SAR of non-hydrolysable analogs of pyridoxal 5'-phosphate against low molecular weight protein tyrosine phosphatase isoforms.

Kinases and phosphatases are key enzymes in cell signal transduction pathways. Imbalances in these enzymes have been linked to numerous disease states ranging from cancer to diabetes to autoimmune disorders. The two isoforms (IFA and IFB) of Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) appear to play a role in these diseases. Pyridoxal 5'-phosphate (PLP) has been shown to act as a potent but, impractical micromolar inhibitor for both isoforms. In this study, a series of non-hydrolysable phosphonate analogs of PLP were designed, synthesized and tested against the two isoforms of LMW-PTP. Assay results demonstrated that the best inhibitor for both isoforms was compound 5 with a Kis of 1.84 µM (IFA) and 15.6 µM (IFB). The most selective inhibitor was compound 16, with a selectivity of roughly 370-fold for IFA over IFB.

An Exploratory Study of Financial Health as an Antecedent of Economic Abuse Among Women Seeking Help for Intimate Partner Violence.

Economic abuse is a common component of intimate partner violence (IPV). This study explored whether IPV victim and perpetrator financial health at relationship outset are associated with two types of economic abuse-restriction and exploitation-during the relationship. With a sample of 315 women seeking services for male-perpetrated IPV, the study showed increased use of economic restriction when perpetrators were advantaged in terms of assets or disadvantaged in terms of debt. There was increased use of economic exploitation when victims were advantaged in terms of assets or credit and when perpetrators were disadvantaged in terms of assets, debt, or credit. Implications for research and intervention are discussed.

Weight Loss Expectations of Adults With Binge Eating: Cross-sectional Study With a Human-Centered Design Approach.

BACKGROUND: People tend to overestimate their expectations for weight loss relative to what is achievable in a typical evidence-based behavioral weight management program, which can impact treatment satisfaction and outcomes. We are engaged in formative research to design a digital intervention that addresses binge eating and weight management; thus, understanding expectations among this group can inform more engaging intervention designs to produce a digital intervention that can achieve greater clinical success. Studies examining weight loss expectations have primarily focused on people who have overweight or obesity. Only one study has investigated weight loss expectations among people with binge eating disorder, a population that frequently experiences elevated weight and shape concerns and often presents to treatment with the goal of losing weight. OBJECTIVE: The aim of the study is to investigate differences in weight loss expectations among people with varying levels of binge eating to inform the design of a digital intervention for binge eating and weight management. Such an evaluation may be crucial for people presenting for a digital intervention, given that engagement and dropout are notable problems for digital behavior change interventions. We tested the hypotheses that (1) people who endorsed some or recurrent binge eating would expect to lose more weight than those who did not endorse binge eating and (2) people who endorsed a more severe versus a low or moderate overvaluation of weight and shape would have higher weight loss expectations. METHODS: A total of 760 adults (n=504, 66% female; n=441, 58% non-Hispanic White) completed a web-based screening questionnaire. One-way ANOVAs were conducted to explore weight loss expectations for binge eating status as well as overvaluation of shape and weight. RESULTS: Weight loss expectations significantly differed by binge eating status. Those who endorsed some and recurrent binge eating expected to lose more weight than those who endorsed no binge eating. Participants with severe overvaluation of weight or shape expected to lose the most weight compared to those with low or moderate levels of overvaluation of weight and shape. CONCLUSIONS: In the sample, people interested in a study to inform a digital intervention for binge eating and weight management overestimated their expectations for weight loss. Given that weight loss expectations can impact treatment completion and success, it may be important to assess and modify weight loss expectations among people with binge eating prior to enrolling in a digital intervention. Future work should design and test features that can modify these expectations relative to individuals' intended treatment goals to facilitate engagement and successful outcomes in a digital intervention.

Positive affect dysregulation and its relation to binge eating size and frequency.

Negative affect is an established predictor of binge eating, yet less is known about positive affect. Low positive affect has been theorized to increase binge eating, but a better understanding is needed on the relationship between positive affect and binge eating frequency and size. Participants were 182 treatment-seeking adults (76% self-identified as female; 45% self-identified their race as Black and 40% as White; and 25% self-identified their ethnicity as Hispanic/Latino) with self-reported recurrent binge eating (≥12 binge episodes in the past 3 months). Participants completed the positive and negative affect schedule (PANAS) survey and the eating disorder examination to assess frequency of objective binge episodes (OBEs) and subjective binge episodes (SBEs) over the past 3 months. OBEs and SBEs also were combined to yield total binge episodes over the past 3 months. Independent t-tests and linear regression analyses were used to test associations between positive affect scores and binge episode size and frequencies, and to compare low versus higher positive affect on binge frequency. Additional exploratory models were conducted controlling for negative affect, identity characteristics, and socio-demographic variables. Lower positive affect was significantly associated with more frequent total binge episodes, but not OBEs and SBEs when assessed independently. Findings remained consistent when controlling for covariates and when comparing individuals with the lowest versus higher positive affect levels. Overall, results lend support to the theory that low positive affect is associated with binge eating. Increasing positive affect may be an important treatment consideration for those with recurrent binge eating.

A Novel Microfluidic Dielectrophoresis Technology to Enable Rapid Diagnosis of Mycobacteria tuberculosis in Clinical Samples.

To achieve the global efforts to end tuberculosis, affordable diagnostics suitable for true point-of-care implementation are required to reach the missing millions. In addition, diagnostics with increased sensitivity and expanded drug susceptibility testing are needed to address drug resistance and to diagnose low-bacterial burden cases. The laboratory-on-a-chip technology described herein used dielectrophoresis to selectively isolate Mycobacterium tuberculosis from sputum samples, purifying the bacterial population ahead of molecular confirmation by multiplex real-time quantitative PCR. After optimization using a panel of 50 characterized sputum samples, the performance of the prototype was assessed against the current gold standards, screening 100 blinded sputum samples using characterized and biobanked sputum provided by Foundation for Innovative New Diagnostics. Concordance with culture diagnosis was 100% for smear-negative samples and 87% for smear-positive samples. Of the smear-positive samples, the high burden sample concordance was 100%. Samples were diagnosed on the basis of visual assessment of the dielectrophoresis array and by multiplex real-time quantitative PCR assay. The results described herein demonstrate the potential of the CAPTURE-XT technology to provide a powerful sample preparation tool that could function as a front-end platform for molecular detection. This versatile tool could equally be applied as a visual detection diagnostic, potentially associated with bacterial identification for low-cost screening or coupled with an expanded PCR assay for genotypic drug susceptibility testing.

Therapeutic phlebotomy procedures and their impact on a rural hospital's red blood cell inventory and fiscal stature.

BACKGROUND: Therapeutic phlebotomy (TP) programs offer an important community service and often provide financial and donor unit resources for the hospital. This study assessed the financial impact and red blood cell (RBC) inventory contribution of a small, rural hospital-based TP program. STUDY DESIGN AND METHODS: TP procedures over 13 months were evaluated at a 142-bed rural hospital. The hospital had a Food and Drug Administration variance for a hereditary hemochromatosis (HH) donor program. The revenue for the non-HH therapeutic phlebotomies and the savings attained for units added to RBC inventory from allogeneic eligible HH donors were compiled. RESULTS: During the study, 84 patients were involved in the TP program. Of the 62 HH patients, 43 met eligibility requirements for allogeneic donations resulting in 207 donor units collected for the blood bank inventory and a savings of $21,000 in blood costs. Additionally, 22 non-HH patients underwent 183 TP procedures earning the hospital over $15,000 in net revenue. CONCLUSION: The TP program at this small, rural 142-bed hospital provided a financial gain of $36,000 during the 13-month study period. The HH donor program contributed approximately 4% to the RBC inventory. The TP program at this small, rural 142-bed hospital proved to be financially lucrative and provided a community service to patients.

Boat anchoring contributes substantially to coral reef degradation in the British Virgin Islands.

Community decline is often linked to anthropogenic activities. Coral reef declines, for example, have been linked to overfishing and climate change, but impacts of coastal development, pollution, and tourism have received increasing attention. Here, we isolated the impact of one little-studied aspect of recreational activity on coral reefs-damage from boat anchoring-by performing a survey of 24 sites in the British Virgin Islands (BVI) subject to varying levels of anchoring activity. The percent cover of hard corals and sea fans was reduced by a factor of ∼1.7 and ∼2.6 respectively at highly anchored sites. Hard coral colonies were  40% smaller in surface area and ∼60% less dense at sites experiencing high anchoring frequency. In addition, highly anchored sites supported only ∼60% of the species richness of little anchored sites. Frequently anchored sites were ∼60% as structurally complex and supported less than half as many fish as those rarely anchored, with 5 of 7 fish functional groups affected. Roughly 24% of BVI coral reef by area appears suitable for anchoring, suggesting that impacts associated with boat anchoring may be both locally severe and more pervasive than previously appreciated.

Episodic Disturbance from Boat Anchoring Is a Major Contributor to, but Does Not Alter the Trajectory of, Long-Term Coral Reef Decline.

Isolating the relative effects of episodic disturbances and chronic stressors on long-term community change is challenging. We assessed the impact of an episodic disturbance associated with human visitation (boat anchoring) relative to other drivers of long-term change on coral reefs. A one-time anchoring event at Crab Cove, British Virgin Islands, in 2004 caused rapid losses of coral and reef structural complexity that were equal to the cumulative decline over 23 years observed at an adjacent site. The abundance of small site-attached reef fishes dropped by approximately one quarter after the anchoring event, but this drop was not immediate and only fully apparent two years after the anchoring event. There was no obvious recovery from the impact, and no evidence that this episodic impact accelerated or retarded subsequent declines from other causes. This apparent lack of synergism between the effect of this episodic human impact and other chronic stressors is consistent with the few other long-term studies of episodic impacts, and suggests that action to mitigate anchor damage should yield predictable benefits.