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This article describes an interdisciplinary approach to nutrition assessment and intervention in children and adults with a wide range of severe physical and developmental disabilities. The challenge was to collaborate with other health and education disciplines, and to integrate the nutritional rehabilitation goals with the goals of overall health care, in order to provide a comprehensive interdisciplinary nutrition intervention program. The interdisciplinary team approach enhanced a sense of cooperation among all staff united by a common goal of achieving optimal medical and nutritional support for all residents. Copyright © 2001 by Aspen Publishers, Inc. [ABSTRACT FROM AUTHOR]

Mitochondrial transplantation and transfer are being explored as therapeutic options in acute and chronic diseases to restore cellular function in injured tissues. To limit potential immune responses and rejection of donor mitochondria, current clinical applications have focused on delivery of autologous mitochondria. We recently convened a Mitochondrial Transplant Convergent Working Group (CWG), to explore three key issues that limit clinical translation: (1) storage of mitochondria, (2) biomaterials to enhance mitochondrial uptake, and (3) dynamic models to mimic the complex recipient tissue environment. In this review, we present a summary of CWG conclusions related to these three issues and provide an overview of pre-clinical studies aimed at building a more robust toolkit for translational trials., (© 2024. The Author(s).)

Background: Peripheral artery disease (PAD) is associated with high morbidity and mortality and has been commonly described as a coronary heart disease equivalent. Statin medications are recommended for primary prevention of atherosclerotic cardiovascular disease (CVD) among other indications. Therefore, understanding the longitudinal relationship of incident PAD is necessary to inform future research on how to prevent the disease. Depression complicates CVD patients' ability to properly adhere to their medications, yet the effect of depression on the relationship between statin use and incident PAD is understudied. People with PAD have a higher incidence of depressive symptoms than people without PAD. Black American and Hispanic populations are disproportionately affected by both PAD and depression yet research on the modifying effect of either race or depression on the relationship between statin use and onset of PAD is minimal. While statin utilization is highest for ages 75-84 years, there is minimal evidence of favorable risk-benefit balance. Consequently, in this project, we examined the relationship between statin use and incident PAD and whether this relationship is modified by race/ethnicity, depressive symptoms, or age., Methods: We used data on participants from the Multi-Ethnic Study of Atherosclerosis from visit 1 (2000) through study visit 6 (2020) who had three separate measurements of the ankle-brachial index (ABI) taken at visit 1, visit 3, and visit 5. Incident PAD was defined as 1) incident lower extremity amputation or revascularization or 2) ABI less than 0.90 coupled with ABI decrease greater than 0.15 over the follow-up period. Statin use was noted on the study visit prior to incident PAD diagnosis while depressive symptoms were measured at exam 1, visit 3, and visit 5. Propensity score matching was implemented to create balance between the participants in the two treatment groups, that is, statin-treated and statin-untreated groups, to reduce the problem of confounding by indication. Propensity scores were calculated using multivariate logistic regression model to estimate the probability of receiving statin treatment. We used Cox proportional hazards regression to investigate the relationship between time-dependent statin use as well as other risk factors with incident PAD, overall and stratified by 1) race, 2) depression status, and 3) age., Results: A total of 4,210 participants were included in the final matched analytic cohort. There were 810 incident cases (19.3%) of PAD that occurred over an average (mean) of 11.3 years (SD = 5.7) of follow-up time. In the statin-treated group, and with an average follow-up time of 12.5 years (SD = 5.6), there were 281 cases (13.4%) of incident PAD with the average follow-up time of 10.1 years (SD = 5.5), whereas in the statin-untreated group, there were 531 cases (25.2%) (P < 0.001). Results demonstrate a lower risk of PAD event in the statin-treated group compared to the untreated group (hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.33-0.62) over the span of 18.5 years. The interactions between 1) depression and 2) race with statin use for incident PAD were not significant. However, other risk factors which were significant included Black American race that had approximately 30% lower hazard of PAD compared to non-Hispanic White (HR = 0.70, 95% CI: 0.58-0.84); age-stratified models were also fitted, and stain use was still a significant treatment factor for ages 45-54 (HR = 0.45, 95% CI: 0.33-0.63), 55-64 (HR = 0.61, 95% CI: 0.46-0.79), and 65-74 years (HR = 0.61, 95% CI: 0.48-0.78) but not for ages 75-84 years., Conclusions: Statin use was associated with a decreased risk of incident PAD for those under the age of 75 years. Neither race nor depression significantly modified the relationship between statin use and incident PAD; however, the risk of incident PAD was lower among Black Americans. These findings highlight that the benefit of statin may wane for those over the age of 75 years. Findings also suggest that statin use may not be compromised in those living with depression., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Anatomy is critical in risk stratification and therapeutic decision making in coronary disease. The relationship between anatomy and outcomes is not well described in PAD. We sought to develop an angiographic core lab within the VOYAGER-PAD trial. The current report describes the methods of creating this core lab, its study population, and baseline anatomic variables. Methods: Patients undergoing lower-extremity revascularization for symptomatic PAD were randomized in VOYAGER-PAD. The median follow up was 2.25 years. Events were adjudicated by a blinded Clinical Endpoint Committee. Angiograms were collected from study participants; those with available angiograms formed this core lab cohort. Angiograms were scored for anatomic and flow characteristics by trained reviewers blinded to treatment. Ten percent of angiograms were evaluated independently by two reviewers; inter-rater agreement was assessed. Clinical characteristics and the treatment effect of rivaroxaban were compared between the core lab cohort and noncore lab participants. Anatomic data by segment were analyzed. Results: Of 6564 participants randomized in VOYAGER-PAD, catheter-based angiograms from 1666 patients were obtained for this core lab. Anatomic and flow characteristics were collected across 16 anatomic segments by 15 reviewers. Concordance between reviewers for anatomic and flow variables across segments was 90.5% (24,417/26,968). Clinical characteristics were similar between patients in the core lab and those not included. The effect of rivaroxaban on the primary efficacy and safety outcomes was also similar. Conclusions: The VOYAGER-PAD angiographic core lab provides an opportunity to correlate PAD anatomy with independently adjudicated outcomes and provide insights into therapy for PAD. (ClinicalTrials.gov Identifier: NCT02504216) ., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs Rogers, Hogan, Nehler, Capell, Berkowitz, Hess, Yčas, and Bonaca receive salary support from CPC, a nonprofit academic research organization affiliated with the University of Colorado that receives or has received research grant/consulting funding between February 2021 and June 2023 from the following organizations: Abbott Laboratories, Adamis Pharmaceuticals Corporation, Agios Pharmaceuticals, Inc., Alexion Pharma, Alnylam Pharmaceuticals, Inc., Amgen Inc., Angionetics, Inc., ARCA Biopharma, Inc., Array BioPharma, Inc., AstraZeneca and Affiliates, Atentiv LLC, Audentes Therapeutics, Inc., Bayer and Affiliates, Beth Israel Deaconess Medical Center, Better Therapeutics, Inc., BIDMC, Boston Clinical Research Institute, Bristol-Meyers Squibb Company, Cambrian Biopharma, Inc., Cardiol Therapeutics Inc., CellResearch Corp., Cook Medical Incorporated, Covance, CSL Behring LLC, Eidos Therapeutics, Inc., EP Trading Co. Ltd, EPG Communication Holdings Ltd, Epizon Pharma, Inc., Esperion Therapeutics, Inc., Everly Well, Inc., Exicon Consulting Pvt Ltd, Faraday Pharm-aceuticals, Inc., Foresee Pharmaceuticals Co. Ltd, Fortress Biotech, Inc., HDL Therapeutics Inc., HeartFlow Inc., Hummingbird Bioscience, Insmed Inc., Ionis Pharmaceuticals, IQVIA Inc., JanOne Biotech Holdings Inc., Janssen and Affiliates, Kaneka, Kowa Research Institute, Inc., Kyushu University, Lexicon Pharm-aceuticals, Inc., LSG Kyushu University, Medimmune Ltd, Medpace, Merck & Affiliates, Novartis Pharmaceuticals Corp., Novate Medical, Ltd, Novo Nordisk, Inc., Pan Industry Group, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PPD Development, LP, Prairie Education and Research Cooperative, Prothena Biosciences Limited, Regeneron Pharmaceuticals, Inc., Regio Biosciences, Inc., Rexgenero, Sanifit Therapeutics S.A., Sanofi-Aventis Groupe, Silence Therapeutics PLC, Smith & Nephew plc, Stealth Bio-Therapeutics Inc., State of Colorado CCPD Grant, The Brigham & Women’s Hospital, Inc., The Feinstein Institutes for Medical Research, Thrombosis Research Institute, University of Colorado, University of Pittsburgh, VarmX, Virta Health Corporation, WCT Atlas, Worldwide Clinical Trials Inc., WraSer, LLC, and Yale Cardiovascular Research Group. Dr Bonaca receives support from the AHA SFRN under award numbers 18SFRN3390085 (BWH-DH SFRN Center) and 18SFRN-33960262 (BWH-DH Clinical Project). Dr Bonaca also reports stock in Medtronic and Pfizer.

Competing Interests: Disclosures Drs Hogan, Nehler, Berkowitz, and Bonaca receive salary support from CPC through funds transferred to the University of Colorado. CPC, a nonprofit academic research organization affiliated with the University of Colorado, receives research funding from Abbott, Agios, Alexion Pharma, Alnylam, Amgen, Angionetics, ARCA Biopharma, Array, AstraZeneca, Atentiv, Audentes, Bayer, Better Therapeutics, Brigham and Women’s Hospital, Bristol Myers Squibb, Cardiol Therapeutics, CellResearch, Cook Medical, Cook, CSL Behring, Eidos Therapeutics, EP Trading Co, Esperion Therapeutics, EverlyWell, Faraday, Fortress Biotech, DHL Therapeutics, Hearflow, Hummingbird Bioscience, Insmed, Janssen, Kowa Research, Lexicon, Merck, Medtronic, Moderna, Novate Medical, Novo Nordisk, Pfizer, PhasBio, PPD Development, Prairie Education and Research, Prothena Biosciences, Regeneron, Regio Biosciences, Sanifit Therapeutics, Sanofi, Smith and Nephew, Stealth BioTherapeutics, University of Colorado, Worldwide Clinical Trials, Wraser, and Yale Cardiovascular Research Group. Dr Debus receives grant support from Cook and Terumo Aortic. Dr Patel receives grant support, advisory board fees, and consulting fees from AstraZeneca, Bayer, and Janssen, grant support from Medtronic and Philips Healthcare, and grant support and advisory board fees from Heartflow. Dr Anand receives lecture fees from Bayer and Janssen. Dr Muehlhofer is employed by Bayer. Dr Haskell is employed full time by Janssen Pharmaceuticals, LLC. Dr Berkowitz was employed as a clinical research physician by Bayer at the time VOYAGER PAD was performed. Dr Bauersachs receives consulting fees and lecture fees from Bayer, Bristol Myers Squibb, and Pfizer. Dr Bonaca is the Executive Director of CPC and receives grant support from Amgen, AstraZeneca, Merck, Novo Nordisk, Pfizer, and Sanofi and support from the American Heart Association Strategically Focused Research Network under award numbers 18SFRN3390085 (BWH-DH SFRN Center) and 18SFRN33960262 (BWH-DH Clinical Project). Dr Bonaca also reports stock in Medtronic and Pfizer and consulting fees from Audentes.

Importance: Trials showing equivalent or better outcomes with initial evaluation using coronary computed tomography angiography (cCTA) compared with stress testing in patients with stable chest pain have informed guidelines but raise questions about overtesting and excess catheterization., Objective: To test a modified initial cCTA strategy designed to improve clinical efficiency vs usual testing (UT)., Design, Setting, and Participants: This was a pragmatic randomized clinical trial enrolling participants from December 3, 2018, to May 18, 2021, with a median of 11.8 months of follow-up. Patients from 65 North American and European sites with stable symptoms of suspected coronary artery disease (CAD) and no prior testing were randomly assigned 1:1 to precision strategy (PS) or UT., Interventions: PS incorporated the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) minimal risk score to quantitatively select minimal-risk participants for deferred testing, assigning all others to cCTA with selective CT-derived fractional flow reserve (FFR-CT). UT included site-selected stress testing or catheterization. Site clinicians determined subsequent care., Main Outcomes and Measures: Outcomes were clinical efficiency (invasive catheterization without obstructive CAD) and safety (death or nonfatal myocardial infarction [MI]) combined into a composite primary end point. Secondary end points included safety components of the primary outcome and medication use., Results: A total of 2103 participants (mean [SD] age, 58.4 [11.5] years; 1056 male [50.2%]) were included in the study, and 422 [20.1%] were classified as minimal risk. The primary end point occurred in 44 of 1057 participants (4.2%) in the PS group and in 118 of 1046 participants (11.3%) in the UT group (hazard ratio [HR], 0.35; 95% CI, 0.25-0.50). Clinical efficiency was higher with PS, with lower rates of catheterization without obstructive disease (27 [2.6%]) vs UT participants (107 [10.2%]; HR, 0.24; 95% CI, 0.16-0.36). The safety composite of death/MI was similar (HR, 1.52; 95% CI, 0.73-3.15). Death occurred in 5 individuals (0.5%) in the PS group vs 7 (0.7%) in the UT group (HR, 0.71; 95% CI, 0.23-2.23), and nonfatal MI occurred in 13 individuals (1.2%) in the PS group vs 5 (0.5%) in the UT group (HR, 2.65; 95% CI, 0.96-7.36). Use of lipid-lowering (450 of 900 [50.0%] vs 365 of 873 [41.8%]) and antiplatelet (321 of 900 [35.7%] vs 237 of 873 [27.1%]) medications at 1 year was higher in the PS group compared with the UT group (both P < .001)., Conclusions and Relevance: An initial diagnostic approach to stable chest pain starting with quantitative risk stratification and deferred testing for minimal-risk patients and cCTA with selective FFR-CT in all others increased clinical efficiency relative to UT at 1 year. Additional randomized clinical trials are needed to verify these findings, including safety., Trial Registration: ClinicalTrials.gov Identifier: NCT03702244.

Importance: Guidelines recommend deferral of testing for symptomatic people with suspected coronary artery disease (CAD) and low pretest probability. To our knowledge, no randomized trial has prospectively evaluated such a strategy., Objective: To assess process of care and health outcomes in people identified as minimal risk for CAD when testing is deferred., Design, Setting, and Participants: This randomized, pragmatic effectiveness trial included prespecified subgroup analysis of the PRECISE trial at 65 North American and European sites. Participants identified as minimal risk by the validated PROMISE minimal risk score (PMRS) were included., Intervention: Randomization to a precision strategy using the PMRS to assign those with minimal risk to deferred testing and others to coronary computed tomography angiography with selective computed tomography-derived fractional flow reserve, or to usual testing (stress testing or catheterization with PMRS masked). Randomization was stratified by PMRS risk., Main Outcome: Composite of all-cause death, nonfatal myocardial infarction (MI), or catheterization without obstructive CAD through 12 months., Results: Among 2103 participants, 422 were identified as minimal risk (20%) and randomized to deferred testing (n = 214) or usual testing (n = 208). Mean age (SD) was 46 (8.6) years; 304 were women (72%). During follow-up, 138 of those randomized to deferred testing never had testing (64%), whereas 76 had a downstream test (36%) (at median [IQR] 48 [15-78] days) for worsening (30%), uncontrolled (10%), or new symptoms (6%), or changing clinician preference (19%) or participant preference (10%). Results were normal for 96% of these tests. The primary end point occurred in 2 deferred testing (0.9%) and 13 usual testing participants (6.3%) (hazard ratio, 0.15; 95% CI, 0.03-0.66; P = .01). No death or MI was observed in the deferred testing participants, while 1 noncardiovascular death and 1 MI occurred in the usual testing group. Two participants (0.9%) had catheterizations without obstructive CAD in the deferred testing group and 12 (5.8%) with usual testing (P = .02). At baseline, 70% of participants had frequent angina and there was similar reduction of frequent angina to less than 20% at 12 months in both groups., Conclusion and Relevance: In symptomatic participants with suspected CAD, identification of minimal risk by the PMRS guided a strategy of initially deferred testing. The strategy was safe with no observed adverse outcome events, fewer catheterizations without obstructive CAD, and similar symptom relief compared with usual testing., Trial Registration: ClinicalTrials.gov Identifier: NCT03702244.

Background: Peripheral artery disease (PAD) is associated with high morbidity and mortality, particularly once patients develop critical limb threatening ischemia (CLTI). Minorities and vulnerable populations often present with CLTI and experience worse outcomes. The use of directional atherectomy (DA) and drug-coated balloon (DCB) during lower-extremity revascularization (LER) has not been previously described in a safety-net population., Objective: To review demographic and clinical characteristics, and short- intermediate term outcomes of patients presenting to a safety-net hospital with PAD treated with DA and DCB during LER., Methods: In this retrospective, observational cohort study, chart review was performed of all patients who underwent DA and DCB during LER for PAD from April 2016 to January 2020 in a safety-net hospital., Results: The analysis included 58 patients, with 41% female, 24% Black/African American, and 31% Hispanic. From this group, 17% spoke a non-English primary language and 10% reported current or previous housing insecurity. Most (65%) presented with CLTI and had undergone a previous index leg LER (58%). The combination of DA and DCB was efficacious, resulting in low rates of bail-out stenting (16%) and target-vessel revascularization (26%) at 2 years. Low complication rates (tibial embolism in 12% and vessel perforation in 2% of cases) were also observed. Most patients (67%) with Rutherford category 5 experienced wound healing by 2 years., Conclusion: In this safety-net population, the majority presented with CLTI and a previous LER of the index leg. The combination of DA and DCB resulted in low complication rates, and good short-intermediate outcomes in this frequently undertreated population.

Background: Peripheral artery disease (PAD) affects 200 million people worldwide and is associated with impaired quality of life, increased morbidity, and mortality. Supervised exercise therapy (SET) and lower-extremity revascularization (LER) are both proven strategies to improve patient symptoms. Short and long-term functional outcomes after LER for symptomatic PAD in a large, international cohort have not previously been described., Methods: The VOYAGER PAD trial (ClinicalTrials.gov identifier: NCT02504216) enrolled subjects after LER for symptomatic PAD (Rutherford category 2-6). Participants completed the Walking Impairment Questionnaire (WIQ) at baseline, 1, 3 and 6 months, and every 6 months thereafter. The primary outcome analysis was degree of difficulty walking two blocks at each of the aforementioned time points. Difficulty walking three blocks and climbing one flight of stairs at these time points was also analyzed. Data about supervised and home exercise therapy before or after revascularization were not collected in the VOYAGER PAD trial., Results: Of the 5614 VOYAGER PAD participants completing the WIQ at baseline, three-quarters presented with claudication and one-quarter with critical limb ischemia. Of these, the majority (62% with claudication and 74% with CLI) reported inability or much difficulty walking two blocks prior to LER. Walking improved after LER regardless of revascularization strategy, but one-fifth with claudication and one-third with CLI reported continued inability or much difficulty walking two blocks 1 month after LER. Participants who reported improved walking ability 1 month after LER experienced a durable functional result out to 3 years. Although the proportion of participants reporting significant baseline difficulty climbing one flight of stairs or walking three blocks differed, the trend in immediate and sustained improvement after LER was similar to that observed for walking two blocks., Conclusion: In this large, international cohort undergoing LER for symptomatic PAD, nearly two-thirds reported inability or much difficulty walking two blocks at baseline. Although many participants reported improved walking ability after LER, a substantial proportion remained severely disabled. These observations may help motivate providers, patients, and medical systems to improve awareness and engagement in SET referral after LER.

In the outpatient setting, ambulatory electrocardiography is the most frequently used diagnostic modality for the evaluation of patients in whom cardiac arrhythmias or conduction abnormalities are suspected. Proper selection of the device type and monitoring duration is critical for optimizing diagnostic yield and cost-effective resource utilization. However, despite guidance from major professional societies, the lack of systematic guidance for proper test selection in many institutions results in the need for repeat testing, which leads to not only increased resource utilization and cost of care, but also suboptimal patient care. To address this unmet need at our own institution, we formed a multidisciplinary panel to develop a concise, yet comprehensive algorithm, incorporating the most common indications for ambulatory electrocardiography, to efficiently guide clinicians to the most appropriate test option for a given clinical scenario, with the goal of maximizing diagnostic yield and optimizing resource utilization. The algorithm was designed as a single-page, color-coded flowchart to be utilized both as a rapid reference guide in printed form, and a decision support tool embedded within the electronic medical records system at the point of order entry. We believe that systematic adoption of this algorithm will optimize diagnostic efficiency, resource utilization, and importantly, patient care and satisfaction., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Objectives: High-frequency electroencephalographic activity (> 16 Hz activity) is often elevated during nonrapid eye movement sleep among individuals with insomnia, in line with the hyperarousal theory of insomnia. Evidence regarding sleep depth marked by slow-wave activity (< 4 Hz) is more mixed. Distinguishing subcomponents of slow-wave activity (slow-oscillation [< 1 Hz] or delta activity [1-4 Hz)]) may be critical in understanding these discrepancies, given that these oscillations have different neural generators and are functionally distinct. Here we tested the effects of insomnia diagnosis and insomnia treatment on nonrapid eye movement electroencephalography in older adults, distinguishing slow-oscillation and delta power., Methods: In 93 older adults with insomnia and 71 good sleeper control participants (mean ages 68 years), effects of insomnia and cognitive behavioral therapy for insomnia (insomnia group only) on electroencephalographic spectral power were analyzed. Main effects and interactions with nonrapid eye movement period were assessed for the following frequency bands: slow-oscillation (0.5-1 Hz), delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), sigma (12-16 Hz), and beta (16-32 Hz)., Results: Slow-oscillation absolute and relative power were lower in the insomnia group compared with controls. There were no group differences in delta power. Insomnia was also associated with elevated 4-32 Hz absolute and relative power. After cognitive behavioral therapy for insomnia, absolute sigma and beta activity decreased., Conclusions: Deficits in slow-wave activity in insomnia are specific to the slow-oscillation. Elevated high frequency activity is reduced for sigma and beta power following cognitive behavioral therapy for insomnia . These findings inform the pathophysiology of insomnia, including the mechanisms underlying cognitive behavioral therapy for insomnia in older adults., (© 2020 American Academy of Sleep Medicine.)

Secreted exosomes are bioactive particles that elicit profound responses in target cells. Using targeted metabolomics and global microarray analysis, we identified a role of exosomes in promoting mitochondrial function in the context of pulmonary arterial hypertension (PAH). Whereas chronic hypoxia results in a glycolytic shift in pulmonary artery smooth muscle cells (PASMCs), exosomes restore energy balance and improve O 2 consumption. These results were confirmed in a hypoxia-induced mouse model and a semaxanib/hypoxia rat model of PAH wherein exosomes improved the mitochondrial dysfunction associated with disease. Importantly, exosome exposure increased PASMC expression of pyruvate dehydrogenase (PDH) and glutamate dehydrogenase 1 (GLUD1), linking exosome treatment to the TCA cycle. Furthermore, we show that although prolonged hypoxia induced sirtuin 4 expression, an upstream inhibitor of both GLUD1 and PDH, exosomes reduced its expression. These data provide direct evidence of an exosome-mediated improvement in mitochondrial function and contribute new insights into the therapeutic potential of exosomes in PAH.

Purpose: Compliance with oral nutrition support (ONS) is poorly reported in the literature. Many factors influence compliance, which could mask the true benefits of preoperative ONS. Surgical oncology patients, including pelvic exenteration patients, are often requested by healthcare workers to consume nutrition supplements before surgery. Exploration of barriers and enablers to compliance with nutrition supplements is needed to improve patient compliance and understand the real impact of preoperative ONS., Method: A qualitative study using semi-structured interviews was performed to investigate enablers and barriers to preoperative nutrition supplement compliance. Twenty participants who had been asked to consume 15 nutrition supplements, either immunonutrition or standard polymeric supplements, were interviewed. Inductive thematic analysis was used to determine major themes associated with compliance., Results: Twelve out of 20 participants were not compliant with recommended dosing. Well-nourished participants were more compliant than malnourished participants. Major themes associated with compliance were flavour, volume, texture, impact on dietary intake and motivation to consume supplements. Flavour differed between the two groups, negatively impacting compliance in the immunonutrition group. Volume, texture and impact on dietary intake also negatively impacted compliance whereas motivation positively impacted compliance., Conclusion: To overcome barriers and enforce enablers with nutrition supplement compliance, it is essential healthcare workers implement individualised interventions, taking into account nutritional status. A range of flavours, minimal volume and low viscosity supplements should be provided to address individual preference and minimise poor compliance. Better-targeted education and regular motivation are needed to improve compliance.

Purpose of Review: This review summarizes the risks of lower extremity amputation associated with critical limb ischemia (CLI) and discusses current therapies that can prevent amputation in CLI., Recent Findings: CLI remains an under-recognized condition associated with high rates of major amputation and disparities in care. Optimal medical therapy can reduce the risk of major adverse cardiovascular and limb events, but revascularization combined with close wound care remains the cornerstone of amputation prevention. Endovascular revascularization has become more common over time and has been associated with a reduction in amputation rates. Ongoing clinical trials will help inform best practices for revascularization strategies and techniques. Vascular care is inconsistent across the USA, with significant variation in access to care revascularization rates and rates of major amputation. Major amputation can be prevented in patients with CLI when optimal medical therapy, lifestyle modification, and revascularization are provided in a multidisciplinary setting.

The bcl-2 family of survival and death promoting proteins play a key role in regulating cell numbers during nervous system development. Bcl-x L , an anti-apoptotic bcl-2 family member is highly expressed in the developing nervous system. However; the early embryonic lethality of the bcl-x germline null mouse precluded an investigation into its role in nervous system development. To identify the role of bcl-x in spinal cord neurogenesis, we generated a central nervous system-specific bcl-x conditional knockout (BKO) mouse. Apoptotic cell death in the BKO embryo was initially detected at embryonic day 11 (E11) in the ventrolateral aspect of the spinal cord corresponding to the location of motor neurons. Apoptosis reached its peak at E13 having spread across the ventral and into the dorsal spinal cord. By E18, the wave of apoptosis had passed and only a few apoptotic cells were observed. The duration and direction of spread of apoptosis across the spinal cord is consistent with the spatial and temporal sequence of neuronal differentiation. Motor neurons, the first neurons to become post mitotic in the spinal cord, were also the first apoptotic cells. As neurogenesis spread across the spinal cord, later born neuronal populations such as Lim2 + interneurons were also affected. The onset of apoptosis occurred in cells that had exited the cell cycle within the previous 24h and initiated neural differentiation as demonstrated by BrdU birthdating and βIII tubulin immunohistochemistry. This data demonstrates that spinal cord neurons become Bcl-x L dependent at an early post mitotic stage in developmental neurogenesis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The relationship between body composition and resting energy expenditure (REE) was investigated in two boys and two men with Duchenne muscular dystrophy (DMD) (ages 11 to 22.4 years) and two boys with Becker muscular dystrophy (BMD) (ages 7.75 and 13.75 years)., Methods: The REE was assessed by indirect calorimetry; body composition indices (weight, height, skinfolds, and mid-arm circumference) were measured using standardized techniques and compared with healthy reference data., Results: Those with DMD had reduced corrected mid-upper-arm muscle area (C-MUMA) in comparison with healthy peers, and approximately twice the subcutaneous fat levels of subjects with BMD and healthy peers. Boys with BMD had remarkably lower muscle status than did boys with DMD and healthy peers. In both groups, REE was lower than in healthy peers; REE was associated with body weight (r=0.85), height (r=0.92), mid-upper arm fat area (MUFA) (r=0.97), and C-MUMA (r=0.65)., Conclusions: Individuals with muscular dystrophy (MD) exhibit considerable disease-specific alterations in body composition. The REE had a stronger relationship with growth (weight and height) and subcutaneous body fat composition and a weaker association with C-MUMA. Understanding the effect of MD on body composition and REE will allow dietitians to individualize energy recommendations.

Background: The optimal hydration strategy for prevention of contrast-induced acute kidney injury (AKI) remains unknown. The purpose of this meta-analysis is to compare the effectiveness of normal saline (NS) versus sodium bicarbonate hydration (NaHCO(3)) for prevention of contrast-induced AKI., Methods: We performed a meta-analysis of randomized controlled trials that compared saline-based hydration with sodium bicarbonate-based hydration regimen for prophylaxis of contrast-induced AKI. The literature search included MEDLINE, EMBASE, and Cochrane databases (2000 to October 2007); conference proceedings; and bibliographies of retrieved articles. Information was extracted on study design, sample characteristics, and interventions. Random-effects models were used to calculate summary risk ratios for contrast-induced AKI, need for hemodialysis, and death., Results: Seven trials with 1,307 subjects were included. Preprocedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of contrast-induced AKI (5.96% in the NaHCO(3) arm versus 17.23% in the NS arm, summary risk ratio 0.37, 95% CI 0.18-0.714, P = .005). There was no difference in the rates of postprocedure hemodialysis or death. Formal testing revealed moderate heterogeneity and a strong likelihood of publication bias., Conclusions: Although sodium bicarbonate hydration was found to be superior to NS in prevention of contrast-induced AKI, these results are in the context of study heterogeneity and, likely, publication bias. An adequately powered randomized controlled trial is warranted to define the optimal hydration strategy in patients at high risk of contrast-induced AKI who are scheduled to undergo contrast administration.

Energy requirements of children and adolescents with cerebral palsy appear to be disease-specific and different from the current recommendations for healthy children, varying depending upon functional capacity, degree of mobility, severity of disease, and level of altered metabolism. Feeding problems are prevalent in many of these children, and can result in inadequate energy intake. Wasting of voluntary muscles, a common symptom of cerebral palsy, contributes to reduced resting energy needs; nevertheless, the location of the central nervous system lesion may also influence energy requirements. To guarantee individualized, accurate, and optimal energy recommendations for this population, resting energy expenditure should preferentially be measured by indirect calorimetry. Equations and formulae to predict healthy people's resting energy expenditure are available, but tend to overestimate these children's energy needs. Future studies should address the role of the central nervous system in regulating energy metabolism in this population. When adequately nourished, children and adolescents with cerebral palsy appear more tranquil and require decreased feeding time, which gives caregivers time to develop the child's functional independence and character. Understanding energy requirements of this population will provide caregivers and health professionals with guidelines for providing optimal nutritional status.

Objective: To identify risk factors for Kaposi's sarcoma (KS) among men seropositive for both human herpesvirus 8 (HHV-8) and HIV., Design: Cross-sectional study of 91 HHV-8 seropositive, HIV seropositive men who have sex with men (57 with KS), and 70 controls at lower risk for KS., Methods: Patients received clinical evaluations. Blood, oral fluids, semen, rectal brush, rectal swab, and urine were collected, and tests for HHV-8 were performed., Results: Men with KS were more likely to have HHV-8 DNA in peripheral blood mononuclear cells (PBMC) than men without KS [35.1 versus 5.9%, odds ratio (OR), 8.6, 95% confidence interval (CI), 1.9-39.9]. The prevalence of HHV-8 DNA in oral fluids was similar for the two groups (37.0 versus 32.4%; OR, 1.2; 95% CI, 0.5-3.0). HHV-8 DNA was rarely detected in specimens of other types from these men, or in any specimens from the 70 controls. Among men with KS, HHV-8 DNA in PBMC was associated with new KS lesions (OR, 4.5; 95% CI, 1.4-14.5), and HHV-8 DNA in oral fluids was associated with oropharyngeal KS lesions (OR, 3.1; 95% CI, 1.0-10.1). Men with high HHV-8 antibody titers were more likely to have KS (OR, 9.6; 95% CI, 1.2-78.2), but were less likely to have new KS lesions (OR, 0.2; 95% CI, 0.0-1.1) or HHV-8 DNA in PBMC (OR, 0.2; 95% CI, 0.0-1.6) or oral fluids (OR, undefined; = 0.001)., Conclusions: In HHV-8- and HIV-seropositive men, HHV-8 DNA is associated with KS. Among men without KS, HHV-8 DNA is most commonly found in oral fluids. High HHV-8 antibody titers may protect against circulating HHV-8 and new KS lesions.

Mass loss at elevated RH is an established method for determining the occurrence of crystallisation of an amorphous material. Through the combination of near infrared spectroscopy and gravimetric vapour sorption, it has been possible to show the transition of raffinose from its spray-dried amorphous form to a crystalline form without this characteristic mass loss. It has also been possible to observe changes in the crystalline material for a period of 30 h subsequent to exposure to elevated relative humidity by near infrared spectroscopy that are not associated with changes in mass, but are related to repacking of hydrate molecules. Drying of the crystalline pentahydrate in the DVS-NIR was seen to show changes in the NIR peak related to -OH. From this, NIR peaks were tentatively ascribed as relating to a penta-, tetra-, tri- and a di-hydrate form, but the sample returned to the amorphous response by the time the water content fell to the equivalent of the monohydrate, indicating that crystallinity had been lost. These observations would be compatible with the hypothesis that lower hydrates of raffinose exist. Due to the absence of mass loss in association with crystallisation, it was found that the enthalpy of crystallisation of amorphous raffinose, as determined by isothermal microcalorimetry, is similar to the enthalpy of fusion determined by differential scanning calorimetry. Finally, it was observed that the early part of the response in the isothermal microcalorimeter was related to mobility of molecules when Tg was above T. This mobility was able to give the bulk morphology of a crystal before the sample developed long range order and crystalline properties.

Purpose: To explore the use of a combined near infrared spectroscopy and gravimetric sorption apparatus in providing an accurate quantification of amorphous contents of predominantly crystalline lactose., Methods: Key wavelengths on the near infrared spectra of amorphous and crystalline lactose were used to construct a calibration plot of spectral fit to amorphous content. The extent of water sorption and desorption at 75% relative humidity (RH) was used to quantify the amount of amorphous material in the sample., Results: Near infrared spectroscopy was used to quantify the amorphous contents of a set of 10 partially amorphous lactose samples using a calibration equation generated from an independent set of 17 samples. The results were found to be accurate to within 1% w/w amorphous content. Dynamic vapor sorption quantification relates the mass of water sorbed and subsequently desorbed during the crystallization process with the amount of amorphous material originally contained within the sample. It was possible to quantitatively detect as little as 1 mg of amorphous content in the sample. The percent amorphous content determination will thus be sample mass dependent, however, assuming a sample mass of 150 mg, the best detection would be ca. 0.7%., Conclusions: It has been found that both techniques may be used to quantify small quantities of amorphous material. The combination of the two techniques lends itself to added verification of results and thus increased reliability.

There is a realisation that small quantities of amorphous material can have a significant impact on the properties of crystalline solids. Consequently there is a growing interest in quantifying the amount of amorphous material that is present in "crystalline powders". Success has been reported when using isothermal microcalorimetry and vapour sorption techniques, however, the use of solution calorimetry has largely been ignored. In this study the enthalpies of solution of mixtures of amorphous and crystalline lactose are reported concentrating on the range 0-10% w/w amorphous content. It was found that there was a possible error due to water vapour penetration into the ampoule, resulting in crystallisation of the amorphous content, however this was overcome by double sealing the ampoules with wax. Subsequently there was a good correlation between the enthalpy of solution and the amorphous content, which was not adversely affected by stirring rate used during the experiment. Over the range from 0 to 10% amorphous content, quantification of the amorphous content of an unknown would be good to +/-0.5%. The effects of residual moisture retained within a sample were also investigated. Storage at 33% or 43% RH resulted in a much reduced wetting (exothermic) response compared with that seen for completely dry samples, which in turn led to a higher net enthalpy of solution.

From January 1991 through September 1994, we observed people who were infected with HIV to assess the impact of enteric parasite-associated diarrhea. Respondents answered comprehensive questionnaires covering clinical and epidemiologic information and provided stool specimens monthly, which were examined unstained as well as stained with trichrome, chromotrope 2R, and with Kinyoun carbol-fuchsin, and with indirect immunofluorescence for Cryptosporidium. In all, 602 participants, who were interviewed, provided stool specimens at 3254 monthly visits. Parasites were associated with 50 of 354 (14.1%) acute diarrheal episodes (lasting < or = 28 days) and with 97 of 279 (34.8%) chronic episodes (lasting > 28 days). A parasite was associated with 31 of 222 (14.0%) episodes that occurred when CD4+ counts were > or = 200 cells/microl and with 150 of 566 (26.5%) episodes that occurred when CD4+ counts were < 200 cells/microl. The most commonly identified parasite was C. parvum, which was associated with 18 of 354 (5.1%) acute episodes and 36 (12.9%) of the 279 chronic episodes of diarrhea. In this patient population, enteric protozoan parasites were commonly associated with illness, particularly as immunosuppression worsened, and were more likely to be associated with chronic rather than acute diarrhea.

Our purpose was to design and implement a nutritional rehabilitation program for persons with severe developmental disabilities who resided in a long-term-care facility or a group home. We used weight for height (WH) to classify residents of both facilities into three groups: group 1 (n=32), WH less than 5th percentile (Z scores < or = -1.650), goal=gain weight; group 2 (n=21), WH between the 5th and 85th percentile (Z scores ranging from -1.645 to +1.030), goal=maintain present rate of weight gain; and group 3 (n=8), WH greater than 85th percentile (Z scores > or = +1.036), goal=slow down rate of weight gain. The challenge in all groups was to bring about these changes without increasing the quantity of food (as assessed by 3-day food records) fed to the residents and to increase their fluid intake. For each subject, the project dietitian developed individualized menus that specified quantities and consistencies of food. Foodservice delivery was changed to a centralized system in the long-term-care facility to allow for closer control of the subjects' intake. A dietitian monitored the program with biweekly visits to the wards and frequent consultation with staff. Only a limited increase in fluid intake was noted; however, after 6 months of the program, the other goals were met. Our results suggest that nutritional rehabilitation of residents with developmental disabilities is enhanced by the involvement of a dietitian.

Objective: To report the clinical response to atovaquone in HIV-1-infected patients with symptomatic intestinal microsporidiosis., Design: A retrospective review of a cohort of AIDS patients with symptomatic intestinal microsporidiosis who received atovaquone., Setting: Infectious Disease Program of the Grady Memorial Hospital, Veterans Affairs Medical Center and private physicians' offices in Atlanta, Georgia., Patients and Methods: HIV-1-infected patients (n = 371) were offered a complete stool evaluation and monthly follow-up. Among them, 22 were diagnosed with intestinal microsporidial infection using stool smears stained with modified trichrome stain. Species confirmation was made by light microscopy or electron microscopy on small intestinal biopsy specimens in some patients., Main Outcome Measure: Differences in symptoms, number of stools, and body weight were compared before and after a minimum of 1 month of atovaquone therapy., Results: Eight patients received atovaquone treatment. The mean onset of clinical improvement after beginning treatment was 13 days (SEM, +/- 2). The mean number of stools per day decreased from 10 +/- 2.5 to 2 +/- 1 (P = 0.02, paired t test). The mean weight gain was 3 +/- 2 kg. The parasite was continuously present in the repeated stool specimens. However, semiquantitative analysis performed on two patients' stool specimens showed a decreased parasite burden. Four patients underwent small intestinal endoscopy was consistent with Enterocytozoon bieneusi in all four patients. Only one out of these four patients demonstrated a decrease in parasite burden in the biopsy specimen. Ultrastructural analysis performed in another of these four patients following treatment demonstrated the presence of electron-dense granules in spores, suggestive of toxic effects., Conclusion: Atovaquone demonstrates promise as a symptomatic treatment for intestinal microsporidiosis. A double-blind and placebo-controlled clinical trial is currently in progress.

The cell walls of Mycobacterium smegmatis contained a number of serologically active polysaccharides such as arabinomannan, mannan, and glucan in addition to arabinogalactan. The biosynthetic pathways of these polysaccharides are not well understood. Characterization of the sugar nucleotide pool of M. smegmatis showed the presence of (uridine diphosphate-) UDP-glucose, UDP-galactose, UDP-mannose, UDP-arabinose and UDP-hexuronic acid(s). It is suggested that these compounds may be intermediates in the biosynthesis of a number of mycobacterial polysaccharides.

The O-specific polysaccharide from the lipopolysaccharide of Pseudomonas aeruginosa NCTC 8505 (IATS serotype O:3) consists of a tetrasaccharide repeating unit comprising L-rhamnose, N-acetyl-D-glucosamine (GlcNAc), bacillosamine, and N-acetyl-L-galactosaminuronic acid (L-GalNAcA) (Y. Tahara and S. G. Wilkinson, Eur. J. Biochem. 134:299-304, 1983). Incubation of GlcN or UDP-GlcNAc with cell extracts or EDTA-treated cells of P. aeruginosa NCTC 8505 yielded a mixture of UDP-ManNAc, UDP-GalNAc, UDP-GlcNAcA, UDP-ManNAcA, UDP-L-GalNAc, and UDP-L-GalNAcA. The last two compounds, here identified for the first time, may be intermediates in the synthesis of the L-GalNAcA moiety of the O-specific portion of the lipopolysaccharide of P. aeruginosa.

Nine adolescents with phenylketonuria (PKU), who had been on unrestricted diets for 2 to 11 years, underwent serial neuropsychological testing over two consecutive 4- to 5-week periods during which each was maintained on a low-phe diet supplemented in a triple-blind fashion either with L-phe (high phe) or L-alanine (low phe). Assignment to the initial condition was done randomly, and the alternate condition was substituted at the end of the first 4- to 5-week period. In 6 of 7 subjects with PKU, baseline median choice reaction times (RTs) were slower than those of controls matched for age, sex, handedness, and Full-Scale IQ (WISC-R). A highly significant improvement occurred during the low-phe phases of the study. Results suggest that adolescents with PKU on unrestricted diets have a neuropsychological deficit that is out of proportion to their overall intellectual handicap. Moreover, this deficit appears to be at least partly reversible by return to dietary phe restriction despite years of hyperphenylalaninemia.