Lifestyle and health factors associated with progressing and remitting trajectories of untreated lower urinary tract symptoms among elderly men.

BackgroundKnowledge of factors associated with the course of lower urinary tract symptoms (LUTS) before treatment is needed to inform preventive interventions. In a prospective study of elderly men untreated for LUTS, we identified factors associated with symptom progression and remission.MethodsIn community-dwelling US men aged ≥65 years, the American Urological Association Symptom Index (AUA-SI) was repeated four times, once at baseline (2000-2002) and then every 2 years thereafter. Analyses included 1740 men with all four AUA-SI assessments, who remained free from diagnosed prostate cancer, and who reported no treatment for LUTS or BPH during follow-up that averaged 6.9 (±0.4) years. LUTS change was determined with group-based trajectory modelingof the repeated AUA-SI measures. Multivariable logistic regression was then used to determine the baseline factors associated with progressing compared with stable trajectories, and with remitting compared with progressing trajectories. Lifestyle, body mass index (BMI) (kg/m(2)), mobility, mental health (Short-Form 12), medical history and prescription medications were considered for selection. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for variables in each model.ResultsWe identified 10 AUA-SI trajectories: 4 stable (1277 men, 73%), three progressing (345 men, 20%), two remitting (98 men, 6%) and one mixed (20 men, 1%). Men in progressing compared with stable trajectories were more likely to have mobility limitations (OR=2.0, 95% CI: 1.0-3.8), poor mental health (OR=1.9, 95% CI: 1.1-3.4), BMI≥25.0 kg m(-2) (OR=1.7, 95% CI: 1.0-2.8), hypertension (OR=1.5, 95% CI: 1.0-2.4) and back pain (OR=1.5, 95% CI: 1.0-2.4). Men in remitting compared with progressing trajectories more often used central nervous system medications (OR=2.3, 95% CI: 1.1-4.9) and less often had a history of problem drinking (OR=0.4, 95% CI: 0.2-0.9).ConclusionsSeveral non-urological lifestyle and health factors were independently associated with risk of LUTS progression in older men

A sediment-based reconstruction of Caribbean effective precipitation during the Little Ice Age from Freshwater Pond, Barbuda

Contemporary climate dynamics of the circum-Caribbean region are characterised by significant precipitation variability on interannual and interdecadal timescales controlled primarily by El Niño Southern Oscillation (ENSO) and the Atlantic Multidecadal Oscillation (AMO). However, our understanding of pre-industrial climate variability in the region is hampered by the sparse geographic distribution of palaeoclimate archives. Here, we present a high-resolution reconstruction of effective precipitation for Barbuda since the mid-16th century, based on biostratigraphic and stable isotope analyses of fossil ostracods and gastropods recovered from lake sediment cores from Freshwater Pond, the only freshwater lake on the island. We interpret episodic fluctuations in shell accumulation in the sediment record to represent changes in the balance between precipitation and evaporation during the ‘Little Ice Age’ (LIA; ~1400–1850 CE) and Industrial (1850–present) periods. Comparisons between indices of reconstructed ENSO and AMO variability, the abundance of the freshwater gastropod Pyrgophorus parvulus and the δ18O records from ostracod calcite suggest that the relative influence of ENSO and AMO on long-term rainfall patterns in Barbuda has changed over the last 400 years. Our findings are in agreement with other high-resolution palaeoclimate studies that suggest that long-term changes in effective precipitation during the LIA were much more variable, temporally and spatially, than previously suggested

Use of a twelve month's self referral reminder to faciliate uptake of bowel scope (flexible sigmoidoscopy screening) in previous non-responders: a London-based feasibility study

Background: In March 2013, NHS England extended its national Bowel Cancer Screening Programme to include ‘one-off’ Flexible Sigmoidoscopy screening (NHS Bowel Scope Screening, BSS) for men and women aged 55. With less than one in two people currently taking up the screening test offer, there is a strong public health mandate to develop system-friendly interventions to increase uptake while the programme is rolling out. This study aimed to assess the feasibility of sending a reminder to previous BSS non-responders, 12 months after the initial invitation, with consideration for its potential impact on uptake. Method: This study was conducted in the ethnically diverse London Boroughs of Brent and Harrow, where uptake is below the national average. Between September and November 2014, 160 previous non-responders were randomly selected to receive a reminder of the opportunity to self-refer 12 months after their initial invitation. The reminder included instructions on how to book an appointment, and provided options for the time and day of the appointment and the gender of the endoscopist performing the test. To address barriers to screening, the reminder was sent with a brief locally tailored information leaflet designed specifically for this study. Participants not responding within 4 weeks were sent a follow-up reminder, after which there was no further intervention. Self-referral rates were measured 8 weeks after the delivery of the follow-up reminder and accepted as final. Results: Of the 155 participants who received the 12 months’ reminder (returned to sender, n=5), 30 (19.4%) self-referred for an appointment, of which 24 (15.5%) attended and were successfully screened. Attendance rates differed by gender, with significantly more women attending an appointment than men (20.7% vs 8.8%, respectively; OR=2.73, 95% CI=1.02–7.35, P=0.05), but not by area (Brent vs Harrow) or area-level deprivation. Of the 30 people who self-referred for an appointment, 27 (90%) indicated a preference for a same-sex practitioner, whereas three (10%) gave no preference. Preference for a same-sex practitioner was higher among women than men (χ2=7.78, P<0.05), with only 67% of men (six of nine) requesting a same-sex practitioner, compared with 100% of women (n=21). Conclusions: Sending previous non-responders a 12 months’ reminder letter with a brief information leaflet is a feasible and efficacious intervention, which merits further investigation in a randomised controlled trial

Parentage test in broad-snouted caimans (Caiman latirostris, Crocodylidae) using microsatellite DNA

In this study, microsatellite markers, developed for Alligator mississipiensis and Caiman latirostris, were used to assess parentage among individuals from the captive colony of Caiman latirostris at the University of São Paulo, in Piracicaba, São Paulo, Brazil. Many of the females in the colony were full siblings, which made maternal identification difficult due to genotypic similarity. Even so, the most likely mother could be identified unambiguously among offspring in most of the clutches studied. Two non-parental females displayed maternal behavior which would have misled managers in assigning maternity based on behavior alone. This set of variable loci demonstrates the utility of parentage testing in captive propagation programs

High glucose up-regulates ENaC and SGK1 expression in HCD-cells

Background/Aim: Diabetic nephropathy is associated with progressive renal damage, leading to impaired function and end-stage renal failure. Secondary hypertension stems from a deranged ability of cells within the kidney to resolve and appropriately regulate sodium resorption in response to hyperglycaemia. However, the mechanisms by which glucose alters sodium re-uptake have not been fully characterised. Methods: Here we present RT-PCR, western blot and immunocytochemistry data confirming mRNA and protein expression of the serum and glucocorticoid inducible kinase (SGK1) and the a conducting subunit of the epithelial sodium channel (ENaC) in a model in vitro system of the human cortical collecting duct (HCD). We examined changes in expression of these elements in response to glucose challenge, designed to mimic hyperglycaemia associated with type 2 diabetes mellitus. Changes in Na+ concentration were assessed using single-cell microfluorimetry. Results: Incubation with glucose, the Ca2+-ionophore ionomycin and the cytokine TGF-beta 1 were all found to evoke significant and time-dependent increases in both SGK1 and alpha ENaC protein expression. These molecular changes were correlated to an increase in Na+-uptake at the single-cell level. Conclusion: Together these data offer a potential explanation for glucose-evoked Na+-resorption and a potential contributory role of SGK1 and ENaCs in development of secondary hypertension, commonly linked to diabetic nephropathy

Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

Systemic but not local rehydration restores dehydration-induced changes in pulmonary function in healthy adults

Copyright © 2021 The Authors. Water transport and local (airway) hydration are critical for the normal functioning of lungs and airways. Currently, there is uncertainty regarding the effects of systemic dehydration on pulmonary function. Our aims were 1) to clarify the impact of exercise- or fluid restriction-induced dehydration on pulmonary function in healthy adults; and 2) to establish whether systemic or local rehydration can reverse dehydration-induced alterations in pulmonary function. Ten healthy participants performed four experimental trials in a randomized order (2 h exercise in the heat twice and 28 h fluid restriction twice). Pulmonary function was assessed using spirometry and whole body plethysmography in the euhydrated, dehydrated, and rehydrated states. Oral fluid consumption was used for systemic rehydration and nebulized isotonic saline inhalation for local rehydration. Both exercise and fluid restriction induced mild dehydration (2.7 ± 0.7% and 2.5 ± 0.4% body mass loss, respectively; P < 0.001) and elevated plasma osmolality (P < 0.001). Dehydration across all four trials was accompanied by a reduction in forced vital capacity (152 ± 143 mL, P < 0.01) and concomitant increases in residual volume (216 ± 177 mL, P < 0.01) and functional residual capacity (130 ± 144 mL, P < 0.01), with no statistical differences between modes of dehydration. These changes were normalized by fluid consumption but not nebulization. Our results suggest that, in healthy adults: 1) mild systemic dehydration induced by exercise or fluid restriction leads to pulmonary function impairment, primarily localized to small airways; and 2) systemic, but not local, rehydration reverses these potentially deleterious alterations

Comparison of techniques for handling missing covariate data within prognostic modelling studies: a simulation study

Background: There is no consensus on the most appropriate approach to handle missing covariate data within prognostic modelling studies. Therefore a simulation study was performed to assess the effects of different missing data techniques on the performance of a prognostic model. Methods: Datasets were generated to resemble the skewed distributions seen in a motivating breast cancer example. Multivariate missing data were imposed on four covariates using four different mechanisms; missing completely at random (MCAR), missing at random (MAR), missing not at random (MNAR) and a combination of all three mechanisms. Five amounts of incomplete cases from 5% to 75% were considered. Complete case analysis (CC), single imputation (SI) and five multiple imputation (MI) techniques available within the R statistical software were investigated: a) data augmentation (DA) approach assuming a multivariate normal distribution, b) DA assuming a general location model, c) regression switching imputation, d) regression switching with predictive mean matching (MICE-PMM) and e) flexible additive imputation models. A Cox proportional hazards model was fitted and appropriate estimates for the regression coefficients and model performance measures were obtained. Results: Performing a CC analysis produced unbiased regression estimates, but inflated standard errors, which affected the significance of the covariates in the model with 25% or more missingness. Using SI, underestimated the variability; resulting in poor coverage even with 10% missingness. Of the MI approaches, applying MICE-PMM produced, in general, the least biased estimates and better coverage for the incomplete covariates and better model performance for all mechanisms. However, this MI approach still produced biased regression coefficient estimates for the incomplete skewed continuous covariates when 50% or more cases had missing data imposed with a MCAR, MAR or combined mechanism. When the missingness depended on the incomplete covariates, i.e. MNAR, estimates were biased with more than 10% incomplete cases for all MI approaches. Conclusion: The results from this simulation study suggest that performing MICE-PMM may be the preferred MI approach provided that less than 50% of the cases have missing data and the missing data are not MNAR

Composite Dirac Neutrinos

We present a mechanism that naturally produces light Dirac neutrinos. The basic idea is that the right-handed neutrinos are composite. Any realistic composite model must involve `hidden flavor' chiral symmetries. In general some of these symmetries may survive confinement, and in particular, one of them manifests itself at low energy as an exact $B-L$ symmetry. Dirac neutrinos are therefore produced. The neutrinos are naturally light due to compositeness. In general, sterile states are present in the model, some of them can naturally be warm dark matter candidates.Comment: 12 pages; Sec. IIC updated; minor corrections; published versio