Effect of dietary protein on Masheri-induced drug metabolising enzymes

The modulation of drug metabolising enzymes by Masheri extract (ME) and Benzo(a)Pyrene [B(a)P] was studied in male Sprague Dawley rats fed different dietary protein levels. Two groups of 21 days old male Sprague Dawley rats were put on a high protein diet (SHP) with 20% Casein, and a low protein diet (SLP) with 3% Casein semisynthetic based diets for 12 weeks. The SLP fed animals showed lower basal levels of the Phase I activating enzymes viz. Cytochrome P450, Benzo(a)Pyrene hydroxylase, Benzphetamine demethylase and Phase II glutathione detoxification system viz. Glutathione (GSH) and Glutathione-S-transferase. ME and B(a)P treatment significantly depleted the glutathione detoxification system in the SLP group whereas an opposite effect was observed in the SHP group. Interstingly, ME and B(a)P treated rats in the SLP group showed a higher percent increase in the hepatic and pulmonary Phase I enzyme activities than those observed in the treated ME/B(a)P treated SHP rats. Furthermore, both ME and B(a)P significantly decreased the hepatic pool of vitamin A while a concomittant increase in that of vitamin C was observed.     

Classical and anaplastic seminoma: difference in survival

Classical and anaplastic seminoma are traditionally treated with radiation therapy and are said to have the same prognosis. A retrospective study was undertaken of 90 seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 71 patients of whom 50 had stage I and 21 had stage II disease. The anaplastic group consisted of 19 patients of whom ten had stage I and nine had stage II disease. The median follow-up time was 64 months for the entire group. The 10-year relapse-free survival rate for the classical group was 94% and for the anaplastic group was 70% (P less than .05). For patients with classical stage I disease, the relapse-free actuarial survival rate was 98%; for patients with anaplastic stage I disease, it was 64% (P less than .02). For the classical stage II disease group, the relapse-free actuarial survival rate was 84% and for the anaplastic stage II disease group, 75% (P less than .70). Four patients in the classical group (6%) had relapses; of these, one patient had local recurrence of tumor, and three had distant metastases. In the anaplastic group, four patients (21%) had relapses; two patients had local recurrence of tumor, and two had distant metastases. Therefore the data suggest a difference in survival and relapse rates between classical and anaplastic seminoma.     

BRCA2与LIM结构域蛋白FHL2的相互作用

目的：应用酵母双杂交方法筛选BRCA2相互作用蛋白编码基因，验证其相互作用并研究其功能联系。方法：以BRCA2基因3′端片段构建酵母双杂交质粒，筛选正常人乳腺上皮细胞cDNA库，获得编码相互作用蛋白的基因，采用免疫共沉淀、哺乳细胞双杂交和荧光酶测定等方法进一步验证蛋白间相互作用和功能联系．结果：采用酵母双杂交系统筛选，获得了多个编码BRCA2相互作用蛋白的基因，其中包括已知的FHL2蛋白；免疫共沉淀和哺乳动物细胞双杂交试验显示BRCA2和FHL2在体内特异性结合，并证实FHL2在体内形成同源二聚体；转录活性分析发现BRCA2与FHL2有协同转录激活作用。结论：发现BRCA2与FHL2蛋白间相互作用和功能联系，为BRCA2功能研究提供了新的方向。     

Development and evaluation of NucliSens basic kit NASBA for diagnosis of parainfluenza virus infection with 'end-point' and 'real-time' detection

New methods for the detection of human parainfluenza viruses (HPIVs) were developed. These were based on nucleic acid sequence-based amplification (NASBA) and utilised the NucliSens Basic Kit. Primers and probes were selected from the haemagglutinin neuraminidase (HN) gene of HPIV1, HPIV2 and HPIV3, and from the phosphoprotein (P) of HPIV4a and -4b. Synthetic RNA, titrated control virus stocks and respiratory specimens (n=44) were utilised to evaluate performance of the assays. Detection of NASBA products was by probe hybridisation and electrochemiluminescence (ECL) ('end-point' detection) or using molecular beacons ('real-time' detection). The assays using ECL detection proved to be both sensitive and specific. Typically, less than or equal to 100 RNA copies or one TCID(50) input was detectable with no cross-reaction between the specific HPIV assays and other respiratory viruses. Results for clinical samples were concordant with those obtained by 'conventional' procedures by classical viral diagnostic methods. 'Real-time' detection utilised probes specific for either HPIV1 or HPIV3 with similar performance characteristics to the assays with 'end-point' detection. The feasibility of multiplexing targets together was confirmed using a combined HPIV1 and HPIV3 assay with good results for ECL and molecular beacon detection on control material and clinical samples.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Sex in the Era of COVID-19 in a U.S. National Cohort of Cisgender Men,Transgender Women,and Transgender Men Who Have Sex with Men: April–May 2020

Since the emergence of the COVID-19 pandemic, there has been an increasing body of research focused on the effects that measures like stay-at-home orders and social distancing are having on other aspects of health, including mental health and sexual health. Currently, there are limited extant data on the effects of the pandemic on sexual and gender minorities. Between April 15, 2020, and May 15, 2020, we invited participants in an ongoing U.S. national cohort study (Together 5000) to complete a cross-sectional online survey about the pandemic, and its effects on mental and sexual health and well-being (n?=?3991). Nearly all (97.7%) were living in an area where they were told they should only leave their homes for essentials. Most (70.1%) reported reducing their number of sex partners as a result of the pandemic. Among the 789 participants prescribed HIV pre-exposure prophylaxis (PrEP), 29.9% said they stopped taking their PrEP entirely, and 14.2% started selectively skipping doses. For those who had been taking PrEP, discontinuing PrEP was associated with having no new sex partners (β?=?0.90, 95% CI 0.40–1.40). Among the 152 HIV-positive participants, 30.9% said they were unable to maintain an HIV-related medical appointment because of the pandemic and 13.8% said they had been unable to retrieve HIV medications. Additionally, 35.3% of participants were experiencing moderate to severe anxiety because of the pandemic and 36.7% reported symptoms of depression. In a multivariable logistic regression, reporting a new sex partner in the prior 30 days was significantly associated with being aged 30 or older (vs. not, AOR?=?1.21), being Black (AOR?=?1.79) or Latinx (AOR?=?1.40, vs. white), and being unsure if they had been in close contact with someone diagnosed with COVID-19 (AOR?=?1.32, vs. no contact). It was unassociated with COVID-19-induced anxiety, depression, or knowing someone hospitalized with COVID-19. The pandemic has caused disruptions in sexual behavior (partner reduction) as well as difficulties navigating PrEP and HIV care continua. Findings will guide more comprehensive public health responses to optimize HIV prevention and treatment in the era of COVID-19.

     

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165