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Introduction: National data indicate a higher prevalence of obesity among American Indian (AI) populations and greater disparity of morbidity and mortality among younger age groups compared with other ethnicities. Diet and physical activity are important obesity preventive behaviors, but no published data exist that describe these behaviors in relation to obesity in AI young adults at tribal colleges. Study purposes were to: (1) identify fruit and vegetable intake and physical activity practices of AI young adults from three U.S. tribal colleges according to BMI categories; (2) identify the accuracy of body weight perceptions; and (3) identify predictor variables for weight misperception., Methods: In this observational study during 2011-2014, a total of 1,256 participants were recruited from three participating U.S. tribal colleges to complete an online survey addressing issues related to diet, physical activity, and weight perception. Reported height and weight were used to calculate BMI categories, and differences between BMI categories were examined. Gender differences related to accuracy of weight perception by BMI categories were also examined. Analyses were conducted in 2016., Results: Based on self-reported height and weight, 68% of the sample was overweight or obese (BMI ≥25) and mean BMI was 28.9 (SD=6.9). Most did not meet recommendations for fruit intake (78.7%), vegetable intake (96.6%), or physical activity (65.6%). More than half (53.7%%) who were overweight/obese underestimated their weight category. Men more often underestimated their weight category (54.2%) than women (35.1%)., Conclusions: Interventions are needed to improve weight-related lifestyle behaviors of AI tribal college students., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

The relationship between military absenteeism and mental health problems has been noted; however, factors affecting military absenteeism by enlisted personnel have not been studied systematically. In a medical center in Taiwan, we performed a chart review of 26 forensic psychiatric evaluations of enlisted personnel who were absent without leave (AWOL) or deserted their service from 1994 to 2014. The findings showed that many of these recruits had a lower level of education (50.00% had just nine years of education), intellectual disability (46.15%), depressive disorders (30.76%), and suicidal ideation (53.85%). Depressive disorder was overrepresented in comparison with findings in a previous study. Further study is needed to confirm whether psychiatric screening before service enlistment and early psychiatric intervention for service members with mental illness or emotional disturbance could help in the prevention of desertion or going AWOL., (© 2016 American Academy of Psychiatry and the Law.)

Background: The military is a unique occupational group and, because of this, military personnel face different kinds of stress than civilian populations. Sleep problems are an example. The purpose of this study was to investigate the relationship between sleep problems, depression level and coping strategies among military personnel., Materials and Methods: In this cross-sectional study, military personnel completed the Beck Depression Inventory, the Pittsburgh Sleep Quality Index and the Jalowiec Coping Scale., Results: An evaluation of the test scores showed that officers had better sleep quality and fewer depressive symptoms than enlisted personnel. Military personnel with higher educational levels and less physical illness also had fewer depressive symptoms. Officers and noncommissioned officers preferred problem-focused strategies. Those with higher Beck Depression Inventory and Pittsburgh Sleep Quality Index scores and those who drank alcohol frequently preferred affective-focused strategies., Conclusions: Our results revealed that sleep quality, physical illness and alcohol consumption were associated with the mental health of military personnel. Treating these factors may improve the mental health of military personnel and enhance effective coping strategies., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy ((1)H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs. normal low fat chow. We detected lower concentrations of total creatine (tCr) and a lower glutamate-to-glutamine ratio in the hippocampus of high fat rats. Additional effects observed in the hippocampus of high fat rats included higher N-acetylaspartylglutamic acid (NAAG), and lower myo-inositol (mIns) and serine (Ser) concentrations. Post-mortem tissue analyses revealed lower phosphorylated AMP-activated protein kinase (pAMPK) in the striatum but not in the hippocampus of high fat rats. Hippocampal pAMPK levels correlated significantly with tCr, aspartate (Asp), phosphoethanolamine (PE), and taurine (Tau), indicating beneficial effects of AMPK activation on brain metabolic and energetic function, membrane turnover, and edema. A negative correlation between pAMPK and glucose (Glc) indicates a detrimental effect of brain Glc on cellular energy response. Overall, these changes indicate alterations in neurotransmission and in metabolic and bioenergetic function in the hippocampus and in the striatum of rats fed a high fat diet., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The guinea pig is a frequently used animal model for human pregnancy complications, such as oxygen deprivation or hypoxia, which result in altered brain development. To investigate the impact of in utero chronic hypoxia on brain development, pregnant guinea pigs underwent either normoxic or hypoxic conditions at about 70 % of 65-day term gestation. After delivery, neurochemical profiles consisting of 19 metabolites and macromolecules were obtained from the neonatal cortex, hippocampus, and striatum from birth to 12 weeks postpartum using in vivo (1)H MR spectroscopy at 9.4 T. The effects of chronic fetal hypoxia on the neurochemical profiles were particularly significant at birth. However, the overall developmental trends of neurochemical concentration changes were similar between normoxic and hypoxic animals. Alterations of neurochemicals including N-acetylaspartate (NAA), phosphorylethanolamine, creatine, phosphocreatine, and myo-inositol indicate neuronal loss, delayed myelination, and altered brain energetics due to chronic fetal hypoxia. These observed neurochemical alterations in the developing brain may provide insights into hypoxia-induced brain pathology, neurodevelopmental compromise, and potential neuroprotective measures.

Understanding the dynamic disease process is vital in early detection, diagnosis, and measuring progression. Continuous-time Markov chain (CTMC) methods have been used to estimate state-change intensities but challenges arise when stages are potentially misclassified. We present an analytical likelihood approach where the hidden state is modeled as a three-state CTMC model allowing for some observed states to be possibly misclassified. Covariate effects of the hidden process and misclassification probabilities of the hidden state are estimated without information from a 'gold standard' as comparison. Parameter estimates are obtained using a modified expectation-maximization (EM) algorithm, and identifiability of CTMC estimation is addressed. Simulation studies and an application studying Alzheimer's disease caregiver stress-levels are presented. The method was highly sensitive to detecting true misclassification and did not falsely identify error in the absence of misclassification. In conclusion, we have developed a robust longitudinal method for analyzing categorical outcome data when classification of disease severity stage is uncertain and the purpose is to study the process' transition behavior without a gold standard., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Cerebral β-amyloid angiopathy (CAA) occurs when β-amyloid (Aβ) is deposited in the vascular media and adventitia. It is a common pathology in the brains of older individuals and has been linked to cognitive decline, but relatively little is known about the influence that CAA has on the clinical manifestation of Alzheimer's disease (AD). The aim of this retrospective analysis was to quantify the effect that CAA had on the manifestation of initial AD-related cognitive change and subsequent progression of dementia., Methods: We analyzed neuropathological data from the National Alzheimer's Coordinating Center's data set, performing parametric analyses to assess differences in age of progression to moderate-stage dementia., Results: We found that individuals with both CAA burden and Aβ neuritic plaque burden at death had the greatest risk of earlier conversion to very mild and moderate-stage dementia, but not necessarily faster progression., Conclusions: Our results suggest that CAA contributes to changes in early AD pathogenesis. This supports the idea that vascular change and neuritic plaque deposition are not just parallel processes but reflect additive pathological cascades that influence the course of clinical AD manifestation. Further inquiry into the role of CAA and its contribution to early cognitive change in AD is suggested., (© 2016 S. Karger AG, Basel.)

Background: We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly., Design of Study: Case-crossover design., Methods and Materials: Elderly enrollees (n = 6010) in Taiwan's National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures., Results: After adjusting for medications such as antipsychotics, antidepressants, and diuretics, or comorbidities such as hypertension, osteoarthritis, osteoporosis, rheumatoid arthritis and depression, neither zolpidem nor benzodiazepine was found to be associated with increased risk in all-sites fractures. Subjects without depression were found to have an increased risk of fractures. Diazepam is the only benzodiazepine with increased risk of fractures after adjusting for medications and comorbidities. Hip and spine were particular sites for increased fracture risk, but following adjustment for comorbidities, the associations were found to be insignificant., Conclusion: Neither zolpidem nor benzodiazepine was associated with increased risk of all-site fractures in this case cross-over study after adjusting for medications or comorbidities in elderly individuals with insomnia. Clinicians should balance the benefits and risks for prescribing zolpidem or benzodiazepine in the elderly accordingly.

An efficient, homogeneous synthesis of phospholipid conjugation of S-Neu5Acα2-6Galβ1-4GluNAcβ1-3 (3) and its 6-sulphate analogue 4 has been developed. The self-assembled micelles and liposomes of these trisaccharides formed in solution were found to be inhibitors interfering with the entry of the H1N1 influenza virus into MDCK cells. Compound 3 bearing a liposome and a micelle displayed superior inhibitory activity than its 6-sulfate congener 4 in both the virus neutralization assay and the hemagglutination inhibition assay.

Introduction: There are an estimated 60,000 new cases of ductal carcinoma in situ (DCIS) each year. A lack of understanding in DCIS pathobiology has led to overtreatment of more than half of patients. We profiled the temporal molecular changes during DCIS transition to invasive ductal carcinoma (IDC) using in vivo DCIS progression models. These studies identified B cell lymphoma-9 (BCL9) as a potential molecular driver of early invasion. BCL9 is a newly found co-activator of Wnt-stimulated β-catenin-mediated transcription. BCL9 has been shown to promote progression of multiple myeloma and colon carcinoma. However BCL9 role in breast cancer had not been previously recognized., Methods: Microarray and RNA sequencing were utilized to characterize the sequential changes in mRNA expression during DCIS invasive transition. BCL9-shRNA knockdown was performed to assess the role of BCL9 in in vivo invasion, epithelial-mesenchymal transition (EMT) and canonical Wnt-signaling. Immunofluorescence of 28 patient samples was used to assess a correlation between the expression of BCL9 and biomarkers of high risk DCIS. The cancer genome atlas data were analyzed to assess the status of BCL9 gene alterations in breast cancers., Results: Analysis of BCL9, by RNA and protein showed BCL9 up-regulation to be associated with DCIS transition to IDC. Analysis of patient DCIS revealed a significant correlation between high nuclear BCL9 and pathologic characteristics associated with DCIS recurrence: Estrogen receptor (ER) and progesterone receptor (PR) negative, high nuclear grade, and high human epidermal growth factor receptor2 (HER2). In vivo silencing of BCL9 resulted in the inhibition of DCIS invasion and reversal of EMT. Analysis of the TCGA data showed BCL9 to be altered in 26 % of breast cancers. This is a significant alteration when compared to HER2 (ERBB2) gene (19 %) and estrogen receptor (ESR1) gene (8 %). A significantly higher proportion of basal like invasive breast cancers compared to luminal breast cancers showed BCL9 amplification., Conclusion: BCL9 is a molecular driver of DCIS invasive progression and may predispose to the development of basal like invasive breast cancers. As such, BCL9 has the potential to serve as a biomarker of high risk DCIS and as a therapeutic target for prevention of IDC.

Objective: Changes in food-cue neural reactivity associated with behavioral and surgical weight loss interventions have been reported. Resting functional connectivity represents tonic neural activity that may contribute to weight loss success. This study explores whether intervention type is associated with differences in functional connectivity after weight loss., Methods: Fifteen participants with obesity were recruited prior to adjustable gastric banding surgery. Thirteen demographically matched participants with obesity were selected from a separate behavioral diet intervention. Resting-state functional magnetic resonance imaging was collected 3 months after surgery/behavioral intervention. ANOVA was used to examine post-weight loss differences between the two groups in connectivity to seed regions previously identified as showing differential cue-reactivity after weight loss., Results: Following weight loss, behavioral dieters exhibited increased connectivity between left precuneus/superior parietal lobule (SPL) and bilateral insula pre- to postmeal and bariatric patients exhibited decreased connectivity between these regions pre- to postmeal (P(corrected) <0.05)., Conclusions: Behavioral dieters showed increased connectivity pre- to postmeal between a region associated with processing of self-referent information (precuneus/SPL) and a region associated with interoception (insula) whereas bariatric patients showed decreased connectivity between these regions. This may reflect increased attention to hunger signals following surgical procedures and increased attention to satiety signals following behavioral diet interventions., (© 2015 The Obesity Society.)

Objective: To examine short-term changes in patients' clinical status following lumbar spine surgery (LSS) and to explore presurgical variables that predict surgical outcomes., Methods: Prospective cohort study. A total of 46 patients underwent LSS. Patients completed the following questionnaires 1 week before LSS and 2 weeks after discharge from the hospital: back and leg visual pain analogue scale, Ronald Morris questionnaire (RMQ), Modified Somatic Perception questionnaire (MSPQ), SF-36, Fear-Avoidance Beliefs Questionnaire, Beck's Depression Inventory, EuroQol questionnaire, and patient-perception of improvement. Regression models were constructed to examine predictors of pain, function, quality of life, and patient-perception of improvement at 2 weeks postsurgery., Results: Patients demonstrated significant improvement in back and leg pain and function. MSPQ and symptom duration were significant predictors of back pain, while type of diagnosis and use of opioids were significant predictors of leg pain. Preoperative MSPQ and RMQ were significant predictors of postoperative RMQ. MSPQ, gender, and back pain were significant predictors of quality of life. Back pain, leg pain, depression, smoking, and worker's compensation were significantly associated with patient-perception of improvement., Conclusions: This preliminary study could be viewed as a directory to identify potential risk factors for unfavorable outcomes at early stages following LSS., Competing Interests: Disclosure/Conflict of Interest No duality of interest to declare.

Objectives: Stenotrophomonas maltophilia is a bacterial pathogen associated with health-care associated infections, particularly in immunocompromised patients. Members of the fluoroquinolone drug class are frequently used to treat S. maltophilia infection; however, S. maltophilia resistance to fluoroquinolones, especially levofloxacin, has been increasing., Methods: We sought to identify risk factors associated with levofloxacin resistance using a case-control study. We examined sputum from 76 S. maltophilia-positive patients admitted to our hospital between January 1, 2010 and June 30, 2011. Case groups were defined as patients who had S. maltophilia infections resistant to levofloxacin, and control groups were defined as patients who had S. maltophilia infections susceptible to levofloxacin treatment. Patient information including demographics, previous antibiotic use, and other traits were recorded. In addition, S. maltophilia isolates from patient sputum were assessed for antibiotic resistance as well as for the presence of genes associated with drug resistance., Results: Previous antibiotic treatment with first- or second-generation cephalosporin was found more often in the levofloxacin-susceptible group; by contrast, previous piperacillin/tazobactam treatment occurred more often in the levofloxacin-resistant group. Three genes associated with drug resistance, including SmeA, SmeD, and SpgM were not significantly different between these groups., Conclusion: Piperacillin/tazobactam treatment is associated with subsequent isolation of levofloxacin-resistant S. maltophilia from the respiratory tract., (Copyright © 2013. Published by Elsevier B.V.)

Colorectal cancer (CRC) screening uptake among minorities and those with lower incomes is suboptimal. Behavioral interventions specifically tailored to these populations can increase screening rates and save lives. The Precaution Adoption Process Model (PAPM) allows assignment of a decisional stage for adoption of a behavior such as CRC screening. Here, we characterize the PAPM decisional stage distribution among 470 low income, racially and ethnically diverse study participants at intake into a behavioral intervention study designed to increase CRC screening uptake. We staged participants for stool blood test (SBT) and colonoscopy separately and used the highest stage for the two tests as the 'overall' stage for CRC screening. For SBT, sex, language (English versus Spanish) and doctor recommendation were significantly related to PAPM stage for CRC screening. For colonoscopy, language, education level, doctor recommendation and self-efficacy were related to stage. For overall CRC screening stage, all the variables associated with either SBT or colonoscopy, with the exception of language were significant. This study suggests attending to these key variables in designing interventions to promote CRC screening, particularly with respect to medically underserved populations., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: A substantial amount of evidence suggests that dysfunction of the dopamine transporter may be involved in the pathophysiology of amphetamine dependence (AD). The aim of this study was to examine whether the dopamine transporter gene (DAT1, SLC6A3) is associated with development of AD and whether this gene influences personality traits in patients with AD., Methods: Eighteen polymorphisms of the DAT1 gene were analyzed in a case-control study that included 909 Han Chinese men (568 patients with AD and 341 control subjects). The patients fulfilled the DSM-IV-TR criteria for AD. The Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits and to examine the association between these traits and DAT1 gene variants., Results: A weak association was found between the rs27072 polymorphism and development of AD, but these borderline associations were unconfirmed by logistic regression and haplotype analysis. Although harm avoidance and novelty seeking scores were significantly higher in patients than in controls, DAT1 polymorphisms did not influence these scores., Conclusions: This study suggests that high harm avoidance and novelty seeking personality traits may be a risk factor for the development of AD. However, the DAT1 gene may not contribute to AD susceptibility and specific personality traits observed in AD among Han Chinese men., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background Context: Length-of-hospital stay (LOS) after lumbar spine surgery (LSS) can be affected by many factors. However, few studies have evaluated predictors of LOS, and all have used limited number of variables as predictors., Purpose: The purpose of the study was to identify presurgical, surgical, and postsurgical predictors of LOS after LSS., Study Design/setting: Retrospective review of consecutive patients who had LSS at the University of Kansas Hospital from October 2008 to April, 2012., Patient Sample: Five hundred ninety-three patients underwent LSS consisting of laminotomy, laminectomy, or arthrodesis., Dependent Variable: LOS. Multiple presurgical, surgical, and postsurgical variables were extracted from the patients' medical records and considered as possible predictors (independent variables) of LOS., Methods: Potential predictors that were significantly correlated with LOS were used as indicators to construct three latent factors presurgical, surgical, and postsurgical, which were in turn used to predict LOS in a structural equation model., Results: The average LOS was 4.01±2.73 days. The presurgical factor was indicated by age (61.97±14.49 years), previous level of function (60.5% were totally independent), previous hemoglobin level (13.70±1.36 mg/dL), and use of assistive devices (60% were assistive device users). The surgical factor was indicated by severity of illness (50.2% had minor disease severity), presence of complications (1.9%), and stay in an intensive care unit (4.0%). The postsurgical factor was indicated by postsurgical walking distance (166.43±175.75 ft), level of assistance during walking (5.18±0.81 out of 7 points), balance scores (6.18±1.82 out of 10 points), and bed mobility and transfer dependency scores (9.81±1.99 out of 14 points). These three latent factors explained 47% of variation in LOS., Conclusions: Postsurgical factors predicted the highest variation in LOS in comparison with presurgical and surgical factors and should be taken into consideration for discharge planning. Postsurgical factors are related to the patient's function, modifiable with rehabilitation, and can be improved to shorten LOS. Inclusion of more reliable and standardized presurgical variables could improve the predictability of the model., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Obesity rates are associated with public health consequences and rising health care costs. Weight loss interventions, while effective, do not work for everyone, and weight regain is a significant problem. Eating behavior is influenced by a convergence of processes in the brain, including homeostatic factors and motivational processing that are important contributors to overeating. Initial neuroimaging studies have identified brain regions that respond differently to visual food cues in obese and healthy weight individuals that are positively correlated with reports of hunger in obese participants. While these findings provide mechanisms of overeating, many important questions remain. It is not known whether brain activation patterns change after weight loss, or if they change differentially based on amount of weight lost. Also, little is understood regarding biological processes that contribute to long-term weight maintenance. This study will use neuroimaging in participants while viewing food and non-food images. Functional Magnetic Resonance Imaging will take place before and after completion of a twelve-week weight loss intervention. Obese participants will be followed though a 6-month maintenance period. The study will address three aims: 1. Characterize brain activation underlying food motivation and impulsive behaviors in obese individuals. 2. Identify brain activation changes and predictors of weight loss. 3. Identify brain activation predictors of weight loss maintenance. Findings from this study will have implications for understanding mechanisms of obesity, weight loss, and weight maintenance. Results will be significant to public health and could lead to a better understanding of how differences in brain activation relate to obesity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Context: Low-income and racial/ethnic minority populations experience disproportionate colorectal cancer (CRC) burden and poorer survival. Novel behavioral strategies are needed to improve screening rates in these groups., Background: The study aimed to test a theoretically based "implementation intentions" intervention for improving CRC screening among unscreened adults in urban safety-net clinics., Design: Randomized controlled trial., Setting/participants: Adults (N=470) aged ≥50 years, due for CRC screening, from urban safety-net clinics were recruited., Intervention: The intervention (conducted in 2009-2011) was delivered via touchscreen computers that tailored informational messages to decisional stage and screening barriers. The computer then randomized participants to generic health information on diet and exercise (Comparison group) or "implementation intentions" questions and planning (Experimental group) specific to the CRC screening test chosen (fecal immunochemical test or colonoscopy)., Main Outcome Measures: The primary study outcome was completion of CRC screening at 26 weeks based on test reports (analysis conducted in 2012-2013)., Results: The study population had a mean age of 57 years and was 42% non-Hispanic African American, 28% non-Hispanic white, and 27% Hispanic. Those receiving the implementation intentions-based intervention had higher odds (AOR=1.83, 95% CI=1.23, 2.73) of completing CRC screening than the Comparison group. Those with higher self-efficacy for screening (AOR=1.57, 95% CI=1.03, 2.39), history of asthma (AOR=2.20, 95% CI=1.26, 3.84), no history of diabetes (AOR=1.86, 95% CI=1.21, 2.86), and reporting they had never heard that "cutting on cancer" makes it spread (AOR=1.78, 95% CI=1.16, 2.72) were more likely to complete CRC screening., Conclusions: The results of this study suggest that programs incorporating an implementation intentions approach can contribute to successful completion of CRC screening even among very low-income and diverse primary care populations. Future initiatives to reduce CRC incidence and mortality disparities may be able to employ implementation intentions in large-scale efforts to encourage screening and prevention behaviors., (Copyright © 2014. Published by Elsevier Inc.)

We discuss a mixed methodology for analyzing pile sorting data. We created a list of 14 barriers to colon cancer screening and recruited 18, 13, and 14 participants from three American Indian (AI) communities to perform pile sorting. Quantitative data were analyzed by cluster analysis and multidimensional scaling. Differences across sites were compared using permutation bootstrapping. Qualitative data collected during sorting were compiled by AI staff members who determined names for the clusters found in quantitative analysis. Results showed 5 clusters of barriers in each site although barriers in the clusters varied slightly across sites. Simulation demonstrated type I error rates around the nominal 0.05 level whereas power depended on the numbers of clusters, and between and within cluster variability.

Altered brain metabolism is likely to be an important contributor to normal cognitive decline and brain pathology in elderly individuals. To characterize the metabolic changes associated with normal brain aging, we used high-field proton magnetic resonance spectroscopy in vivo to quantify 20 neurochemicals in the hippocampus and sensorimotor cortex of young adult and aged rats. We found significant differences in the neurochemical profile of the aged brain when compared with younger adults, including lower aspartate, ascorbate, glutamate, and macromolecules, and higher glucose, myo-inositol, N-acetylaspartylglutamate, total choline, and glutamine. These neurochemical biomarkers point to specific cellular mechanisms that are altered in brain aging, such as bioenergetics, oxidative stress, inflammation, cell membrane turnover, and endogenous neuroprotection. Proton magnetic resonance spectroscopy may be a valuable translational approach for studying mechanisms of brain aging and pathology, and for investigating treatments to preserve or enhance cognitive function in aging., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To explore factors associated with discharge placement (DP) and need for skilled assistance after patients are discharged from hospital following lumbar laminectomy., Methods: A retrospective analysis of 339 patients who underwent lumbar laminectomy was conducted. We used multivariable logistic regression analysis to identify significant covariates and to construct two regression models: a primary model to predict DP, home vs inpatient rehabilitation/skilled nursing facility (IR/SNF), and a secondary model to predict the need for skilled assistance once patients are discharged to home., Results: The sample included 48.7% females, 68.2% married, 56.3% independent in daily activities, and 85.2% discharged to home. Subjects were a mean 56.06 ± 12.75 years old and had a BMI of 31.35 ± 6.2. Of those discharged to home, 17.7% needed skilled assistance. Patients stayed 4.41 ± 3.55 days in the hospital and walked 203.38 ± 144.87 ft during hospital stay. Age, distance walked during hospital stay, and length of hospital stay (LOS) were significant positive predictors for discharge to home vs IR/SNF, whereas single living status, diminished prior level of function, and longer LOS were predictors of need for skilled assistance after discharge to home., Conclusion: Age, mobility, marital status, prior level of function, and LOS are key variables in determining healthcare needs following lumbar laminectomy.

In biological systems, methylation is most commonly performed by methyltransferases (MTs) using the electrophilic methyl source S-adenosyl-L-methionine (SAM) via the S(N)2 mechanism. (2S,3S)-β-Methylphenylalanine, a nonproteinogenic amino acid, is a building unit of the glycopeptide antibiotic mannopeptimycin. The gene product of mppJ from the mannopeptimycin-biosynthetic gene cluster is the MT that methylates the benzylic C atom of phenylpyruvate (Ppy) to give βMePpy. Although the benzylic C atom of Ppy is acidic, how its nucleophilicity is further enhanced to become an acceptor for C-methylation has not conclusively been determined. Here, a structural approach is used to address the mechanism of MppJ and to engineer it for new functions. The purified MppJ displays a turquoise colour, implying the presence of a metal ion. The crystal structures reveal MppJ to be the first ferric ion SAM-dependent MT. An additional four structures of binary and ternary complexes illustrate the molecular mechanism for the metal ion-dependent methyltransfer reaction. Overall, MppJ has a nonhaem iron centre that bind, orients and activates the α-ketoacid substrate and has developed a sandwiched bi-water device to avoid the formation of the unwanted reactive oxo-iron(IV) species during the C-methylation reaction. This discovery further prompted the conversion of the MT into a structurally/functionally unrelated new enzyme. Through stepwise mutagenesis and manipulation of coordination chemistry, MppJ was engineered to perform both Lewis acid-assisted hydration and/or O-methyltransfer reactions to give stereospecific new compounds. This process was validated by six crystal structures. The results reported in this study will facilitate the development and design of new biocatalysts for difficult-to-synthesize biochemicals.

Background: Abnormal task-related activation in primary motor cortices (M1) has been consistently found in functional imaging studies of subcortical stroke. Whether the abnormal activations are associated with neuronal alterations in the same or homologous area is not known., Objective: Our goal was to establish the relationships between M1 measures of motor-task-related activation and a neuronal marker, N-acetylaspartate (NAA), in patients with severe to mild hemiparesis., Methods: A total of 18 survivors of an ischemic subcortical stroke (confirmed on T2-weighted images) at more than six months post-onset and 16 age- and sex-matched right-handed healthy controls underwent functional MRI during a handgrip task (impaired hand in patients, dominant hand in controls) and proton magnetic resonance spectroscopy ((1)H-MRS) imaging. Spatial extent and magnitude of blood oxygen level-dependent response (or activation) and NAA levels were measured in each M1. Relationships between activation and NAA were determined., Results: Compared with controls, patients had a greater extent of contralesional (ipsilateral to impaired hand, P < .001) activation and a higher magnitude of activation and lower NAA in both ipsilesional (P = .008 and P < .001, respectively) and contralesional (P < .0001, P < .05) M1. There were significant negative correlations between extent of activation and NAA in each M1 (P = .02) and a trend between contralesional activation and ipsilesional NAA (P = .08) in patients but not in controls., Conclusions: Our results suggest that after stroke greater neuronal recruitment could be a compensatory response to lower neuronal metabolism. Thus, dual-modality imaging may be a powerful tool for providing complementary probes of post-stroke brain reorganization., (© The Author(s) 2013.)

Background: Tigecycline resistance in Acinetobacter baumannii is primarily acquired through overexpression of the AdeABC efflux pump. Besides AdeRS, other two-component regulatory systems (TCSs) involving the regulation of this transporter have not been clarified., Results: In this study, we found that the TCS genes baeR and baeS are co-transcribed and function as stress responders under high osmotic conditions. The baeSR and adeAB genes showed increased transcription in both the laboratory-induced and clinical tigecycline-resistant strains compared with the wild-type strain. The deletion of baeR in the ATCC 17978 strain led to 67-73% and 68% reduction in adeA and adeB expression, respectively, with a resultant 2-fold decrease in the tigecycline minimal inhibition concentration (MIC). In contrast, the overexpression of baeR resulted in a doubled tigecycline MIC, with a more than 2-fold increase in adeA and adeB expression. The influence of baeR knockout on adeAB gene expression can also be observed in the laboratory-induced tigecycline-resistant strain. A time-kill assay showed that the baeR deletion mutant showed an approximate 1-log10 reduction in colony forming units (CFUs) relative to the wild-type strain when the tigecycline concentration was 0.25 μg/mL throughout the assay period. The wild-type phenotype could be restored by trans-complementation with pWH1266-kanr-baeR. Increasing the tigecycline concentration to 0.5 μg/mL produced an even more marked 4.7-log10 reduction in CFUs of the baeR deletion mutant at 8 h, while only a 2.1-log10 reduction was observed for the wild-type strain., Conclusions: Taken together, these data show for the first time that the BaeSR TCS influences the tigecycline susceptibility of A. baumannii through the positive regulation of the resistance-nodulation-division efflux pump genes adeA and adeB.

Most preclinical studies of amyotrophic lateral sclerosis (ALS) have focused on spinal symptoms, despite the importance of bulbar deficits in progression of the disease. We sought to determine how bulbar deficits are related to spinal deficits and survival in the SOD1-G93A rat model of ALS. We examined forelimb and hindlimb grip force and tongue motility in SOD1-G93A rats using statistical cluster analysis. Decrements in forelimb grip force, hindlimb grip force, and tongue motility were used to cluster affected rats into groups. The analysis clustered one group that exhibited primarily forelimb deficits (forelimb group) and a second group that exhibited forelimb and tongue motility deficits (forelimb+bulbar group). The analysis did not identify a distinct hindlimb phenotype group because all SOD1-G93A rats exhibited deficits in hindlimb grip force. Rats in the forelimb+bulbar group exhibited earlier and greater forelimb deficits, and earlier mortality than rats without bulbar deficits. Hindlimb deficits were similar in both groups. There was a significant correlation between forelimb grip force and tongue motility deficits, but not between forelimb and hindlimb deficits. These data extend clinical findings of a more rapid disease progression in individuals with bulbar symptoms to the SOD1-G93A rat model of ALS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Texts and software that we are currently using for teaching multivariate analysis to non-statisticians lack in the delivery of confirmatory factor analysis (CFA). The purpose of this paper is to provide educators with a complement to these resources that includes CFA and its computation. We focus on how to use CFA to estimate a "composite reliability" of a psychometric instrument. This paper provides guidance for introducing, via a case-study, the non-statistician to CFA. As a complement to our instruction about the more traditional SPSS, we successfully piloted the software R for estimating CFA on nine non-statisticians. This approach can be used with healthcare graduate students taking a multivariate course, as well as modified for community stakeholders of our Center for American Indian Community Health (e.g. community advisory boards, summer interns, & research team members). The placement of CFA at the end of the class is strategic and gives us an opportunity to do some innovative teaching: (1) build ideas for understanding the case study using previous course work (such as ANOVA); (2) incorporate multi-dimensional scaling (that students already learned) into the selection of a factor structure (new concept); (3) use interactive data from the students (active learning); (4) review matrix algebra and its importance to psychometric evaluation; (5) show students how to do the calculation on their own; and (6) give students access to an actual recent research project.

The prevalence of obesity is high resulting from chronic imbalances between energy intake and expenditure. On the expenditure side, regular exercise is associated with health benefits, including enhanced brain function. The benefits of exercise are not immediate and require persistence to be realized. Brain regions associated with health-related decisions, such as whether or not to exercise or controlling the impulse to engage in immediately rewarding activities (e.g., sedentary behavior), include reward processing and cognitive control regions. A 9 month aerobic exercise study will be conducted in 180 sedentary adults (n = 90 healthy weight [BMI = 18.5 to 26.0 kg/m(2)]; n = 90 obese [BMI = 29.0 to 41.0 kg/m(2)) to examine the brain processes underlying reward processing and impulse control that may affect adherence in a new exercise regimen. The primary aim is to use functional magnetic resonance imaging (fMRI) to examine reward processing and impulse control among participants that adhere (exercise >80% of sessions) and those that do not adhere to a nine-month exercise intervention with secondary analyses comparing sedentary obese and sedentary healthy weight participants. Our results will provide valuable information characterizing brain activation underlying reward processing and impulse control in sedentary obese and healthy weight individuals. In addition, our results may identify brain activation predictors of adherence and success in the exercise program along with measuring the effects of exercise and improved fitness on brain activation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We conducted a phase II feasibility study of a 6-month behavioral weight loss intervention in postmenopausal overweight and obese women at increased risk for breast cancer and the effects of weight loss on anthropomorphic, blood, and benign breast tissue biomarkers. 67 women were screened by random peri-areolar fine-needle aspiration, 27 were registered and 24 participated in the interventional phase. The 24 biomarker evaluable women had a median baseline BMI of 34.2 kg/m(2) and lost a median of 11 % of their initial weight. Significant tissue biomarker modulation after the 6-month intervention was noted for Ki-67 (if restricted to the 15 women with any Ki-67 at baseline, p = 0.041), adiponectin to leptin ratio (p = 0.003); and cyclin B1 (p = 0.001), phosphorylated retinoblastoma (p = 0.005), and ribosomal S6 (p = 0.004) proteins. Favorable modulation for serum markers was observed for sex hormone-binding globulin (p < 0.001), bioavailable estradiol (p < 0.001), bioavailable testosterone (p = 0.033), insulin (p = 0.018), adiponectin (p = 0.001), leptin (p < 0.001), the adiponectin to leptin ratio (p < 0.001), C-reactive protein (p = 0.002), and hepatocyte growth factor (p = 0.011). When subdivided by <10 or >10 % weight loss, change in percent total body and android (visceral) fat, physical activity, and the majority of the serum and tissue biomarkers were significantly modulated only for women with >10 % weight loss from baseline. Some factors such as serum PAI-1 and breast tissue pS2 (estrogen-inducible gene) mRNA were not significantly modulated overall but were when considering only those with >10 % weight loss. In conclusion, a median weight loss of 11 % over 6 months resulted in favorable modulation of a number of anthropomorphic, breast tissue and serum risk and mechanistic markers. Weight loss of 10 % or more should likely be the goal for breast cancer risk reduction studies in obese women.

Novel C-aryl-d-glucofuranosides were synthesized and evaluated for their capacity to inhibit human sodium-dependent glucose co-transporter 2 (hSGLT2) and hSGLT1. Compound 21q demonstrated the best in vitro inhibitory activity against SGLT2 in this series (EC50=0.62μM)., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The aims of this study were to understand the molecular epidemiology of integron-associated gene cassettes in Acinetobacter baumannii across four hospitals in northern Taiwan and to clarify the relationship between the presence of integrons and antibiotic-resistant phenotypes., Methods: Sixty-five A. baumannii isolates, collected from the patients of four regional hospitals in northern Taiwan in 2009, were tested for the presence of integrons and their associated gene cassettes. The susceptibility difference between integron-positive and integron-negative A. baumannii strains was analyzed. Antibiotic-resistant phenotypes among A. baumannii with different types of gene cassette array combinations were also compared., Results: Around 72% of the A. baumannii isolates carried class 1 integrase genes. Despite this, only three gene cassette arrays were found in the integrons. Integron-positive strains were significantly more resistant to all the tested antibiotics than the integrase-negative strains. All the four types of A. baumannii with different gene cassette array combinations were multidrug-resistant in nature. Gene cassette array aacA4-catB8-aadA1 existed in all the integron-positive A. baumannii isolates. Repetitive-sequence-based PCR (rep-PCR) results revealed the prevalence of one major cluster of imipenem-resistant A. baumannii strains (84%) in the four regional hospitals., Conclusions: The presence of integrons with associated antimicrobial resistance gene cassettes can be used as a representative marker of multidrug resistance in A. baumannii. Some prevalent gene cassette arrays may exist among epidemiologically unrelated A. baumannii strains.

Naturally occurring spirostanol saponins bear a chacotriose, α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β-D-glucopyranose residue as the oligosaccharide moiety which is believed to be important for biological activity. Herein the development of a concise, combinatorial method for the synthesis of two series of glycan variants at the 2' and/or 4' positions of chacotriose is described and the structure-activity relationships of the glycone part at 3-OH of chlorogenin investigated. These compounds were found to be weakly-cytotoxic toward leukemia cell lines CCRF and HL-20, indicating that the chacotriose moiety is important for anticancer activity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies., Objective: We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand representation in bilateral motor and premotor areas and correlated with distal and proximal arm motor impairment in hemiparetic persons., Methods: In 20 participants at >6 months postonset of a subcortical ischemic stroke and 16 age- and sex-matched healthy controls, the concentrations of N-acetylaspartate and myo-inositol were quantified by proton magnetic resonance spectroscopy. Regions of interest identified by functional magnetic resonance imaging included primary (M1), dorsal premotor (PMd), and supplementary (SMA) motor areas. Relationships between metabolite concentrations and distal (hand) and proximal (shoulder/elbow) motor impairment using Fugl-Meyer Upper Extremity (FMUE) subscores were explored., Results: N-Acetylaspartate was lower in M1 (P = .04) and SMA (P = .004) and myo-inositol was higher in M1 (P = .003) and PMd (P = .03) in the injured (ipsilesional) hemisphere after stroke compared with the left hemisphere in controls. N-Acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (P = .04). Significant positive correlations were also found between N-acetylaspartate in ipsilesional M1, PMd, and SMA and in contralesional M1 and shoulder/elbow FMUE subscores (P = .02, .01, .02, and .02, respectively)., Conclusions: Our preliminary results demonstrated that proton magnetic resonance spectroscopy is a sensitive method to quantify relevant neuronal changes in spared motor cortex after stroke and consequently increase our knowledge of the factors leading from these changes to arm motor impairment.

We performed a retrospective chart review of 50 youths with Autism Spectrum Disorder (ASD), prescribed amitriptyline (AMI) for hyperactivity and impulsivity. Data was systematically extracted from 50 outpatient clinic charts, including AMI treatment duration, dose, trough levels and adverse events. Mean age was 9.4 years (4.6-17.9); 40 were males and 10 females. 30 % had failed atomoxetine and 40 % had failed ≥3 ADHD medications. Mean dose was 1.3 ± 0.6 mg/kg/day, mean trough level 114.1 ± 50.5 ng/ml, mean duration 3.4 years. Clinical Global Impressions Scale-Improvement (CGI-I) was ≤2 in 60 % of patients at the final visit, and in 82 % of patients for at least 50 % of follow-ups. Cautious use of low dose AMI shows promise for treatment-resistant youth with ASD accompanied by hyperactivity, impulsivity, aggression and self injury.

DHA (22:6n-3) supplementation during infancy has been associated with lower heart rate (HR) and improved neurobehavioral outcomes. We hypothesized that maternal DHA supplementation would improve fetal cardiac autonomic control and newborn neurobehavior. Pregnant women were randomized to 600 mg/day of DHA or placebo oil capsules at 14.4 (+/-4) weeks gestation. Fetal HR and HRV were calculated from magnetocardiograms (MCGs) at 24, 32 and 36 weeks gestational age (GA). Newborn neurobehavior was assessed using the Neonatal Behavioral Assessment Scale (NBAS). Post-partum maternal and infant red blood cell (RBC) DHA was significantly higher in the supplemented group as were metrics of fetal HRV and newborn neurobehavior in the autonomic and motor clusters. Higher HRV is associated with more responsive and flexible autonomic nervous system (ANS). Coupled with findings of improved autonomic and motor behavior, these data suggest that maternal DHA supplementation during pregnancy may impart an adaptive advantage to the fetus., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Ethnic and racial minority groups in the U.S. receive fewer colorectal cancer (CRC) screening tests and are less likely to be up-to-date with CRC screening than the population as a whole. Access, limited awareness of CRC and barriers may, in part, be responsible for inhibiting widespread adoption of CRC screening among racial and ethnic minority groups. The purpose of this study was to examine the role of self-efficacy, fatalism and CRC risk perception across racial and ethnic groups in a diverse sample. This study was a cross-sectional analysis from baseline measures gathered on a group of patients recruited into a trial to track colorectal cancer screening in underserved adults over 50. Out of 470 Participants, 42% were non-Hispanic; 27% Hispanic and 28% non-Hispanic White. Hispanic and non-Hispanic Blacks were more likely to have fatalistic beliefs about CRC than non-Hispanic Whites. Non-Hispanic Blacks perceived higher risk of getting colon cancer. Self-efficacy for completing CRC screening was higher among Non-Hispanic Blacks than among Hispanics. Racial and ethnic differences in risk perceptions, fatalism and self-efficacy should be taken into consideration in future CRC interventions with marginalized and uninsured populations.

Basic science researchers transplant human cancer tissues from patients with ductal carcinoma in situ (DCIS) to animals and observe the progression of the disease. Successful transplants show invasion of human tissues across mammary ducts in animal fat pads and cause DCIS-like lesions in one or more ducts. In this work, we consider data from a recent publication of breast cancer research where positive counts of affected ducts may be subject to censoring. We fit the data with zero-truncated Poisson (ZTP) models with an informative prior of gamma. Due to the zero-truncation and right censoring, posterior distributions may not be conventional gamma and are estimated through Markov chain Monte Carlo and grid approximation. For each of the two cell lines, we fit a model with group-specific parameters for DCIS subtypes classified by the cell surface biomarkers, and another model with a homogeneous parameter across groups. Models are compared by the Deviance Information Criterion (DIC). For the chosen prior parameter values, Bayes estimates are comparative to the maximum likelihood estimates, and the DIC favors the simpler model in both cell lines.

Specific neurochemicals measured with proton magnetic resonance spectroscopy ((1)H-MRS) may serve as biomarkers of pathological mechanism in the brain. We used high field in vivo (1)H-MRS to measure a detailed neurochemical profile after experimental traumatic brain injury (TBI) in rats. We characterized neurochemical changes in the contused cortex and the normal-appearing perilesional hippocampus over a time course from 1 hour to 2 weeks after injury. We found significant changes in 19 out of 20 neurochemicals in the cortex, and 9 out of 20 neurochemicals in the hippocampus. These changes provide evidence of altered cellular metabolic status after TBI, with specific compounds proposed to reflect edema, excitotoxicity, neuronal and glial integrity, mitochondrial status and bioenergetics, oxidative stress, inflammation, and cell membrane disruption. Our results support the utility of (1)H-MRS for monitoring cellular mechanisms of TBI pathology in animal models, and the potential of this approach for preclinical evaluation of novel therapies.

We propose to analyze positive count data with right censoring from Behbod et al. (2009) using the censored zero-truncated Poisson model (CZTP). The comparison in truncated means across subgroups in each cell line is carried out through a log-linear model that links the un-truncated Poisson parameter and regression covariates. We also perform simulation to evaluate the performance of the CZTP model in finite and large sample sizes. In general, the CZTP model provides accurate and precise estimates. However, for data with small means and small sample sizes, it may be more proper to make inference based on the mean counts rather than on the regression coefficients. For small sample sizes and moderate means, the likelihood ratio test is more reliable than the Wald test. We also demonstrate how power analysis can be used to justify and/or guide the choice of censoring thresholds in study design. A SAS macro is provided in Appendix for readers' reference.

Background: GEE and mixed models are powerful tools to compare treatment effects in longitudinal smoking cessation trials. However, they are not capable of assessing the relapse (from abstinent back to smoking) simultaneously with cessation, which can be studied by transition models., Methods: We apply a first-order Markov chain model to analyze the transition of smoking status measured every 6 months in a 2-year randomized smoking cessation trial, and to identify what factors are associated with the transition from smoking to abstinent and from abstinent to smoking. Missing values due to non-response are assumed non-ignorable and handled by the selection modeling approach., Results: Smokers receiving high-intensity disease management (HDM), of male gender, lower daily cigarette consumption, higher motivation and confidence to quit, and having serious attempts to quit were more likely to become abstinent (OR = 1.48, 1.66, 1.03, 1.15, 1.09 and 1.34, respectively) in the next 6 months. Among those who were abstinent, lower income and stronger nicotine dependence (OR = 1.72 for ≤ vs. > 40 K and OR = 1.75 for first cigarette ≤ vs. > 5 min) were more likely to have relapse in the next 6 months., Conclusions: Markov chain models allow investigation of dynamic smoking-abstinence behavior and suggest that relapse is influenced by different factors than cessation. The knowledge of treatments and covariates in transitions in both directions may provide guidance for designing more effective interventions on smoking cessation and relapse prevention.

We explored whether maternal exercise during pregnancy moderates the effect of fetal breathing movements on fetal cardiac autonomic control assessed by metrics of heart rate (HR) and heart rate variability (HRV). Thirty women were assigned to Exercise or Control group (n=15/group) based on the modifiable physical activity questionnaire (MPAQ). Magnetocardiograms (MCG) were recorded using a dedicated fetal biomagnetometer. Periods of fetal breathing activity and apnea were identified using the fetal diaphragmatic magnetomyogram (dMMG) as a marker. MCG R-waves were marked. Metrics of fetal HR and HRV were compared using 1 breathing and 1 apneic epoch/fetus. The main effects of group (Exercise vs. Control) and condition (Apnea vs. Breathing) and their interactions were explored. Fetal breathing resulted in significantly lower fetal HR and higher vagally-mediated HRV. Maternal exercise resulted in significantly lower fetal HR, higher total HRV and vagally-mediated HRV with no difference in frequency band ratios. Significant interactions between maternal exercise and fetal breathing were found for metrics summarizing total HRV and a parasympathetic metric. Post hoc comparison showed no group difference during fetal apnea. Fetal breathing was associated with a loss of Total HRV in the Control group and no difference in the Exercise group. Both groups show enhanced vagal function during fetal breathing; greater in the Exercise group. During in utero breathing movements, the fetus of the exercising mother has enhanced cardiac autonomic function that may give the offspring an adaptive advantage., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: Our previous research found lower fetal HR and increased HR variability (HRV) in women who exercised during pregnancy. This finding is similar to the adult heart training response at rest due to aerobic exercise. Dose-response associations have been found between physical activity and cardiorespiratory fitness in adults. Therefore, our objective was to determine whether there is a dose-response relationship between maternal physical activity and fetal HR, HRV, and sympathovagal balance., Methods: Pregnant women completed a physical activity questionnaire and magnetocardiogram (magnetic correlate to ECG) recordings at 36-wk gestational age. Women reported the duration, intensity, and frequency of each activity for each month of pregnancy as well as 3 months before pregnancy. These values were used to calculate maternal physical activity measures for each participant. Relationships between fetal HR, HRV, and sympathovagal balance at 36-wk gestational age and maternal physical activity (n = 50 pairs) during the third trimester were assessed by Spearman correlations. Regression analysis was performed to further examine these relationships after controlling for maternal and fetal covariates (maternal age, maternal resting HR, maternal weight gain, prepregnancy body mass index (BMI), and fetal activity state)., Results: The regression analyses showed that maternal physical activity intensity (kcal·min(-1)) was negatively associated with HR in the active fetal state (P < 0.05), and physical activity duration (minutes during the third trimester) was positively associated with fetal HRV (P < 0.05). There were no statistically significant relationships with maternal physical activity on measures of fetal sympathovagal balance., Conclusions: Maternal physical activity dose during the third trimester is associated with resting fetal heart effects similar to a trained response. Future studies on the health benefits of this fetal response are highly warranted.

Whether functional changes of the non-primary motor areas, e.g., dorsal premotor (PMd) and supplementary motor (SMA) areas, after stroke, reflect reorganization phenomena or recruitment of a pre-existing motor network remains to be clarified. We hypothesized that cellular changes in these areas would be consistent with their involvement in post-stroke reorganization. Specifically, we expected that neuronal and glial compartments would be altered in radiologically normal-appearing, i.e., spared, PMd and SMA in patients with arm paresis. Twenty survivors of a single ischemic subcortical stroke and 16 age-matched healthy controls were included. At more than six months after stroke, metabolites related to neuronal and glial compartments: N-acetylaspartate, myo-inositol, and glutamate/glutamine, were quantified by proton magnetic resonance spectroscopy in PMd and SMA in both injured (ipsilesional) and un-injured (contralesional) hemispheres. Correlations between metabolites were also calculated. Finally, relationships between metabolite concentrations and arm motor impairment (total and proximal Fugl-Meyer Upper Extremity, FMUE, scores) were analyzed. Compared to controls, stroke survivors showed significantly higher ipsilesional PMd myo-inositol and lower SMA N-acetylaspartate. Significantly lower metabolite correlations were found between ipsilesional and contralesional SMA. Ipsilesional N-acetylaspartate was significantly related to proximal FMUE scores. This study provides evidence of abnormalities in metabolites, specific to neuronal and glial compartments, across spared non-primary motor areas. Ipsilesional alterations were related to proximal arm motor impairment. Our results suggest the involvement of these areas in post-stroke reorganization., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Chronic hyperglycemia could lead to cerebral metabolic alterations and CNS injury. However, findings of metabolic alterations in poorly managed diabetes in humans and animal models are rather inconsistent. We have characterized the cerebral metabolic consequences of untreated hyperglycemia from the onset to the chronic stage in a streptozotocin-induced rat model of diabetes. In vivo ¹H magnetic resonance spectroscopy was used to measure over 20 neurochemicals longitudinally. Upon the onset of hyperglycemia (acute state), increases in brain glucose levels were accompanied by increases in osmolytes and ketone bodies, all of which remained consistently high through the chronic state of over 10 weeks of hyperglycemia. Only after over 4 weeks of hyperglycemia, the levels of other neurochemicals including N-acetylaspartate and glutathione were significantly reduced and these alterations persisted into the chronic stage. However, glucose transport was not altered in chronic hyperglycemia of over 10 weeks. When glucose levels were acutely restored to euglycemia, some neurochemical changes were irreversible, indicating the impact of prolonged uncontrolled hyperglycemia on the CNS. Furthermore, progressive changes in neurochemical levels from control to acute and chronic conditions demonstrated the utility of ¹H magnetic resonance spectroscopy as a non-invasive tool in monitoring the disease progression in diabetes., (© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.)

Some empirical studies and recent developments in pharmacokinetic theory suggest that statistical random-effects linear models are valuable tools that allow describing simultaneously patient populations as a whole and patients as individuals. This remarkable characteristic indicates that these models may be useful in the development of personalized medicine, which aims at finding treatment regimes that are appropriate for particular patients, not just appropriate for the average patient. In fact, published developments show that random-effects linear models may provide a solid theoretical framework for drug dosage individualization in chronic diseases. In particular, individualized dosages computed with these models by means of an empirical Bayesian approach may produce better results than dosages computed with some methods routinely used in therapeutic drug monitoring. This is further supported by published empirical and theoretical findings that show that random effects linear models may provide accurate representations of phase III and IV steady-state pharmacokinetic data, and may be useful for dosage computations. These models have applications in the design of clinical algorithms for drug dosage individualization in chronic diseases; in the computation of dose correction factors; computation of the minimum number of blood samples from a patient that are necessary for calculating an optimal individualized drug dosage in therapeutic drug monitoring; measure of the clinical importance of clinical, demographic, environmental or genetic covariates; study of drug-drug interactions in clinical settings; the implementation of computational tools for web-site-based evidence farming; design of pharmacogenomic studies; and in the development of a pharmacological theory of dosage individualization.

Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Opiates are well known to modulate immune responses by preventing the development of cell-mediated immune responses. Their effect on the pathogenesis of HIV-1 infection however remains controversial. Using the simian immunodeficiency virus/macaque model of HIV pathogenesis, we sought to explore the impact of morphine on disease progression and pathogenesis. Sixteen rhesus macaques were divided into two groups; four were administered saline and 12 others morphine routinely. Both groups of animals were then inoculated with SIVmacR71/17E and followed longitudinally for disease pathogenesis. The morphine group (M+V) exhibited a trend towards higher mortality rates and retardation in weight gain compared to the virus-alone group. Interestingly, a subset of M+V animals succumbed to disease within weeks post-infection. These rapid progressors also exhibited a higher incidence of other end-organ pathologies. Despite the higher numbers of circulating CD4+ and CD8+ T cells in the M+V group, CD4/CD8 ratios between the groups remained unchanged. Plasma and CSF viral load in the M+V group was at least a log higher than the control group. Similarly, there was a trend toward increased virus build-up in the brains of M+V animals compared with controls. A novel finding of this study was the increased influx of infected monocyte/macrophages in the brains of M+V animals.

Objective: To examine the potential of dextrose injection versus lidocaine injection versus supervised usual care to reduce sport alteration and sport-related symptoms in adolescent athletes with Osgood-Schlatter disease., Patients and Methods: Girls aged 9 to 15 and boys aged 10 to 17 were randomly assigned to either therapist-supervised usual care or double-blind injection of 1% lidocaine solution with or without 12.5% dextrose. Injections were administered monthly for 3 months. All subjects were then offered dextrose injections monthly as needed. Unaltered sport (Nirschl Pain Phase Scale < 4) and asymptomatic sport (Nirschl Pain Phase Scale = 0) were the threshold goals., Results: Sixty-five knees in 54 athletes were treated. Compared with usual care at 3 months, unaltered sport was more common in both dextrose-treated (21 of 21 vs 13 of 22; P = .001) and lidocaine-treated (20 of 22 vs 13 of 22; P = .034) knees, and asymptomatic sport was more frequent in dextrose-treated knees than either lidocaine-treated (14 of 21 vs 5 of 22; P = .006) or usual-care-treated (14 of 21 vs 3 of 22; P < .001) knees. At 1 year, asymptomatic sport was more common in dextrose-treated knees than knees treated with only lidocaine (32 of 38 vs 6 of 13; P = .024) or only usual care (32 of 38 vs 2 of 14; P < .0001)., Conclusions: Our results suggest superior symptom-reduction efficacy of injection therapy over usual care in the treatment of Osgood-Schlatter disease in adolescents. A significant component of the effect seems to be associated with the dextrose component of a dextrose/lidocaine solution. Dextrose injection over the apophysis and patellar tendon origin was safe and well tolerated and resulted in more rapid and frequent achievement of unaltered sport and asymptomatic sport than usual care.

Breathing movements are one of the earliest fetal motor behaviors to emerge and are a hallmark of fetal well-being. Fetal respiratory sinus arrhythmia (RSA) has been documented but efforts to quantify the influence of breathing on heart rate (HR) and heart rate variability (HRV) are difficult due to the episodic nature of fetal breathing activity. We used a dedicated fetal biomagnetometer to acquire the magnetocardiogram (MCG) between 36 and 38 weeks gestational age (GA). We identified and characterized a waveform observed in the raw data and independent component decomposition that we attribute to fetal diaphragmatic movements during breathing episodes. RSA and increased high frequency power in a time-frequency analysis of the IBI time-series was observed during fetal breathing periods. Using the diaphragmatic magnetomyogram (dMMG) as a marker, we compared time and frequency domain metrics of heart rate and heart rate variability between breathing and non-breathing epochs. Fetal breathing activity resulted in significantly lower HR, increased high frequency power, greater sympathovagal balance, increased short-term HRV and greater parasympathetic input relative to non-breathing episodes confirming the specificity of fetal breathing movements on parasympathetic cardiac influence. No significant differences between breathing and non-breathing epochs were found in two metrics reflecting total HRV or very low, low and intermediate frequency bands. Using the fetal dMMG as a marker, biomagnetometry can help to elucidate the electrophysiologic mechanisms associated with diaphragmatic motor function and may be used to study the longitudinal development of human fetal cardiac autonomic control and breathing activity., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Despite substantial evidence of maternal and infant benefits of breastfeeding, adolescent mothers initiate breastfeeding less often and maintain breastfeeding for shorter durations when compared to their adult counterparts. A randomized controlled trial drawing on the theory of planned behavior and developmental theory was conducted to determine if an education and counseling intervention provided by a lactation consultant-peer counselor team increased breastfeeding initiation and duration up to 6 months postpartum among adolescent mothers. Study participants ( N = 289) enrolled from multiple prenatal clinic and school settings, were 15 to 18 years old, and predominately African American, single, and primiparous. The intervention, which started in the second trimester of pregnancy and extended through 4 weeks postpartum, positively influenced breastfeeding duration (p < .001) within the experimental group, but not breastfeeding initiation or exclusive breastfeeding rates. This education/support intervention was partially effective in enhancing breastfeeding outcomes. Implications for research and practice are described.

Background: Cigarette smoking is the number one cause of preventable death among American Indian and Alaska Natives, AI/ANs. Two out of every five AI/AN will die from tobacco-related diseases if the current smoking rates of AI/ANs (40.8%) persist. Currently, there is no proven, effective culturally-tailored smoking cessation program designed specifically for a heterogeneous population of AI.The primary aim of this group randomized clinical trial is to test the efficacy of "All Nations Breath of Life" (ANBL) program compared to a non-tailored "Current Best Practices" smoking cessation program among AI smokers., Methods: We will randomize 56 groups (8 smokers per group) to the tailored program or non-tailored program for a total sample size of 448 American Indian smokers. All participants in the proposed study will be offered pharmacotherapy, regardless of group assignment. This study is the first controlled trial to examine the efficacy of a culturally-tailored smoking cessation program for American Indians. If the intervention is successful, the potential health impact is significant because the prevalence of smoking is the highest in this population., Trial Registration: ClinicalTrials.gov: NCT01106456.

Background: The distribution and characterization of OXA-type carbapenemases in Acinetobacter sp in Taiwan has less been reported. The aim of the study was to investigate the molecular epidemiology and OXA-type carbapenemase genes in a regional hospital in Taiwan., Methods: Imipenem-resistant Acinetobacter sp were collected between 2005 and 2007 in a regional hospital. Genotyping was performed by pulsed-field gel electrophoresis. OXA-type carbapenemase genes were determined by multiplex polymerase chain reaction (PCR) and gene sequencing., Results: A total of 136 isolates were collected. Fifty-six pulsotypes were identified. None of the pulsotypes established predominance throughout the 3-year period. Multiplex PCR of blaOXA genes showed that 99% (135/136) of the Acinetobacter sp possessed blaOXA51-like genes. The coexistences of blaOXA51-like/blaOXA-23-like and blaOXA51-like/blaOXA-24-like were detected in 19% (26/136) and 1% (2/136) of the isolates, respectively. Among blaOXA-23-like gene-carrying isolates, two isolates (Pulsotypes 18 and 20) were found in 2006 and the remainder (n=24), including Pulsotypes 27 (n=18), 29 (n=1), 52 (n=3), and 53 (n=2), were found in 2007. Sequencing performed on the 26 representative isolates confirmed the presence of the blaOXA-23 carbapenemase gene. Analysis of the genetic content of blaOXA-23 showed that these genes were presumably chromosomal and associated with the upstream-located insertion sequence ISAba1., Conclusions: The emergence and imminent widespread of blaOXA-23-carrying imipenem-resistant Acinetobacter sp appeared in Taiwan during the period from 2006 to 2007., (Copyright © 2011. Published by Elsevier B.V.)