Vigorous cool room treadmill training to improve walking ability in people with multiple sclerosis who use ambulatory assistive devices: a feasibility study.

BACKGROUND: Aerobic training has the potential to restore function, stimulate brain repair, and reduce inflammation in people with Multiple Sclerosis (MS). However, disability, fatigue, and heat sensitivity are major barriers to exercise for people with MS. We aimed to determine the feasibility of conducting vigorous harness-supported treadmill training in a room cooled to 16 °C (10 weeks; 3times/week) and examine the longer-term effects on markers of function, brain repair, and inflammation among those using ambulatory aids. METHODS: Ten participants (9 females) aged 29 to 74 years with an Expanded Disability Status Scale ranging from 6 to 7 underwent training (40 to 65% heart rate reserve) starting at 80% self-selected walking speed. Feasibility of conducting vigorous training was assessed using a checklist, which included attendance rates, number of missed appointments, reasons for not attending, adverse events, safety hazards during training, reasons for dropout, tolerance to training load, subjective reporting of symptom worsening during and after exercise, and physiological responses to exercise. Functional outcomes were assessed before, after, and 3 months after training. Walking ability was measured using Timed 25 Foot Walk test and on an instrumented walkway at both fast and self-selected speeds. Fatigue was measured using fatigue/energy/vitality sub-scale of 36-Item Short-Form (SF-36) Health Survey, Fatigue Severity Scale, modified Fatigue Impact Scale. Aerobic fitness (maximal oxygen consumption) was measured using maximal graded exercise test (GXT). Quality-of-life was measured using SF-36 Health Survey. Serum levels of neurotrophin (brain-derived neurotrophic factor) and cytokine (interleukin-6) were assessed before and after GXT. RESULTS: Eight of the ten participants completed training (attendance rates ≥ 80%). No adverse events were observed. Fast walking speed (cm/s), gait quality (double-support (%)) while walking at self-selected speed, fatigue (modified Fatigue Impact Scale), fitness (maximal workload achieved during GXT), and quality-of-life (physical functioning sub-scale of SF-36) improved significantly after training, and improvements were sustained after 3-months. Improvements in fitness (maximal respiratory exchange ratio and maximal oxygen consumption during GXT) were associated with increased brain-derived neurotrophic factor and decreased interleukin-6. CONCLUSION: Vigorous cool room training is feasible and can potentially improve walking, fatigue, fitness, and quality-of-life among people with moderate to severe MS-related disability. TRIAL REGISTRATION: The study was approved by the Newfoundland and Labrador Health Research Ethics Board (reference number: 2018.088) on 11/07/2018 prior to the enrollment of first participant (retrospectively registered at ClinicalTrials.gov: NCT04066972. Registered on 26 August 2019.

Exercise-Induced Brain Excitability Changes in Progressive Multiple Sclerosis: A Pilot Study.

BACKGROUND AND PURPOSE: Even a single bout of aerobic exercise (AE) enhances corticospinal excitability (CSE), a biomarker of neuroplasticity. Because neurodegeneration limits capacity for neuroplasticity, it is not clear whether AE would induce CSE changes in people with progressive multiple sclerosis (MS). METHODS: People with progressive MS (n = 10) requiring ambulatory assistive devices completed a graded maximal exercise test. Dual-energy x-ray absorptiometry was used to quantify body fat and lean mass. Before and following one 40-minute AE session using body weight-supported (<10% support) treadmill at moderate intensity, CSE was measured using transcranial magnetic stimulation. Variables included resting and active motor thresholds, motor evoked potential (MEP) amplitudes, recruitment curves, and length of the cortical silent period (CSP). RESULTS: Aerobic exercise reduced inhibition (shorter CSP) and increased excitation (increased MEP amplitude) only in the hemisphere corresponding to the stronger hand. Controlling for age, higher fitness and lower body fat significantly predicted exercise-induced reduction in resting motor threshold (ΔR = +0.458, P = 0.046) and CSP (ΔR = +0.568, P = 0.030), respectively. DISCUSSION AND CONCLUSIONS: Despite high levels of disability, capacity for exercise-induced neuroplasticity was retained among people with progressive MS. The hemisphere contralateral to the weaker hand was resistant to exercise-induced CSE changes, suggesting less neuroplastic potential. Lower fitness and higher body fat were associated with diminished exercise-induced CSE benefits, suggesting that therapists should consider interventions aimed at improving fitness and combating sedentarism to ultimately enhance the benefits of exercise on the brain.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A302).

Oxygen Cost During Mobility Tasks and Its Relationship to Fatigue in Progressive Multiple Sclerosis.

OBJECTIVE: To compare the oxygen costs of mobility tasks between individuals with progressive multiple sclerosis (MS) using walking aids and matched controls and to determine whether oxygen cost predicted fatigue. DESIGN: Cross-sectional descriptive. SETTING: A rehabilitation research laboratory. PARTICIPANTS: A total of 14 adults with progressive MS (mean age ± SD [y], 54.07±8.46) using walking aids and 8 age- and sex-matched controls without MS (N=22). INTERVENTIONS: Participants performed 5 mobility tasks (rolling in bed, lying to sitting, sitting to standing, walking, climbing steps) wearing a portable metabolic cart. MAIN OUTCOME MEASURES: Oxygen consumption (V˙o2) during mobility tasks, maximal V˙o2 during graded maximal exercise test, perceived exertion, and task-induced fatigue were measured on a visual analog scale before and after mobility tasks. RESULTS: People with progressive MS had significantly higher oxygen cost in all tasks compared to controls (P<.05): climbing steps (3.60 times more in MS), rolling in bed (3.53), walking (3.10), lying to sitting (2.50), and sitting to standing (1.82). There was a strong, positive correlation between task-induced fatigue and oxygen cost of walking, (ρ [13]=0.626, P=.022). CONCLUSIONS: People with progressive MS used 2.81 times more energy on average for mobility tasks compared to controls. People with progressive MS experienced accumulation of oxygen cost, fatigue, and exertion when repeating tasks and higher oxygen cost during walking was related to greater perception of fatigue. Our findings suggest that rehabilitation interventions that increase endurance during functional tasks could help reduce fatigue in people with progressive MS who use walking aids.

Interferon Gamma ELISPOT Testing as a Risk-Stratifying Biomarker for Kidney Transplant Injury: Results From the CTOT-01 Multicenter Study.

Previous studies suggest that quantifying donor-reactive memory T cells prior to kidney transplantation by interferon gamma enzyme-linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation-01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6- or 12-month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell-depleting, rabbit anti-thymocyte globulin (ATG). Within the no-ATG subset, IFNγELISPOT(neg) subjects had higher 6- and 12-month eGFRs than IFNγELISPOT(pos) subjects, independent of biopsy-proven AR, peak PRA, human leukocyte antigen mismatches, African-American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor-reactive memory T cells.

Fulminant endocarditis and disseminated infection caused by carbapenem-resistant Acinetobacter baumannii in a renal-pancreas transplant recipient.

Acinetobacter baumannii is an important cause of healthcare-associated infections, and is particularly problematic among patients who undergo organ transplantation. We describe a case of fulminant sepsis caused by carbapenem-resistant A. baumannii harboring the blaOXA-23 carbapenemase gene and belonging to international clone II. This isolate led to the death of a patient 6 days after simultaneous kidney-pancreas transplantation. Autopsy findings revealed acute mitral valve endocarditis, myocarditis, splenic and renal emboli, peritonitis, and pneumonia. This case highlights the severe nature of certain A. baumannii infections and the vulnerability of transplanted patients to the increasingly intractable "high-risk" clones of multidrug-resistant organisms.

Cutaneous histoplasmosis in renal transplant recipients.

Cutaneous histoplasmosis is a rare entity, although it can be seen in a substantial portion of renal transplant recipients with disseminated disease. The prognosis of disseminated disease is worse than isolated cutaneous involvement, and significant delays in diagnosis are reported. We reviewed reports of cutaneous histoplasmosis with and without dissemination in the setting of renal transplantation to examine incidence, timing of diagnosis, clinical features, and prognosis. Remarkable morphologic variability and the non-specific appearance of skin findings suggest that tissue culture is required for definitive diagnosis. Cutaneous lesions represent an easily accessible source for early diagnosis.

Effect of a single bout of resistance exercise on arterial stiffness following a high-fat meal.

Consumption of a high-fat meal (HFM) causes postprandial lipemia and vascular dysfunction. Acute resistance exercise (RE) alone may also have a negative effect on vascular function. The purpose of this study was to measure arterial stiffness and postprandial lipemia after a HFM with or without acute RE. 9 recreationally active men (age 24±5 years, BMI 25±3 kg/m2) completed both: (1) HFM alone and (2) HFM+RE in a randomized order. Pulse wave velocity (PWV) from carotid to femoral artery and carotid to radial artery were used as measures of central/aortic and peripheral arterial stiffness, respectively. Circulating triglycerides (TRG) were obtained from finger stick samples as a marker of lipemia. There was a significant condition-by-time interaction for TRG (p<0.05). TRG levels increased significantly following both conditions with a significantly attenuated increase following HFM+RE (p<0.05). There was a significant condition-by-time interaction for peripheral PWV as this parameter increased following HFM, but decreased following HFM+RE (p=0.021). Central PWV did not change with HFM or HFM+RE (p>0.05). Following a HFM, acute RE attenuates postprandial lipemia and improves peripheral arterial stiffness without having a negative effect on central arterial stiffness.

Endometriosis in Patients Undergoing Plastic Surgical Procedures: A Case Report and Review of the Literature.

Background: Endometriosis is a common gynecological disorder described as the presence of functional endometrial tissue outside the uterus, which can also be found in extrapelvic locations. Although patients seeking treatment for endometriosis usually present to gynecologists, there are rare cases of endometriosis encountered by plastic surgeons in routine practice, either incidentally or as a concomitant finding. Methods: We present a rare case of a 36-year-old woman with symptoms of panniculitis desiring panniculectomy. During surgery, an abdominal mass was excised and confirmed by pathological analysis to be endometriosis. A comprehensive literature review was conducted using the PubMed search engine of the National Institutes of Health to identify cases of endometriosis in plastic surgery. Following screening of the results, 14 articles were included in this analysis that fit the criteria of our search. Results: Of the 14 articles reviewed, cutaneous endometriosis was the most common subtype found in plastic surgery. None of the studies described findings of endometriosis in routine panniculectomies. Several identified endometriosis discovered during cosmetic abdominoplasties. Conclusions: Endometriosis encountered in plastic surgery is a rare but clinically important occurrence, with the cutaneous subtype representing the majority of cases. Endometriosis should always be on the differential diagnosis when an abdominal mass is found in a patient with a history of abdominal surgery. Abdominal masses found during routine aesthetic or reconstructive surgery should be submitted for tissue analysis to guide possible secondary treatments.

Association of suicide rates, gun ownership, conservatism and individual suicide risk.

OBJECTIVES: The purpose of the study was to examine the association of suicide rates, firearm ownership, political conservatism, religious integration at the state level, and individual suicide risk. Social structural and social learning and social integration theories were theoretical frameworks employed. It was hypothesized that higher suicide rates, higher state firearm availability, and state conservatism elevate individual suicide risk. METHOD: Data were pooled from the Multiple Cause of Death Files. Multilevel logistic regression models were fitted to all deaths occurring in 2000 through 2004 by suicide. RESULTS: The state suicide rate significantly elevated individual suicide risk (AOR = 1.042, CI = 1.037, 1.046). Firearm availability at the state level was associated with significantly higher odds of individual suicide (AOR = 1.004, CI = 1.003, 1.006). State political conservatism elevated the odds of individual suicides (AOR = 1.005, CI = 1.003, 1.007), while church membership at the state level reduced individual odds of suicide (AOR = 0.995, CI = 0.993, 0.996). The results held even after controlling for socioeconomic and demographic variables at the individual level. CONCLUSION: It was concluded that the observed association between individual suicide odds and national suicide rates, and firearm ownership cannot be discounted. Future research ought to focus on integrating individual level data and contextual variables when testing for the impact of firearm ownership. Support was found for social learning and social integration theories.

Lifting the lid over the pearl: A histological insight.

Epithelial pearls and Keratin pearls are pathognomonic of squamous cell carcinoma. However, their histogenesis is not well understood. Only a handful of studies have been conducted in the past in this regard. This brief communication aims to understand the formation of these pearls with a few of our own experiences.

Biodiversity inventories and conservation of the marine fishes of Bootless Bay, Papua New Guinea.

BACKGROUND: The effective management and conservation of biodiversity is predicated on clearly defined conservation targets. Species number is frequently used as a metric for conservation prioritization and monitoring changes in ecosystem health. We conducted a series of synoptic surveys focusing on the fishes of the Bootless Bay region of Papua New Guinea to generate a checklist of fishes of the region. Bootless Bay lies directly south of Port Moresby, the capital of Papua New Guinea, and experiences the highest human population density of any marine area in the country. Our checklist will set a baseline against which future environmental changes can be tracked. RESULTS: We generated a checklist of 488 fish species in 72 families found in Bootless Bay during a two-week sampling effort. Using incident-based methods of species estimation, we extrapolate there to be approximately 940 fish species in Bootless Bay, one of the lowest reported numbers in Papua New Guinea. CONCLUSIONS: Our data suggest that the Bootless Bay ecosystem of Papua New Guinea, while diverse in absolute terms, has lower fish biodiversity compared to other shallow marine areas within the country. These differences in faunal diversity are most likely a combination of unequal sampling effort as well as biophysical factors within Bootless Bay compounded by historical and/or contemporary anthropogenic disturbances.

Design of the Reducing Diagnostic Error to Improve Patient Safety (REDEfINE) in COPD and asthma study: A cluster randomized comparative effectiveness trial.

Although spirometry is a simple, portable test and recommended for the diagnosis of asthma and chronic obstructive pulmonary disease (COPD), it is not routinely used in the primary care setting. Minorities and underserved populations are less likely to have spirometry assessment, leading to both over and misdiagnosis of asthma and COPD. Because dyspnea is a common symptom across multiple diseases, use of spirometry as a diagnostic tool is important. Missed, delayed, or misdiagnosis of asthma and COPD, which are considered diagnostic errors (DE), can lead to poor quality of care, increased morbidity and mortality, and increased costs to patients and health systems. Barriers to the use of spirometry have been identified at clinician/clinic and health systems levels. The REDEFINE program is designed to overcome identified barriers to spirometry use in primary care by utilizing health promoters (HPs) who perform spirometry within primary care clinics and work collaboratively with clinicians to incorporate the results at the point of care without interrupting clinic workflow. The REDEFINE trial is a comparative effectiveness study comparing outcomes of the REDEFINE program with usual care (UC) in primary care patients determined to be at increased risk of DE for asthma and COPD. The primary outcome will be all-cause hospitalizations. The secondary outcomes will be the proportion of accurate diagnosis of COPD, asthma, or asthma-COPD overlap based on initial diagnosis and spirometry and all cause and respiratory-related acute outpatient care and emergency department visits. In this report, we describe the design and methods for the REDEFINE trial. Trial registration: NCT03137303https://clinicaltrials.gov/ct2/show/NCT03137303?term=REDEFINE&draw=2&rank=1.

Religion and suicide acceptability: a cross-national analysis.

Four perspectives (moral community thesis, religious integration, religious commitment, and social networks) guide the selection of variables in this study. Data are from the combined World Values/European Values Surveys for 2000 (50,547 individuals nested in 56 nations). The results of a multivariate hierarchical linear model support all four perspectives. Persons residing in nations with relatively high levels of religiosity, who are affiliated with one of four major faiths, are religiously committed, and are engaged with a religious network are found to be lower in suicide acceptability. The religious integration perspective, in particular, is empirically supported; affiliation with Islam is associated with low suicide acceptability. The findings provide strong support for an integrated model and demonstrate the usefulness of the moral community thesis in understanding suicide acceptability.

Disability Status, Unemployment, and Alcohol-Related Liver Disease (ALD) Mortality: A Large Sample Individual Level Longitudinal Study.

PURPOSE: Unlike previous research, we evaluate disability within expanded employment status factors and stratify gender, race and ethnicity in alcohol-related liver disease (ALD) mortality in a large sample individual level longitudinal study. MATERIALS AND METHODS: The National Longitudinal Mortality Study (NLMS) was used covering the period 1990-2011. Statistical analysis involved the use of proportional hazards regression on a sample of almost 1.4 million people aged 18 and older, of whom 2638 died of ALD by the end of the follow-up period. RESULTS: With expanded employment status factors, disability (HR=3.76 [95%] CI 3.22, 4.39), unemployment (HR=1.90, CI 1.56, 2.31), and those not otherwise in the labor force (HR=2.31, CI 2.08, 2.56) were strongly related to ALD mortality compared to the employed. When stratified, gender, race, and ethnicity were not important modifiers in the relationships between disability, unemployment, those not in the labor force and subsequent ALD mortality. Consistent with other studies, males, minority status, living in a highly urban area, renting as opposed to owning a home, lower educational attainment, marital statuses other than marriage, low income, and age were related to ALD mortality. CONCLUSION: In addition to unemployment which has been previously studied in a large longitudinal sample, disabled people who were unable to work and those not looking for work had a higher risk of ALD mortality. Alcohol consumption, abuse and morbidity in these populations are of considerable clinical concern.

Diabetes Mellitus and Marital Status: Evidence from the National Longitudinal Mortality Study on the Effect of Marital Dissolution and the Death of a Spouse.

PURPOSE: This study evaluates the full impact of marital status on diabetes mellitus by stratifying the analysis by gender, including socioeconomic covariates and, unlike most studies, extending marital status by separating out previously conflated status categories. METHODS: Release 5 of the National Longitudinal Mortality Study (NLMS) was used for the data. Logistic regression was applied to the data from 1990 to 2011. The effective sample size consists of 1,384,507 individuals age 18 and above recruited into the study (via the Current Population Surveys), 3,955 of whom had died of diabetes mellitus by 2011. RESULTS: For minority men and non-Hispanic white men, divorced/separated status was significantly related to diabetes mortality, respectively (OR=1.318, CI=1.010, 1.719; and OR=1.283, CI=1.054, 1.562). For minority women and non-Hispanic white women, widowed status was related to diabetes mortality, respectively (OR=1.349, CI=1.107, 1.643; and OR=1.262, CI=1.113, 1.431). CONCLUSION: Contrary to recent epidemiological studies in which divorced/separated and widowed status were combined into one covariate, this United States study finds that divorced/separated men and widowed women are at increased risk for diabetes mellitus mortality, and that among these populations at risk, minorities are at higher risk than whites. The study highlights the importance of marital status and gender differences in the risk of death from diabetes.

Task-Oriented Circuit Training as an Alternative to Ergometer-Type Aerobic Exercise Training after Stroke.

Moderate-intensity aerobic exercise training is an important treatment strategy to enhance functional recovery and decrease cardiometabolic risk factors after stroke. However, stroke related impairments limit access to ergometer-type exercise. The aims of the current study were (1) to evaluate whether our task-oriented circuit training protocol (intermittent functional training; IFT) could be used to sustain moderate-intensity aerobic workloads over a 10-week intervention period, and (2) to investigate its preliminary effects on cardiorespiratory fitness and metabolic profiles compared to constant-load ergometer-type exercise (CET). Forty chronic hemiparetic stroke survivors were randomized to receive 30 sessions of IFT or CET over ten weeks. Similar proportions of participants were randomized to IFT (7/19) and CET (9/18) sustained workloads associated with moderate-intensity aerobic exercise over the study period (p = 0.515). However, CET was associated with more substantial changes in maximal oxygen uptake (MD = 2.79 mL min-1 kg-1 CI: 0.84 to 4.74) compared to IFT (MD = 0.62 mL min-1 kg-1 CI: -0.38 to 1.62). Pre to post changes in C-reactive protein (-0.9 mg/L; p =0.017), short-term glycemia (+14.7 mol/L; p = 0.026), and resting whole-body carbohydrate oxidation (+24.2 mg min-1; p = 0.046) were observed when considering both groups together. Accordingly, IFT can replicate the aerobic intensities sustained during traditional ergometer-type exercise training. More work is needed to evaluate the dose-response effects of such task-oriented circuit training protocols on secondary prevention targets across the continuum of stroke recovery.

Clinical predictors of proteinuria after conversion to sirolimus in kidney transplant recipients.

Proteinuria is an increasingly recognized effect of sirolimus (SRL) therapy in kidney transplant recipients. Predictors of proteinuria after conversion to SRL are not well described, and in particular the risk in African-American (AA) kidney recipients is unknown. We sought to analyze risk factors for proteinuria with SRL therapy in a cohort of 39 patients (44% AA) converted from tacrolimus to SRL at a mean time of 4 months posttransplantation. Patients were maintained on therapy with mycophenolate mofetil while most patients underwent early steroid withdrawal. Urinary protein to creatinine ratio (Up/cr) at a mean of 14 months postconversion increased to > or =500 mg/g in 65% of AAs versus 14% of non-AAs (p = 0.001). Mean arterial blood pressure at the time of conversion and pretransplant proteinuric kidney disease were also predictors of proteinuria after SRL conversion. In conclusion, AAs appear to be at high risk for proteinuria and should be monitored closely after conversion to SRL in calcineurin inhibitor sparing protocols.

Association of temporal factors and suicides in the United States, 2000-2004.

OBJECTIVE: The purpose of the study was to examine the association of temporal factors, in particular days of the week and seasons of the year and death from suicide in the United States. METHOD: Data were pooled from the Multiple Cause of Death Files. Hierarchical logistic regression models were fitted to all deaths occurring in 2000 through 2004 by suicide. RESULTS: The incidence of suicide was significantly higher on Wednesdays, compared to Sunday. Specifically, individuals were 99% more likely to kill themselves on Wednesday than on Sunday. Suicides were more prevalent in the summer months, and they were less likely to occur in winter. The state suicide rate significantly elevated individual suicide risk. The results held even after controlling for the potentially confounding effects of socio-economic and demographic variables at both the individual and state levels. CONCLUSION: It was concluded that the observed association between seasonality and suicide cannot be discounted as a mere coincidence. Future research ought to focus on integrating individual level data and contextual variables when testing for seasonality effects.

Comparative forensic analysis of reverse root canal filing and conventional method for DNA isolation from extracted teeth under different environmental conditions: A prospective study.

The grinding of a whole tooth specimen has been considered the conventional method to extract genomic deoxyribonucleic acid (DNA) in forensic science. However, we have tried the less destructive reverse root canal filing (RRCF) method without disturbing the morphology of the tooth to achieve competent amplifiable DNA. A total of 27 pairs of bilateral intact extracted teeth from the same subject were used in three different simulated environmental conditions for the respective RRCF and conventional methods: (a) soil burial for six months, (b) incineration at 200º C for four minutes, and (c) immersion in water for two months. Qualitative agarose gel electrophoresis assessment and downstream amplification were performed. The results showed significantly higher mean DNA concentration for the RRCF method in all three environmental conditions (p value = 0.008) in comparison to the conventional method. However, comparable qualitative results were found in both methods for the mean DNA concentration for incinerated (159.49 ng/ml), soil (119.52 ng/ml), and water (108.60 ng/ml) samples. It was concluded that the RRCF method is better quantitively (ng/ml) and comparable in terms of quality with respect to the conventional method, with the added advantage of preservation of the tooth morphology.