Efficacy of Eye Movement Desensitization and Reprocessing Therapy in the Treatment of Trauma: A Systematic Review

This systematic review examines the efficacy of Eye Movement Desensitization and Reprocessing (EMDR) Therapy as an intervention in the treatment of trauma in adults. Upon careful review of present literature, 14 articles met criteria. Common themes were identified throughout the reviewed studies, including treatment intervention comparison, variation in EMDR model, treatment fidelity, longitudinal follow-up, and co-morbidity. While results show that EMDR is an effective treatment intervention for the treatment of trauma, the majority of studies found it to be no more effective than other treatment interventions

Efficacy of Eye Movement Desensitization and Reprocessing Therapy in the Treatment of Trauma: A Systematic Review

This systematic review examines the efficacy of Eye Movement Desensitization and Reprocessing (EMDR) Therapy as an intervention in the treatment of trauma in adults. Upon careful review of present literature, 14 articles met criteria. Common themes were identified throughout the reviewed studies, including treatment intervention comparison, variation in EMDR model, treatment fidelity, longitudinal follow-up, and co-morbidity. While results show that EMDR is an effective treatment intervention for the treatment of trauma, the majority of studies found it to be no more effective than other treatment interventions

Targeting Coenzyme A Biosynthesis for Antifungal Development.

An estimated 1.5 million people die each year from invasive fungal infections (IFIs) involving dissemination to the deeper organs via the bloodstream, with estimated healthcare costs of over $7 billion in the U.S. alone. Collectively, several Candida species account for more than 75% of disseminated fungal infections in the U.S., with attributable mortality rates ranging 35-75%. Unfortunately, the prospect of curing these infections is limited by the modest efficacy of the available antifungal drugs: the azoles, echinocandins, and amphotericin B. Approximately one-third of patients with disseminated Candida infections are non-responsive to treatment with the azoles, and favorable response rates are just 52-73% for the echinocandins and just 62% for amphotericin B. As such, there is an urgent need for development of new antifungal drugs with improved clinical efficacy. Coenzyme A (CoA) is a universal and essential cofactor for several key metabolic pathways including fatty acid oxidation and synthesis, the tricarboxylic acid cycle, and sterol biosynthesis. Nearly all organisms must synthesize their own CoA from pantothenic acid (vitamin B5-PA) through a five-step sequence of reactions requiring ATP and cysteine. Several bacterial species can take up exogenous PA through the PanF transporter, or produce it de novo from beta-alanine and pantoate, in a reaction catalyzed by pantothenate synthetase (PS). Similarly, the model yeast, Saccharomyces cerevisiae, can acquire exogenous PA through the pantothenate symporter (Fen2p) or synthesize it de novo using PS, encoded by the PAN6 gene. In contrast, mammalian cells lack the enzymes required for endogenous PA production, instead depending upon a sodium-driven multivitamin transporter to import from exogenous sources. Thus, this has raised interest in exploiting the fundamental difference in physiology to develop pathogen-selective antimicrobial agents targeting enzymes involved in PA production. Pantothenate kinase (PanK), encoded by the CAB1 gene in S. cerevisiae, catalyzes the first step in the conversion of PA to CoA. PanK has been confirmed to be essential for the viability of S. cerevisiae as well as several bacterial species. However, the CoA biosynthetic pathway is not well characterized in one of the most medically important human fungal pathogens, C. albicans. Therefore, we sought to investigate the importance of pantothenate uptake, synthesis, and conversion to CoA for C. albicans survival and virulence. A Candida albicans fen2∆/∆ mutant was viable in vitro and virulent in a mouse model of disseminated infection. In contrast, the growth of C. albicans strains with doxycycline repressible expression of PAN6 (PTETO-PAN6) or CAB1 (PTETO-CAB1), was arrested in the presence of doxycycline, even in medium supplemented with pantothenate. Furthermore, overexpression of C. albicans FEN2 was not sufficient to restore growth of PTETO-PAN6 even in the presence of PA. This suggests that C. albicans is unable to uptake sufficient exogenous PA to support growth. Moreover, neither strain was virulent in doxycycline treated mice. Collectively, these results establish that Cab1p and Pan6p are essential for C. albicans survival and virulence, and therefore, are valid targets for antifungal development. To facilitate the discovery of Pan6p or Cab1p inhibitors, we validated high-throughput compatible screening assays. Target-based whole-cell and biochemical screens identified small molecules that specifically target C. albicans Cab1p or Pan6p. This includes a compound that targets CaCab1p and has broad spectrum antifungal activity as well as in vivo efficacy. In addition, we solved the first eukaryotic pantothenate synthetase crystal structure, C. albicans PS, to support identification and optimization of compounds that specifically interact with the fungal protein in an effort to expand development of novel antifungal therapies with improved patient outcomes

Extra-articular arthroscopic release of lateral epicondylitis: a prospective study

Background: Operative management of lateral epicondylitis can be managed with percutaneous, arthroscopic, or open surgical release. Extraarticular arthroscopic release is a new technique, and no study has compared its outcomes and risk profile. Methods: A 26-patient cohort was reviewed before and after extraarticular arthroscopic release, which was performed by the senior author. The Mayo Elbow Performance Scores were used as a functional outcome score and obtained via a phone interview. Results were analyzed using a paired t-test with a statistical significance set at P \u3c .05. Results: Of the 26 patients, 10 were being treated under workers compensation. Preoperative Mayo Elbow Performance Score was 47.5, and the postoperative score was 90.2 with a significant difference of 42.7 (P value 1⁄4 .05). The workers compensation group scored 13.3 points lower postoperatively than the remainder of patients, which was shown to also be significant with a P value of .002. Discussion and Conclusion: The advantage of extraarticular arthroscopic release was better visualiza- tion of affected structures, which improved accuracy of debridement, and a small capsulotomy, which decreased the risk of a transient radial nerve palsy. Overall, extraarticular arthroscopic results were found to be good and comparable to the results of other operative techniques with the added advantage of a lower risk profile

Why Wait?: Early Enteral Feeding After Pediatric Gastrostomy Tube Placement

Purpose Early initiation of feedings after gastrostomy tube (GT) placement may reduce associated hospital costs, but many surgeons fear complications could result from earlier feeds. We hypothesized that, irrespective of placement method, starting feedings within the first 6 h following GT placement would not result in a greater number of post-operative complications. Methods An IRB-approved retrospective review of all GTs placed between January 2012 and December 2014 at three academic institutions was undertaken. Data was stratified by placement method and whether the patient was initiated on feeds at less than 6 h or after. Baseline demographics, operative variables, post-operative management and complications were analyzed. Descriptive statistics were used and P-values < 0.05 were considered significant. Results One thousand and forty-eight patients met inclusion criteria. GTs were inserted endoscopically (48.9%), laparoscopically (44.9%), or via an open approach (6.2%). Demographics were similar in early and late fed groups. When controlling for method of placement, those patients who were fed within the first 6 h after gastrostomy placement had shorter lengths of stay compared to those fed greater than 6 h after placement (P < 0.05). Total post-operative outcomes were equivalent between feeding groups for all methods of placement (laparoscopic (P = 0.87), PEG (P = 0.94), open (P = 0.81)). Conclusions Early initiation of feedings following GT placement was not associated with an increase in complications. Feeds initiated earlier may shorten hospital stays and decrease overall hospital costs

A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ∼50% of patients with HF, the mechanisms of disease are poorly understood, and therapies are generally ineffective in reducing HF progression. Animal models of HFpEF not due to pressure or volume overload are lacking, therefore limiting in-depth understanding of the pathophysiological mechanisms and the development of novel therapies. We hypothesize that a continuous infusion of low-dose angiotensin II (AT(II)) is sufficient to induce left ventricular (LV) diastolic dysfunction and HFpEF, without increasing blood pressure or inducing LV hypertrophy or dilatation. Osmotic pumps were implanted subcutaneously in 8-wk-old male mice assigned to the AT(II) (0.2 mg·kg(−1)·day(−1)) or volume-matched vehicle (N = 8/group) for 4 wk. We measured systolic and diastolic arterial blood pressures through a tail-cuff transducer, LV dimensions and ejection fraction through echocardiography, and LV relaxation through pulsed-wave Doppler and LV catheterization. Myocardial fibrosis and cardiomyocyte cross-sectional area were measured. AT(II) infusion had no effects on systemic arterial blood pressure. AT(II) induced significant impairment in LV diastolic function, as measured by an increase (worsening) in LV isovolumetric relaxation time, myocardial performance index, isovolumetric relaxation time constant, and LV end-diastolic pressure without altering LV dimensions, mass, or ejection fraction. Chronic infusion of low-dose AT(II) recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF

Overexpression of the astrocyte glutamate transporter GLT1 exacerbates phrenic motor neuron degeneration, diaphragm compromise, and forelimb motor dysfunction following cervical contusion spinal cord injury.

A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, in bacterial artificial chromosome-GLT1-enhanced green fluorescent protein reporter mice following unilateral midcervical (C4) contusion SCI, numbers of GLT1-expressing astrocytes in ventral horn and total intraspinal GLT1 protein expression were reduced soon after injury and the decrease persisted for ≥6 weeks. We used intraspinal delivery of adeno-associated virus type 8 (AAV8)-Gfa2 vector to rat cervical spinal cord ventral horn for targeting focal astrocyte GLT1 overexpression in areas of PhMN loss. Intraspinal delivery of AAV8-Gfa2-GLT1 resulted in transduction primarily of GFAP(+) astrocytes that persisted for ≥6 weeks postinjury, as well as increased intraspinal GLT1 protein expression. Surprisingly, we found that astrocyte-targeted GLT1 overexpression increased lesion size, PhMN loss, phrenic nerve axonal degeneration, and diaphragm neuromuscular junction denervation, and resulted in reduced functional diaphragm innervation as assessed by phrenic nerve-diaphragm compound muscle action potential recordings. These results demonstrate that GLT1 overexpression via intraspinal AAV-Gfa2-GLT1 delivery exacerbates neuronal damage and increases respiratory impairment following cervical SCI

Assessments of residential and global positioning system activity space for food environments, body mass index and blood pressure among low-income housing residents in New York City

Research has examined how the food environment affects the risk of cardiovascular disease (CVD). Many studies have focused on residential neighbourhoods, neglecting the activity spaces of individuals. The objective of this study was to investigate whether food environments in both residential and global positioning system (GPS)-defined activity space buffers are associated with body mass index (BMI) and blood pressure (BP) among low-income adults. Data came from the New York City Low Income Housing, Neighborhoods and Health Study, including BMI and BP data (n=102, age=39.3±14.1 years), and one week of GPS data. Five food environment variables around residential and GPS buffers included: fast-food restaurants, wait-service restaurants, corner stores, grocery stores, and supermarkets. We examined associations between food environments and BMI, systolic and diastolic BP, controlling for individual- and neighbourhood-level sociodemographics and population density. Within residential buffers, a higher grocery store density was associated with lower BMI (β=- 0.20 kg/m2, P<0.05), and systolic and diastolic BP (β =-1.16 mm Hg; and β=-1.02 mm Hg, P<0.01, respectively). In contrast, a higher supermarket density was associated with higher systolic and diastolic BP (β=1.74 mm Hg, P<0.05; and β=1.68, P<0.01, respectively) within residential buffers. In GPS neighbourhoods, no associations were documented. Examining how food environments are associated with CVD risk and how differences in relationships vary by buffer types have the potential to shed light on determinants of CVD risk. Further research is needed to investigate these relationships, including refined measures of spatial accessibility/exposure, considering individual’s mobility