Co-circulation of Multidrug-resistant Shigella Among Men Who Have Sex With Men in Australia.

BACKGROUND: In urban Australia, the burden of shigellosis is either in returning travelers from shigellosis-endemic regions or in men who have sex with men (MSM). Here, we combine genomic data with comprehensive epidemiological data on sexual exposure and travel to describe the spread of multidrug-resistant Shigella lineages. METHODS: A population-level study of all cultured Shigella isolates in the state of Victoria, Australia, was undertaken from 1 January 2016 through 31 March 2018. Antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatic analyses of 545 Shigella isolates were performed at the Microbiological Diagnostic Unit Public Health Laboratory. Risk factor data on travel and sexual exposure were collected through enhanced surveillance forms or by interviews. RESULTS: Rates of antimicrobial resistance were high, with 17.6% (95/541) and 50.6% (274/541) resistance to ciprofloxacin and azithromycin, respectively. There were strong associations between antimicrobial resistance, phylogeny, and epidemiology. Specifically, 2 major MSM-associated lineages were identified: a Shigellasonnei lineage (n = 159) and a Shigella flexneri 2a lineage (n = 105). Of concern, 147/159 (92.4%) of isolates within the S. sonnei MSM-associated lineage harbored mutations associated with reduced susceptibility to recommended oral antimicrobials: namely, azithromycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. Long-read sequencing demonstrated global dissemination of multidrug-resistant plasmids across Shigella species and lineages, but predominantly associated with MSM isolates. CONCLUSIONS: Our contemporary data highlight the ongoing public health threat posed by resistant Shigella, both in Australia and globally. Urgent multidisciplinary public health measures are required to interrupt transmission and prevent infection

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Reactive oxygen species and male reproductive hormones

Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility

High serum cholesterol levels in persons with `high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism?

Objective: The association between established hypothyroidism and high cholesterol levels is well known. The aim of the present study was to investigate the effect of thyroxine (T-4) administration on cholesterol levels in hypercholesterolemic subjects with TSH levels within the normal range (’high-normal’ TSH compared with ‘low-normal’ TSH). Design and Methods: We determined TSH levels in 110 consecutive patients referred for hypercholesterolemia (serum cholesterol > 7.5 mmol/l). Those with ‘high-normal’ TSH (2.0-4.0 mu U/ml) as well as those with ‘low-normal’ TSH (0.40-1.99 mu U/ml) were randomly assigned to receive either 25 or 50 mu g T-4 daily for two months. Thus, groups A and B (low-normal TSH) received 25 and 50 mu g T-4 respectively and groups C and D (high-normal TSH) received 25 and 50 mu g T-4 respectively. Serum T-4, tri-iodothyronine (T-3), TSH, free thyroxine index, resin T-3 uptake and thyroid autoantibodies (ThAab) as well as total cholesterol, high and low density lipoprotein cholesterol (HDL. LDL), and triglycerides were determined before and at the end of the two-month treatment period. Results: TSH levels were reduced in all groups, The most striking effect was observed in group D (TSH levels before: 2.77 +/- 0.55, after: 1.41 +/- 0.85 mu U/ml, P < 0.01). Subjects in groups C and D had a higher probability of having positive ThAabs. A significant reduction in total cholesterol (P < 0.01) and LDL (P < 0.01) was observed after treatment only in group D. In those subjects in group D who were ThAab negative, there was no significant effect of thyroxine on cholesterol levels. Conclusions: Subjects with high-normal TSH levels combined with ThAabs may, in fact, have subclinical hypothyroidism presenting with elevated cholesterol levels. It is possible that these patients might benefit from thyroxine administration