Antimicrobial resistance in enteric bacteria: current state and next-generation solutions.

Antimicrobial resistance is one of the largest threats to global health and imposes substantial burdens in terms of morbidity, mortality, and economic costs. The gut is a key conduit for the genesis and spread of antimicrobial resistance in enteric bacterial pathogens. Distinct bacterial species that cause enteric disease can exist as invasive enteropathogens that immediately evoke gastrointestinal distress, or pathobionts that can arise from established bacterial commensals to inflict dysbiosis and disease. Furthermore, various environmental reservoirs and stressors facilitate the evolution and transmission of resistance. In this review, we present a comprehensive discussion on circulating resistance profiles and gene mobilization strategies of the most problematic species of enteric bacterial pathogens. Importantly, we present emerging approaches toward surveillance of pathogens and their resistance elements as well as promising treatment strategies that can circumvent common resistance mechanisms.

Phylogeny to function: PE/PPE protein evolution and impact on Mycobacterium tuberculosis pathogenicity.

The pe/ppe genes represent one of the most intriguing aspects of the Mycobacterium tuberculosis genome. These genes are especially abundant in pathogenic mycobacteria, with more than 160 members in M. tuberculosis. Despite being discovered over 15 years ago, their function remains unclear, although various lines of evidence implicate selected family members in mycobacterial virulence. In this review, we use PE/PPE phylogeny as a framework within which we examine the diversity and putative functions of these proteins. We report on the evolution and diversity of the respective gene families, as well as the implications thereof for function and host immune recognition. We summarize recent findings on pe/ppe gene regulation, also placing this in the context of PE/PPE phylogeny. We collate data from several large proteomics datasets, providing an overview of PE/PPE localization, and discuss the implications this may have for host responses. Assessment of the current knowledge of PE/PPE diversity suggests that these proteins are not variable antigens as has been so widely speculated; however, they do clearly play important roles in virulence. Viewing the growing body of pe/ppe literature through the lens of phylogeny reveals trends in features and function that may be associated with the evolution of mycobacterial pathogenicity.

Helping the helpers. A unique colleague support system for mental health professionals-consumers.

1. There are many professionals in the mental health workforce who have a mental illness themselves (prosumers), but who do not disclose that fact to their employers or colleagues for fear of stigma and discrimination. 2. Prosumers are in a particularly difficult situation; if they disclose, they risk being viewed as their illness, and if they do not disclose, they may not get the kinds of reasonable accommodations and support that would make their job more manageable. 3. Mutual support groups of colleagues are a viable and valuable way for prosumers to assist each other in coping with the stigma and stressors inherent in working in the mental health field.

Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury.

OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency.

Increased pressure of dilated episcleral veins with open-angle glaucoma without exophthalmos.

Six unilateral cases and one bilateral case of dilated episcleral veins with elevated intraocular pressure without exophthalmos are described. Episcleral venous pressure measured on six unilateral cases showed increased pressure in the affected eye compared to the other eye and to normal controls. Two eyes had typical glaucomatous disc and visual field changes. Five had more optic disc cupping and pallor in the eye with the elevated episcleral venous pressure and intraocular pressure. A thorough work-up, including orbital venography in two unilateral cases, carotid arteriography in one and episcleral fluorescein angiography in five cases, failed to show venous obstruction or direct arterio-venous communications. The different diagnoses are discussed. This condition should be considered in unilateral or asymmetrical intraocular pressure elevation and in those patients with chronically red eyes without discharge.

Fluorescein angiographic defects of the optic disc in glaucoma.

An improved technique for high-contast, high-resolution fluorescein angiography of the optic disc has been developed that almost eliminates pseudofluorescence. Fluorescein angiography of the optic disc was performed on normal, ocular hypertensive, and glaucomatous patients. Rapid-sequence angiograms in the early arterial phases have demonstrated localized areas of hypofluorescence or filling defects of the optic disc. Two types of fluorescein filling defects were observed-absolute and relative. The number of absolute filling defects, which increased with degree of visual field loss, was greater in glaucomatous than in ocular hypertensive or normal eyes. Similarly, ocular hypertensive eyes showed a larger number of discs with filling defects than normal eyes. It is postulated that relative defects progress to absolute filling defects, which may be an indication of impending loss of visual field.

Optic disc in glaucoma: Topography and extent of fluorescein filling defects.

The topography and extent of localized areas of hypofluorescence or absolute filling defects of the optic discs of glaucomatous patients correlated positively with the loss of visual field. Filling defects tended to cluster at the inferior and superior poles of the optic disc and were closer to the disc margin than to the center. The location of the defects corresponded with the expected site of visual field loss. There was a positive correlation between the percent area of the filling defects and the degree of visual field loss. These observations support the concept that fluorescein filling defects of the optic disc in glaucoma represent areas of ischemia that are highly correlated with loss of visual field.