. The aim of this review was to consider dietitians’ level of knowledge and the stance they take towards dietary supplements. For this purpose, a dietary supplement is the collective term used to describe both nutrient-based dietary supplements and herbal-based dietary supplements. Methods: A literature search focussed on journal articles published in English between January 2000 and February 2013, in the following databases; Proquest, Science Direct and EBSCO Host searching; Ahmed, Cinhal and Medline. A combination of the following search terms were used; ‘dietitian(s)’, ‘dietician(s)’, ‘knowledge’, ‘attitude(s)’, ‘opinion(s)’, ‘perception(s)’, ‘belief(s)’, ‘dietary supplement(s)’, ‘nutraceutical(s)’, ‘vitamin(s)’, ‘mineral(s)’ and ‘herb(s)’. Ten primary research articles pertinent to the aim of this study were selected for inclusion from a total of 483 articles which were retrieved from this search and one other from an unrelated ‘Google’ search. Results: The eleven studies were of cross-sectional design. Nine studies conducted their research across various states of America, with one extending to Germany, Hungary and Canada, one focussed their research in Canada; and one in the Netherlands. Each study carried out their research using a questionnaire, in one of the following formats; postal, email, online or telephone survey; with the number of eligible subjects ranging from 57 to 1,268. Discussion: Dietitians have a greater knowledge of nutrient-based dietary supplements than herbal-based dietary supplements, Lee et al. [3]. Findings suggested dietitians are more knowledgeable on the intended use of dietary supplements and least knowledgeable on the pharmacological effects and risks of these products, including supplement-drug interactions and side effects. A greater knowledge was positively associated with the personal use of dietary supplements and specifically of the particular products used. Dietitians’ knowledge, attitudes and opinions were reflected in their recommendations for use of dietary supplements in practice. There was a recognised need among dietitians for further training regarding dietary supplements. Conclusion: It can be concluded that dietary supplements warrant further recognition within the dietetic curriculum and also within the practice setting. In addition, there is a general consensus that advising patients on dietary supplements should be a shared responsibility between the multi-disciplinary team. Further Recommendations; A standardised tool is developed to further explore this subject area, within the European dietetic population.

Mental health policy and service system development in the English-speaking Caribbean / Políticas para la salud mental y desarrollo de sistemas de servicio en el Caribe anglófono

The countries and territories comprising the English-speaking Caribbean (ESC) have made some strides in the development of mental health policy, services and systems with the expenditure in mental health as a percentage of health budgets ranging from 1% to 7%. The ESC countries have well developed primary healthcare systems. However, mental health legislations in many countries are in need of reform. Some countries have developed an innovative community based, secondary care treatment model: treatment in the medical wards of general hospitals. These countries have made progress in integrating mental health into primary healthcare and have made psychotropic medication widely available at the primary care level. Notwithstanding the progress in some countries, greater effort is required in phasing out mental hospitals and integrating mental health into primary care in other ESC countries.

Los países y territorios que comprenden el Caribe Anglófono (CAF) han dado pasos extraordinarios en relación con el desarrollo de políticas, servicios y sistemas de salud mental, de modo tal que los gastos en salud mental en término del porcentaje de presupuestos de salud fluctúan entre el 1% y el 7%. Los países del CAF poseen sistemas de atención primaria de la salud bien desarrollados. Sin embargo, las legislaciones con respecto a la salud mental en muchos países necesitan reformas. Algunos países han desarrollado un modelo innovador comunitario para tratamientos de atención secundaria: tratamiento en las salas de los hospitales generales. Estos países han tenido progresos en cuanto a integrar la salud mental a la atención primaria de la salud, y han puesto la medicación psicotrópica ampliamente a la disposición del nivel de atención primaria. A pesar del progreso en algunos países, se requiere un mayor esfuerzo en cuanto a reducir gradualmente los hospitales psiquiátricos y acelerar la integración de la atención a la salud mental con la atención primaria en otros países anglófonos.

Diabetes y su impacto en el territorio periodontal / Diabetes and its impact in periodontal tissues

Diabetes y enfermedad periodontal corresponden probablemente al mejor ejemplo de cómo una enfermedad sistémica puede tener un efecto en el territorio periodontal. Si bien esta asociación ha sido extensamente estudiada, muchas de las asociaciones propuestas presentan contradicciones. En la presente revisión de la literatura se analizan los siguientes tópicos relevantes para la práctica clínica en periodoncia e implantología: i) Identificación de enfermedad periodontal severa y su capacidad para diagnosticar casos de diabetes; ii) Efectos de la diabetes sobre la enfermedad periodontal; iii) Efectos de la diabetes sobre la reparación periodontal y periimplantaria; iv) Efecto del tratamiento periodontal sobre el control metabólico de la diabetes.

Diabetes and periodontal disease correspond to conditions that probably exemplify how a systemic disease may have a strong impact in the periodontium. Although this association has been studied for several years, many of these studies still show contradictory results. The present review analyses the following questions relevant for the clinician in the fields of periodontology: i) Value of the diagnosis of severe periodontitis and its capacity to identify previously un-diagnosed cases of diabetes; ii) Effects of diabetes on periodontal disease; iii) Effects of diabetes on periodontal and peri-implant tissue repair and regeneration and; iv) Effect of periodontal therapy on the metabolic control of diabetes.

Single exposure of human oral mucosa fibroblasts to ultraviolet B radiation reduces proliferation and induces COX-2 expression and activation

The lip vermillion constitutes a transition tissue, between oral mucosa and skin, where oral mucosal cells from epithelial and connective tissue compartments are exposed to ultraviolet (UV) sunlight. Fibroblasts are abundant resident cells of the connective tissue which are key regulators of extracellular matrix composition, as well as, epithelial and endothelial cell function. UVB light, an inherent component of sunlight, causes several alterations in skin fibroblasts, including premature senescence and increased cyclooxygenase (COX)-2 expression. To assess if UVB irradiation had similar effects on fibroblasts derived from human oral mucosa (HOM), primary cultures of HOM fibroblasts were irradiated with a single dose of 30 or 60 mJ/cm²of UVB light or sham-irradiated. Fibroblast proliferation was assessed from 3 to 48 hrs after UVB-irradiation utilizing [³H]-thymidine incorporation and MTT assays. In addition, COX-2 mRNA expression was detected by RT-PCR, and PGE2 production was assessed using enzyme immunoassay from 0.5 to 24 hrs after UVB-irradiation. The results showed a significant decrease in proliferation of UVB-irradiated HOM fibroblasts as compared to controls as measured by both [³H]-thymidine incorporation and MTT assays (p<0.001). HOM fibroblasts had increased COX-2 mRNA expression at 0.5 and 12 hrs after irradiation, and PGE2 production was elevated at 12 and 24 hrs post-irradiation as compared to controls (p<0.05). The results showed an inhibitory effect of a single dose of UVB irradiation on HOM fibroblast proliferation with an increase in COX-2 expression and activation. Therefore, photodamaged fibroblasts may play and important role in the pathogenesis of UV-induced lesions of the lip.

Food allergy in children.

Food allergies are increasing in prevalence and as a disease burden throughout the world, however they seem to increasingly affect countries with a formerly low prevalence. Consideration and diagnosis of food allergies are important as it has ramifications that affect a child's diet, care at school and home and is recognised to be associated with anxiety of parents, family and care takers. Food allergies vary significantly between countries, however nut allergies appear to be widely associated with serious reactions and death. The value of specific food immunoglobulin E (IgE) and skin prick tests (SPT) has been extensively analysed in children in recent years and can provide very useful information in an appropriately selected population. Diagnosis may require formal challenges to confirm a genuine allergic reaction condition rather than an intolerance reaction due to other mechanisms. The medical care of a food allergic child requires concurrent dietary advice and management, risk avoidance and emergency management plans. Reintroduction of foods occurs when the risk profile is appropriate based mainly on the predictive information obtained by SPTs and specific IgE levels. Fortunately allergies to egg and milk resolve by 3-5 years in about 80% of children. There have been some recent advances in immunotherapeutic approaches to food allergy although this has not translated to success in human treatment to date.

Humoral immune response anti K99 pilus from enterotoxigenic Escherichia coli in experimentally inoculated calves

The bovine model is extremely interesting to study several basic aspects of mucosal local immunity. Many reports have shown that, in young calves, the infectivity of enterotoxigenic Escherichia coli may be inhibited by passively administered antibodies anti K99 pilus. We have measured, by immunoradiometric assays, the IgG response anti K99 pilus in the serum of calves, deprived of colostrum and orally inoculated with enteropathogenic K99+ E. coli. Although variable levels of IgG anti K99 pilus were detected, their protective value could not be ascertained in vivo due to the acute development of the infection. In an effort to correlate the presence of serum antibodies anti K99 pilus with their protective capacity, an ex-vivo assay to monitor the interaction of radiolabeled K99 pilus with the bovine mucosa was standardized. Paradoxically, although K99 pilus, purified by standard procedures, was recognized by polyclonal rabbit and calf antisera, its interaction with the bovine intestinal mucosa, quantitated in the ex-vivo system, was not inhibited by these reagents, indicating that the antibodies did not effectively block those K99 pilus domains involved in the interaction with mucosal receptors

Discrimination between normal and malignant hepatocytes in man by the monoclonal antibody RL23/36: comparison with the Ca1 and 791T/36 monoclonal antibodies.

The monoclonal antibody RL23/36 has been shown to discriminate normal from malignant hepatocytes in man. In frozen sections of liver tissue from 25 Thai patients without hepatocellular carcinomas, the antibody reacted strongly and preferentially with hepatocytes. Reactivity with 7 hepatocellular carcinomas was invariably abnormal, being totally absent in 5 and partially lost in 2. This discrimination was superior to that achieved with Ca1 and 791T/36 monoclonal antibodies. In 2 cases of hepatocellular carcinoma, binding of RL23/36 to associated apparently non-malignant hepatocytes was abnormal, being absent in one and partially lost in the other. These data show that RL23/36 detects an antigenic determinant which is lost during malignant transformation of human hepatocytes, sometimes before the development of frank malignancy.

Lack of in vitro spontaneous activity following axotomy of hamster sensory neurones.

Although peripheral axotomy of dorsal root ganglion cells in mice, rats and cats has been reported to generate spontaneous activity in sensory nerves, we did not find evidence for such activity in the hamster. In vitro, intracellular recording from L6-S1 dorsal root ganglion cells up to 6 weeks after axotomy did not reveal any evidence for either increased membrane excitability or spontaneous activity. Also, in the sciatic nerve-sectioned hamsters, there was a total absence of the self-mutilatory behaviour which has been reported in other rodents. These results support the hypothesis that species specific factors are important for the development of ongoing activity in sensory nerves following injury.

Distrofia miotónica: estudio clínico genético de 21 casos en 18 familias / Myotonic distrophy: clinical and genetic study of 21 cases in 18 families

La distrofia miotónica es una enfermedad multisistémica que se manifesta entre la segunda y tercera década de la vida y se hereda en forma autosómica dominante con elevada penetrancia y expresividad variable pudiendo algunos individuos afectados pasar desapercibidos. El objeto de este trabajo es estudiar 21 pacientes con distrofia miotónica pertenecientes a 18 familias para conocer en esta muestra la edad de inicio, características clínicas, variabilidad en su expresión y problemas que se presentan para dar consejo genético. De los 21 pacientes 14 fueron de sexo masculino y 7 femenino. La edad promedio de inicio de la enfermedad fue de 23.4 años. El sítoma más común fue debilidad muscular. A la exploración física los hallazgos más frecuentes fueron miotonía, atrofia muscular, facies característica y calvicie frontal. El estudio oftalmológico reveló alteraciones en cristalino en el 95% de los pacientes. El estudio psicológico se realizó en 14 pacientes y mostró un C.I. normal en 71.4% y anormal en 28.6%. Una de las pacientes presentó las complicaciones obstétricas comunes de la enfermedad. Encontramos en esta muestra que la edad de inicio y manifestacicones clínicas en los pacientes y sus familiares son muy variables, siendo difícil en ocasiones determinar si una persona es o no heterocigoto. Según Bundey et al un individuo en riesgo asintomático que a los 30 años tiene una electromiografía y examen oftalmológico normal pero tiene familiares con inicio del padecimiento después de los 20 años todavía riesgo de 1 en 4 de haber heredado el padecimiento

Time trends in the analysis of incidence rate of leprosy among household contacts.

Analysis of time trends in the Incidence Rates among 9.598 household contacts of 1,614 primary cases of leprosy, showed that the incidence rates (IR) remained high even 10 years after treatment was started in the Primary Case. The IR during the 1st year of follow-up was 3.8 per 1000 person years of risk (PYR) and the IR was 3 per 1000 PYR after 10 or more years of follow-up. The significance of these findings in relationship to the Epidemiology of leprosy among household contacts in an endemic area for leprosy is discussed.

Incidence rates of leprosy among household contacts of "primary cases".

The data consisted of information from 1,564 "Primary cases" of leprosy of all classification and 9,162 of their household contacts. Household contacts of Indeterminate (Ind), Borderline (BL) and Lepromatous (LL), "Primary case" (PC) had an incidence rate (IR) of 5 per 1000 person years of risk (PYR). Household contacts of Tuberculoid (TT) and borderline tuberculoid (BT) patients had an IR of 3.2 and 3.8 per 1000 PYR respectively. Compared with an incidence rate of leprosy of 1.6 per 1000 PYR among individuals not exposed to leprosy in the same area, household contacts of Non-lepromatous patients had a relative risk of twice as high and contacts of lepromatous and borderline lepromatous patients a relative risk of 3 times as high. The incidence rate was higher among household contacts of bacteriologically positive patients, among contacts closely related and in households with multiple cases. The peak age specific incidence rate among household contacts was between the ages 5-9 years of age. The significance of these findings are discussed.