Bilateral deep transcranial magnetic stimulation of motor and prefrontal cortices in Parkinson’s disease: a comprehensive review

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by both motor and non-motor symptoms, many of which are resistant to currently available treatments. Since the discovery that non-invasive transcranial magnetic stimulation (TMS) can cause dopamine release in PD patients, there has been growing interest in the use of TMS to fill existing gaps in the treatment continuum for PD. This review evaluates the safety and efficacy of a unique multifocal, bilateral Deep TMS protocol, which has been evaluated as a tool to address motor and non-motor symptoms of PD. Six published clinical trials have delivered a two-stage TMS protocol with an H-Coil targeting both the prefrontal cortex (PFC) and motor cortex (M1) bilaterally (220 PD patients in total; 108 from two randomized, sham-controlled studies; 112 from open label or registry studies). In all studies TMS was delivered to M1 bilaterally (Stage 1) and then to the PFC bilaterally (Stage 2) with approximately 900 pulses per stage. For Stage 1 (M1), two studies delivered 10 Hz at 90% motor threshold (MT) while four studies delivered 1 Hz at 110% MT. For Stage 2 (PFC), all studies delivered 10 Hz at 100% MT. The results suggest that this two-stage Deep TMS protocol is a safe, moderately effective treatment for motor symptoms of PD, and that severely impaired patients have the highest benefits. Deep TMS also improves mood symptoms and cognitive function in these patients. Further research is needed to establish optimal dosing and the long-term durability of treatment effects

Optimising selective deuteration of proteins for 2D 1H NMR detection and assignment studies Application to the Phe residues of Lactobacillus casei dihydrofolate reductase

AbstractA selectively deuterated dihydrofolate reductase from L. casei has been prepared containing partially deuterated aromatic amino acids. This provides simplified 2D NMR spectra and allows signals from all 8 Phe residues to be identified. The pattern of deuteration is such that (i) the only cross-peaks detected in the aromatic region of the 2D COSY spectrum are those between the Phe 2′,6′ and 3′,5′ protons and (ii) chemical shift degeneracy in the aromatic region is removed thus allowing unambiguous assignment of cross-peaks in 2D NOESY spectra required for specific assignment purposes

Characterization of a Non-Contact Imaging Scintillator-Based Dosimetry System for Total Skin Electron Therapy.

Surface dosimetry is required for ensuring effective administration of total skin electron therapy (TSET); however, its use is often reduced due to the time consuming and complex nature of acquisition. A new surface dose imaging technique was characterized in this study and found to provide accurate, rapid and remote measurement of surface doses without the need for post-exposure processing. Disc-shaped plastic scintillators (1 mm thick  ×  15 mm [Formula: see text]) were chosen as optimal-sized samples and designed to attach to a flat-faced phantom for irradiation using electron beams. Scintillator dosimeter response to radiation damage, dose rate, and temperature were studied. The effect of varying scintillator diameter and thickness on light output was evaluated. Furthermore, the scintillator emission spectra and impact of dosimeter thickness on surface dose were also quantified. Since the scintillators were custom-machined, dosimeter-to-dosimeter variation was tested. Scintillator surface dose measurements were compared to those obtained by optically stimulated luminescence dosimeters (OSLD). Light output from scintillator dosimeters evaluated in this study was insensitive to radiation damage, temperature, and dose rate. Maximum wavelength of emission was found to be 422 nm. Dose reported by scintillators was linearly related to that from OSLDs. Build-up from placement of scintillators and OSLDs had a similar effect on surface dose (4.9% increase). Variation among scintillator dosimeters was found to be 0.3  ±  0.2%. Scintillator light output increased linearly with dosimeter thickness (~1.9  ×  /mm). All dosimeter diameters tested were able to accurately measure surface dose. Scintillator dosimeters can potentially improve surface dosimetry-associated workflow for TSET in the radiation oncology clinic. Since scintillator data output can be automatically recorded to a patient medical record, the chances of human error in reading out and recording surface dose are minimized

Molecular and biological characterization of low-pathogenic H9N2 influenza viruses isolated in Israel

All Israeli H9N2-strain viruses used in the present study were subdivided among three groups: groups A and B viruses contained – in all eight segments – 90658/00-like and 1304/03-like sequences, respectively; Group C comprised viruses isolated in 2006-2010, which contained four 1304/03-like segments and four 1525/06-like segments. Molecular analysis revealed that most of the isolates had an RSSR motif at the cleavage site of haemagglutinin. Most of the viruses had an haemagglutinin with L216 typical of humans, and internal proteins associated with the avian host specificity. The studied viruses infected the majority of the directly inoculated birds. Exposure to the virus with full8length PB1-F2 protein for 24 h caused destruction of mitochondria and cell death in cultures of human macrophages, and this effect was not associated with activation of protein p53. A virus with truncated PB1-F2 protein exhibited no destructive effect on mitochondria, but induced enhanced production of pro-apoptotic P53 proteinВсі ізраїльські віруси штаму H9N2, що використовуються в цьому дослідженні, були розділені на групи: віруси груп А і В містили відповідно - у всіх восьми сегментах - 90658/00-подібні і 1304/03-подібні послідовності; група C складалася з вірусів, виділених у 2006-2010 роках, які містили чотири 1304/03-подібних сегмента і чотири 1525/06-подібних сегмента. Молекулярний аналіз показав, що більшість штамів мали RSSR-мотив в сайті розщеплення гемаглютиніну. Більшість вірусів містили гемаглютинін з типовим для людей L216, і, крім того, внутрішні білки, характерні для птахів. Вивчені віруси заразили більшість щеплених птахів безпосередньо. Вплив вірусу з повнорозмірною PB1-F2 білка протягом 24 год викликав руйнування мітохондрій і загибель клітин в культурах людських макрофагів, і цей ефект не був пов’язаний з активацією білка р53. Вірус з усіченою ланцюгом білка PB1-F2 не чинив руйнівного впливу на мітохондрії, але індукував підвищений сінтез проапоптотического білка Р53.Всі ізраїльські віруси штаму H9N2, що використовуються в цьому дослідженні, були розділені на групи: віруси груп А і В містили відповідно - у всіх восьми сегментах - 90658/00-подібні і 1304/03-подібні послідовності; група C складалася з вірусів, виділених у 2006-2010 роках, які містили чотири 1304/03-подібних сегмента і чотири 1525/06-подібних сегмента. Молекулярний аналіз показав, що більшість штамів мали RSSR-мотив в сайті розщеплення гемаглютиніну. Більшість вірусів містили гемаглютинін з типовим для людей L216, і, крім того, внутрішні білки, характерні для птахів. Вивчені віруси заразили більшість щеплених птахів безпосередньо. Вплив вірусу з повнорозмірною PB1-F2 білка протягом 24 год викликав руйнування мітохондрій і загибель клітин в культурах людських макрофагів, і цей ефект не був пов’язаний з активацією білка р53. Вірус з усіченою ланцюгом білка PB1-F2 не чинив руйнівного впливу на мітохондрії, але індукував підвищений сінтез проапоптотического білка Р53

Strategic management of the health workforce in developing countries: what have we learned?

The study of the health workforce has gained in prominence in recent years, as the dynamic interconnections between human resource issues and health system effectiveness have come into sharper focus. This paper reviews lessons relating to strategic management challenges emerging from the growing literature in this area. Workforce issues are strategic: they affect overall system performance as well as the feasibility and sustainability of health reforms. Viewing workforce issues strategically forces health authorities to confront the yawning gaps between policy and implementation in many developing countries. Lessons emerge in four areas. One concerns imbalances in workforce structure, whether from a functional specialization, geographical or facility lens. These imbalances pose a strategic challenge in that authorities must attempt to steer workforce distribution over time using a limited range of policy tools. A second group of lessons concerns the difficulties of central-level steering of the health workforce, often critically weak due to the lack of proper information systems and the complexities of public sector decentralization and service commercialization trends affecting the grassroots. A third cluster examines worker capacity and motivation, often shaped in developing countries as much by the informal norms and incentives as by formal attempts to support workers or to hold them accountable. Finally, a range of reforms centering on service contracting and improvements to human resource management are emerging. Since these have as a necessary (but not sufficient) condition some flexibility in personnel practices, recent trends towards the sharing of such functions with local authorities are promising. The paper identifies a number of current lines of productive research, focusing on the relationship between health policy reforms and the local institutional environments in which the workforce, both public and private, is deployed

When urban modernisation entails service delivery co-production: a glance from Medellin

International audienceThrough the example of Ciudadela Nuevo Occidente, a large social housing district in Medellín, this article describes a process that primarily involves co-learning and micro-negotiations that help produce the cognitive alignment necessary to the management of services. The hypothesis put forward in this article is that the frictions caused by the residents' difficulties in adapting to the socioeconomic , cultural and cognitive frameworks of their new environment, imposed by urban modernisation running processes, engender forms of service co-production that ultimately strengthen the utility's capacity to extend and adapt its delivery model while enhancing the quality of services

Gastric Outlet Obstruction at Bugando Medical Centre in Northwestern Tanzania: A Prospective Review of 184 Cases.

Gastric outlet obstruction poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. There is a paucity of published data on this subject in our setting. This study was undertaken to highlight the etiological spectrum and treatment outcome of gastric outlet obstruction in our setting and to identify prognostic factors for morbidity and mortality. This was a descriptive prospective study which was conducted at Bugando Medical Centre between March 2009 and February 2013. All patients with a clinical diagnosis of gastric outlet obstruction were, after informed consent for the study, consecutively enrolled into the study. Statistical data analysis was done using SPSS computer software version 17.0. A total of 184 patients were studied. More than two-third of patients were males. Patients with malignant gastric outlet obstruction were older than those of benign type. This difference was statistically significant (p < 0.001). Gastric cancer was the commonest malignant cause of gastric outlet obstruction where as peptic ulcer disease was the commonest benign cause. In children, the commonest cause of gastric outlet obstruction was congenital pyloric stenosis (13.0%). Non-bilious vomiting (100%) and weight loss (93.5%) were the most frequent symptoms. Eighteen (9.8%) patients were HIV positive with the median CD 4+ count of 282 cells/μl. A total of 168 (91.3%) patients underwent surgery. Of these, gastro-jejunostomy (61.9%) was the most common surgical procedure performed. The complication rate was 32.1 % mainly surgical site infections (38.2%). The median hospital stay and mortality rate were 14 days and 18.5% respectively. The presence of postoperative complication was the main predictor of hospital stay (p = 0.002), whereas the age > 60 years, co-existing medical illness, malignant cause, HIV positivity, low CD 4 count (<200 cells/μl), high ASA class and presence of surgical site infection significantly predicted mortality ( p< 0.001). The follow up of patients was generally poor as more than 60% of patients were lost to follow up. Gastric outlet obstruction in our setting is more prevalent in males and the cause is mostly malignant. The majority of patients present late with poor general condition. Early recognition of the diagnosis, aggressive resuscitation and early institution of surgical management is of paramount importance if morbidity and mortality associated with gastric outlet obstruction are to be avoided

Public sector reform and demand for human resources for health (HRH)

This article considers some of the effects of health sector reform on human resources for health (HRH) in developing countries and countries in transition by examining the effect of fiscal reform and the introduction of decentralisation and market mechanisms to the health sector. Fiscal reform results in pressure to measure the staff outputs of the health sector. Financial decentralisation often leads to hospitals becoming "corporatised" institutions, operating with business principles but remaining in the public sector. The introduction of market mechanisms often involves the formation of an internal market within the health sector and market testing of different functions with the private sector. This has immediate implications for the employment of health workers in the public sector, because the public sector may reduce its workforce if services are purchased from other sectors or may introduce more short-term and temporary employment contracts. Decentralisation of budgets and administrative functions can affect the health sector, often in negative ways, by reducing resources available and confusing lines of accountability for health workers. Governance and regulation of health care, when delivered by both public and private providers, require new systems of regulation. The increase in private sector provision has led health workers to move to the private sector. For those remaining in the public sector, there are often worsening working conditions, a lack of employment security and dismantling of collective bargaining agreements. Human resource development is gradually being recognised as crucial to future reforms and the formulation of health policy. New information systems at local and regional level will be needed to collect data on human resources. New employment arrangements, strengthening organisational culture, training and continuing education will also be needed