Search

Background: Obesity is a chronic multifactorial disease affecting approximately one in five youth. Many pediatric clinical strategies focus on behavioral change/lifestyle modification efforts, but are limited by their intensity and muted by their inability to address the sociocultural contexts of obesity. The primary objective of the study was to explore primary care pediatric clinicians' current barriers/management practices of patients with obesity. Methods: A mixed-methods study was conducted by distributing an electronic survey to pediatric providers in Washington, DC, and its surrounding metropolitan area. Three focus groups were conducted with a subgroup of these primary care clinicians to further explore their responses. Results: Pediatric clinicians ( n  = 81) completed the survey out of 380 invitations sent, and 20 took part in 3 focus groups, ranging in size between 4 and 8 clinicians. Over 90% of clinicians felt comfortable advising patients. However, 52% lacked confidence in addressing obesity and over 80% indicated that time constraint is a barrier to care and emphasized the need for more training in obesity management. Six themes emerged regarding clinician barriers to addressing obesity, including (1) limited time, (2) clinician perceived familial resistance, (3) challenges with racial and ethnic concordance, (4) perceived environmental barriers, (5) limited knowledge of community resources, and (6) inadequate collaborative support. Conclusions: Clinicians have difficulty implementing obesity management strategies into their everyday practice due to a variety of barriers. This study emphasized the need for better implementation strategies, tools, and collaboration with community stakeholders for clinicians to engage weight management more effectively.

Produce prescription programs aim to improve food insecurity (FI) and nutrition but their effectiveness is unclear. We conducted a pilot study to demonstrate the feasibility and explore the potential impact of a family-based, home-delivery produce prescription and nutrition education program. We measured enrollment, satisfaction, participation, and retention as measure of feasibility. Adult participants answered pre-post self-report questionnaires assessing FI, child and adult fruit and vegetable intake, and culinary literacy and self-efficacy. To understand participants' lived experiences, qualitative interviews were conducted at the 6-month time point. Twenty-five families were enrolled. Feasibility measures indicate participants were generally satisfied with the program but there were important barriers to participation. Qualitative data revealed themes around reduced food hardship, healthy eating, budget flexibility, and family bonding. Fruit and vegetable consumption increased in a small subgroup of children, but post-intervention intake remained below recommended levels, particularly for vegetables. FI scores were not significantly different post-intervention, but qualitative findings indicated improved access and reliability of food. This is the first intervention of its kind to be evaluated for feasibility and our results suggest the intervention is well-received and supportive. However, further study, with a larger sample size, is needed to understand factors influencing participation and assess effectiveness.

Purpose of Review: (1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients., Sources of Information: The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD., Methods: The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions., Key Findings: We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool., Limitations: The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.M.H. has received investigator-initiated research funding from OPKO Health, Inc (OPKO Renal Division) and Sanofi. R.A.M. has received research funding from the Patient-Centered Outcomes Research Institute (PCORI), the American Society of Hematology (ASH), and the American College of Rheumatology (ACR). R.T.A. has received consulting honoraria from Ardelyx, Inc and from Advicenne. M.B. has received honoraria for advisory board membership with Otsuka Canada Pharmaceutical Inc (OCPI) and AstraZeneca. M.U.B. has received honoraria for consultation, advisory board membership, speaking engagements, or research funding from Janssen, OCPI, and Sanofi. G.K. declared no conflicts of interest. F.M.-W. has received honoraria for conferences, advisory board membership, or research funding from Amgen Inc, Otsuka Canada Pharmaceutical Inc, and Sanofi. M.R. declared no conflicts of interest. R.W. declared no conflicts of interest. P.D.A. declared no conflicts of interest. P.F. has no conflicts of interest. A.G. declared no conflicts of interest. K.K.J. has received honoraria for consultation or advisory board membership from Boehringer Ingelheim, Baxter, Amgen Inc, Sanofi, Eli Lilly and Company, LEO Pharma Inc Canada, and AstraZeneca. M.K. declared no conflicts of interest. B.A.K. declared no conflicts of interest. S.M. has received honoraria for consultation, advisory board membership, research funding, unrestricted grants, and educational grants from the Ontario Ministry of Health, NGX, Health Canada, Nutrigenomix Inc, Mitacs, Central East Local Health Integration Network, Ontario Renal Network (ORN), Sanofi, Shire, Amgen Inc, Sanofi Genzyme, Boehringer Ingelheim, and Baxter. K.M. declared no conflicts of interest. A.M. declared no conflicts of interest. M.P. declared no conflicts of interest. C.R. declared no conflicts of interest. S.D.S. has received honoraria for consultation, advisory board membership, and Canadian Medical Education (CME) lectures from the, Sanofi, Pfizer Inc, Janssen Inc, Amgen Inc, and Otsuka Canada Pharmaceutical Inc. A.J.V. has received honoraria for consultation from Paladin Labs Inc. D.Z. has received investigator-initiated research funding from Sanofi and has been a member of advisory boards for Otsuka Canada Pharmaceutical Inc, and Amgen Inc. C.M.C. has received honoraria for consultation, advisory board membership, or research funding from the Ontario Ministry of Health, Sanofi, Pfizer Inc, LEO Pharma Inc Canada, Astellas, Janssen Inc, Amgen Inc, Boehringer Ingelheim, and Baxter., (© The Author(s) 2020.)

The mitochondrial deubiquitylase USP30 negatively regulates the selective autophagy of damaged mitochondria. We present the characterisation of an N-cyano pyrrolidine compound, FT3967385, with high selectivity for USP30. We demonstrate that ubiquitylation of TOM20, a component of the outer mitochondrial membrane import machinery, represents a robust biomarker for both USP30 loss and inhibition. A proteomics analysis, on a SHSY5Y neuroblastoma cell line model, directly compares the effects of genetic loss of USP30 with chemical inhibition. We have thereby identified a subset of ubiquitylation events consequent to mitochondrial depolarisation that are USP30 sensitive. Within responsive elements of the ubiquitylome, several components of the outer mitochondrial membrane transport (TOM) complex are prominent. Thus, our data support a model whereby USP30 can regulate the availability of ubiquitin at the specific site of mitochondrial PINK1 accumulation following membrane depolarisation. USP30 deubiquitylation of TOM complex components dampens the trigger for the Parkin-dependent amplification of mitochondrial ubiquitylation leading to mitophagy. Accordingly, PINK1 generation of phospho-Ser65 ubiquitin proceeds more rapidly in cells either lacking USP30 or subject to USP30 inhibition., (© 2020 Rusilowicz-Jones et al.)

Background: Gulf War Illness (GWI) is a chronic condition involving symptoms across multiple body systems. Previous research has implicated the vestibular system as a potential underlying factor in the symptoms experienced by veterans with GWI, due in part to exposure to potentially ototoxic chemicals and events., Purpose: To characterize the presence of vertigo and dizziness symptoms in a sample of veterans with GWI using validated self-report instruments, accounting for mental health comorbidities., Research Design: This is a case series, follow-up, prospective interview of clinical veterans; results presented are purely descriptive., Study Sample: Our sample of 50 veterans was a follow-up to a case series of clinical Gulf War veterans evaluated at the War Related Illness and Injury Study Center., Data Collection and Analysis: Veterans participated in a 70-min phone interview where the following questionnaires were administered: Vertigo Symptom Scale (VSS), Patient Health Questionnaire (depression scale), Patient Health Questionnaire (somatization scale), Beck Anxiety Inventory, Posttraumatic Stress Disorder (PTSD) Checklist, Defense and Veterans Brain Injury Center Traumatic Brain Injury Questionnaire, and GWI (Kansas) Questionnaire. We used descriptive (mean/median, standard deviation, interquartile range, and percentage) statistics to describe our sample and illuminate possible relationships between measures., Results: Our primary finding is a substantial report of vertigo symptoms in our sample, according to the VSS. Ninety percent of participants scored above the VSS threshold (>12), suggesting "severe dizziness." The most commonly endorsed symptom on the VSS was "headache or pressure in the head.", Conclusions: We conclude that there is significant burden of vertigo symptoms in veterans with GWI, suggesting a need for objective tests of vestibular function in this population. Furthermore, the relationship between symptoms of vertigo and dizziness, vestibular function, and PTSD warrants further exploration using objective measures., (American Academy of Audiology.)

Introduction: We characterized the presence of autonomic symptoms in a sample of Veterans with Gulf War Illness (GWI) using the Composite Autonomic Symptom Scale (COMPASS-31). In addition, we examined the report of autonomic symptoms across comorbid mental health conditions in this sample., Materials and Methods: Case-series follow-up of Gulf War veterans evaluated by the War Related Illness and Injury Study Center (WRIISC) between 2011 and 2016 (n = 153). Phone-based interview consisted of questionnaires designed to investigate autonomic symptoms, physical symptoms, mental health conditions, and GWI. Sixty-One Veterans agreed to participate in this follow-up arm of the study. We restricted our analysis to only those Veterans meeting CDC and/or Kansas criteria for GWI, leaving us with a sample of 56 Veterans., Results: Veterans in our sample were, male (n = 55, 98%), 49 (±6.8) years old and used 8 (±6.6) medications. The mean COMPASS-31 score for our sample was 45.6 (±18.3). There were no differences in reports of autonomic symptoms between participants who screened positive or negative for depression or post-traumatic stress disorder, but COMPASS-31 scores were higher among those who screened positive for anxiety (49.6 (±16.0)) compared with those who screened negative (29.3 (±18.9)) (p < 0.001)., Conclusions: The elevated COMPASS-31 scores suggest that there may be autonomic dysfunction present in our sample of Veterans with GWI, consistent with other published reports. Additionally, we believe that the high scores on the anxiety measure may reflect assessment of physiological symptoms that are not specific to anxiety, and may reflect GWI symptoms. Objective physiological tests of the autonomic nervous system are warranted to better characterize autonomic function and the clinical relevance of COMPASS-31 in this population., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2018.)

Veterans of all war eras have a high rate of chronic disease, mental health disorders, and chronic multi-symptom illnesses (CMI).(1-3) Many veterans report symptoms that affect multiple biological systems as opposed to isolated disease states. Standard medical treatments often target isolated disease states such as headaches, insomnia, or back pain and at times may miss the more complex, multisystem dysfunction that has been documented in the veteran population. Research has shown that veterans have complex symptomatology involving physical, cognitive, psychological, and behavioral disturbances, such as difficult to diagnose pain patterns, irritable bowel syndrome, chronic fatigue, anxiety, depression, sleep disturbance, or neurocognitive dysfunction.(2-4) Meditation and acupuncture are each broad-spectrum treatments designed to target multiple biological systems simultaneously, and thus, may be well suited for these complex chronic illnesses. The emerging literature indicates that complementary and integrative medicine (CIM) approaches augment standard medical treatments to enhance positive outcomes for those with chronic disease, mental health disorders, and CMI.(5-12.)

Background: Trichotillomania (TM) is a chronic disorder in which patients traumatically remove their own hair in a bizarre pattern. TM histopathological findings are not well defined., Methods: Twenty-eight scalp biopsies of TM were reviewed. Multiple vertical sections and special stains were used to evaluate the specimens. Twenty-six patients (24 female, 2 male) were in the cohort, 2 patients had 2 sets of biopsies., Results: Age range was 13-78 years (mean 41 years), most of them presented with chronic TM. Specific histological findings included trichomalacia (57%) and pigmented casts (46%). Non-specific histological findings included: follicular plugging (96%), decreased number of follicles (96%), reversed anagen:telogen ratio (86%), decreased number of sebaceous glands (68%), melanoderma (68%), increased number of fibrous tracts (64%) and vellus hairs (57%), superficial dermal inflammation (57%), evidence of hemorrhage (18%) and presence of hair granulomas (18%)., Conclusions: Even though TM is often a disease of the young people, middle aged and elderly patients with TM have more often a biopsy to confirm the diagnosis. This paper suggests diagnostic criteria for TM. Specific histological findings and clinical suspicion of TM were considered major criteria, while the non-specific histological findings were considered minor diagnostic criteria for TM.

Objective: To examine the neuropathologic findings seen in the setting of orthotopic liver transplantation (OLT) and to asses the role, if any, that the neuropathology had in the patient's death., Design: Retrospective autopsy series of 16 patients., Setting: Tertiary referral center with a high volume of liver transplantation., Patients: Sixteen OLT patients who died and in whom a complete autopsy, including examination of the brain and spinal cord, was performed., Results: Sixteen patients, including 13 women and 3 men, comprised the study group. Patients ranged in age from 25 to 64 years (mean 44.8 years). Postoperative OLT survival ranged from 1 to 1962 days (mean 236 days). Reasons for the initial OLT included hepatitis (n = 6), fulminant hepatic failure (n = 4), cryptogenic cirrhosis (n = 2), methotrexate toxicity (n = 1), postoperative complication (n = 1), primary biliary cirrhosis (n = 1), and hepatocellular carcinoma (n = 1). Autopsies in 13 (81%) patients showed neuropathology; in only 2 patients, however, was the primary cause of death attributable to these findings. The most common neuropathology was related to anoxia or infarction, specifically, ischemia or focal neuronal necrosis (n = 9), infarction (n = 4), and diffuse anoxic encephalopathy (n = 3). Other central nervous system findings included infection with Aspergillus, Candida, and Toxoplasma (n = 3). The most common cause of death was infection-related in 8 patients. One patient died of pulmonary hypertension, 1 of acute rejection, and 1 of possible hyperacute rejection. Two patients died directly as a consequence of neuropathology findings; one had massive central edema with herniation, and the other had a large intracerebral hemorrhage with herniation. The exact cause of death was unclear in 3 patients., Conclusions: The most common neuropathology findings in this series were related to ischemia and infarction. Neuropathology findings are a significant cause of morbidity, but were only rarely the main cause of death (n = 2) in the OLT patients in this study.

Plexiform neurofibroma (PNF) is an important part of the diagnostic criteria for neurofibromatosis type 1 (NF1) and is a known precursor lesion of malignant peripheral nerve sheath tumor (MPNST). We studied the clinicopathologic features of 54 cases of PNF for which the hematoxylin- and eosin-stained slides and paraffin blocks were available and adequate clinical follow-up could be obtained. In addition, in all cases, a representative section of the PNF and, when present, MPNST, was evaluated immunohistochemically with an antibody for p53 (DO7). The cohort included 28 male patients and 26 female patients, with an age range from 4 to 79 years (mean, 27 yr). Of these 54 patients, 46 (85%) met the strict diagnostic criteria for NF1. Thirty-nine patients had PNF alone; 15 patients had an MPNST arising from the PNF (PNF/MPNST). Those patients with PNF/MPNST tended to be older (38 yr vs. 22 yr) and to have larger tumors (10.5 cm mean vs. 7.4 cm mean) than those with PNF alone. In 9 patients (23%) of 39 with PNF alone, local recurrence developed, whereas in 7 patients (47%) of 15 with PNF/MPNST, recurrent MPNST developed, and metastases developed in 3 (20%) of the 15. Immunohistochemically, only 1 case (2.5%) of 39 cases of PNF alone stained for p53. On the other hand, 12 (80%) of 15 cases of PNF/MPNST showed p53 immunoreactivity in the MPNST component, 2 of which also showed staining in the PNF areas. In conclusion, we found that the vast majority of patients with PNF met the strict diagnostic criteria for NF1. The immunohistochemical detection of intranuclear p53 protein is common in the malignant areas of PNF/MPNST but is rare in the PNF regions. The rarity of p53 staining in the PNF regions precludes its use in predicting those tumors that are likely to progress to MPNST.

We present the case of a 71-year-old white male with paraneoplastic pemphigus associated with a B-cell non-Hodgkin's lymphoma. Diagnosis of paraneoplastic pemphigus was made by the characteristic findings on immunoprecipitation performed on a serum specimen. Paraneoplastic pemphigus is a severe autoimmune disease comprised of polymorphous mucocutaneous lesions, characteristic laboratory findings, association with one of several types of neoplasms, and a very poor prognosis.

In this article, an educator and a clinician address issues involved in implementing a course that helped rehabilitation nurses forge the critical link between theory and practice. A combination of strategies was used to present the material in a three-session inservice program.

A case study illustrates the usefulness of behavioral analysis and paradoxical strategy in the treatment of life-long urgency incontinence in a cerebral palsy patient. Volitional increase in diurnal enuresis appeared to result in rapid (within 5 days) acquisition of continence. From pretreatment to 13 month follow-up interview, the weekly wetting frequency decreased from an average of 25 to 0.5 episodes. Symptom rehearsal is believed to have interrupted the typical pathobehavioral sequence between the urge to void and micturition.

On the hypothesis that schizophrenia is an immunological disorder in which antibody is produced against a unique antigen sequestered principally or exclusively in the septal region of the brain, we used crossed-immunoelectrophoresis (CIE) to evaluate reactivity of a gamma G immunoglobulin (IgG) fraction from serum of schizophrenic patients and nonschizophrenic control subjects with homogenates of tissues of septal region, hippocampus, vermal cerebellum, frontal cortex, and liver of rhesus monkeys. When IgG fractions of unmedicated schizophrenic patients and schizophrenic patients who had received neuroleptic medication for less than 24 hr were tested against septal region homogenate, a precipitin arc was identified, indicating a positive result, with more than 95% of the fractions. In contrast, IgG fractions of schizophrenic patients who had received neuroleptic medication for more than 24 hr were rarely positive. When schizophrenic fractions that tested positive against septal region homogenate were tested against homogenates of the other tissues, they were negative. Fractions of all nonschizophrenic control subjects were negative against all homogenates.