Role of the Nijmegen breakage syndrome 1 gene in familial and sporadic prostate cancer.

The Nijmegen breakage syndrome 1 (NBS1) gene, which participates in DNA double strand break repair, has been postulated to be a susceptibility factor for a number of cancers, including prostate cancer. Numerous mutations have been identified in NBS1, including the founder mutation 657del5. In this study, a number of analyses were done to determine whether mutations in NBS1 are associated with an increased risk for prostate cancer. The frequency of the 657del5 mutation in both familial prostate cancer cases (1,819 affected men among 909 families) and sporadic prostate cancer cases (1,218 affected men) collected from five centers participating in the International Consortium for Prostate Cancer Genetics were compared with that found in 697 normal controls. Seven individuals were identified to carry the mutation among the 3,037 cases screened: four in the familial group (three from one family and one from another) and three in the sporadic cases. The carrier frequency was 0.22% (2 of 909) for the probands and 0.25% (3 of 1,218) for the sporadic cases of prostate cancer. The 657del5 mutation was not detected in either the 293 unaffected members of the prostate cancer families or in the 697 control samples tested. The entire NBS1 gene was also sequenced in 20 of the youngest affected individuals from the Finnish group of familial cases to identify the presence of possible mutations in this high-risk group. One rare (D95N) and one common (E185Q) missense alteration was identified. More detailed analyses of the E185Q polymorphism, along with a third rare variant (R215W), failed to show an association with prostate cancer. Because the 657del5 mutation was absent from the control population, we are unable to determine if this alteration predisposes to prostate cancer. However, our data does suggest that mutations within NBS1, and in particular, 657del5, do not significantly contribute to the overall prostate cancer burden within our patient samples.     

Alcohol Use,High Risk Behaviors,and Experiences of Discrimination Among Transgender Women in the Dominican Republic

Objectives: This study examines associations between alcohol use, high risk sexual behaviors, and experiences of stigma among transgender women across the Dominican Republic. Data from the 2015 Transgender Health Needs Study were analyzed using bivariate analyses (N?=?291). Results: High rates of stigma, verbal abuse, alcohol use, and sex work are found and are associated with each other. Almost 45% of regular alcohol users are engaging in sex work (43.6%), compared with 31.1% of the non-regular alcohol users (χ²=4.82, p?<?.05). Having sex under the influence of alcohol is statistically associated with high risk behaviors, such as engaging in sex work, sometimes or never using a condom when receiving anal sex, and higher numbers of sexual partners. Furthermore, transgender women who have had sex under the influence of alcohol report statistically significantly higher levels of verbal abuse, discrimination, and levels of perceived transgender stigma. Conclusions/Importance: Findings suggest that although anti-discrimination laws exist, policies may not protect transgender women from experiencing stigma and discrimination at work, potentially forcing them to seek alternative careers and engage in behaviors that expose them to greater personal risk and harm. This intersection of factors may indicate a notable public health gap in transgender health in the Dominican Republic.     

Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men

We investigated the association of glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes with amino acid levels in the population-based Metabolic Syndrome in Men (METSIM) Study, including 9,369 nondiabetic or newly diagnosed type 2 diabetic Finnish men. Plasma levels of eight amino acids were measured with proton nuclear magnetic resonance spectroscopy. Increasing fasting and 2-h plasma glucose levels were associated with increasing levels of several amino acids and decreasing levels of histidine and glutamine. Alanine, leucine, isoleucine, tyrosine, and glutamine predicted incident type 2 diabetes in a 4.7-year follow-up of the METSIM Study, and their effects were largely mediated by insulin resistance (except for glutamine). We also found significant correlations between insulin sensitivity (Matsuda insulin sensitivity index) and mRNA expression of genes regulating amino acid degradation in 200 subcutaneous adipose tissue samples. Only 1 of 43 risk single nucleotide polymorphisms for type 2 diabetes or hyperglycemia, the glucose-increasing major C allele of rs780094 of GCKR, was significantly associated with decreased levels of alanine and isoleucine and elevated levels of glutamine. In conclusion, the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia, reflecting, at least in part, insulin resistance. Only one single nucleotide polymorphism regulating hyperglycemia was significantly associated with amino acid levels.     

MRI-guided brachytherapy for locally advanced cervical cancer: Program initiation,learning curve and dose delivery results in Kuopio University Hospital

Background and purposeImage guided adaptive brachytherapy, the standard treatment for locally advanced cervical cancer (LACC), is a complex medical procedure that requires an experienced multidisciplinary team. The aims of this analysis were to assess (1) the learning curve of brachytherapy team, (2) dose-volume parameters, (3) the use of an interstitial component, and (4) the overall treatment time (OTT).Materials and methodsOur study cohort comprised 117 LACC patients treated in Kuopio University Hospital with magnetic resonance imaging guided intracavitary (IC) or combined intracavitary/interstitial (IC/IS) high dose rate brachytherapy during 2009-2018. Target volumes and organs at risk (OAR) were contoured according to ICRU/GEC-ESTRO recommendations. Treatment plans were optimized individually without using standard loading patterns.ResultsMean dose to 90% of the high-risk clinical target volume (HR-CTV D90) improved after the first 15 patients, however the team's learning curve to reliably fulfill the main planning aim (PA) of 85 Gy required a total 43 patients and more than 10 patients annually. Significant difference was detected between IC and IC/IS brachytherapy in achieving the PA of HR-CTV D90. Especially, HR-CTV volumes >30 cm³ benefitted from IS needles. Needle insertion did not cause serious complications. With the brachytherapy program, the OTT of patients from outside institutions was reduced to the same level as our own patients.ConclusionBrachytherapy requires good experience of multidisciplinary team and the continuous development of the program to fulfill PA and to avoid OTT prolongation. The use of IS needles is safe and improves the fulfillment of PA to target volume.     

Validation and application of an instrument for measuring patient relatives' perception of quality of geriatric care.

OBJECTIVE: To test and validate a questionnaire concerning patient relatives' perception of the quality of geriatric care. DESIGN: Three anonymous questionnaire studies. SETTINGS: A community-based geriatric care organization and a university hospital in Sweden. STUDY PARTICIPANTS: Three hundred and eighteen relatives of patients within the geriatric care organization and 38 relatives of patients at the university hospital. MAIN OUTCOME MEASURES: A questionnaire composed of eight quality of care indices and an overall quality rating. Reliability and validity estimates were compared between the results from the three surveys. RESULTS: Internal reliability estimates for all indices were >0.65 and consistent over time. Inter-index correlations were >0.60 between certain indices, indicating some overlap. Second order factor analysis resulted in three distinct index groupings: personnel, relative's role, and care content. These three dimensions summarize relatives' perceptions of the quality of geriatric care. CONCLUSIONS: There is a need for a confidential patient relatives' questionnaire in geriatric care. The results revealed good questionnaire reliability and validity. The questionnaire needs to be tested in larger, independent samples in order to validate the indices further.