Virulence determinants in Pseudomonas aeruginosa strains from urinary tract infections.

A total of 121 uropathogenic Pseudomonas aeruginosa strains were examined for production of several virulence-related factors. These strains were distributed in five predominant O-serotypes, i.e. O 4, O 12, O 11, O 6 and O 5, which accounted respectively for 23.9, 23.1, 12.3, 8.2 and 5.7% of isolates. Pyochelin and pyoverdin siderophores were produced by most of the isolates, defective variants occurring at very low frequency (2.4% for pyochelin and 7.4% for pyoverdin). Adherence to uroepithelial cells and production of cytotoxins was demonstrated in 52.8 and 67.7% of the strains, respectively, with higher frequencies for epidemiologically related strains belonging to serotypes O 4 and O 12. Titration of total proteases, elastase and phospholipase C revealed a high degree of heterogeneity among isolates. However, examination of individual O-serotypes by exoenzyme production showed that elevated levels of total proteases and elastase were characteristics of serotypes of minor numerical importance, i.e. O 1, O 10, O 11 and O 17, whilst low levels of elastase were produced by strains belonging to the predominant serotypes, namely O 4 and O 12. Moreover, epidemiologically related strains belonging to serotypes O 4 and O 12 appeared more homogeneous than the whole serogroup, when compared with other groups on the basis of exoenzyme levels.     

Emerging Patterns in Adolescent Drug Use: The Belfast Youth Development Study 2000-2002

This paper reports the findings from the first 2 years of the Belfast Youth Development Study. The Belfast Youth Development Study is a 5-year longitudinal investigation of the onset and development of adolescent drug using behaviours, the findings of the first 2 years from the study in relation to drug use patterns among the young people participating in the research are reported here. The findings show that while the majority of young people have not yet used an illicit substance, the study has seen a substantial increase in the numbers using such substances between year 1 and year 2. Boys still make up the majority of drug users in this period but there has been a substantial increase in the number of girls using illicit drugs and, more generally, an increase in the frequency of use among all those using such substances during this period.     

Continuous Glucose Monitoring Use in Clinical Trials for On-Market Diabetes Drugs

To the best of our knowledge, there are no published data on the historical and recent use of CGM in clinical trials of pharmacological agents used in the treatment of diabetes. We analyzed 2,032 clinical trials of 40 antihyperglycemic therapies currently on the market with a study start date between 1 January 2000 and 31 December 2019. According to ClinicalTrials.gov, 119 (5.9%) of these trials used CGM. CGM usage in clinical trials has increased over time, rising from <5% before 2005 to 12.5% in 2019. However, it is still low given its inclusion in the American Diabetes Association’s latest guidelines and known limitations of A1C for assessing ongoing diabetes care.

The availability of reliable continuous glucose monitoring (CGM) systems has proven to be a major innovation in diabetes management and research. Most current CGM systems are approved for 7- to 14-day use and use a wire-tipped glucose oxidase sensor inserted in subcutaneous tissue to monitor glucose concentrations in interstitial fluid. One implanted CGM system is approved for longer-term use (90–180 days); it operates with fluorescence-based technology. CGM sensors record a glucose data point every 1–15 minutes (depending on the system), collecting far more granular data and information on glycemic patterns than self-monitoring of blood glucose (SMBG) alone. Real-time CGM or intermittently scanned CGM systems send data continuously or intermittently to dedicated receivers or smartphones, whereas professional CGM systems provide retrospective data, either blinded or unblinded, for analysis and can be used to identify patterns of hypo- and hyperglycemia. Professional CGM can be helpful to evaluate patients when other CGM systems are not available to the patient or the patient prefers a blinded analysis or a shorter experience with unblinded data.In the 20 years since CGM systems first became available to people with diabetes, technological improvements, particularly pertaining to accuracy and form factor, have made CGM increasingly viable for both patient use and clinical investigation (1,2). Average sensor MARD (mean absolute relative difference; a summary accuracy statistic) has decreased from >20 to <10% (3–10), including two systems that do not require fingerstick calibrations and three that are approved to be used for insulin dosing (11). Concurrently, size, weight, and cost of CGM systems have all decreased, while user-friendliness and convenience have increased (12).To encourage use of CGM-derived data, researchers and clinicians have worked to develop a standard set of glycemic metrics beyond A1C. In 2017, two international groups of leading diabetes clinical and research organizations published consensus definitions for key metrics, including clinically relevant glycemic cut points for hypoglycemia (<70 and <54 mg/dL), hyperglycemia (>180 and >250 mg/dL), and time in range (TIR; 70–180 mg/dL) (13,14).CGM-derived metrics provide far greater precision and granularity than is possible with SMBG or A1C data alone (Table 1), enabling clinicians and investigators to better represent inter- and intraday glycemic differences with metrics such as TIR, glycemic variability, and time in hypoglycemia and hyperglycemia (15). Crucially, CGM also allows for the accurate measurement and detection of nocturnal glycemia (16). The use of these metrics enables a more comprehensive understanding of glycemic management that can facilitate individualized treatment for people with diabetes or prediabetes. Although A1C is a useful estimate of mean glucose over the previous 2–3 months, especially when evaluating population health, it is important to include other glycemic outcomes in clinical trials. Furthermore, there is emerging evidence suggesting that TIR predicts the development of microvascular complications at least as well as A1C (17,18).TABLE 1Benefits of CGM Compared With A1C Alone in Assessing Glycemia

Association between A218C polymorphism of the tryptophan-hydroxylase-1 gene,harm avoidance and binge eating behavior in bulimia nervosa

Genes involved in serotonin transmission are likely involved in the biological predisposition to bulimia nervosa. We investigated whether the A218C polymorphism of the tryptophan-hydroxylase-1 gene was associated to bulimia nervosa and/or to some phenotypic aspects of the disorder. One hundred eighty Caucasian women (91 patients with bulimia nervosa and 89 healthy controls) were enrolled into the study. They underwent a blood sample collection for A218C polymorphism of the tryptophan-hydroxylase-1 genotyping and a clinical evaluation assessing comorbidity for Axis I and II psychiatric disorders, harm avoidance personality dimension and bulimic symptoms. The distribution of both tryptophan-hydroxylase-1 A218C genotypes and alleles did not significantly differ between patients and controls. Bulimic women with the AA genotype exhibited a more severe binge eating behavior and higher harm avoidance scores than those with CC genotype. These findings support the idea that tryptophan-hydroxylase-1 A218C polymorphism does not play a part in the genetic susceptibility to bulimia nervosa, but it seems to be involved in predisposing bulimic patients to a more disturbed eating behavior and higher harm avoidance.     

An Investigation of Sexual and Relationship Adjustment During COVID-19

The COVID-19 pandemic and the mitigation measures put in place have resulted in universal disruption in the usual ways of life for individuals. The current study sought to investigate how aspects of sexual health (well-being and functioning) and relationship satisfaction changed or remained stable during the pandemic. During two separate time points (Time 1 including Time 1 and a retrospective baseline, Time 2), participants completed online measures of sexual well-being (sexual pleasure, partnered and solitary orgasm frequency, sexual distress), sexual functioning, and relationship satisfaction. Participants reported slight declines in sexual pleasure, frequency of orgasms with a partner, and frequency of solitary orgasms from pre-COVID-19 (retrospective baseline) to Time 1, with no significant differences in sexual distress and relationship satisfaction. For individuals with vulvas, sexual functioning improved from Time 1 to Time 2, whereas no significant differences in sexual functioning were observed for individuals with penises. Aspects of sexual health and relational satisfaction did not sufficiently change across time points to be considered meaningful health outcome changes. Given that minimal disruptions were noted in pre-COVID-19 to COVID-19 sexuality, these results highlight the potential resiliency of individuals’ sexuality when facing sudden changes in their daily lives. Implications of COVID-19’s effects on sexual well-being and relationship satisfaction research are broadly discussed.

     

Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults.

Folate and methionine metabolism is involved in DNA synthesis and methylation processes. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In a case-control study, we evaluated whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase reductase (MTRR A66G) genes may have a role in altering susceptibility to adult acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types. Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20, 95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR 677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR 0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show any significant difference for all the polymorphisms investigated, but in the low-grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95% CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation.     

Postnatal development of orexin/hypocretin in rats

We examined developmental changes of orexins/hypocretins and their receptors (OX1R and OX2R) in the rat hypothalamus from postnatal day 0 to 10 weeks, using in situ hybridization histochemistry for the prepro-orexin, OX1R and OX2R mRNAs and immunohistochemistry for orexin-A and orexin-B. The prepro-orexin mRNA was weakly detected in the lateral hypothalamic area (LHA) from days 0 to 15. Orexin-A- and -B-like immunopositive cells and fibers were not detected from days 0 to 10, but they were observed after day 15. The prepro-orexin mRNA in the LHA markedly increased between days 15 and 20. The OX1R mRNA was detected in the ventromedial hypothalamic area (VMH) at day 0. The OX2R mRNA was not detected in the paraventricular nucleus (PVN) at days 0 and 1, but weakly observed on day 5. The OX1R mRNA in the VMH and OX2R mRNA in the PVN gradually increased throughout the postnatal period. Next, we examined the effects of milk deprivation and intraperitoneal (i.p.) administration of leptin on the hypothalamic prepro-orexin mRNA in pups. Although 24-h milk deprivation did not affect the level of the prepro-orexin mRNA at days 5 and 10, i.p. administration of leptin from days 0 to 3 caused a significant increase in the prepro-orexin mRNA on days 5 and 10. These results suggest that the development of orexins may be associated with developmental changes such as increase of leptin, weaning, feeding and sleep/wakefulness states.     

The effect of regular antenatal perineal massage on postnatal pain and anal sphincter injury: a prospective observational study.

OBJECTIVE: Antenatal perineal massage has been shown to reduce the incidence of perineal tears in primiparous women. The aim of this study was to determine whether perineal massage impacts on primary prevention of symptomatic disruption of the fecal continence mechanism. METHODS: An observational study recruited two cohorts of women. The first, massage group (MG) chose to perform daily perineal massage from 34 weeks gestation, and the second, control group (CG) was asked to avoid massage. Perineal injury and postnatal pain were documented and all women were invited to attend at three months postpartum for continence assessment, anal manometry, and endoanal ultrasound. RESULTS: Of 179 women recruited, 100 were in the MG while 79 women were controls. Mode of delivery was not influenced by perineal massage. Although the impact did not reach statistical significance, women aged over 30 years in the MG were more likely to be delivered with an intact perineum than controls. Postnatal perineal pain was much reduced in the MG compared with the CG (p = 0.029). Of the women recruited, 136 (75.9%) returned for a postnatal continence assessment. Manometry pressures, continence scores, and endoanal ultrasound findings were similar in both groups. CONCLUSION: Antenatal perineal massage was found to significantly affect postnatal perineal pain scores although it did not impact on the incidence of intact perineum at delivery, postnatal continence scores, anal manometry pressures, or endoanal ultrasound findings.