The effects of short-term, progressive exercise training on disease activity in smouldering multiple myeloma and monoclonal gammopathy of undetermined significance: a single-arm pilot study.

BACKGROUND: High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study (N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity. METHODS: In this single-arm pilot study, N = 20 participants diagnosed with MGUS or SMM were allocated to receive a 16-week progressive exercise programme. Primary outcome measures were feasibility and safety. Secondary outcomes were pre- to post-exercise training changes to blood biomarkers of MGUS and SMM disease activity- monoclonal (M)-protein and free light chains (FLC)- plus cardiorespiratory and functional fitness, body composition, quality of life, blood immunophenotype, and blood biomarkers of inflammation. RESULTS: Fifteen (3 MGUS and 12 SMM) participants completed the exercise programme. Adherence was 91 ± 11%. Compliance was 75 ± 25% overall, with a notable decline in compliance at intensities > 70% V̇O2PEAK. There were no serious adverse events. There were no changes to M-protein (0.0 ± 1.0 g/L, P =.903), involved FLC (+ 1.8 ± 16.8 mg/L, P =.839), or FLC difference (+ 0.2 ± 15.6 mg/L, P =.946) from pre- to post-exercise training. There were pre- to post-exercise training improvements to diastolic blood pressure (- 3 ± 5 mmHg, P =.033), sit-to-stand test performance (+ 5 ± 5 repetitions, P =.002), and energy/fatigue scores (+ 10 ± 15%, P =.026). Other secondary outcomes were unchanged. CONCLUSIONS: A 16-week progressive exercise programme was feasible and safe, but did not reverse MGUS/SMM disease activity, contrasting a prior case study showing that five years of exercise training reversed SMM in a 44-year-old former athlete. Longer exercise interventions should be explored in a group of MGUS/SMM patients, with measurements of disease biomarkers, along with rates of disease progression (i.e., MGUS/SMM to MM). REGISTRATION: https://www.isrctn.com/ISRCTN65527208 (14/05/2018).

Cytologic, histopathologic, and clinical features of granulomatous colitis in a French Bulldog.

A young French Bulldog was presented with clinical signs of chronic gastrointestinal disease, unresponsive to medical therapies. Parasite screenings and abdominal ultrasound failed to identify the etiology of the clinical signs. Cytologic evaluation of a rectal scraping sample diagnosed presumptive granulomatous colitis (GC) based on the presence of numerous macrophages with characteristic abundant, pink, granular cytoplasm, which showed an intense pink color when stained with periodic acid-Schiff. Tissue biopsy samples and Escherichia coli fluorescence in situ hybridization analysis confirmed the cytologic diagnosis. The cytologic, histopathologic, and clinical features and staining properties of GC in a French Bulldog are reported. Rectal scraping should be considered a part of the diagnostic evaluation in patients with suspected GC.

Metabolic Activation and Scaling in Two Species of Colonial Cnidarians.

Metabolic activation can have a profound impact, for instance, by more than compensating for the lower resting metabolic rates of large organisms compared to smaller ones. In some animals, activity can easily be judged by the rate of muscle-driven movement. In sessile organisms, however, judging activity is less straightforward, although feeding often results in metabolic activation. Two colonial cnidarians were examined in this context, using entirely lab-grown material to remove any artifactual effects of experimental manipulations. Hydractinia symbiolongicarpus is a carnivorous hydroid that uses active muscular contractions to drive its gastrovascular fluid. Sympodium sp., on the other hand, is an octocoral that hosts photosynthetic Symbiodinium and uses cilia to propel its gastrovascular fluid. Measures of oxygen uptake indicated that feeding activated metabolism in H. symbiolongicarpus. While light treatment had no effect on subsequent dark metabolism in Sympodium sp., stress activated metabolism to an extent comparable to H. symbiolongicarpus. In both taxa, different individual size measures or synthetic size measures derived from principal component analysis produced different scaling relationships between metabolism and size. On balance, the data suggest that scaling was negatively allometric in Sympodium sp. and nearly isometric in H. symbiolongicarpus; yet metabolic activation was comparable in the two species. Regardless of the size measure used, active and resting colonies of H. symbiolongicarpus exhibited similar scaling relationships. Colonial animals may lack the large difference between resting and active metabolic rates found in highly active animals, and this may be related to how their metabolism scales with size.

Parents' role in early adolescent self-injury: An application of self-determination theory.

OBJECTIVE: We applied self-determination theory to examine a model whereby perceived parental autonomy support directly and indirectly affects nonsuicidal self-injury (NSSI) through difficulties in emotion regulation. METHOD: 639 participants (53% female) with a mean age of 13.38 years (SD = 0.51) completed the How I Deal with Stress Questionnaire as a screener for NSSI, the Perceptions of Parents Scale, and the Difficulties in emotion Regulation Scale. Participants who indicated having ever hurt themselves on purpose without the intent to die (n = 116, 66% female) were classified in the NSSI lifetime group. RESULTS: A mediation analysis with bootstrapping procedure revealed that adolescents who reported their parents as being less supportive of their need for autonomy were more likely to have engaged in NSSI. Further, this relationship was partially mediated by emotion regulation. CONCLUSION: Adolescents who do not perceive autonomy support from their parents, have more difficulties regulating their emotions, and may turn to NSSI as a means to cope. Clinical implications of the findings suggest involving the family, and specifically, targeting parental autonomy support may be beneficial when working with young adolescents who self-injure. (PsycINFO Database Record

The Role of Basic Need Satisfaction in the Onset, Maintenance, and Cessation of Non-Suicidal Self-Injury: An Application of Self-Determination Theory.

The present study applied self-determination theory to examine the onset, maintenance, and cessation of non-suicidal self-injury (NSSI) in adolescents. Specifically, the study examined the relationship between the basic psychological needs of autonomy, competence, and relatedness, and NSSI status. Participants were classified into the NSSI Maintain (n = 30), NSSI Start (n = 44), NSSI Stop (n = 21), or Control (n = 98) groups based on NSSI status over 2 time points within a 12-month period. Repeated measures multiple analysis of variance was employed. Satisfaction of the need for competence decreased over time in all adolescents. Adolescents who maintained NSSI behavior reported significantly lower levels of need satisfaction compared to adolescents reporting no history of NSSI engagement, and adolescents who began NSSI over the course of the study reported significantly lower levels of need satisfaction compared to those reporting no history of NSSI engagement. The findings suggest that need satisfaction varies as a function of NSSI status.

Dog Ecology and Barriers to Canine Rabies Control in the Republic of Haiti, 2014-2015.

An estimated 59 000 persons die annually of infection with the rabies virus worldwide, and dog bites are responsible for 95% of these deaths. Haiti has the highest rate of animal and human rabies in the Western Hemisphere. This study describes the status of animal welfare, animal vaccination, human bite treatment, and canine morbidity and mortality in Haiti in order to identify barriers to rabies prevention and control. An epidemiologic survey was used for data collection among dog owners during government-sponsored vaccination clinics at fourteen randomly selected sites from July 2014 to April 2015. A total of 2005 surveys were collected and data were analysed using parametric methods. Over 50% of owned dogs were allowed to roam freely, a factor associated with rabies transmission. More than 80% of dog owners reported experiencing barriers to accessing rabies vaccination for their dogs. Nearly one-third of the dog population evaluated in this study died in the year preceding the survey (32%) and 18% of these deaths were clinically consistent with rabies. Dog bites were commonly reported, with more than 3% of the study population bitten within the year preceding the survey. The incidence of canine rabies in Haiti is high and is exacerbated by low access to veterinary care, free-roaming dog populations and substandard animal welfare practices. Programmes to better understand the dog ecology and development of methods to improve access to vaccines are needed. Rabies deaths are at historical lows in the Western Hemisphere, but Haiti and the remaining canine rabies endemic countries still present a significant challenge to the goal of rabies elimination in the region.

A possible heterozygous advantage in muscular dystrophy.

In certain autosomal recessive disorders there is suggestive evidence that heterozygous carriers may have some selective advantage over normal homozygotes. These include, for example, cystic fibrosis, Tay-Sachs disease and phenylketonuria. The best example so far, however, is that of significant heterozygous advantage in sickle-cell anaemia with increased resistance to falciparum malaria.

Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons.

Repetitive acute intermittent hypoxia (rAIH) increases growth/trophic factor expression in respiratory motor neurons, thereby eliciting spinal respiratory motor plasticity and/or neuroprotection. Here we demonstrate that rAIH effects are not unique to respiratory motor neurons, but are also expressed in non-respiratory, spinal alpha motor neurons and upper motor neurons of the motor cortex. In specific, we used immunohistochemistry and immunofluorescence to assess growth/trophic factor protein expression in spinal sections from rats exposed to AIH three times per week for 10weeks (3×wAIH). 3×wAIH increased brain-derived neurotrophic factor (BDNF), its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and phosphorylated TrkB (pTrkB) immunoreactivity in putative alpha motor neurons of spinal cervical 7 (C7) and lumbar 3 (L3) segments, as well as in upper motor neurons of the primary motor cortex (M1). 3×wAIH also increased immunoreactivity of vascular endothelial growth factor A (VEGFA), the high-affinity VEGFA receptor (VEGFR-2) and an important VEGF gene regulator, hypoxia-inducible factor-1α (HIF-1α). Thus, rAIH effects on growth/trophic factors are characteristic of non-respiratory as well as respiratory motor neurons. rAIH may be a useful tool in the treatment of disorders causing paralysis, such as spinal injury and motor neuron disease, as a pretreatment to enhance motor neuron survival during disease, or as preconditioning for cell-transplant therapies.

Basic Psychological Need Satisfaction, Emotion Dysregulation, and Non-suicidal Self-Injury Engagement in Young Adults: An Application of Self-Determination Theory.

Non-suicidal self-injury (NSSI) is a public health concern that affects young adults at alarming rates. The present study examines the role of satisfaction of self-determination theory's three basic needs for autonomy, competence, and relatedness in young adults' NSSI engagement. University students who reported ever having engaged in NSSI (n = 40, 85 % female; Mage = 20.10, SD = 1.66) reported significantly lower levels of the satisfaction of all three needs, as well as more difficulties with all aspects of emotion regulation (non-acceptance of emotional responses, difficulty engaging in goal directed behavior, impulse control, lack of emotional awareness, limited access to regulation strategies, lack of emotional clarity), compared to students with no history of NSSI (n = 46, 91 % female; Mage = 19.79, SD = 1.37). Results of a logistic regression analysis revealed that need satisfaction added to the prediction of NSSI group membership after controlling for the effects of emotion regulation. Satisfaction of the need for competence and limited access to emotion regulation strategies accounted for significant variance in NSSI in the final model. The findings suggest that self-determination theory may be a useful framework under which to conceptualize NSSI and that the need for competence may be particularly salient for University students.

Erratum to: Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium.

Unfortunately, the original version of this article [1], contained a mistake. In Table 1, the primers for Sh6 and Sh9 were included incorrectly. Instead of GGGATGTATGCAGACTTG TTGTTTGGCTGCAGTAAC and GCTGAGCTTGAGATTG CTTCTGTCCCATCGATACC they should have been Sh6 Forward Primer GGTGGATTACGCAATAG, Sh6 Reverse Primer TTTAATCAACCGGGTGTC and Sh9 Forward Primer GGGATGTATGCAGACTTG, Sh9 Reverse Primer TTGTTTGGCTGCAGTAAC respectively. A corrected version of Table 1 is included below

Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium.

BACKGROUND: Human urogenital schistosomiasis caused by Schistosoma haematobium is widely distributed across Africa and is increasingly targeted for control and regional elimination. The development of new high-throughput, cost-effective molecular tools and approaches are needed to monitor and evaluate the impact of control programs on the parasite populations. Microsatellite loci are genetic markers that can be used to investigate how parasite populations change over time and in relation to external influences such as control interventions. FINDINGS: Here, 18 existing S. haematobium microsatellite loci were optimised to enable simultaneous amplification across two novel multiplex microsatellite PCR's, each containing nine loci. Methods were developed for the cost effective and rapid processing and microsatellite analysis of S. haematobium larval stages stored on Whatman-FTA cards and proved robust on miracidia and cercariae collected from Zanzibar and Niger. CONCLUSION: The development of these novel and robust multiplex microsatellite assays, in combination with an improved protocol to elute gDNA from Whatman-FTA fixed schistosome larval stages, enables the high-throughput population genetic analysis of S. haematobium. The molecular resources and protocols described here advance the way researchers can perform multi locus-based population genetic analyses of S. haematobium as part of the evaluation and monitoring of schistosomiasis control programmes.

Discerning applicants' interests in rural medicine: a textual analysis of admission essays.

BACKGROUND: Despite efforts to construct targeted medical school admission processes using applicant-level correlates of future practice location, accurately gauging applicants' interests in rural medicine remains an imperfect science. This study explores the usefulness of textual analysis to identify rural-oriented themes and values underlying applicants' open-ended responses to admission essays. METHODS: The study population consisted of 75 applicants to the Rural Physician Leadership Program (RPLP) at the University of Kentucky College of Medicine. Using WordStat, a proprietary text analysis program, applicants' American Medical College Application Service personal statement and an admission essay written at the time of interview were searched for predefined keywords and phrases reflecting rural medical values. From these text searches, derived scores were then examined relative to interviewers' subjective ratings of applicants' overall acceptability for admission to the RPLP program and likelihood of practicing in a rural area. RESULTS: The two interviewer-assigned ratings of likelihood of rural practice and overall acceptability were significantly related. A statistically significant relationship was also found between the rural medical values scores and estimated likelihood of rural practice. However, there was no association between rural medical values scores and subjective ratings of applicant acceptability. CONCLUSIONS: That applicants' rural values in admission essays were not related to interviewers' overall acceptability ratings indicates that other factors played a role in the interviewers' assessments of applicants' acceptability for admission.

The N-terminal ß-sheet of the hyperthermophilic endoglucanase from Pyrococcus horikoshii is critical for thermostability.

The ß-1,4-endoglucanase (EC 3.2.1.4) from the hyperthermophilic archaeon Pyrococcus horikoshii (EGPh) has strong hydrolyzing activity toward crystalline cellulose. When EGPh is used in combination with ß-glucosidase (EC 3.2.1.21), cellulose is completely hydrolyzed to glucose at high temperature, suggesting great potential for EGPh in bioethanol industrial applications. The crystal structure of EGPh shows a triosephosphate isomerase (TIM) (ß/α)(8)-barrel fold with an N-terminal antiparallel ß-sheet at the opposite side of the active site and a very short C-terminal sequence outside of the barrel structure. We describe here the function of the peripheral sequences outside of the TIM barrel core structure. Sequential deletions were performed from both N and C termini. The activity, thermostability, and pH stability of the expressed mutants were assessed and compared to the wild-type EGPh enzyme. Our results demonstrate that the TIM barrel core is essential for enzyme activity and that the N-terminal ß-sheet is critical for enzyme thermostability. Bioinformatics analyses identified potential key residues which may contribute to enzyme hyperthermostability.

Population genetics of Schistosoma haematobium: development of novel microsatellite markers and their application to schistosomiasis control in Mali.

The recent implementation of mass drug administration (MDA) for control of uro-genital schistosomiasis has identified an urgent need for molecular markers to both directly monitor the impact of MDA, for example to distinguish re-infections from uncleared infections, as well as understand aspects of parasite reproduction and gene flow which might predict evolutionary change, such as the development and spread of drug resistance. We report the development of a novel microsatellite tool-kit allowing, for the first time, robust genetic analysis of individual S. haematobium larvae collected directly from infected human hosts. We genotyped the parasite populations of 47 children from 2 schools in the Ségou region of Mali, the first microsatellite study of this highly neglected parasite. There was only limited evidence of population subdivision between individual children or between the two schools, suggesting that few barriers to gene flow exist in this population. Complex relationships between parasite reproductive success, infection intensity and host age and gender were identified. Older children and boys harboured more diverse infections, as measured by the number of unique adult genotypes present. Individual parasite genotypes had variable reproductive success both across hosts, a pre-requisite for evolutionary selection, and, phenotypically, in hosts of different ages and genders. These data serve as a baseline against which to measure the effect of treatment on parasite population genetics in this region of Mali, and the tools developed are suitable to further investigate this important pathogen, and its close relatives, throughout their range.

Abraham Flexner of Kentucky, his report, Medical Education in the United States and Canada, and the historical questions raised by the report.

One hundred years ago, the time was right and the need was critical for medical education reform. Medical education had become a commercial enterprise with proprietary schools of variable quality, lectures delivered in crowded classrooms, and often no laboratory instruction or patient contact. Progress in science, technology, and the quality of medical care, along with political will and philanthropic support, contributed to the circumstances under which Abraham Flexner produced his report. Flexner was dismayed by the quality of many of the medical schools he visited in preparing the report. Many of the recommendations in Medical Education in the United States and Canada are still relevant, especially those concerning the physician as a practitioner whose purpose is more societal and preventive than individual and curative. Flexner helped establish standards for prerequisite education, framed medical school admission criteria, aided in the design of a curriculum introduced by the basic and followed by the clinical sciences, stipulated the resources necessary for medical education, and emphasized medical school affiliation with both a university and a strong clinical system. He proposed integration of basic and clinical sciences leading to contextual learning, active rather than passive learning, and the importance of philanthropy. Flexner's report poses several questions for the historian: How were his views on African American medical education shaped by his post-Civil War upbringing in Louisville? Was the report original or derivative? Why did it have such a large impact? This article describes Flexner's early life and the report's methodology and considers several of the historical questions.

Increasing the medical school applicant pool: a key to training more rural physicians.

CONTEXT: Workforce studies show shortages of physicians in many areas of the United States. These shortages are especially severe in states such as Kentucky with many rural counties and are predicted to worsen in the future unless there are changes throughout our educational system to build aspirations and prepare students for medical school education. PURPOSE: To examine rural-urban differences and community characteristics of applicants and matriculants to Kentucky's two allopathic medical schools and influences on the educational aspirations of young students who wish to become physicians. METHODS: The number of Kentucky applicants and matriculants to allopathic medical schools was obtained from the Association of American Medical College's data warehouse for the period from 2002-2006. A continuous, multidimensional measure was used to classify counties by degree of rurality. Socio-demographic variables were selected for the counties of residence for applicants and matriculants. Model variables were tested in a least squares multiple regression model for their ability to explain patterns among Kentucky's 120 counties in the number of both resident applicants and matriculants to medical school. Data from a survey of middle school participants in summer health camps were analyzed to help identify important influences on young students aspiring to a career as a health professional, especially becoming a physician, and how these might be supported to increase the supply of rural medical school applicants. FINDINGS: The low number of rural applicants to medical school was highly correlated with the relative rurality of their county of residence, a low physician-to-population ratio and a low number of total primary care physicians. The percentage of county residents having a bachelor's degree level of education or higher had a positive impact on the application rate. Respondents became interested in health careers at age 15 or younger, and parents and grandparents, teachers, and close associates stimulated their aspirations, with teachers being the most influential. CONCLUSIONS: Prospective students respond to their perception of need for physicians. Rural students are influenced by those who are more highly educated. To overcome the shortage of physicians in rural communities efforts must be made to increase the aspirations for medical education of prospective students from rural counties.

The impact of health on Kentucky's economy.

All states are strongly committed to economic development policies and activities as participants in national and global competition. However, a sometimes overlooked and perhaps under appreciated influence on economic development is the health of a state's citizens. This study focuses on how the health status of Kentucky profoundly influences its economy, workforce, productivity, and general quality of life. If Kentucky's economy is to improve significantly, as compared to other states, significant improvements in the health status of its citizens must be achieved in the near future and sustained over time. In an era of growing concern about rising health insurance costs and maintaining a reliable and productive workforce, employers are increasingly likely to locate in communities where measures of health status are strongly positive. The latest report from the United Health Foundation indicates that in 2007 Kentucky had the 8th worst health status in the nation based on a set of risk factors and outcomes. These risk factors include personal behaviors, community and environment, and public health policies that culminate in key health outcomes related to quality of life and longevity. While it is a serious challenge, our research demonstrates that many of these risk factors can be lowered through relatively low cost and effective interventions that produce substantial improvements in health and Kentucky's rank. Health education is very effective when it begins early in life and continues to emphasize the importance of healthy behaviors, such as not smoking, healthy diets and exercise, and weight control. Preventive health services that identify and treat diseases and conditions that lead to premature death increase both longevity and economic growth through lower treatment costs for chronic diseases and an increase in human capital. Policy changes, such as primary enforcement of motor vehicle seat belt use and encouragement of the use of safety equipment at work, also saves lives and contributes to economic development. Kentucky has already implemented many programs to begin the necessary transformation to a healthier Commonwealth. Creation of additional programs and expansion of those successful ones in place are keys to producing both significant health change and economic growth.

Detection of schistosomes polymerase chain reaction amplified DNA by oligochromatographic dipstick.

The applications of highly specific and sensitive molecular techniques based on polymerase chain reaction (PCR) have constituted a valuable tool for the diagnosis of schistosomiasis and also for the detection of schistosome infections in the snail intermediate hosts. The common method of detecting PCR amplicons is gel electrophoresis in the presence of ethidium bromide, a carcinogen, which is followed by UV transillumination. Other methods, which are available for detecting PCR products, are real-time PCR, PCR-enzyme-linked immunosorbent assay (PCR-ELIZA) and mass spectrometry but they are cumbersome while they are sometimes complex and expensive. Therefore, a simple method of PCR product detection would be a welcome idea and a most valuable tool particularly in disease endemic countries with limited research facilities and resources. In this study, we applied a simple and rapid method for the detection of Schistosoma haematobium and Schistosoma mansoni PCR amplified DNA products using oligochromatographic (OC) dipstick. The amplicons are visualized by hybridization with a gold conjugated probe, while a control for the chromatographic migration is incorporated in the assay. The lower detection limit observed was 10fg of genomic DNA from each of the two species, while the dipstick was also specific for each of the species used in this study.

Isolation and characterization of the first polymorphic microsatellite markers for Schistosoma haematobium and their application in multiplex reactions of larval stages.

The ability of microsatellite loci to reveal genetic diversity within the trematode Schistosoma haematobium is demonstrated for the first time. Nine novel polymorphic microsatellite markers were isolated and their viability assessed on 36 S. haematobium adult worm individuals from three geographical populations. Allelic diversity and gene diversity ranged from two to seven and from 0.29 to 0.76, respectively, suggesting high variability between individuals and between unrelated populations. Three primers also amplified Schistosoma mansoni and two Schistosoma japonicum. The results suggest these primers are useful for population genetic analyses of S. haematobium.