Effect Of Rifampicin And Omeprazole In Combination With Chloroquine On Chloroquine Resistant Plasmodia In Vitro And In Vivo [RM666.C5215 L9 2007 f rb].

Kekebalan terhadap chloroquine telah mengakibatkan peningkatan kematian dan morbiditi daripada penyakit malaria P. falciparum. Ketiadaan vaksin yang berkesan mengakibatkan terapi malaria bergantung pada kombinasi ubat alternatif seperti Mefloquine dan Artesunate dan tahap kekebalan terhadap ubat-ubat alternatif tersebut kerap meningkat. Chloroquine resistance has resulted in a resurgence of morbidity and mortality from P. falciparum malaria. The lack of an effective vaccine forces dependence on alternative drug combination therapies based on mefloquine or artesunate, of which the incidence of multidrug resistance is steadily rising

Shoestring Democracy: Gated Condominiums and Market Rate Co-operatives in New York [pre-print]

This article develops the concept of shoestring democracy as a way to characterize the resulting social relations of private governance structures embedded in two types of collective housing schemes found in New York City and the adjoining suburbs: gated condominium communities (gated condominiums) and market-rate cooperative apartment complexes (co-ops). Drawing from ethnographies of gated condominiums and co-ops in New York City and neighboring Nassau County, New York, we compare these two forms of collective home ownership regarding the impact of private governance structures on residents and their sense of representation and participation in ongoing community life. “Shoestring democracy” encompasses a broad range of behaviors utilized to insulate residents from local conflicts and disagreements, and limits rather than promotes political participation. The greatest differences between the co-ops and gated condominiums were found in discussions of safety and security, in that condominium residents have developed an elaborate discourse of the fear of crime and others, especially racialized others, to explain why they moved to their secured communities. Co-op interviewees, on the other hand, generally felt a sense of safety in their buildings, often due to the gatekeeper effect of the co-op board and doormen. In gated communities, covenants, contracts, and deed restrictions (CC&Rs) guarantee that most problems are resolved before they start. While the same can be said for co-ops, interviewees find that these rules and regulations seem to mystify everyday governing practices for the average co-op resident. Moral minimalism and a lack of structural and procedural knowledge may insulate residents from local conflicts and disagreement, but also may discourage civic participation. Exploring the apathy residents expressed about participation and a lack of representation suggests that although the Rochdale principles of cooperation that are the legal and social basis for co-ops may have been important at one time, current practices of private governing boards do more to restrict participatory democratic practices than encourage them. The policy implications are outlined with suggestions of how to make homeowners associations and co-op boards more accountable and encourage greater adherence to the original co-op mandate

Roles and recommendations from primary care physicians towards managing low-risk breast cancer survivors in a shared-care model with specialists in Singapore-a qualitative study.

BackgroundBreast cancer is prevalent and has high cure rates. The resultant increase in numbers of breast cancer survivors (BCS) may overwhelm the current oncology workforce in years to come. We postulate that primary care physicians (PCPs) could play an expanded role in comanaging survivors, provided they are given the appropriate tools and training to do so.ObjectiveTo explore the perspectives of PCPs towards managing BCS in a community-based shared-care programme with oncologists.MethodsEleven focus groups and six in-depth interviews were conducted with seventy PCPs recruited by purposive sampling. All sessions were audio-recorded, transcribed verbatim and coded by three independent investigators. Thematic data analysis was performed and the coding process facilitated by NVivo 12.ResultsMajority of PCPs reported currently limited roles in managing acute and non-cancer issues, optimizing comorbidities and preventive care. PCPs aspired to expand their role to include cancer surveillance, risk assessment and addressing unmet psychosocial needs. PCPs preferred to harmonize cancer survivorship management of their primary care patients who are also BCS, with defined role distinct from oncologists. Training to understand the care protocol, enhancement of communication skills, confidence and trust were deemed necessary. PCPs proposed selection criteria of BCS and adequacy of their medical information; increased consultation time; contact details and timely access to oncologists (if needed) in the shared-care programme.ConclusionsPCPs were willing to share the care of BCS with oncologists but recommended role definition, training, clinical protocol, resources and access to oncologist's consultation to optimize the programme implementation

Vitamin D associated inflammation and atherosclerosis

Vitamin D is known to play a crucial role in mineral homeostasis and bone metabolism. Recent discoveries showed that the vitamin also regulate the inflammatory mediators. A number of studies have reported on the association of low vitamin D levels with increased level of inflammatory parameters; which predisposes to atherosclerosis and development of cardiovascular diseases (CVD). Since inflammation is implicated in the pathogenesis of CVD, measurement of inflammatory marker levels has been proposed as a method to improve the prediction of these events. In this review, the mechanism of inflammation and role of vitamin D in combating inflammation are discusse

Delirium Reduction Strategies For The Critically Ill

Delirium, an acute and fluctuating disturbance of consciousness and cognition, is a common manifestation of acute brain dysfunction in critically ill patients. Patients with delirium have longer hospital stays and a lower 6-month survival rate than do patients without delirium. Preliminary research suggests that delirium may be associated with cognitive impairment that persists months to years after discharge. In a large acute care hospital, the cardiac intensive care staff became interested in mitigating their unit’s high delirium rate of ventilated patients. At baseline, many members of the healthcare team did not believe that delirium could be prevented and the predominant view was that critically ill patients were too ill to mobilize. An extensive literature review suggested that early mobilization was extremely beneficial in delirium reduction. As a result, the goal of this performance improvement project was to reduce the prevalence and severity of delirium through progressive mobilization. Several barriers to preventing delirium were identified through a root cause analysis. Using improvement measures of operational excellence, a number of countermeasures were established. Several positive outcomes of this project were realized to include the development of an early mobility pathway and a bedside mobility assessment tool. Next steps include a prospective study of the effect this KPI might have on decreasing duration of ventilation days as well as overall length of hospital stay

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The Corticofugal Neuron-Associated Genes ROBO1, SRGAP1, and CTIP2 Exhibit an Anterior to Posterior Gradient of Expression in Early Fetal Human Neocortex Development

Developing neocortical progenitors express transcription factors in gradients that induce programs of region-specific gene expression. Our previous work identified anteriorly upregulated expression gradients of a number of corticofugal neuron-associated gene probe sets along the anterior–posterior axis of the human neocortex (8-12 postconceptional weeks [PCW]). Here, we demonstrate by real-time polymerase chain reaction, in situ hybridization and immunohistochemistry that 3 such genes, ROBO1, SRGAP1, and CTIP2 are highly expressed anteriorly between 8-12 PCW, in comparison with other genes (FEZF2, SOX5) expressed by Layer V, VI, and subplate neurons. All 3 were prominently expressed by early postmitotic neurons in the subventricular zone, intermediate zone, and cortical plate (CP) from 8 to 10 PCW. Between 12 and 15 PCW expression patterns for ER81 and SATB2 (Layer V), TBR1 (Layer V/VI) and NURR1 (Layer VI) revealed Layer V forming. By 15 PCW, ROBO1 and SRGAP1 expression was confined to Layer V, whereas CTIP2 was expressed throughout the CP anteriorly. We observed ROBO1 and SRGAP1 immunoreactivity in medullary corticospinal axons from 11 PCW onward. Thus, we propose that the coexpression of these 3 markers in the anterior neocortex may mark the early location of the human motor cortex, including its corticospinal projection neurons, allowing further study of their early differentiation

Microvascular Pathology and Morphometrics of Sporadic and Hereditary Small Vessel Diseases of the Brain

Small vessel diseases (SVDs) of the brain are likely to become increasingly common in tandem with the rise in the aging population. In recent years, neuroimaging and pathological studies have informed on the pathogenesis of sporadic SVD and several single gene (monogenic) disorders predisposing to subcortical strokes and diffuse white matter disease. However, one of the limitations toward studying SVD lies in the lack of consistent assessment criteria and lesion burden for both clinical and pathological measures. Arteriolosclerosis and diffuse white matter changes are the hallmark features of both sporadic and hereditary SVDs. The pathogenesis of the arteriopathy is the key to understanding the differential progression of disease in various SVDs. Remarkably, quantification of microvascular abnormalities in sporadic and hereditary SVDs has shown that qualitatively the processes involved in arteriolar degeneration are largely similar in sporadic SVD compared with hereditary disorders such as cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Important significant regional differences in lesion location within the brain may enable one to distinguish SVDs, where frontal lobe involvement appears consistently with almost every SVD, but others bear specific pathologies in other lobes, such as the temporal pole in CADASIL and the pons in pontine autosomal dominant microangiopathy and leukoencephalopathy or PADMAL. Additionally, degenerative changes in the vascular smooth muscle cells, the cerebral endothelium and the basal lamina are often rapid and more aggressive in genetic disorders. Further quantification of other microvascular elements and even neuronal cells is needed to fully characterize SVD pathogenesis and to differentiate the usefulness of vascular interventions and treatments on the resulting pathology

Dynein-Dynactin Complex Is Essential for Dendritic Restriction of TM1-Containing Drosophila Dscam

BACKGROUND: Many membrane proteins, including Drosophila Dscam, are enriched in dendrites or axons within neurons. However, little is known about how the differential distribution is established and maintained. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the mechanisms underlying the dendritic targeting of Dscam[TM1]. Through forward genetic mosaic screens and by silencing specific genes via targeted RNAi, we found that several genes, encoding various components of the dynein-dynactin complex, are required for restricting Dscam[TM1] to the mushroom body dendrites. In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl. Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest multiple mechanisms of dendritic protein targeting. Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport

Acute Pain and a Motivational Pathway in Adult Rats: Influence of Early Life Pain Experience

The importance of neonatal experience upon behaviour in later life is increasingly recognised. The overlap between pain and reward pathways led us to hypothesise that neonatal pain experience influences reward-related pathways and behaviours in adulthood