Family-centred services for young children with intellectual disabilities and their families: Theory, policy and practice.

This paper outlines the reported discrepancies between the aims of the welfare services in Iceland and the experiences of parents raising young children with intellectual disabilities. Prevailing views on disability and service delivery were also considered. A multi case study design was employed to reflect the situation in different parts of the country. Families of eight children with intellectual disabilities and professionals in three different municipalities formed the cases. The findings reveal a high convergence between the three cases with variations based on individual experiences rather than geographical location. Overall, parents praised the preschools but experienced support services often as fragmented and uncompromising. Particular components of the services were consistently regarded as hard to reach and not in accordance with the needs of the family. Cultural-historical activity theory is introduced as a beneficial framework for further study and system improvement.

Otubain 2 is a novel promoter of beta cell survival as revealed by siRNA high-throughput screens of human pancreatic islets.

AIMS/HYPOTHESIS: Pro-inflammatory cytokines induce death of beta cells and hamper engraftment of transplanted islet mass. Our aim was to reveal novel genes involved in this process, as a platform for innovative therapeutic approaches. METHODS: Small interfering RNA (siRNA) high-throughput screening (HTS) of primary human islets was employed to identify novel genes involved in cytokine-induced beta cell apoptosis. Dispersed human islets from nine human donors, treated with a combination of TNF-α, IL-1ß and IFN-γ were transfected with ∼730 different siRNAs. Caspase-3/7 activity was measured, results were analysed and potential anti- and pro-apoptotic genes were identified. RESULTS: Dispersed human pancreatic islets appeared to be suitable targets for performance of siRNA HTS. Using this methodology we found a number of potential pro- and anti-apoptotic target hits that have not been previously associated with pancreatic beta cell death. One such hit was the de-ubiquitinating enzyme otubain 2 (OTUB2). OTUB2 knockdown increased caspase-3/7 activity in MIN6 cells and primary human islets and inhibited insulin secretion and increased nuclear factor-κB (NF-κB) activity both under basal conditions and following cytokine treatment. CONCLUSIONS: Use of dispersed human islets provides a new platform for functional HTS in a highly physiological system. Employing this technique enabled the identification of OTUB2 as a novel promoter of viability and insulin secretion in human beta cells. OTUB2 acts through the inhibition of NF-κB signalling, which is deleterious to beta cell survival. siRNA screens of human islets may therefore identify new targets, such as OTUB2, for therapeutic intervention in type 1 diabetes and islet transplantation.

Glucose starvation induces a drastic reduction in the rates of both transcription and degradation of mRNA in yeast.

Gradual depletion of essential nutrients in yeast cultures induces a complex physiological response, leading initially to induction of pathways required for the utilization of alternative nutrients and, when such sources are depleted, to entry into stationary phase. Abrupt removal of sugar does not allow the proper establishment of stationary phase. Here we report that abrupt removal of glucose from the growth medium elicits a coordinated response in yeast cells that resembles, in some aspects, the gradual passage to stationary phase. Phosphorylation of RNA polymerase II at a subset of sites in the COOH-terminal domain (CTD) is decreased. Transcription by RNA polymerases I and II is shut down almost completely, whereas transcription by RNA polymerase III continues. In parallel, the rate of mRNA degradation is drastically reduced, at a stage preceding poly(A) shortening. This response is suited for conservation of scarce resources while preserving the ability of cells to recover when nutrients become available.

Involvement of yeast carboxy-terminal domain kinase I (CTDK-I) in transcription elongation in vivo.

Yeast cells lacking transcription elongation factor genes such as PPR2 (TFIIS) and ELP (Elongator) are viable and show deleterious phenotypes only when transcription is rendered less effective by RNA polymerase mutations or by decreasing nucleotide pools. Here we demonstrate that deletion of the CTK1 gene, encoding the kinase subunit of RNA polymerase II carboxy-terminal domain kinase I (CTDK-I), is synthetically lethal when combined with deletion of PPR2 or ELP genes. The inviability of ctk1 elp3 double mutants can be rescued by expression of an Elp3 mutant that has retained its ability to form the Elongator complex but has severely diminished histone acetyltransferase activity, suggesting that the functional overlap between CTDK-I and Elongator is in assembly of RNA polymerase II elongation complexes. Our results suggest that CTDK-I plays an important role in transcriptional elongation in vivo, possibly by creating a form of RNA polymerase that is less prone to transcriptional arrest.

Genetic variation for resistance to chlorpyrifos in Drosophila melanogaster (Diptera: Drosophilidae) infesting grapes in Israel.

Five species of drosophilid flies were observed breeding in grapes growing in Israel; of these, 2 species, Drosophila melanogaster (Meigen) and D. simulans Sturtevant, are major pests. Natural populations of both species were sampled and tested for resistance to chlorpyrifos; the 2 more intensively sampled populations were D. melanogaster in commercial vineyards. One vineyard had been treated repeatedly with chlorpyrifos to control this secondary pest species; the other had never been treated with an organophosphorus compound. The LC50 to chlorpyrifos of a genetically heterogeneous line of D. melanogaster from the exposed population (Be'er Tuvia) was 99 ng/cm2, and the LC50 of a corresponding line from the unexposed population (Sde Eliahu) was 52 ng/cm2; the wild-caught lines were much more resistant than a laboratory strain, Canton-S, whose LC50 was 0.25 ng/cm2. Genetic variance for resistance existed in both natural populations but realized heritability did not differ significantly between the populations. In crosses between a highly resistant strain and several sensitive laboratory strains of D. melanogaster, resistance was dominant. A resistance factor was mapped to a locus on chromosome 2 (approximately 2-72).

Body satisfaction and sexual health in Dutch female university students.

Studies in the field of body image have primarily addressed its negative aspects, such as body dissatisfaction. The present study focused instead on women who are satisfied with their bodies and on how body satisfaction relates to sexual health. A sample of 319 Dutch female university students completed an online survey that included items about body image evaluation, body image investment, overweight preoccupation, body image affect during sexual activity, sexual frequency, sexual functioning, and sexual self-esteem. We found that the level of body dissatisfaction was minimal in our sample. The majority reported neutral or mildly positive body evaluations, and in 30% of the sample these evaluations were clearly positive. Comparisons between women who reported positive versus neutral body evaluations showed that the body-satisfied women had lower body mass indexes (BMIs) and reported less body image investment, less overweight preoccupation, and less body self-consciousness during sexual activity. With regard to sexual health, they reported higher sexual self-esteem and better sexual functioning. Furthermore, we found that body image self-consciousness was negatively associated with sexual functioning, sexual self-esteem, and frequency of sexual activity with a partner. Body satisfaction did not account for a portion of the relationship of body self-consciousness during sexual activity with sexual health.

Herbal Medicine: Regulation and Marketing

@#Given the expansion of herbal medicine, the overall quality, safety and efficacy must be subjected to critical examination if the intention is to safeguard public health. There are quality concerns on the products already in the market. Adulteration of contents, ingredients differing from label and unsupported or misleading claims are reported in several studies. This article proposes three areas that can be standardized to ensure quality, safety and efficacy of herbal medicines. The first is ensuring good agriculture and harvesting practices for the plant raw materials. Second is good manufacturing practice of producing medicinal preparation (liquid or solid form) from the raw materials. Third, develop a standardized and acceptable clinical trial design to demonstrate safety and efficacy. The regulatory agencies of some developed countries have published guidelines to ensure the quality of herbal medicines. Example of these guidelines are the botanical drug product guidance of the US FDA, the evidence for quality of finished natural health products guidance of the Health Canada and the guideline on quality of herbal medicinal products by the EMA. They specify different registration pathways. Registration pathways in Europe are traditional herbal registration (THR) or conventional marketing authorization (CMA). In the USA, it can be registered as dietary supplement (DS) or botanical drug (BD). In the Philippines herbal medicines taken orally can be registered as herbal medicine (HM), traditional use herbal product (TUHP) and dietary supplement (DS). Requirements for registration in the three regions compared include quality control and good manufacturing practices, evidence of safety and toxicologic studies and evidence of efficacy or clinical trials, but it all depends on the product to be registered or the chosen pathway for registration. After approval for marketing, there must be a methodological approach for post-marketing safety based on sales data and information on adverse drug reactions of newly introduced herbal medicinal products in the market.

Herbal supplements for diabetes: A qualitative review of current evidence on local indigenous plants

Background@#Herbal supplementation has been used by diabetic patients, unfortunately it has regulatory, safety, and efficacy concerns.@*Objective@#This review was conducted to determine the best evidence in terms of the identified active substance, mechanism of action, pre-clinical and clinical studies of commonly used local herbal preparations.@*Methods@#This is a qualitative review of both local and international published medical literature to identify and summarize information on the use of herbal supplementation in diabetes. @*Results@#After the initial review, the authors identified thirteen herbal preparations that have been investigated for its anti-diabetic properties. Six have extensive studies including randomized controlled trials but cinnamon and fenugreek seed are not readily available locally. Their detailed review eventually focused on four locally available herbal preparations i.e. bitter melon, turmeric, aloe vera and banaba. They decrease glucose absorption and gluconeogenesis, improve glucose utilization and insulin production. Unlike conventional anti-diabetics, herbal preparations also have favorable effect on lipid metabolism and anti-oxidant effect. Bitter melon seems to be the best herbal preparation. But human studies of bitter melon showed it is inferior to conventional anti-diabetic drugs in terms of its anti-diabetic effect but better in terms of its effect on lipid metabolism and anti-oxidant properties. Turmeric, aloe vera and banaba have also been shown to have anti-diabetic effects. @*Conclusion@#In summary, herbal preparation may have multiple beneficial effect for patients with diabetes. Use of combined preparations can produce complementation of the effects and may be a promising approach to the use of herbal supplementation as treatment standard among patients with diabetes.

Topical herbal preparation with anti-inflammatory and analgesic effects: Qualitative review of evidence

Background@#In the past musculoskeletal complaints were treated with topical preparations from medicinal plants until the advent of NSAIDs. However, because of the side effects of NSAIDs, interest has increased on going back to the use of topical traditional herbal medicines in patients with musculoskeletal pain.@*Objective@#This review was conducted to identify the active substance, its mechanism of action, pre-clinical and clinical studies and propose a topical herbal formulation balancing its analgesic and anti-inflammatory effect with skin care effect among patients with various somatic pain conditions.@*Methods@#This is a qualitative review of both local and international published medical literature to identify and summarize information on the use of topical herbal preparation for the treatment of musculo-skeletal pain.@*Results@#After the initial review, the authors identified six herbal preparations that have been investigated for its analgesic and anti-inflammatory properties in clinical trials. They eventually arrived at a consensus to consider the final combination of ginger, capsaicin, peppermint and virgin coconut oil. Gingerol, a naturally occurring plant phenol, is one of the major components of ginger known to have diverse pharmacologic effects including anti-oxidant, anti-apoptotic, and anti-inflammatory activities in vitro and in vivo. Capsaicin is a highly selective agonist for the transient receptor potential vanilloid 1 receptor expressed in nociceptive sensory nerves. The mechanisms underlying capsaicin-induced analgesia likely involve reversible ablation of nociceptor terminals. Local application of peppermint oil generates a long-lasting cooling effect on the skin and result to muscle relaxation. Ginger, capsicum and peppermint have been shown in clinical trials to relieve musculoskeletal pain and inflammation. Virgin coconut oil on the other hand has no analgesic effect but has been shown in some studies to be favorable for skin conditions and facilitate skin penetration of some substances. @*Conclusion@#Using combined preparation may have the advantage of complementation of its effect i.e. analgesic and anti-inflammatory effect of ginger, warm sensation of capsicum and the cold sensation of peppermint.

[Measurement of anxiety in a population of prisoners]. / Misurazione dell'ansia in una popolazione di detenuti.

The Cattle's IPAT anxiety scale test has been used in a population of prisoners during a three years period. The specific features of these subjects suggest great caution in the interpretation of this tests, that was originally validated on different populations. For psychodiagnostic and therapeutic purposes each score should be specifically checked. Other observations are made and some suggestions are also given.

Late effect of tobanum and tobanum + furosemide therapy on the glucose tolerance of patients and on the insulin response to oral glucose doses.

The authors examined the effect of beta-blocker monotherapy (Tobanum tab = 5 mg cloranololum hydrochloricum) and beta-blocker + diuretic (Tobanum + Furosemide) combination therapy on glucose tolerance and insulin secretion in response to oral glucose doses in hypertensive non-diabetic patients. Twenty-six patients were examined (13 men, 13 women). The patients were followed up for 28 weeks after a 2-week drug-free period. The hypotensive dose was adjusted individually within 4 weeks. Oral glucose tolerance test and immuno-reactive insulin determination were performed concurrently before starting hypotensive therapy and on weeks 6, 14, and 28 of therapy. The results of the examinations were evaluated separately in two patient groups. Fifteen patients were given daily 10-20 mg Tobanum (Group I) while 11 patients received daily 10-20 mg Tobanum + 40-80 mg Furosemide (Group II). The glucose area of patients on Tobanum monotherapy did not change, insulin secretion decreased gradually (from 804 to 495 pmol/l). The decrease was significant (p less than 0.05). The glucose area of Tobanum + Furosemide-treated patients increased from 13.2 +/- 3.2 mmol/l to 16.1 + 4.9, the insulin secretion decreased from 1039 + 339 to 706 + 411 pmol/l during therapy (p less than 0.02 and p less than 0.05, resp.). When evaluating the results the decrease of insulin secretion is attributed to Tobanum effect while the deterioration of glucose tolerance may be correlated to the action of Furosemide on extrapancreatic metabolism.

Serum lipids during starvation in obesity.

The HDL-cholesterol level was found to decrease during the first week of therapeutic starvation in hyperlipoproteinaemic (hypertriglyceridaemic), diabetic (non-insulin dependent) patients. The possible causes of the finding are discussed, and the view is expressed that the fall in HDL given no cause for discontinuing the caloric restriction or starvation as the therapeutic measures in obesity.

Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding.

DRP-1 is a pro-apoptotic Ca2+/calmodulin (CaM)-regulated serine/threonine kinase, recently isolated as a novel member of the DAP-kinase family of proteins. It contains a short extra-catalytic tail required for homodimerization. Here we identify a novel regulatory mechanism that controls its pro-apoptotic functions. It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain. A negative charge at this site reduces both the binding to CaM and the formation of DRP-1 homodimers. Conversely, the dephosphorylation of Ser308, which takes place in response to activated Fas or tumour necrosis factor-alpha death receptors, increases the formation of DRP-1 dimers, facilitates the binding to CaM and activates the pro-apoptotic effects of the protein. Thus, the process of enzyme activation is controlled by two unlocking steps that must work in concert, i.e. dephosphorylation, which probably weakens the electrostatic interactions between the CaM regulatory domain and the catalytic cleft, and homodimerization. This mechanism of negative autophosphorylation provides a safety barrier that restrains the killing effects of DRP-1, and a target for efficient activation of the kinase by various apoptotic stimuli.