Antibiotic-resistant bacteria in wastewater and potential human exposure through wastewater reuse

As community-acquired antibiotic-resistant bacterial infections occur with increasing frequency, it is important to identify possible environmental reservoirs for these organisms. My dissertation evaluated the presence of antibiotic-resistant bacteria in U.S. wastewater intended for reuse and the related public health implications. My objectives were to: 1) Evaluate wastewater from four U.S. wastewater treatment plants (WWTPs) for the presence of methicillin-resistant Staphylococcus aureus (MRSA); 2) Evaluate the occurrence of vancomycin-resistant enterococci (VRE) at four U.S. WWTPs from which treated wastewater is reused; and 3) Determine and compare MRSA, methicillin-susceptible S. aureus (MSSA), VRE, and vancomcyin-susceptible enterococci (VSE) colonization among American reclaimed water spray irrigators and controls. Between 2009 and 2010, 44 wastewater samples were collected from four WWTPs, two in the Mid-Atlantic and two in the Midwest regions of the U.S. I analyzed samples for MRSA and VRE using standard membrane filtration. For the third objective, I collected 94 nasal and dermal swabs from 19 spray irrigators and 24 controls and analyzed them for MRSA, MSSA, VRE, and VSE. I confirmed all isolates and performed antimicrobial susceptibility testing by microbroth dilution. Statistical analyses included two-sample proportion tests and logistic regression. MRSA and VRE were detected at all WWTPs. The percentage of MRSA-positive samples and concentration of VRE decreased as treatment progressed. Neither MRSA nor VRE were identified in tertiary-treated samples, but I identified both in an un-chlorinated effluent sample. No MRSA or VRE were detected in nasal or dermal samples from spray irrigators or controls. MSSA and VSE were detected in 26% and 11% of spray irrigators and 29% and 0% of controls, respectively. The odds of MSSA, MDR MSSA, and either MSSA or VSE colonization were not significantly different between the spray irrigators and controls. My dissertation includes the first reports of MRSA at U.S. WWTPs and VRE at WWTPs whose effluent is intended for reuse. This is also the first U.S. evaluation of occupational exposure to antibiotic-resistant bacteria in reclaimed water. My findings provide additional scientific evidence that antibiotic-resistant bacteria can survive secondary-treated wastewater and may cause increased risks for infection among individuals exposed to reclaimed water

EVALUATION OF ANTIBIOTIC-RESISTANT BACTERIA IN TERTIARY TREATED WASTEWATER, RECLAIMED WASTEWATER USED FOR SPRAY IRRIGATION, AND RESULTING OCCUPATIONAL EXPOSURES

Occupational exposures to vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) in reclaimed wastewater used for spray irrigation were evaluated. In 2009, wastewater was collected from a tertiary-treatment facility, and reclaimed wastewater, nasal and dermal swab samples from an irrigation site. Samples were evaluated for MRSA and VRE using standard methods, PCR, and susceptibility testing. MRSA and VRE were isolated from all wastewater samples except effluent. While wastewater MRSA isolates were multidrug resistant (98%), no MRSA was isolated in irrigation water or swabs. VRE was isolated in one irrigation water sample. Fewer irrigation workers were colonized with S. aureus (31%) compared to controls (46%), but they harbored more multidrug resistant S. aureus. This is the first study to 1) evaluate antibiotic-resistant bacteria (ARB) in U.S. reclaimed wastewater and resulting occupational exposures, and 2) detect MRSA in U.S. wastewater. The findings suggested that tertiary wastewater treatment effectively reduced MRSA and VRE

Children of Holocaust Survivors on Middle-Age: A Phenomenological Inquiry

Children of Holocaust survivors are vulnerable to experiencing secondary trauma which typically manifests in emotional and psychological difficulties. Despite,their exposure to a traumatized family environment, many children of Holocaust survivors do not develop emotional or adaptive difficulties. Some demonstrate psychological resilience, reflected by their ability to adapt,to adversity and problems. The purpose of this study was to gain insight into how well-adjusted,middle aged children of Holocaust survivors developed and maintained resilience.In line with resilience theory,which explains how an individual bounces back from negative circumstances, the research questions for this study examined the factors that the participants used to develop and maintain tesilience. The sample for this study included 13 middle aged children of Holocaust survivors who described themselves as well-adjusted. The researcher collected data by conducting in-depth interviews and qualitatively analyzed the data using the modified van Kaam method of phenomenological analysis. Results showed that well-adjusted children of Holocaust survivors managed and maintained resiliency through middle age by incorporating lessons learned from their parents, including the notion that nothing can keep a person down. These findings contributed to the body of knowledge on trauma prevention and may be useful to social service providers and organizations that seek to aid individuals\u27 development of resiliency in the,wake of traumatic experiences

Necrotizing Pancreatitis: New Definitions and a New Era in Surgical Management

Background: Necrotizing pancreatitis is a challenging condition that requires surgical treatment commonly and is associated with substantial morbidity and mortality. Over the past decade, new definitions have been developed for standardization of severity of acute and necrotizing pancreatitis, and new management techniques have emerged based on prospective, randomized clinical trials. Methods: Review of English-language literature. Results: A new international classification of acute pancreatitis has been developed by PANCREA (Pancreatitis Across Nations Clinical Research and Education Alliance) to replace the Atlanta Classification. It is based on the actual local (whether pancreatic necrosis is present or not, whether it is sterile or infected) and systemic determinants (whether organ failure is present or not, whether it is transient or persistent) of severity. Early management requires goal-directed fluid resuscitation (with avoidance of over-resuscitation and abdominal compartment syndrome), assessment of severity of pancreatitis, diagnostic computed tomography (CT) imaging to assess for necrotizing pancreatitis, consideration of endoscopic retrograde cholangiopancreatography (ERCP) for biliary pancreatitis and early enteral nutrition support. Antibiotic prophylaxis is not recommended. Therapeutic antibiotics are required for treatment of documented infected pancreatic necrosis. The initial treatment of infected pancreatic necrosis is percutaneous catheter or endoscopic (transgastric/transduodenal) drainage with a second drain placement as required. Lack of clinical improvement after these initial procedures warrants consideration of minimally invasive techniques for pancreatic necrosectomy including video-assisted retroperitoneal debridement (VARD), minimally invasive retroperitoneal pancreatectomy (MIRP), or transluminal direct endoscopic necrosectomy (DEN). Open necrosectomy is associated with substantial morbidity, but to date no randomized trial has documented superiority of either minimally invasive or open surgical technique. Additional trials are underway to address this. Conclusions: Severe acute and necrotizing pancreatitis requires a multi-disciplinary treatment strategy that must be individualized for each patient. Optimal treatment of necrotizing pancreatitis now requires a staged, multi-disciplinary, minimally invasive ?step-up? approach that includes a team of interventional radiologists, therapeutic endoscopists, and surgeons.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140218/1/sur.2014.123.pd

Biobehavioral effects of Tai Chi Qigong in men with prostate cancer: Study design of a three-arm randomized clinical trial.

Fatigue is often one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions in sleep quality, and impairments in health-related quality of life. Moreover, inflammatory processes and changes related to the hypothalamic-pituitary-adrenal (HPA) axis and/or autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in prostate cancer survivors represent a current unmet need. Prior research has shown that Tai Chi Qigong, a mind-body exercise intervention, can improve physical and emotional health. Herein, we describe the protocol of the ongoing 3-arm randomized controlled Health Empowerment & Recovery Outcomes (HERO) clincal trial. One hundred sixty-six prostate cancer survivors with fatigue are randomized to a modified Tai Chi Qigong intervention (TCQ), intensity-matched body training intervention (BT), or usual care (UC) condition. Guided by biopsychosocial and psychoneuroimmunology models, we propose that TCQ, as compared to BT or UC will: i) reduce fatigue (primary outcome) in prostate cancer survivors; ii) reduce inflammation; and iii) regulate the expression of genes from two major functional clusters: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Assessments are conducted at baseline, the 6-week midpoint of the intervention, and 1 week, 3 months, and 12 months post-intervention. If our findings show that TCQ promotes recovery from prostate cancer and its treatment, this type of intervention can be integrated into survivorship care plans as the standard of care. The study's findings will also provide novel information about underlying biobehavioral mechanisms of cancer-related fatigue. Trial registration number:NCT03326713; clinicaltrials.gov

Loss of the <i>Arabidopsis thaliana</i> P4-ATPases ALA6 and ALA7 impairs pollen fitness and alters the pollen tube plasma membrane

Members of the P4 subfamily of P-type ATPases are thought to create and maintain lipid asymmetry in biological membranes by flipping specific lipids between membrane leaflets. In Arabidopsis, 7 of the 12 Aminophospholipid ATPase (ALA) family members are expressed in pollen. Here we show that double knockout of ALA6 and ALA7 (ala6/7) results in siliques with a ~2-fold reduction in seed set with a high frequency of empty seed positions near the bottom. Seed set was reduced to near zero when plants were grown under a hot/cold temperature stress. Reciprocal crosses indicate that the ala6/7 reproductive deficiencies are due to a defect related to pollen transmission. In-vitro growth assays provide evidence that that ala6/7 pollen tubes are short and slow, with ~2-fold reductions in both maximal growth rate and overall length relative to wild-type. Outcrosses show that when ala6/7 pollen are in competition with wild-type pollen, they have a near 0% success rate in fertilizing ovules near the bottom of the pistil, consistent with ala6/7 pollen having short and slow growth defects. The ala6/7 phenotypes were rescued by the expression of either an ALA6-YFP or GFP-ALA6 fusion protein, which showed localization to both the plasma membrane and highly-mobile endomembrane structures. A mass spectrometry analysis of mature pollen grains revealed significant differences between ala6/7 and wild-type, both in the relative abundance of lipid classes and in the average number of double bonds present in acyl side chains. A change in the properties of the ala6/7 plasma membrane was also indicated by a ~10-fold reduction of labeling by lipophilic FM-dyes relative to wild-type. Together, these results indicate that ALA6 and ALA7 provide redundant activities that function to directly or indirectly change the distribution and abundance lipids in pollen, and support a model in which ALA6 and ALA7 are critical for pollen fitness under normal and temperature-stress conditions

Acceptability and feasibility of cash transfers for HIV prevention among adolescent South African women

Women are at increased risk of HIV infection in much of sub-Saharan Africa. Longitudinal and cross-sectional studies have found an association between school attendance and reduced HIV risk. We report feasibility and acceptability results from a pilot of a cash transfer intervention conditional on school attendance paid to young women and their families in rural Mpumalanga, South Africa for the prevention of HIV infection. Twenty-nine young women were randomised to intervention or control and a cash payment based on school attendance made over a 2-month period. Quantitative (survey) and qualitative (focus group and interview) data collection was undertaken with young women, parents, teachers and young men in the same school. Qualitative analysis was conducted in Atlas.ti using a framework approach and basic descriptive analysis in Excel was conducted on the quantitative data. Results indicate it was both feasible and acceptable to introduce such an intervention among this population in rural South Africa. There was good understanding of the process of randomisation and the aims of the study, although some rumours developed in the study community. We address some of the changes necessary to ensure acceptability and feasibility of the main trial

The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS)

Introduction Ductal carcinoma in situ (DCIS) is a noninvasive non-obligate precursor of invasive breast cancer. With guideline concordant care (GCC), DCIS outcomes are at least as favourable as some other early stage cancer types such as prostate cancer, for which active surveillance (AS) is a standard of care option. However, AS has not yet been tested in relation to DCIS. The goal of the COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial for low-risk DCIS is to gather evidence to help future patients consider the range of treatment choices for low-risk DCIS, from standard therapies to AS. The trial will determine whether there may be some women who do not substantially benefit from current GCC and who could thus be safely managed with AS. This protocol is version 5 (11 July 2018). Any future protocol amendments will be submitted to Quorum Centralised Institutional Review Board/local institutional review boards for approval via the sponsor of the study (Alliance Foundation Trials). Methods and analysis COMET is a phase III, randomised controlled clinical trial for patients with low-risk DCIS. The primary outcome is ipsilateral invasive breast cancer rate in women undergoing GCC compared with AS. Secondary objectives will be to compare surgical, oncological and patient-reported outcomes. Patients randomised to the GCC group will undergo surgery as well as radiotherapy when appropriate; those in the AS group will be monitored closely with surgery only on identification of invasive breast cancer. Patients in both the GCC and AS groups will have the option of endocrine therapy. The total planned accrual goal is 1200 patients. Ethics and dissemination The COMET trial will be subject to biannual formal review at the Alliance Foundation Data Safety Monitoring Board meetings. Interim analyses for futility/safety will be completed annually, with reporting following Consolidated Standards of Reporting Trials (CONSORT) guidelines for noninferiority trials