Ecological succession in the vaginal microbiota during pregnancy and birth.

The mother's vaginal microbiota represents the first microbes to which a child is exposed when delivered vaginally. However, little is known about the composition and development of the vaginal microbiota during pregnancy and birth. Here, we analyzed the vaginal microbiota of 57 women in pregnancy week 24, 36 and at birth after rupture of membranes but before delivery, and further compared the composition with that of the gut and airways of the 1-week-old child. The vaginal community structure had dramatic changes in bacterial diversity and taxonomic distribution, yet carried an individual-specific signature. The relative abundance of most bacterial taxa increased stepwise from week 24 of pregnancy until birth, with a gradual decline of Lactobacillus. Mother-to-child vertical transfer, as suggested by sharing, was modest, with the strongest transfer being for Clostridiales followed by Lactobacillales and Enterobacteriales. In conclusion, late gestation is associated with an increase in maternal vaginal microbiota diversity, and vaginal bacteria at birth only modestly predict the composition of the neonatal microbiota.

Reproductive hormones and metabolic syndrome in 24 testicular cancer survivors and their biological brothers.

Testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to healthy controls. However, because of the fetal etiology of testicular cancer, familial unrelated healthy men might not be an optimal control group. The objective of this study was to clarify if testicular cancer survivors have impaired gonadal function and increased risk of metabolic syndrome when compared to their biological brothers. A cross-sectional study of testicular cancer survivors (ClinicalTrials.gov number, NCT02240966) was conducted between 2014 and 2016. Of 158 testicular cancer survivors included, 24 had a biological brother who accepted to participate in the study. Serum levels of reproductive hormones and prevalence of metabolic syndrome according to International Diabetes Federation Criteria and National Cholesterol Education Program (Adult Treatment Panel III) criteria comprised the main outcome measures of the study. Median age was similar in testicular cancer survivors and their biological brothers [44 years (IQR 39-50) vs. 46 (40-53) years respectively (p = 0.1)]. In testicular cancer survivors, follow-up since treatment was 12 years (7-19). Serum levels of luteinizing hormone and follicle-stimulating hormone were elevated (p ≤ 0.001), while total testosterone, free testosterone, inhibin B and anti-Müllerian hormone were lower (p ≤ 0.001) in testicular cancer survivors than in their biological brothers. The prevalence of metabolic syndrome was similar and apart from HDL-cholesterol, which was lower in testicular cancer survivors (p = 0.01); there were no differences in the individual components of the metabolic syndrome between testicular cancer survivors and their brothers. In conclusion, gonadal function was impaired in testicular cancer survivors, while we did not detect any difference in the prevalence of metabolic syndrome between testicular cancer survivors and their biological brothers.

Testosterone deficiency in testicular cancer survivors - a systematic review and meta-analysis.

Results concerning treatment of Testicular Germ Cell Cancer (TGCC) and subsequent risk of testosterone deficiency are conflicting. To systematically evaluate and estimate the risk of testosterone deficiency (TD) in TGCC-patients according to treatment to optimize follow-up and for prevention of late effects related to hypogonadism. We performed a critical review of PubMed in January 2015 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Twelve publications were selected for inclusion in this analysis. Eleven studies evaluated the risk of TD in TGCC-patients treated with standard chemotherapy (CT) and the odds ratio for TD was 1.8 (95% CI) (1.3-2.5), (p = 0.0007). Seven studies evaluated the risk of TD in TGCC-patients treated with non-conventional therapy and the odds ratio for TD was 3.1 (95% CI) (2.0-4.8), (p < 0.0001). Six studies evaluated the risk of TD in TGCC-patients treated with infradiaphragmatic radiotherapy (RT), and the odds ratio for TD was 1.6 (95% CI) (1.0-2.4), (p = 0.03). In all treatment groups the risk of TD was compared with TGCC-patients treated with orchiectomy alone. There was no indication of heterogeneity between studies in the three treatment groups. Strong evidence exists that standard CT, non-conventional therapy and infradiaphragmatic RT are associated with an increased risk of TD in TGCC-patients when compared with orchiectomy alone. The risk of testosterone defficiency appears to be highest in patients treated with non-conventional therapy.

Renal impairment and late toxicity in germ-cell cancer survivors.

BACKGROUND: Treatment with bleomycin-etoposide-cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large cohort of germ-cell cancer survivors. PATIENTS AND METHODS: BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity. GFR were measured (51Cr-EDTA clearance) before and after treatment and at 1, 3 and 5-year follow-up. The influence of BEP on GFR was evaluated with a linear mixed model. Risk factors for late toxicity were identified by a landmark analysis adjusting for covariates. The cohort was compared with the background population with standardized hospitalization/mortality rates. RESULTS: GFR changed (ΔGFR) -11.3%, -15.4% and -25.9% after three, four and five+ cycles of BEP. For patients with impaired renal function before treatment the changes were 4.3%, 0.0% and -12.8%, respectively. During follow-up a significant rebound of GFR was documented. Compared with the background population, all patients, irrespective of renal function, had an increased risk of CVD and death. This risk depended on chronic kidney disease stage before treatment but not after treatment. ΔGFR had no influence on risk of late toxicity [death: hazard ratio (HR) 1.06, P = 0.50; CVD: HR 0.97, P = 0.61]. CONCLUSIONS: Renal function after BEP is closely related to number of cycles, but the changes in GFR are partly reversible and have no impact on risk of CVD or death.

Screening for carcinoma in situ in the contralateral testicle in patients with testicular cancer: a population-based study.

BACKGROUND: Screening programmes for contralateral carcinoma in situ (CIS) testis in patients with unilateral germ-cell cancer (GCC) have never been evaluated. We investigated the effect of screening for contralateral CIS in a large nation-wide, population-based study. PATIENTS AND METHODS: A contralateral single-site biopsy was offered to 4130 patients in whom GCC had been diagnosed in 1984-2007 (screened cohort); 462 patients in whom GCC was diagnosed in 1984-1988 comprised the unscreened cohort. Cases with CIS were offered radiotherapy. Initially CIS-negative biopsies in patients with metachronous GCC were revised according to today's standards. Risk for metachronous GCC was estimated using cumulative incidence and the Cox proportional hazards model. RESULTS: In the screened cohort, contralateral CIS was found in 181 (4.4%) patients. The cumulative incidence of metachronous GCC after 20 years was 1.9% in the screened cohort and 3.1% in the unscreened cohort (P = 0.097), hazard ratio (HR) for the unscreened cohort: 1.59 (P = 0.144). Expert revision with contemporary methodology of CIS-negative biopsy samples from patients with metachronous cancer revealed CIS in 17 out of 45 (38%) cases. Decreased risks for metachronous GCC were related to older age at diagnosis (HR 0.52 per 10 years, P < 0.001) and chemotherapy (HR 0.35, P = 0.002). Limitations include the small number of patients in the unscreened cohort and the retrospective study design. CONCLUSIONS: Our evaluation of a national population-based screening programme for contralateral CIS in patients with testicular cancer showed no significant difference in the risk for metachronous GCC between a screened and an unscreened cohort. Single-site biopsy including modern immunohistochemistry does not identify all cases of CIS.

Late gestation over- and undernutrition predispose for visceral adiposity in response to a post-natal obesogenic diet, but with differential impacts on glucose-insulin adaptations during fasting in lambs.

AIM: To investigate if late gestation under- or overnutrition has similar adverse impacts on visceral adiposity, metabolic and endocrine function in sheep, and if subsequent exposure to a high-fat diet in early post-natal life exaggerates the prenatal programming outcomes later in life. METHODS: Thirty-six twin-pregnant ewes were fed a NORM (fulfilling 100% of daily requirements for energy and protein), LOW (50% of NORM) or HIGH diet (150% of energy and 110% of protein requirements) during the last 6 weeks of gestation (term = 147 days). Post-natally, the twin lambs were subjected to a high-fat or a moderate diet until 6 months of age (around puberty), where metabolic and endocrine adaptability to fasting was examined, and subgroups of animals were killed. RESULTS: Animals exposed to either prenatal under- or overnutrition had reduced subcutaneous fat deposition when fed a high-fat diet, resulting in higher ratios of mesenteric and peri-renal fat relative to subcutaneous fat compared to controls. This was not related to prenatal influences on plasma glucose or insulin. Irrespective of the prenatal diet, high-fat-fed lambs underwent changes resembling the metabolic syndrome with higher plasma glucose, cholesterol, non-esterified fatty acids, triglyceride and lactate combined with abdominal obesity. Peri-renal fat appeared to be a particular target of a high-fat diet post-natally. CONCLUSION: Both prenatal under- and overnutrition predisposed for abdominal adiposity, apparently by reducing the expandability of subcutaneous adipose tissue and induced differential physiological adaptations to fasting. This study does not suggest that exposure to gestational overnutrition will provide a protective effect against development of hyperglycaemia later in life.

Treatment options for carcinoma in situ testis.

Carcinoma in situ testis (CIS) is known as the precursor of germ cell cancer of the testis. International guidelines on diagnosis and treatment are inconsistent. Some countries offer routine biopsies of the contralateral testicle in relation to orchidectomy for testicular cancer, whereas other countries only offer this to high-risk patients. The treatment options range from orchidectomy and chemotherapy to radiotherapy and in rare cases surveillance. Results of the different treatment strategies are presented in this review. The optimal radiation dose is still not clarified. Most patients have been treated in the dose range of 16-20 Gy. Higher doses involve a higher risk of androgen insufficiency. Radiotherapy is recommended in patients with contralateral CIS. Orchidectomy should be offered in extragonadal germ cell cancer and CIS in one testicle, whereas patients with bilateral CIS should be offered radiation therapy. Patients who have undergone chemotherapy for testicular cancer are still at risk of developing CIS and we also recommend radiotherapy to the affected testicle in these patients. Cryopreservation should be offered before treatment is initiated and all patients should have their androgen status measured on a regular basis to find those cases where hormone substitution is needed.

Quantitation of added water in milk by using vapor pressure osmometry.

A vapor pressure osmometer (VPO) was successfully studied in 1975. An improved osmometer with greater range and temperature stability was evaluated. Repeatability on 290 mOs/kg standard solution was 289.5 +/- 1.08. The mean and standard deviation on 36 water-free milk samples was 280.5 +/- 4 compared to 280.1 +/- 3 in the previous study. Instrument data from 2 osmometers and 2 cryoscopes produced acceptable chi-square values, and the correlation coefficients between methods were better than 0.99 for samples containing 1--21% added water. In a survey involving 760 samples, more than 37% of producer samples in one cheese plant contained greater than 3% added water. Additional evidence of added water in market milk samples suggests the immediate application of the VPO to help prevent milk adulteration. The vapor pressure osomometer method for quantitating added water in milk has been adopted as official first action.