Phase I Trial of a Lactobacillus crispatus Vaginal Suppository for Prevention of Recurrent Urinary Tract Infection in Women

Objectives: We performed a phase I trial to assess the safety and tolerance of a Lactobacillus vaginal suppository for prevention of recurrent UTI. Methods: Premenopausal women with a history of recurrent UTI were randomized to use L. crispatus CTV-05 or placebo vaginal suppositories daily for five days. Results: 30 women were randomized (15 to L. crispatus CTV-05). No severe adverse events occurred. Mild to moderate vaginal discharge and genital irritation were reported by women in both study arms. Seven women randomized to L. crispatus CTV-05 developed pyuria without associated symptoms. Most women had high concentrations of vaginal H202-producing lactobacilli before randomization. L. crispatus, L. jensenii, and L. gasseri were the most common Lactobacillus species identified, with stable prevalence over time. Conclusions: L. crispatus CTV-05 can be given as a vaginal suppository with minimal sideeffects to healthy women with a history of recurrent UTI. Mild inflammation of the urinary tract was noted in some women

Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI

Obesity Early in Adulthood Increases Risk but Does Not Affect Outcomes of Hepatocellular Carcinoma

Despite the significant association between obesity and several cancers, it has been difficult to establish an association between obesity and hepatocellular carcinoma (HCC). Patients with HCC often have ascites, making it a challenge to accurately determine body mass index (BMI), and many factors contribute to the development of HCC. We performed a case–control study to investigate whether obesity early in adulthood affects risk, age of onset, or outcomes of patients with HCC

Risk Factors for SARS-CoV-2 Infection Among US Healthcare Personnel, May-December 2020

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case-control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living

Trace elements at the intersection of marine biological and geochemical evolution

Life requires a wide variety of bioessential trace elements to act as structural components and reactive centers in metalloenzymes. These requirements differ between organisms and have evolved over geological time, likely guided in some part by environmental conditions. Until recently, most of what was understood regarding trace element concentrations in the Precambrian oceans was inferred by extrapolation, geochemical modeling, and/or genomic studies. However, in the past decade, the increasing availability of trace element and isotopic data for sedimentary rocks of all ages has yielded new, and potentially more direct, insights into secular changes in seawater composition – and ultimately the evolution of the marine biosphere. Compiled records of many bioessential trace elements (including Ni, Mo, P, Zn, Co, Cr, Se, and I) provide new insight into how trace element abundance in Earth's ancient oceans may have been linked to biological evolution. Several of these trace elements display redox-sensitive behavior, while others are redox-sensitive but not bioessential (e.g., Cr, U). Their temporal trends in sedimentary archives provide useful constraints on changes in atmosphere-ocean redox conditions that are linked to biological evolution, for example, the activity of oxygen-producing, photosynthetic cyanobacteria. In this review, we summarize available Precambrian trace element proxy data, and discuss how temporal trends in the seawater concentrations of specific trace elements may be linked to the evolution of both simple and complex life. We also examine several biologically relevant and/or redox-sensitive trace elements that have yet to be fully examined in the sedimentary rock record (e.g., Cu, Cd, W) and suggest several directions for future studies

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Update on acute uncomplicated urinary tract infection in women

UTI continues to be a common problem for otherwise healthy adult women. Treatment of UTI has become more difficult because of the rising levels of resistance to commonly used antibiotics. Further research is needed to develop new antibiotic therapies and nonantibiotic prevention measures

Population-Based Epidemiologic Analysis of Acute Pyelonephritis

Background . Acute pyelonephritis is a potentially severe disease for which there are few population-based studies. We performed a population-based analysis of trends in the incidence, microbial etiology, antimicrobial resistance, and antimicrobial therapy of outpatient and inpatient pyelonephritis. Methods . A total of 4887 enrollees of Group Health Cooperative, based in Seattle, Washington, who received an International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis of acute pyelonephritis from 1997 through 2001 were identified using computerized records. Diagnoses were linked to urine culture and antibiotic prescription data. Case patients (n = 3236) included subjects who had received an inpatient or culture-confirmed outpatient diagnosis of acute pyelonephritis. Results . Among the female population, annual rates of outpatient and inpatient pyelonephritis were 12-13 cases per 10,000 population and 3-4 cases per 10,000 population, respectively; among the male population, the rates were 2-3 cases per 10,000 population and 1-2 cases per 10,000 population, respectively. Rates were relatively stable from year to year. Incidence was highest among young women, followed by infants and the elderly population. The ratio of outpatient to inpatient cases was highest among young women (ranging from 5 : 1 to 6 : 1). Escherichia coli caused 80% of cases of acute pyelonephritis in women and 70% of cases in men and was less dominant in older age groups. Among E. coli strains, the rate of ciprofloxacin resistance increased from 0.2% of isolates to 1.5% of isolates (P = .03), and the rate of trimethoprim-sulfamethoxazole resistance decreased from 25% of isolates to 13% of isolates (P <t; .01) from 1997 to 2001. Among outpatient cases, the rate of fluoroquinolone use increased from 35% to 61%, whereas the rate of trimethoprim-sulfamethoxazole use decreased from 53% to 32% over the 5-year period (P <t; .01). Conclusions . This comprehensive, population-based analysis adds to our limited knowledge of the epidemiology of acute pyelonephritis, especially among outpatients, in whom the majority of cases now occur

Age-associated differences in cognitive performance in older patients with schizophrenia: a comparison with healthy older adults

There are varying results regarding the conjoint influence of aging and schizophrenia on cognitive abilities. Previous studies have been limited by restricted age ranges among schizophrenia and psychiatrically healthy control samples as well as small numbers of control participants. To quantify the association between age and cognitive performance in patients with schizophrenia and psychiatrically healthy older adult controls and to determine if age-associated changes in cognitive performance were different in the two groups. People with schizophrenia (n = 226) and psychiatrically healthy individuals (n = 834) ranging in age from 40 to older than 80 years were compared on a battery of neuropsychological tests. To directly compare the impact of age on cognitive performance, age was also regressed on performance in the two samples. The performance of psychiatrically healthy adults age 70 and older was superior to the performance of the youngest patients with schizophrenia (age 40-49) years on measures of working and episodic memory, executive function, and psychomotor speed. Regression analyses indicated that age effects on cognition were significantly greater for schizophrenia patients on measures of verbal learning and speed of processing. Within both the schizophrenia group, and psychiatrically healthy adults, the greatest age-related differences in performance seemed to occur for individuals aged more than 70 years. In this cross-sectional study, the present findings underscore the fact that schizophrenia is associated with cognitive impairment across all ages and that older schizophrenia patients experience relatively greater age associated differences in cognitive functioning than healthy individuals. These findings have wide-ranging implications regarding the ability of older patients with schizophrenia to function independently and for the development of treatment strategies