The Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation on Advancing Parkinson's Disease With Dysphagia: Double Blind Randomized Clinical Trial

We investigate if rTMS has a therapeutic role in the treatment of dysphagia in patients with Parkinson's disease (PD). MATERIAL AND METHODS: Thirty-three patients with PD and dysphagia were randomly classified with ratio 1:2 to receive sham or real rTMS (2000 pulses; 20 Hz; 90% resting motor threshold; 10 trains of 10 seconds with 25 seconds between each train) over the hand area of each motor cortex (5 minutes between hemispheres) for 10 days (5 days per week) followed by 5 booster sessions every month for 3 months. Assessments included the Unified Parkinson's Disease Rating Scale part III (UPDRS), Instrumental Activities of Daily Living (IADL), and Arabic-Dysphagia Handicap Index (A-DHI) before, after the last session, and 3 months later. Video-fluoroscopy measures of pharyngeal transit time (PTT) and time to maximal hyoid elevation (H1-H2) were taken before and after the treatment sessions. RESULTS: There were no significant differences between groups. There was a significant improvement on all rating scales (analysis of variance) after real rTMS with a significant time × group interaction. In particular, there was a significant and long-lasting (3 months) effect of time on all subitems of the A-DHI (functional, P = .0001; physical, P = .0001; emotional, P = .02) but not in the sham group. This was associated with significant improvement in H1-H2 ( P = .03) and PTT ( P = .01) during solid swallows in the real rTMS but not the sham group. CONCLUSION: Real rTMS improves dysphagia in PD as documented by A-DHI scores and by video-fluoroscopy

The experience of long-term opiate maintenance treatment and reported barriers to recovery: A qualitative systematic review

Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery

Minimum Criteria for DNA Damage-Induced Phase Advances in Circadian Rhythms

Robust oscillatory behaviors are common features of circadian and cell cycle rhythms. These cyclic processes, however, behave distinctively in terms of their periods and phases in response to external influences such as light, temperature, nutrients, etc. Nevertheless, several links have been found between these two oscillators. Cell division cycles gated by the circadian clock have been observed since the late 1950s. On the other hand, ionizing radiation (IR) treatments cause cells to undergo a DNA damage response, which leads to phase shifts (mostly advances) in circadian rhythms. Circadian gating of the cell cycle can be attributed to the cell cycle inhibitor kinase Wee1 (which is regulated by the heterodimeric circadian clock transcription factor, BMAL1/CLK), and possibly in conjunction with other cell cycle components that are known to be regulated by the circadian clock (i.e., c-Myc and cyclin D1). It has also been shown that DNA damage-induced activation of the cell cycle regulator, Chk2, leads to phosphorylation and destruction of a circadian clock component (i.e., PER1 in Mus or FRQ in Neurospora crassa). However, the molecular mechanism underlying how DNA damage causes predominantly phase advances in the circadian clock remains unknown. In order to address this question, we employ mathematical modeling to simulate different phase response curves (PRCs) from either dexamethasone (Dex) or IR treatment experiments. Dex is known to synchronize circadian rhythms in cell culture and may generate both phase advances and delays. We observe unique phase responses with minimum delays of the circadian clock upon DNA damage when two criteria are met: (1) existence of an autocatalytic positive feedback mechanism in addition to the time-delayed negative feedback loop in the clock system and (2) Chk2-dependent phosphorylation and degradation of PERs that are not bound to BMAL1/CLK

Comparison of embedded and added motor imagery training in patients after stroke: Results of a randomised controlled pilot trial

Copyright @ 2012 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Motor imagery (MI) when combined with physiotherapy can offer functional benefits after stroke. Two MI integration strategies exist: added and embedded MI. Both approaches were compared when learning a complex motor task (MT): ‘Going down, laying on the floor, and getting up again’. Methods: Outpatients after first stroke participated in a single-blinded, randomised controlled trial with MI embedded into physiotherapy (EG1), MI added to physiotherapy (EG2), and a control group (CG). All groups participated in six physiotherapy sessions. Primary study outcome was time (sec) to perform the motor task at pre and post-intervention. Secondary outcomes: level of help needed, stages of MT-completion, independence, balance, fear of falling (FOF), MI ability. Data were collected four times: twice during one week baseline phase (BL, T0), following the two week intervention (T1), after a two week follow-up (FU). Analysis of variance was performed. Results: Thirty nine outpatients were included (12 females, age: 63.4 ± 10 years; time since stroke: 3.5 ± 2 years; 29 with an ischemic event). All were able to complete the motor task using the standardised 7-step procedure and reduced FOF at T0, T1, and FU. Times to perform the MT at baseline were 44.2 ± 22s, 64.6 ± 50s, and 118.3 ± 93s for EG1 (N = 13), EG2 (N = 12), and CG (N = 14). All groups showed significant improvement in time to complete the MT (p < 0.001) and degree of help needed to perform the task: minimal assistance to supervision (CG) and independent performance (EG1+2). No between group differences were found. Only EG1 demonstrated changes in MI ability over time with the visual indicator increasing from T0 to T1 and decreasing from T1 to FU. The kinaesthetic indicator increased from T1 to FU. Patients indicated to value the MI training and continued using MI for other difficult-to-perform tasks. Conclusions: Embedded or added MI training combined with physiotherapy seem to be feasible and benefi-cial to learn the MT with emphasis on getting up independently. Based on their baseline level CG had the highest potential to improve outcomes. A patient study with 35 patients per group could give a conclusive answer of a superior MI integration strategy.The research project was partially funded by the Gottfried und Julia Bangerter-Rhyner Foundation

Relationship between site of oesophageal cancer and areca chewing and smoking in Taiwan

Among 309 male patients, those who had heavily consumed betel and tobacco were more likely than nonchewers (OR = 2. 91; 95% CI = 1.36-6.25) and nonsmokers (OR = 2.49; 95% CI = 1.02-6.08) to develop cancer in the upper and middle third of the oesophagus, respectively; the effects of alcohol did not dominate in any third

Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

Background: The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy.\ud Design/Methods: We will conduct a non-inferiority andomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm,participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely.This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation.\ud Outcomes/Follow-up: The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal\ud symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day

Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

The Role of Medical Education in Reducing Health Care Disparities: The First Ten Years of the UCLA/Drew Medical Education Program

BACKGROUND: The University of California, Los Angeles (UCLA)/Charles R. Drew University Medical Education Program was developed to train physicians for practice in underserved areas. The UCLA/Drew Medical Education Program students receive basic science instruction at UCLA and complete their required clinical rotations in South Los Angeles, an impoverished urban community. We have previously shown that, in comparison to their UCLA counterparts, students in the Drew program had greater odds of maintaining their commitment to medically disadvantaged populations over the course of medical education. OBJECTIVE: To examine the independent association of graduation from the UCLA/Drew program with subsequent choice of physician practice location. We hypothesized that participation in the UCLA/Drew program predicts future practice in medically disadvantaged areas, controlling for student demographics such as race/ethnicity and gender, indicators of socioeconomic status, and specialty choice. DESIGN: Retrospective cohort study. PARTICIPANTS: Graduates (1,071) of the UCLA School of Medicine and the UCLA/Drew Medical Education Program from 1985–1995, practicing in California in 2003 based on the address listed in the American Medical Association (AMA) Physician Masterfile. MEASUREMENTS: Physician address was geocoded to a California Medical Service Study Area (MSSA). A medically disadvantaged community was defined as meeting any one of the following criteria: (a) federally designated HPSA or MUA; (b) rural area; (c) high minority area; or (d) high poverty area. RESULTS: Fifty-three percent of UCLA/Drew graduates are located in medically disadvantaged areas, in contrast to 26.1% of UCLA graduates. In multivariate analyses, underrepresented minority race/ethnicity (OR: 1.57; 95% CI: 1.10–2.25) and participation in the Drew program (OR: 2.47; 95% CI: 1.59–3.83) were independent predictors of future practice in disadvantaged areas. CONCLUSIONS: Physicians who graduated from the UCLA/Drew Medical Education Program have higher odds of practicing in underserved areas than those who completed the traditional UCLA curriculum, even after controlling for other factors such as race/ethnicity. The association between participation in the UCLA/Drew Medical Education Program and physician practice location suggests that medical education programs may reinforce student goals to practice in disadvantaged communities