Health workers' use of electronic information concerning children with specific communication needs: research

Information regarding young children who experience barriers to the development of listening, language and learning is limited in the South African context. Health workers, in particular those involved in intervention with these children, such as medical practitioners, speech-language therapists and audiologists as well as occupational therapists, are in a position to disseminate information to parents and other interested persons, including educators and caregivers. These health workers also have access to and are active users of computers and the Internet. They may therefore benefit from receiving relevant and up-to-date electronic information. The study aimed to assess how these groups of health workers use computers and the Internet, as well as to determine their needs for specific electronic information. The results of this study were applied in developing a website containing relevant information. In die Suid-Afrikaanse konteks is daar beperkte inligting oor jong kinders vir wie daar struikelblokke is in die verwerwing van luister-, taal- en leervaardighede. Gesondheidswerkers wat spesifiek betrokke is by die intervensie van bogenoemde kinders, soos mediese praktisyns, spraak-taalterapeute en oudioloรซ asook arbeidsterapeute, bevind hulself in (tm)n posisie waar hulle inligting aan ouers asook ander belanghebbendes, byvoorbeeld onderwysers en versorgers, kan oordra. Hierdie gesondheidswerkers het ook toegang tot en is aktiewe gebruikers van rekenaars en die Internet. Hulle kan dus daarby baat om relevante en resente inligting elektronies te ontvang. Die doel van hierdie studie was om hierdie groepe gesondheidswerkers se rekenaar- en Internetgebruik te bepaal asook om hulle inligtingsbehoeftes vas te stel. Die inligting wat hieruit verkry is, is gebruik om 'n webwerf met relevante inligting te ontwikkel. Health SA Gesondheid Vol.9(2) 2004: 43-5

TNFR1 and TNFR2 regulate the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms

The huge majority of myeloma cell lines express TNFR2 while a substantial subset of them failed to show TNFR1 expression. Stimulation of TNFR1 in the TNFR1-expressing subset of MM cell lines had no or only a very mild effect on cellular viability. Surprisingly, however, TNF stimulation enhanced cell death induction by CD95L and attenuated the apoptotic effect of TRAIL. The contrasting regulation of TRAIL- and CD95L-induced cell death by TNF could be traced back to the concomitant NFκB-mediated upregulation of CD95 and the antiapoptotic FLIP protein. It appeared that CD95 induction, due to its strength, overcompensated a rather moderate upregulation of FLIP so that the net effect of TNF-induced NFκB activation in the context of CD95 signaling is pro-apoptotic. TRAIL-induced cell death, however, was antagonized in response to TNF because in this context only the induction of FLIP is relevant. Stimulation of TNFR2 in myeloma cells leads to TRAF2 depletion. In line with this, we observed cell death induction in TNFR1-TNFR2-costimulated JJN3 cells. Our studies revealed that the TNF-TNF receptor system adjusts the responsiveness of the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms that generate a highly context-dependent net effect on myeloma cell survival

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Surgical Experience Obtained by Urology Registrars – Changes in the Volume and Spectrum of Operative Procedures: 1975 – 2002

Objective: To analyze changes in the operative experience of Urology registrars at Tygerberg Hospital, an academic training hospital attached to the University of Stellenbosch, South Africa. Materials and Methods: Computerized analysis of 32,703 operating room cases (60,096 procedures) performed or assisted by 30 registrars in the period January 1975 to December 2002. Results: The average total number of procedures/registrar decreased by 32% (from 1752 to 1163) for those who started training in the period 1990-99 compared with 1975-90 (p=0.0005), largely due to a 35% reduction in bed numbers and theatre time resulting from budgetary restrictions. Comparison of the period 1994-2002 with 1976-84 showed a >4-fold increase in percutaneous nephrolithotomy, radical prostatectomy and inguinal herniotomy, with a moderate (&ge;50%) increase in bladder rupture repair (54%), circumcision (89%), orchidopexy (105%), insertion of peritoneal dialysis catheter (274%), laparotomy (54%) and surgical debridement (215%). There was a &ge;50% decrease in nephrectomy (57%), renal exploration for trauma (75%), open kidney stone surgery (87%), pyeloplasty (44%), reimplantation of the ureter (60%), ureterolithotomy (66%), suprapubic cysto-tomy (71%), transurethral resection of the prostate (54%), open prostatectomy (90%), urethral dilatation (78%), internal urethrotomy (54%), urethroplasty (72%), varicocelectomy (62%), and creation of arteriovenous fistula for dialysis (58%). Conclusions: There have been substantial changes in the spectrum of surgical procedures performed or assisted by Urology registrars in the period 1975 to 2002. The significant decrease in the total number of procedures per registrar in the past decade is a reason for concern, although it remains unknown what the minimum number of any given urological procedure should be in order to ensure adequate operative training. Key words: surgical training, urology, registrars, residents, operative procedures Expérience chirurgicale obtenue par les résidents d\'urologie – Changements dans le volume et le spectre des procédures en vigueur: 1975 – 2002 Objectif: Analyser les changements dans l\'expérience en vigueur des résidents d\'Urologie à l\'Hôpital Tygerberg, un hôpital de formation universitaire attaché à l\'Université de Stellenbosch, Afrique du Sud. Matériels et Méthodes: On a informatisé l\'analyse de 32.703 cas en salle d\'opération (60.096 procédures) réalisés ou assistées par 30 résidents dans la période : janvier 1975 à décembre 2002. Résultats: Le nombre total moyen de procédures/ résidents a diminué par 32% (de 1752 à 1163) pour ceux qui ont commencé à être formés dans la période 1990-99 comparés à ceux de 1975-90 (p=0.0005), en grande partie dû à une réduction de 35% dans le nombre des lits et la durée d\'hospitalisation qui résultent des restrictions budgétaires. La comparaison de la période 1994-2002 avec 1976-84 a montré une augmentation >4-fois des néphrolithotomies percutanées, prostatectomies radicales et herniotomie inguinale, avec une augmentation modéré (&ge;50%) des réparations de la rupture de la vessie (54%), circoncision (89%), orchidopexie (105%), insertion de sonde de dialyse péritonéale (274%), laparotomie (54%) et débridement chirurgical (215%). Il y avait une baisse de &ge;50% des néphrectomies (57%), exploration rénale pour trauma (75%), rein ouvert chirurgie lithiasique (87%), pyeloplastie (44%), réimplantation de l\'uretère (60%), urétérolithotomie (66%), cystostomie sus-pubienne (71%), résection transuréthrale de la prostate (54%), prostatectomie à ciel ouvert (90%), dilatation de l\'urèthre (78%), urétrotomie interne (54%), urétroplastie (72%), varicocelectomie (62%), et création de fistule artério-veineuse pour dialyse (58%). Conclusions: Il y a eu des changements substantiels dans le spectre des procédures chirurgicales exécutées ou aidées par les résidents d\'Urologie dans la période 1975 à 2002. La baisse considérable dans le nombre total de procédures par résidents dans la décennie passée est une raison d\'inquiétude, bien qu\'il reste inconnu ce que le nombre minimum de toute procédure urologique donnée devrait être pour assurer la formation adéquate en vigueur. African Journal of Urology Vol.11(2) 2005: 82-8