Exposure to solar ultraviolet radiation limits diet-induced weight gain, increases liver triglycerides and prevents the early signs of cardiovascular disease in mice.

BACKGROUND AND AIMS: Sunlight exposure is associated with a number of health benefits including protecting us from autoimmunity, cardiovascular disease, obesity and diabetes. Animal studies have confirmed that ultraviolet (UV)-B radiation, independently of vitamin D, can limit diet-induced obesity, metabolic syndrome and atherosclerosis. The aim of this study is to investigate whether exposure to the UV radiation contained in sunlight impacts on these disease parameters. METHODS AND RESULTS: We have trialled an intervention with solar UV in obese and atherosclerosis-prone mice. We have discovered that solar-simulated UV can significantly limit diet-induced obesity and reduce atheroma development in mice fed a diet high in sugar and fat. The optimal regime for this benefit was exposure once a week to solar UV equivalent to approximately 30 min of summer sun. Exposure to this optimal dose of solar UV also led to a significant increase in liver triglycerides which may protect the liver from damage. CONCLUSION: Our results show that the UV contained in sunlight has the potential to prevent and treat chronic disease at sites distant from irradiated skin. A major health challenge going forward will be to harness the power of the sun safely, without risking an increase in skin cancers.

Oral Tobramycin Prophylaxis Prior to Colorectal Surgery Is Not Associated with Systemic Uptake.

Preoperative oral prophylaxis with nonabsorbable antibiotics has been reported to reduce the risk of surgical site infections after colorectal surgery. This prospective study was conducted to evaluate the risk of toxic side effects by measuring postoperative serum tobramycin levels in patients who received a 3-day prophylaxis with tobramycin and colistin prior to colorectal surgery. In all patients, serum tobramycin concentrations were below the detection limit (0.3 mg/liter), implying a low risk of toxicity.

Health and health-related quality of life in pig farmers carrying livestock-associated methicillin-resistant Staphylococcus aureus.

There is limited knowledge about the effect of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) carriage on health-related quality of life (QoL). With this study, we explored whether LA-MRSA causes infections or affects health-related QoL in pig farmers. This prospective cohort study surveyed persons working on 49 farrowing pig farms in The Netherlands for 1 year (2010-2011). On six sampling moments, nasal swabs, environmental samples and questionnaires on activities and infections were collected. At the end of the study year, persons were asked about their QoL using the validated SF-36 and EQ-5D questionnaires. Of 120 persons, 44 (37%) were persistent MRSA carriers. MRSA carriage was not associated with infections, use of antimicrobials, healthcare contact and health-related QoL items in univariate or multivariate analysis, most likely due to the 'healthy worker effect'. Despite high carriage rates, the impact of LA-MRSA carriage in this population of relatively healthy pig farmers on health and health-related QoL appears limited; more research is needed for confirmation.

Rectal Carriage of Extended-Spectrum-Beta-Lactamase-Producing Enterobacteriaceae in Hospitalized Patients: Selective Preenrichment Increases Yield of Screening.

This study evaluated the added value of selective preenrichment for the detection of rectal carriage of extended-spectrum-beta-lactamase-producing Enterobacteriaceae (ESBL-E). ESBL-E rectal carriage was identified in 4.8% of hospitalized patients, and 25.9% of ESBL-E rectal carriers were identified with selective preenrichment only.

Community-associated methicillin-resistant Staphylococcus aureus transmission in households of infected cases: a pooled analysis of primary data from three studies across international settings.

Diverse strain types of methicillin-resistant Staphylococcus aureus (MRSA) cause infections in community settings worldwide. To examine heterogeneity of spread within households and to identify common risk factors for household transmission across settings, primary data from studies conducted in New York (USA), Breda (The Netherlands), and Melbourne (Australia) were pooled. Following MRSA infection of the index patient, household members completed questionnaires and provided nasal swabs. Swabs positive for S. aureus were genotyped by spa sequencing. Poisson regression with robust error variance was used to estimate prevalence odds ratios for transmission of the clinical isolate to non-index household members. Great diversity of strain types existed across studies. Despite differences between studies, the index patient being colonized with the clinical isolate at the home visit (P < 0·01) and the percent of household members aged <18 years (P < 0·01) were independently associated with transmission. Targeted decolonization strategies could be used across geographical settings to limit household MRSA transmission.

Dutch guideline on the laboratory detection of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has rapidly emerged worldwide, affecting both healthcare and community settings, and intensive livestock industry. The efficient control of MRSA strongly depends on its adequate laboratory detection. This guideline provides recommendations on the appropriate use of currently available diagnostic laboratory methods for the timely and accurate detection of MRSA in patients and healthcare workers. Herewith, it aims to standardise and improve the diagnostic laboratory procedures that are used for the detection of MRSA in Dutch medical microbiology laboratories.

Practice testing of generic quality indicators for responsible antibiotic use in nine hospitals in the Dutch-Belgian border area.

BACKGROUND: Inpatient quality indicators (IQIs) were previously developed to assess responsible antibiotic use. AIM: Practice testing of these QIs in the hospital setting. METHOD: This study was performed within a Dutch-Belgian border network of hospitals implementing the Infection Risk Scan (IRIS) point prevalence survey (PPS) as part of the i-4-1-Health project. Twenty out of 51 DRIVE-AB IQIs, including 13 structure and seven process IQIs, were tested. Data on structure IQIs were obtained through a web-based questionnaire sent to the hospital medical microbiologists. PPS data from October to December 2018 were used to calculate performance scores for the process QIs. FINDINGS: Nine hospitals participated. Regarding structure IQIs: the lowest performance scores were observed for recommendations for microbiological investigations in the guidelines and the use of an approval system for restricted antibiotics. In addition, most hospitals reported that some antibiotics were out of stock due to shortages. Regarding process IQIs: 697 systemic antibiotic prescriptions were used to calculate performance scores. The lowest score was observed for documentation of an antibiotic plan in the medical file (58.8%). Performance scores for IQIs on guideline compliance varied between 74.1% and 82.3% for different aspects of the antibiotic regimen (duration, choice, route, timing). CONCLUSION: This multicentre practice testing of IQIs identified improvement targets for stewardship efforts for both structure and process aspects of antibiotic care (approval system for restricted antibiotics, documentation of antibiotic plan). These results can guide the design of future PPS studies and a more extensive evaluation of the clinimetric properties of the IQIs.

Semen quality of young men in Switzerland: a nationwide cross-sectional population-based study.

BACKGROUND: Sperm counts have been steadily decreasing over the past five decades with regional differences in the Western world. The reasons behind these trends are complex, but numerous insights indicate that environmental and lifestyle factors are important players. OBJECTIVE: To evaluate semen quality and male reproductive health in Switzerland. MATERIALS AND METHODS: A nationwide cross-sectional study was conducted on 2523 young men coming from all regions of Switzerland, recruited during military conscription. Semen volume, sperm concentration, motility, and morphology were analyzed. Anatomy of the genital area and testicular volume was recorded. Testicular cancer incidence rates in the general population were retrieved from Swiss regional registries. RESULTS: Median sperm concentration adjusted for period of sexual abstinence was 48 million/mL. Comparing with the 5th percentile of the WHO reference values for fertile men, 17% of men had sperm concentration below 15 million/mL, 25% had less than 40% motile spermatozoa, and 43% had less than 4% normal forms. Disparities in semen quality among geographic regions, urbanization rates, and linguistic areas were limited. A larger proportion of men with poor semen quality had been exposed in utero to maternal smoking. Furthermore, testicular cancer incidence rates in the Swiss general population increased significantly between 1980 and 2014. DISCUSSION: For the first time, a systematic sampling among young men has confirmed that semen quality is affected on a national level. The median sperm concentration measured is among the lowest observed in Europe. No specific geographical differences could be identified. Further studies are needed to determine to what extent the fertility of Swiss men is compromised and to evaluate the impact of environmental and lifestyle factors. CONCLUSION: A significant proportion of Swiss young men display suboptimal semen quality with only 38% having sperm concentration, motility, and morphology values that met WHO semen reference criteria.

Fosfomycin Etest for Enterobacteriaceae: Interobserver and interlaboratory agreement.

OBJECTIVES: The increasing use of fosfomycin requires reliable susceptibility testing in clinical practice. The reference standard, agar dilution (AD), is rarely used in routine settings. The fosfomycin Etest (BioMérieux) is frequently used, although reading MICs can be hampered by the interpretation of the growth of macrocolonies in the inhibition zone. We investigated the interobserver (IO), interlaboratory (IL), and interobserver-interlaboratory (IOIL) agreement of the fosfomycin Etest and evaluated the agreement with AD. METHODS: Etests were performed for 57 extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae of four bacterial species (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca and Enterobacter cloacae) in two laboratories. Photographs of fosfomycin Etests were interpreted by four observers following manufacturer's instructions. RESULTS: Essential agreement (EA) and categorical agreement (CA) between Etest and AD were 57% and 89% (κ-value 0.68), respectively, with an underestimation of Etest interpretations compared with AD of 0.26 (95% confidence interval [CI] 0.03-0.48) 2-fold dilutions. Between Etest observations, IO-EA and -CA were reached in 82% and 94% of comparisons; IL-EA and -CA in 38% and 85% of comparisons; and IOIL-EA and -CA in 40% and 85% of comparisons, respectively. Agreement of the Etest with AD and between Etests was better for E. coli than for other species. Ignoring all macrocolonies and haze during Etest interpretation improved the agreement with AD (CA κ-value 0.80) and between Etests (CA κ-value from 0.68 to 0.81). CONCLUSIONS: In this study on 57 ESBL-producing Enterobacteriaceae, IOIL agreement was low with an EA of 40% and a CA of 85%, affected most by IL agreement and to a lesser extent by IO agreement.

Molecular characterization and phylogeny of Shiga toxin-producing Escherichia coli isolates obtained from two Dutch regions using whole genome sequencing.

Shiga toxin-producing Escherichia coli (STEC) is one of the major causes of human gastrointestinal disease and has been implicated in sporadic cases and outbreaks of diarrhoea, haemorrhagic colitis and haemolytic uremic syndrome worldwide. In this study, we determined the molecular characteristics and phylogenetic relationship of STEC isolates, and their genetic diversity was compared to that of other E. coli populations. Whole genome sequencing was performed on 132 clinical STEC isolates obtained from the faeces of 129 Dutch patients with gastrointestinal complaints. STEC isolates of this study belonged to 44 different sequence types (STs), 42 serogenotypes and 14 stx subtype combinations. Antibiotic resistance genes were more frequently present in stx1-positive isolates compared to stx2 and stx1 + stx2-positive isolates. The iha, mchB, mchC, mchF, subA, ireA, senB, saa and sigA genes were significantly more frequently present in eae-negative than in eae-positive STEC isolates. Presence of virulence genes encoding type III secretion proteins and adhesins was associated with isolates obtained from patients with bloody diarrhoea. Core genome phylogenetic analysis showed that isolates clustered according to their ST or serogenotypes irrespective of stx subtypes. Isolates obtained from patients with bloody diarrhoea were from diverse phylogenetic backgrounds. Some STEC isolates shared common ancestors with non-STEC isolates. Whole genome sequencing is a powerful tool for clinical microbiology, allowing high-resolution molecular typing, population structure analysis and detailed molecular characterization of strains. STEC isolates of a substantial genetic diversity and of distinct phylogenetic groups were observed in this study.

Karyotypic evidence for the leukemic involvement of the erythroblasts in erythroleukemia.

With the use of a monoclonal anti-glycophorin A antibody and flow cytometric cell sorting, an erythroleukemic bone marrow sample was separated in highly purified erythroblast and myeloblast fractions. Similar karyotypic anomalies were found in both cell populations as in the unseparated bone marrow. This study confirms that acute nonlymphocytic leukemia can originate at the level of a multipotential hemopoietic stem cell.

Review of scientific contributions by the Belgian medical centers concerned with human in vitro fertilization and embryo transfer (IVF).

In vitro fertilization and embryo transfer (IVF) may be considered as a particular application of modern medical therapeutics linked to human reproduction. The treatment of human sterility therefore involves some fundamental human values such as life, love and death. The quality of this highly technological treatment with fast knowledge of outcome at the end of the patient's menstrual cycle has been evaluated since the early 80s. It is a typically multidisciplinary team effort involving medical doctors, biologists, laboratory technicians, nurses and clerks that is representative of modern medical practice. IVF covers much more than just embryology, as this review will explain. IVF developed in close relation with clinical and experimental research protocols, which are the major topics of this paper. The newness of the techniques used led to the necessary interactions between clinicians and biologists working on animal experimental embryology.

Cytogenetic and DNA-flow cytometric studies of separated blasts.

With Percoll density gradients, blasts from peripheral blood and bone marrow could be separated with a significant enrichment, and very often with a high degree of purity. This allowed a study of selected cases, where the separated sample exhibited chromosome abnormalities and/or an abnormal DNA content distribution (as measured by DNA-flow cytometry). The anomalies were shown to be associated with the separated blast fraction.

Coagulase and protein A polymorphisms do not contribute to persistence of nasal colonisation by Staphylococcus aureus.

The nasal carriage rate of Staphylococcus aureus was examined in a longitudinal study of 31 healthy Danish volunteers. Each person was classified as persistent (>8 positive cultures from 10 examinations), an intermittent carrier (50-80% positive cultures) or an ocassional carrier (positive cultures on 10-40% of ocassions only). One hundred and twenty strains from these persons were subjected to phage typing and random amplification of polymorphic DNA (RAPD) analysis. Phage and RAPD typing were in close agreement. RAPD confirmed the spread of a particular S. aureus clone (phage type 95) throughout Denmark. However, no common genotype or phenotype characteristics of S. aureus that could separate persistent from intermittent or incidental colonisers were identified. The immunoglobulin binding protein A and the prothrombin binding coagulase protein are both putative S. aureus virulence or defence factors. Analysis of polymorphisms in the variable repeat regions in the genes for these proteins showed no correlation between the number of repeat units and, consequently, the protein structure with the ability of strains to persist in the human nasal mucosa. The amount of protein A, detectable by its IgG binding activity, appeared not to be correlated to persistence of carriage. Thus protein A and coagulase gene polymorphisms do not seem to play a significant role in the propensity of S. aureus to colonise human nasal epithelium. Furthermore, based on the genetic heterogeneity encountered among the S. aureus strains it is suggested that within the current study population, no single clonal lineage of S. aureus has increased capability to colonise the human nasal epithelium.

Clinical parameters influencing human zona pellucida thickness.

OBJECTIVES: To assess which clinical parameters influence human oocyte zona pellucida (ZP) thickness. PATIENTS: Sixty-five couples undergoing 75 IVF-ET cycles. MAIN OUTCOME MEASURE: Zona pellucida thickness of 827 oocytes measured 16 to 20 hours after in vitro insemination under inverted light microscope. RESULTS: Zona pellucida thickness was 18.9 +/- 3.8 microns (mean +/- SD) for unfertilized, 16.4 +/- 3.1 microns for fertilized, and 15.1 +/- 2.4 microns for polyspermic oocytes (significantly different). Among our patients, a few underwent two (or even three) IVF-ET cycles, and the mean ZP thickness was, in most cases, not significantly different from one cycle to the other(s). Regression analyses were calculated between ZP thickness and available clinical parameters, i.e., the age of the women, the duration of stimulation, the cumulus maturity, the number of retrieved oocytes, the number of hMG doses, the maximum E2 level, and the follicular volume. A significant linear decreasing relationship exists between the mean ZP thickness of each patient and the maximum E2 level and an increasing one with the hMG dose. Relationships with the other parameters appeared to be nonsignificant. CONCLUSION: The ZP thickness is basically an individual feature that influences the fertilization rate. Nevertheless, it may be influenced slightly by the hormonal treatment during stimulation.

Noninvasive assessment of glucose and pyruvate uptake by human embryos after intracytoplasmic sperm injection and during the formation of pronuclei.

OBJECTIVE: To improve in vitro culture conditions and human embryo selection before transfer after IVF with intracytoplasmic sperm injection (ICSI). DESIGN: A controlled, randomized, prospective study. SETTING: University hospital-based IVF-ET program. PATIENT(S): Couples undergoing ICSI. INTERVENTION(S): Culture of human embryos in the presence of 1 mM or 5.56 mM glucose and metabolic measurements with the use of noninvasive microfluorescence assays immediately after ICSI to the time of transfer. MAIN OUTCOME MEASURE(S): Embryo development, implantation rate, and glucose and pyruvate uptake. RESULT(S): Fertilization rates, early embryo development, and implantation rates were not significantly different between 1 mM and 5.56 mM glucose. Pyruvate uptake was significantly higher during the formation of the pronuclei, at 15 +/- 0.7 and 11.4 +/- 1.3 pmol/embryo/h for fertilized and unfertilized oocytes, respectively. Pyruvate uptake did not correlate with cleavage stage or embryo morphology. However, during the second day of incubation, pyruvate uptake was significantly higher for the untransferred embryos of pregnant women compared with nonpregnant women, at 17.9 +/- 1.5 and 10.8 +/- 1.0 pmol/embryo/h, respectively. CONCLUSION(S): The increased level of pyruvate uptake during fertilization reflects the increased demand for energy necessary for the formation of the pronuclei. However, the metabolic measurements could not improve the selection of embryos with the best implantation potential. Finally, the reduction of glucose concentration in the culture medium failed to improve embryo viability.

The long-acting gonadotropin-releasing hormone analogues impaired the implantation rate.

OBJECTIVES: To determine the efficacy and innocuousness of long-acting versus short-acting GnRH analogues (GnRH-a) in long protocol for in IVF-ET. DESIGN: Prospective randomized study. SETTING: The IVF unit at an academic hospital. PATIENTS: One hundred couples admitted for their first IVF-ET attempt. MAIN OUTCOME MEASURES: Serum concentrations of LH, E2, and P during the all cycles and duration of pituitary desensitization were assessed, as well as fertilization rate, embryo quality, and implantation and pregnancy rates. RESULTS: Significantly more days (10.8 +/- 1.8 versus 9.2 +/- 1.7 days) of stimulation and more ampules of hMG (47 +/- 22 versus 33 +/- 16) were necessary to obtain similar numbers of embryos of quality with the long-acting GnRH-a. Implantation and delivery rates were significantly lower with the long-acting GnRH-a (32.8% versus 21.1%; 48.9% versus 29.1%, respectively). CONCLUSIONS: As the long-acting GnRH-a might interfere with the luteal phase and embryo development, short-acting GnRH-a should be preferred for ovarian hyperstimulation in IVF-ET.

Abnormal sperm-mucus penetration test predicts low in vitro fertilization ability of apparently normal semen.

OBJECTIVE: To investigate whether Kremer's sperm-mucus penetration test may predict sperm fertilizing ability in IVF. DESIGN: Kremer's test was prospectively performed on semen samples used for 66 consecutive IVF trials and compared with the fertilization rates and fertilization failure rates observed. RESULTS: Fertilization rates were significantly reduced in cases of abnormal Kremer's test (42% versus 51%; n = 745 oocytes with a statistically insignificant increase in fertilization failure rates (21% versus 10%; n = 66 trials). For abnormal semen, fertilization rates (39% versus 39%; n = 208 oocytes) and fertilization failure rates (20% versus 28%; n = 17 trials) were similar regardless of Kremer's test result. For normal semen, an abnormal Kremer's test implied a significant decrease in fertilization rates (44% versus 54%; n = 537 oocytes) with a statistically insignificant increase in fertilization failure rates (21% versus 6%; n = 49 trials). CONCLUSIONS: Abnormal Kremer's test results identify patients with a decreased in vitro fertilizing ability despite apparently normal semen samples and a group with very low fertilizing failure risk in case of normal semen samples and normal Kremer's test. Kremer's test does not add any predictive value to sperm analysis in the case of abnormal semen samples. These observations point out the importance of the male factor in fertilization failure even in the case of normal semen analysis.

Is the subzonal-insemination procedure an efficient technique in the treatment of extreme oligoasthenoteratozoospermia?

OBJECTIVES: The present study evaluates the usefulness of the sub-zonal insemination (SUZI) for patients with previous IVF failures or affected by severe oligoasthenoteratozoospermia and the necessity of pre-treatment semen analysis. DESIGN: Twenty-five patients underwent 43 cycles of either SUZI or alternate SUZI/IVF procedures according to semen characteristics. RESULTS: Among the 571 retrieved oocytes, 398 were microinjected and 173 were treated by IVF. Among the microinjected oocytes, 19% fertilized (12% 2PN: 7% 3PN) and 96% of the 2PN oocytes developed into embryos. Thirty-one embryo transfers were performed, 8 pregnancies were obtained and 7 embryos were cryopreserved. The 2 PN rates in SUZI and IVF procedures in the same cycle were not significantly different. The analysis of the different semen samples obtained before and during the treatment reveals that the semen quality varies in such a way that the decision of the adequate microinjection strategy to follow should only be taken according to the semen quality at the day of treatment. CONCLUSION: SUZI is not a satisfactory technique for treatment neither in case of previous IVF failures nor for severe oligoasthenoteratozoospermia.

[Impact of the introduction of intracytoplasmic sperm injection (ICSI) on the treatment of severe male sterility]. / L'impact de l'introduction de la microinjection (ICSI) sur le traitement de la sterilite a composante masculine severe.

The introduction of the Intracytoplasmic Single Sperm Injection (ICSI) has been a turning point for the treatment of severe male infertility. ICSI allowed not only to reduce fertilization failure from 35% to 0.7% but created at the same time the opportunity for a group of patients with extremely low sperm counts to procreate. The discovery that breaking the tail of the spermatozoon prior to the injection was the most important step is at the origin of major improvements: fertilization increased from 22% to 77%, pregnancy rate from 16% to 54% and the implantation rate from 7.4% to 26%. From October 1994 to April 1999, 835 ICSI cycles were performed and resulted in 312 ongoing pregnancies (37%), fertilization rate was 75%, with a fertilization failure of only 0.7%. The use of ICSI and IVF on sibling oocytes for semen samples with doubtful fertilizing ability clearly illustrated the superiority of ICSI. No fertilization failures occurred after ICSI and the fertilization rate was 76% versus 27.8% (P < 0.01). Similar benefit of ICSI was shown for crytozoospermia up to then a hopeless situation. A total of 26 pregnancies were obtained out of 87 cycles with a fertilization rate of 58.8%. Similar results were obtained when ICSI was combined with testicular sperm, 20 pregnancies occurred after from 46 transfers (43%) including cycles with cryopreserved testicular sperm. It is now clear that ICSI is the method of choice for the treatment of severe male infertility.