Long-term follow-up of liver-directed, adeno-associated vector-mediated gene therapy in the canine model of hemophilia A.

Questions remain concerning the long-term efficacy, safety, and site(s) of transgene expression following adeno-associated vector (AAV) therapy. We report a long-term follow-up of 8 (male = 4, hemizygous, and female = 4, homozygous) dogs with severe hemophilia A treated with a single portal vein infusion of a B-domain-deleted (BDD)-canine FVIII (cFVIII) AAV vector (median dose = 1.25 × 1013 vg/kg, AAV2 = 4, AAV6 = 3, and AAV8 = 1). After a median follow-up of 10.8 years (8.2-12.0 years), persistent FVIII:C (median one-stage = 12.7%, chromogenic = 7.2%) was seen in all responding dogs (n = 6), with improvement in annualized bleed rates (pre = 3.9 vs post = 0.3 event per year; P = .003). Anti-AAV capsid neutralizing antibodies (nAbs) toward the dosed capsid were detected throughout the study, with limited cross-reactivity to other capsids. nAb titers for all capsid serotypes declined with time, although they remained at levels precluding redosing with the same capsid. AAV-BDD-cFVIII DNA was detected in the liver of all dogs (median = 0.15 vg per diploid genome), with lower levels in the spleen in 4 dogs (median = 0.005 vg per diploid genome). Consistent with the liver-specific promoter, BDD-cFVIII mRNA was only detected in the liver. Postmortem examination demonstrated no evidence of chronic liver disease or liver malignancy. Persistent FVIII expression and an improved bleeding phenotype was seen for more than a decade after vector delivery. This is the longest follow-up reported in a preclinical model supporting long-term efficacy and safety of AAV-mediated gene therapy.

Ear and hearing health in Aboriginal and Torres Strait Islander people aged 15 years and older: A scoping review.

OBJECTIVE: Review empirical research investigating the prevalence, experiences and management of hearing loss and ear disease in Aboriginal and Torres Strait Islander adults. DESIGN: Scoping review. STUDY SAMPLES: Searches of four electronic databases, Advanced Google, and key webpages identified 16,373 studies - 21 met inclusion criteria: original research relating to hearing/ear health and Aboriginal and Torres Strait Islander adults. RESULTS: Fourteen studies measured prevalence of hearing loss or middle-ear dysfunction, with a rate of hearing loss at an estimated 50% (reports ranging from 8% to 100%). Five studies reported views, attitudes, and experiences of hearing loss, with results showing hearing loss negatively impacted individual experiences in health and justice systems, and health professionals had limited understanding of the socioeconomic risk factors of middle ear disease. No articles directly reported on hearing loss management. CONCLUSIONS: There is a lack of research into the hearing health of Aboriginal and Torres Strait Islander adults, despite its critical importance in addressing health and social inequities. Given the widely varying and imprecise estimated rates of hearing loss detected, urgent action is needed to obtain accurate prevalence estimates and, in partnership with Aboriginal and Torres Strait Islander communities, identify the best methods of screening and managing hearing loss.

Campylobacteriosis outbreak associated with consumption of undercooked chicken liver pâté in the East of England, September 2011: identification of a dose-response risk.

A foodborne outbreak with 49 cases (22 culture positive for Campylobacter sp.) following a wedding party in the East of England was investigated. A retrospective cohort study identified an association between consumption of chicken liver pâté and infection with Campylobacter jejuni/coli. There was a statistically significant association between dose (amount of chicken liver pâté eaten) and the risk of disease ['tasted': odds ratio (OR) 1·5, 95% confidence interval (CI) 0·04-∞; 'partly eaten': OR 8·4, 95% CI 1·4-87·5; 'most or all eaten': OR 36·1, 95% CI 3·3-2119). The local authority found evidence that the preparation of chicken livers breached Food Standards Agency's guidelines. This epidemiological investigation established a clear dose-response relationship between consumption of chicken liver pâté and the risk of infection with Campylobacter. The continuing need to raise public awareness of the risk to human health posed by undercooked chicken liver is evident.

[Obsessive compulsive disorder during pregnancy and the postpartum period]. / Obsessieve-compulsieve stoornis tijdens de zwangerschap en post-partumperiode.

Research into psychiatric illnesses during pregnancy and the postpartum period has focused primarily on mood disorders and psychosis. However, recent reports suggest that during pregnancy and the postpartum period psychiatric patients run an increased risk of developing the symptoms of obsessive compulsive disorder (OCD) or if they already have these symptoms, the severity is likely to increase. We report two cases of OCD in pregnancy and in the postpartum period. In addition, we present a brief review of the literature that is currently available on this topic.

Canadian Lung Cancer Conference 2019.

The 19th Canadian Lung Cancer Conference took place 7-8 February 2019 in Vancouver, British Columbia. This annual interdisciplinary education event attracted participants from throughout Canada to review the latest advances in lung cancer care and to learn from world-renowned experts in the field. The highlights of this year's conference were perspectives about biomarkers for immunotherapy, approaches to oligoprogressive disease, and caregiver burnout.

[Rocky Mountain spotted fever in an American tourist]. / 'Rocky mountain spotted fever' bij een Amerikaanse toerist.

In a 28-year-old male American tourist who presented in the hospital with fever, cold shivers, headache, nausea, myalgia and arthralgia, Rocky Mountain spotted fever was suspected, partly because he came from an endemic region (the state of Georgia). The patient was treated with doxycycline, 100 mg b.i.d.; 9 days after the first appearance of the symptoms, the diagnosis was confirmed by the report of a positive antibody titre against Rickettsia rickettsii. The patient did not have exanthema. He was discharged in good general condition after two weeks of treatment. Rocky Mountain spotted fever, caused by the Gram-negative bacterium R. rickettsii, is a serious rickettsiosis. The disease is seen only sporadically in the Netherlands because the ticks in the Netherlands do not carry the bacterium. The travel history is still not a standard component of the anamnesis and is therefore often forgotten. This can lead to under-diagnosis and delayed treatment of diseases that were formerly limited to the continent. The early recognition and treatment of Rocky Mountain spotted fever is important since delayed treatment is associated with a clear increase in both morbidity and mortality.

Evaluation of oncogene amplification in intact and truncated cell nuclei of gastro-esophageal cancer cell lines by DNA in situ hybridisation.

Adenocarcinoma arising around the gastro-esophageal junction (GEJ) is a highly malignant form of cancer. Its incidence is rising sharply. The study of oncogenes in these carcinomas may give information concerning treatment and prognosis. In the present study, the fluorescence in situ hybridisation (FISH) technique was optimised for genetic characterisation of oncogenes in archival cancer specimens. Three cell lines derived from GEJ adenocarcinomas were investigated, i.e. JROECL 19, JROECL 33 and OACM5.1C, both in fresh and paraffin-embedded preparations. Furthermore, paraffin-embedded material of three xenografts was studied, i.e. JROECL 19, JROECL 33, and OACM4.1X. We focussed on the oncogenes MYC and HER2/neu, since they are frequently involved in intestinal cancers. Firstly, our results indicate that it is feasible to detect oncogene-specific probes with the FISH technique in formalin-fixed, paraffin-embedded material. Secondly, it appeared that the optimal section thickness for analysis was 2 microm. This thickness resulted in minimal nuclear overlap, which facilitates counting of FISH spots. Due to the truncation phenomenon, however, the sensitivity of the technique is less than FISH on intact nuclei. Importantly, (high level) oncogene amplifications were easily recognised in 2 microm thick sections. Finally, counting of the individual copy number of the MYC and HER2/neu oncogenes was feasible enabling an arbitrary assessment of low- and high-level amplification. In conclusion, FISH is an accurate technique for detecting amplification of oncogenes in paraffin-embedded patient material.

Attitudes, subjective norms, and intentions to engage in health behaviors.

The theory of reasoned action was used as the conceptual framework for analyzing the relationships among attitudes, subjective norms, and intentions to exercise regularly, maintain/attain recommended weight, and avoid highly stressful life situations. The sample (N = 377) consisted of adults between the ages of 18 and 66 living in two midwestern communities. Data were collected using a structured questionnaire designed according to guidelines developed by Ajzen and Fishbein (1980). The theory was supported in part by study results. Attitudes were useful in explaining intentions to engage in all three health behaviors studied. Subjective norms contributed only to the explanation of intentions to engage in regular exercise. Three factors, attitudes, subjective norms, and weight, affected intentions to engage in regular exercise, R = .364, p less than .01. Attitudes, weight, and perceived health status were the principle determinants of intention to eat a diet consistent with weight control, R = .428, p less than .001. Of the variables studied, only attitude was associated with intention to manage stress, R = .271, p less than .01.

Illness prevention and health promotion services provided by nurse practitioners: predicting potential consumers.

A cross-sectional survey of 388 residents of a northern Illinois county explored the relationships between psychosocial and behavioral characteristics of the population and intentions to use illness prevention and health promotion services provided by nurse practitioners. Results of the study indicated that 61 per cent of the respondents intended to use one or more of the nurse-provided services when they became available within the community. The best predictors of intention to use the services were: expressed interest in use of prevention and health promotion services for direct pay, education beyond high school, and a low level of life stress. Intentions to use the services did not differ significantly between individuals with a regular personal physician and those without a regular physician. These data were interpreted as indicating a need within the community for nurse practitioners to provide prevention and health promotion care. The findings also supported the complementary roles of nurses and physicians in providing health care to ambulatory populations.