Addressing Men and Gender Diversity in Education: A Promising Solution to the HIV/AIDS Epidemic

To date, researchers investigating gender in relation to social issues underscore women and appear to sideline men. Focusing on women in studies concerning sociogender issues may exclude not only men from mainstream research, but also those who do not fit into the binary gender system, including gay, lesbian, bisexual, and transgender (GLBT) people. One area closely related to gender issues is the HIV epidemic. Mainstream discussions of men and other versions of masculinity and femininity including GLBT people in the gender-related studies of the HIV epidemic can decrease the vulnerability of individuals against HIV infections regardless of their biological sex.     

Familial aggregation of malignant mesothelioma in former workers and residents of Wittenoom,Western Australia

Clustering of cases of malignant mesothelioma within families has often been observed, but disentangling genetic and exposure effects has not been done. Former workers and residents exposed to crocidolite at Wittenoom, Western Australia, where many families shared exposure to asbestos, have had high rates of mesothelioma. Our study aimed to estimate the additional risk of mesothelioma in relatives, after allowance for common exposure to crocidolite. More than 11,000 former asbestos workers and residents from Wittenoom have been followed up in cancer and death registries. Levels of exposure for all members of the Wittenoom cohorts have been estimated previously. Relationships between family members of all mesothelioma cases were established from questionnaires, birth and death certificates. Expected numbers of cases of mesothelioma were estimated by fitting a Weibull survival model to all data, based on time from first asbestos exposure, duration and intensity of exposure and age. For each family group, the earliest case was considered the index case. Predicted risk was estimated for each subject from the time of diagnosis of the index case. Familial risk ratios were estimated by dividing observed cases by the sum of risks of all same degree relatives of index cases. There were 369 family groups with at least one case of mesothelioma and a further 25 cases of mesothelioma among relatives in the same families, with 12.9 expected. The risk ratio for blood relatives was 1.9 (95% confidence interval [CI] = 1.3–2.9, p = 0.002). These findings suggest an important, but not large, genetic component in mesothelioma, similar to many other cancers.     

ANTIBODIES TO SACCHAROMYCES CEREVISIAE and ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES IN INFLAMMATORY BOWEL DISEASE: ASSESSMENT and RELEVANCE IN AN AUSTRALIAN POPULATION USING TWO DIFFERENT ASCA ASSAY KITS

A number of North American and European studies have elucidated a relationship between antibodies to the yeast Saccharomyces cerevisiae (ASCA) and Crohn's disease (CD).
Aims  (1) To ascertain whether this relationship is relevant to Australian patients; (2) To compare the results with two different commercial ASCA kits; (3) To examine the usefulness of this test in combination with perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) for distinguishing Crohn's disease from ulcerative colitis (UC).
Methods  Serum samples were obtained from 28 patients with CD, 27 patients with UC and 22 non-IBD patients presenting for investigation of other gastroenterological illnesses. ASCA IgG and IgA were determined by enzyme immunoassay using the two test kits. pANCA was detected by indirect immunofluorescence.
Results  Using the Medizym test kit, the presence of either IgG or IgA ASCA was 50% sensitive and 93% specific for CD. The QUANTA Lite kit yielded a higher sensitivity of 79% but specificity of 74%. The sensitivity of pANCA for UC was 48% but was 100% specific. Used in combination, ASCA+ve/pANCA–ve was only 50% sensitive but 100% specific for CD using the Medizym kit compared with 79% sensitivity and 93% specificity using QUANTA Lite. The combination of ASCA–ve/pANCA+ve was 41% sensitive and 100% specific for ulcerative colitis using the Medizym kit compared with 30% sensitive and 100% specific using QUANTA Lite.
Conclusions  At least 50% of Australian patients with CD have ASCA detectable in serum, confirming the results of overseas studies. Sensitivity was greater with the QUANTA Lite kit whereas the Medizym kit was slightly more specific. ASCA may aid in the diagnosis of CD. When used in combination with pANCA it may also help distinguish CD from UC in difficult cases.     

Naratriptan: biological profile in animal models relevant to migraine

The biological profile of naratriptan (N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethane-sulphona-mide), a novel 5HT_1B/1D receptor agonist, was investigated in a variety of experimental models of relevance to migraine. Naratriptan has high affinity for human recombinant 5HT_1B and 5HT_1D receptors (pKi = 8.70.03 and 8.30.1, respectively) and causes contractions of dog isolated basilar and middle cerebral artery (EC₅₀ values of 0.11 and 0.07 M, respectively). Naratriptan causes small contractions of human isolated coronary arteries (EC₅₀ value of 0.17 M; maximum contraction equivalent to 33% of 5HT maximum). In anaesthetized dogs, naratriptan causes selective vasoconstriction of the carotid arterial bed (CD₅₀ dose = 193 g kg⁻¹) and, in anaesthetized rats, naratriptan selectively inhibits neurogenic plasma protein extravasation in the dura (ID₅₀ = 4.1 g kg⁻¹). In a variety of antinociceptive tests, naratriptan has no effect even at high doses. In conscious rats and dogs, naratriptan has high oral bioavailability (71% and 95%, respectively). The data show that naratriptan is a selective agonist at 5HT_1B/1D receptors, with a pharmacological profile very similar to that of sumatriptan, albeit 2-3 fold more potent. These observations, coupled with high oral bioavailability in animals, suggest that naratriptan has the profile of an orally effective anti-migraine drug.     

Intradermal Vaccinations With RNA Coding for TAA Generate CD8+ and CD4+ Immune Responses and Induce Clinical Benefit in Vaccinated Patients

The aim of this phase I/II nonrandomized trial was to assess feasibility, safety as well as immunological and clinical responses of a mRNA-based vaccination in patients with stage IV renal cell cancer using granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvant. Intradermal injections of in vitro transcribed naked mRNA, which was generated using plasmids coding for the tumor-associated antigens mucin 1(MUC1), carcinoembryonic (CEA), human epidermal growth factor receptor 2 (Her-2/neu), telomerase, survivin, and melanoma-associated antigen 1 (MAGE-A1) were performed in 30 enrolled patients. In the first 14 patients (cohort A) vaccinations were administered on days 0, 14, 28, and 42 (20 µg/antigen) while in the consecutive 16 patients (cohort B) an intensified protocol consisting of injections at days 0–3, 7–10, 28, and 42 (50 µg/antigen) was used. In both cohorts, after this induction period, vaccinations were repeated monthly until tumor progression analyzed by Response Evaluation Criteria In Solid Tumors criteria (RECIST). Vaccinations were well tolerated with no severe side effects and induced clinical responses [six stable diseases (SD) and one partial response in cohort A and nine SD in cohort B]. In cohort A, 35.7% survived 4 years (median survival 24 months) compared to 31.25% in cohort B (median survival 29 months). Induction of CD4⁺ and CD8⁺ T cell responses was shown for several tumor-associated antigens (TAA) using interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and Cr-release assays.     

High-resolution array CGH clarifies events occurring on 8p in carcinogenesis

Background  

Rearrangement of the short arm of chromosome 8 (8p) is very common in epithelial cancers such as breast cancer. Usually there is an unbalanced translocation breakpoint in 8p12 (29.7 Mb – 38.5 Mb) with loss of distal 8p, sometimes with proximal amplification of 8p11-12. Rearrangements in 8p11-12 have been investigated using high-resolution array CGH, but the first 30 Mb of 8p are less well characterised, although this region contains several proposed tumour suppressor genes.     

Metformin therapy in COVID-19: inhibition of NETosis

Journal of Thrombosis and Thrombolysis -     

Real-world effectiveness of BNT162b2 mRNA vaccine: a meta-analysis of large observational studies

Inflammopharmacology - This paper aims to summarize through meta-analyses the overall vaccine effectiveness of the BNT162b2 mRNA vaccine from observational studies. A systematic literature search...     

The risk of mortality in patients with COVID-19 with pre-diagnosis use of NSAIDs: a meta-analysis

Inflammopharmacology - The notion that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes upon acquisition of coronavirus disease 2019 (COVID-19) should be...