Comparative Evaluation of Propolis, Metronidazole with Chlorhexidine, Calcium Hydroxide and Curcuma Longa Extract as Intracanal Medicament Against E.faecalis- An Invitro Study.
The increase of potential side effects and safety concerns of conventional medicaments have led to the recent popularity of herbal alternative medications. The herbal products are known for its high antimicrobial activity, biocompatibility, anti-inflammatory and antioxidant properties. The purpose of this study was to investigate and compare the effectiveness of Propolis, Metronidazole with Chlorhexidine gel, Curcuma Longa and Calcium Hydroxide for elimination of E.faecalis bacteria in extracted teeth samples. Ninety extracted single rooted intact teeth were taken for the study. Decoronation, removal of apices and chemomechanical preparation was done for all samples. These sterilized samples were then contaminated with pure culture of E.faecalis under laminar flow. The samples were incubated for a period of 21 days. The infected samples were assigned to 5 groups: Group I- Propolis; Group II- Metronidazole with Chlorhexidine gel; Group III- Calcium hydroxide; Group IV- Curcuma Longa; and control group- Saline. Efficacy of newer intracanal medicaments against E.faecalis were carried out in the samples at the end of 1, 2 & 5 days for each group with the help of colorimeter. Student paired t-test, ANOVA and multiple tukey test were used for statistical analysis. The value of optical density was statistically significant in all groups when compared to that of control group. Group I (Propolis) produced better antimicrobial efficacy followed by Chlorhexidine Metronidazole combination, Curcuma Longa and Calcium hydroxide. Within the limitations of this study, it can be concluded that Propolis showed better antimicrobial properties against E.faecalis than other medicaments.


Mechanisms of pH-gradient driven transport mediated by organic anion polypeptide transporters.
Organic anion transporting polypeptides (humans OATPs, rodents Oatps) are expressed in most mammalian tissues and mediate cellular uptake of a wide variety of amphipathic organic compounds such as bile salts, steroid conjugates, oligopeptides, and a large list of drugs, probably by acting as anion exchangers. In the present study we aimed to investigate the role of the extracellular pH on the transport activity of nine human and four rat OATPs/Oatps. Furthermore, we aimed to test the concept that OATP/Oatp transport activity is accompanied by extrusion of bicarbonate. By using amphibian Xenopus laevis oocytes expressing OATPs/Oatps and mammalian cell lines stably transfected with OATPs/Oatps, we could demonstrate that in all OATPs/Oatps investigated, with the exception of OATP1C1, a low extracellular pH stimulated transport activity. This stimulation was accompanied by an increased substrate affinity as evidenced by lower apparent Michaelis-Menten constant values. OATP1C1 is lacking a highly conserved histidine in the third transmembrane domain, which was shown by site-directed mutagenesis to be critically involved in the pH dependency of OATPs/Oatps. Using online intracellular pH measurements in OATP/Oatp-transfected Chinese Hamster Ovary (CHO)-K1 cells, we could demonstrate the presence of a 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid-sensitive chloride/bicarbonate exchanger in CHO-K1 cells and that OATP/Oatp-mediated substrate transport is paralleled by bicarbonate efflux. We conclude that the pH dependency of OATPs/Oatps may lead to a stimulation of substrate transport in an acidic microenvironment and that the OATP/Oatp-mediated substrate transport into cells is generally compensated or accompanied by bicarbonate efflux.


A new regioselective Heck vinylation with enamides. Synthesis and investigation of fluorous-tagged bidentate ligands for fast separation.
Internal ligand-controlled Heck vinylations of enamides were performed with high regioselectivity and delivered moderate to good yields of dienamides. Controlled heating by microwave irradiation accelerated the palladium-catalyzed reactions, and full conversions were achieved after reaction times of only 15-30 min. New bidentate fluorous-tagged 1,3-bis(diphenylphosphino)propane ligands (F-dppp's) were synthesized and examined. The cationic vinylations of the enamides with F-dppp ligands rendered essentially the same alpha-selectivity and catalytic activity as in those vinylations where nonfluorous ligands were employed. After reaction, the fluorous-tagged ligand material was easily removed by convenient solid fluorous phase separation. The high selectivity, simplicity, and generality of the experimental procedure should make this approach to 2-acylamino-1,3-butadienes attractive.


Ubiquitous dissolved inorganic carbon assimilation by marine bacteria in the Pacific Northwest coastal ocean as determined by stable isotope probing.
In order to identify bacteria that assimilate dissolved inorganic carbon (DIC) in the northeast Pacific Ocean, stable isotope probing (SIP) experiments were conducted on water collected from 3 different sites off the Oregon and Washington coasts in May 2010, and one site off the Oregon Coast in September 2008 and March 2009. Samples were incubated in the dark with 2 mM (13)C-NaHCO(3), doubling the average concentration of DIC typically found in the ocean. Our results revealed a surprising diversity of marine bacteria actively assimilating DIC in the dark within the Pacific Northwest coastal waters, indicating that DIC fixation is relevant for the metabolism of different marine bacterial lineages, including putatively heterotrophic taxa. Furthermore, dark DIC-assimilating assemblages were widespread among diverse bacterial classes. Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes dominated the active DIC-assimilating communities across the samples. Actinobacteria, Betaproteobacteria, Deltaproteobacteria, Planctomycetes, and Verrucomicrobia were also implicated in DIC assimilation. Alteromonadales and Oceanospirillales contributed significantly to the DIC-assimilating Gammaproteobacteria within May 2010 clone libraries. 16S rRNA gene sequences related to the sulfur-oxidizing symbionts Arctic96BD-19 were observed in all active DIC assimilating clone libraries. Among the Alphaproteobacteria, clones related to the ubiquitous SAR11 clade were found actively assimilating DIC in all samples. Although not a dominant contributor to our active clone libraries, Betaproteobacteria, when identified, were predominantly comprised of Burkholderia. DIC-assimilating bacteria among Deltaproteobacteria included members of the SAR324 cluster. Our research suggests that DIC assimilation is ubiquitous among many bacterial groups in the coastal waters of the Pacific Northwest marine environment and may represent a significant metabolic process.


Reconstruction of major maternal and paternal lineages of the Cape Muslim population.
The earliest Cape Muslims were brought to the Cape (Cape Town - South Africa) from Africa and Asia from 1652 to 1834. They were part of an involuntary migration of slaves, political prisoners and convicts, and they contributed to the ethnic diversity of the present Cape Muslim population of South Africa. The history of the Cape Muslims has been well documented and researched however no in-depth genetic studies have been undertaken. The aim of the present study was to determine the respective African, Asian and European contributions to the mtDNA (maternal) and Y-chromosomal (paternal) gene pool of the Cape Muslim population, by analyzing DNA samples of 100 unrelated Muslim males born in the Cape Metropolitan area. A panel of six mtDNA and eight Y-chromosome SNP markers were screened using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). Overall admixture estimates for the maternal line indicated Asian (0.4168) and African mtDNA (0.4005) as the main contributors. The admixture estimates for the paternal line, however, showed a predominance of the Asian contribution (0.7852). The findings are in accordance with historical data on the origins of the early Cape Muslims.


Omega 3 Fatty Acids Reduce the Triglyceride Levels in Rats with Apical Periodontitis.
The aim of this study was to evaluate the influence of the prophylactic and therapeutic supplementation with omega 3 polyunsaturated fatty acids (w-3 PUFAs) on the lipid profile and periapical bone resorption in rats with apical periodontitis. Forty male rats were divided into groups: control rats (C), rats treated with w-3 PUFAs (C+O), rats with pulp exposure-induced apical periodontitis (AP), and rats with AP treated with w-3 PUFAs (AP+O). The administration of w-3 PUFAs was carried out orally once a day for 15 days before pulp exposure and, subsequently, for an additional 30 days after pulp exposure. AP was induced by exposing pulpal tissues to the oral environment. The samples were collected after 30 days. Triglycerides and cholesterol levels were enzymatically measured using the Trinder method. The jaws were collected and submitted for histological analysis. Two-way analysis of variance and Kruskal-Wallis tests were used for statistical analysis, and the significance was set at p<0.05. The triglyceride levels of the AP group were significantly higher than those of the C, C+O and AP+O groups (p<0.05). However, the difference in the cholesterol levels among the groups was not significant (p>0.05). Rats with AP showed larger areas of bone resorption as well as higher inflammatory intensity compared with rats with AP supplemented with w-3 PUFAs. It may be concluded that the presence of multiple AP foci increased the triglyceride levels. In addition, omega 3 supplementation might reduce these levels in rats with AP, as well as the bone resorption areas of periapical tissues.


Presurgical nasoalveolar molding and primary gingivoperiosteoplasty reduce the need for bone grafting in patients with bilateral clefts.
Preoperative nasoalveolar molding (NAM) in combination with primary gingivoperiosteoplasty (GPP) reduces the need for secondary alveolar bone grafting by 60% in patients with unilateral cleft lip and palate (CL/P). Herein, we investigate the efficacy of NAM and primary GPP in patients with bilateral CL/P. All patients (n = 38) with bilateral CL/P who underwent NAM and primary GPP from 1988 to 1998 with at least 14 years of follow-up were included in this study. Panoramic and periapical radiographs were used to assess dentoalveolar bone formation. A total of 38 patients were identified with median follow-up of 18 years (range 14-26 years). Of the 27 patients who underwent bilateral GPP, 14 (51%) patients had successful dentoalveolar bone formation bilaterally and 13 (49%) had unilateral bone formation. No patient had a bilateral failure. Of the 11 patients who underwent unilateral GPP, 7 (63%) patients had successful dentoalveolar bone formation. Bilateral successful dentoalveolar bone formation following primary bilateral GPP has a dependent probability of 52% and a conditional probability of 82%.


Learning by observation and learning by doing in Down and Williams syndromes.
New skills may be learned by active experience (experiential learning or learning by doing) or by observation of others' experience (learning by observation). In general, learning by observation reduces the time and the attempts needed to learn complex actions and behaviors. The present research aimed to compare learning by observation and learning by doing in two clinical populations with different etiology of intellectual disability (ID), as individuals with Down syndrome (DS) and individuals with Williams syndrome (WS), with the hypothesis that specific profiles of learning may be found in each syndrome. To this end, we used a mixture of new and existing data to compare the performances of 24 individuals with DS, 24 individuals with WS and 24 typically developing children on computerized tasks of learning by observation or learning by doing. The main result was that the two groups with ID exhibited distinct patterns of learning by observation. Thus, individuals with DS were impaired in reproducing the previously observed visuo-motor sequence, while they were as efficient as TD children in the experiential learning task. On the other hand, individuals with WS benefited from the observational training while they were severely impaired in detecting the visuo-motor sequence in the experiential learning task (when presented first). The present findings reinforce the syndrome-specific hypothesis and the view of ID as a variety of conditions in which some cognitive functions are more disrupted than others because of the differences in genetic profile and brain morphology and functionality. These findings have important implications for clinicians, who should take into account the genetic etiology of ID in developing learning programs for treatment and education.


[Incubated osmotic fragility test does not exclude red blood cell membrane disorders! About a case of hereditary elliptocytosis].
We report a case of hereditary elliptocytosis in an infant diagnosed a few months after the birth, in a context of regenerative normocytic normochromic anaemia. The investigations, including incubated osmotic fragility, erythrocytic enzymes study and haemoglobin electrophoresis, were not contributive. Only the persistence of elongated (or cigar-shaped) erythrocytes on blood smears was noted. Hereditary elliptocytosis was confirmed by specialized investigations (rheological study and erythrocytic membrane proteins electrophoresis). Investigations in the mother were realized and led to the discovery of a similar biological pattern. Hereditary elliptocytosis is a red blood cell membrane disorder due to the defect in cytoskeleton proteins (spectrin or 4.1), leading to the loss of deformability properties of erythrocytes. This disorder is considered as rare; however, its incidence is probably underestimated because most cases are pauci- or asymptomatic and the discovery is often fortuitous. The absence of detection of this defect by incubated osmotic fragility should not discard the hypothesis of erythrocytes membrane disorders. The persistent observation of elongated erythrocytes on blood smear must encourage the biologist to evocate a hereditary elliptocytosis.


[Eating habits, physical activity and socioeconomic level in university students of Chile].
University students are vulnerable to poor nutrition; they don't eat snacks between meals, don't eat breakfast or fast for long hours, prefer fast food and don't exercise. University students is considered the key young adult population group for health promotion and prevention for future generations, so it's crucial identify the current nutritional status and frequency of physical activity. To determine the factors involved in the choice of food and frequency of physical activity in university students. 799 volunteers were evaluated from four universities of the fifth region of Chile. Instrument was applied to determine the level of physical activity and eating habits, KIDMED test to determine adherence to the Mediterranean diet and Adimark instrument to determinate the socioeconomic status of the subjects. Finally, anthropometric evaluation to determinate BMI, fat mass and muscle mass. Physical inactivity is higher in women than in men and that the main reason for not exercising is lack of time and laziness. In both sexes don't read nutrition labels and have a low and average adherence to the Mediterranean diet. The low knowledge of nutrition is the cause of the poor food quality of subjects and there isn't greater motivation to perform physical activity.Socioeconomic status isn't related to eating habits and physical activity. It's necessary to integrate programs regular and permanent healthy lifestyle in all universities.


Adverse or acceptable: negotiating access to a post-apartheid health care contract.
As in many fragile and post-conflict countries, South Africa's social contract has formally changed from authoritarianism to democracy, yet access to services, including health care, remains inequitable and contested. We examine access barriers to quality health services and draw on social contract theory to explore ways in which a post-apartheid health care contract is narrated, practiced and negotiated by patients and providers. We consider implications for conceptualizing and promoting more inclusive, equitable health services in a post-conflict setting. Using in-depth interviews with 45 patients and 67 providers, and field observations from twelve health facilities in one rural and two urban sub-districts, we explore access narratives of those seeking and delivering - negotiating - maternal health, tuberculosis and antiretroviral services in South Africa. Although South Africa's right to access to health care is constitutionally guaranteed, in practice, a post-apartheid health care contract is not automatically or unconditionally inclusive. Access barriers, including poverty, an under-resourced, hierarchical health system, the nature of illness and treatment, and negative attitudes and actions, create conditions for insecure or adverse incorporation into this contract, or even exclusion (sometimes temporary) from health care services. Such barriers are exacerbated by differences in the expectations that patients and providers have of each other and the contract, leading to differing, potentially conflicting, identities of inclusion and exclusion: defaulting versus suffering patients, uncaring versus overstretched providers. Conversely, caring, respectful communication, individual acts of kindness, and institutional flexibility and leadership may mitigate key access barriers and limit threats to the contract, fostering more positive forms of inclusion and facilitating easier access to health care. Building health in fragile and post-conflict societies requires the negotiation of a new social contract. Surfacing and engaging with differences in patient and provider expectations of this contract may contribute to more acceptable, accessible health care services. Additionally, the health system is well positioned to highlight and connect the political economy, institutions and social relationships that create and sustain identities of exclusion and inclusion - (re)politicise suffering - and co-ordinate and lead intersectoral action for overcoming affordability and availability barriers to inclusive and equitable health care services.


The Health Of Patients' Eyes (HOPE) Glaucoma study. The effectiveness of a 'glaucoma personal record' for newly diagnosed glaucoma patients: study protocol for a randomised controlled trial.
Glaucoma involves progressive optic nerve fibre loss, subsequently leading to irreversible and disabling visual field defects. In Europe, the prevalence of glaucoma is approximately 2.2 % of all people aged over 40 years; this equates to 12 million people. Glaucoma patients require regular lifelong follow-up, contributing to a large financial and resource burden for the National Health Service (NHS) in the UK. This study aims to determine whether providing newly diagnosed glaucoma patients with a personalised client-held eye health summary ('glaucoma personal record'), improves patients' knowledge of their glaucoma condition. A potential long-term benefit could be improved self-management and henceforth a slower rate of deterioration. HOPE Glaucoma is a 3-year, prospective, parallel-group, pragmatic, single-centred, randomised controlled trial. An anticipated 122 adults, newly diagnosed with glaucoma (including ocular hypertension, suspected glaucoma and/or chronic open-angle glaucoma) will be recruited from a nurse-led ophthalmology outpatient clinic at a medium-sized NHS Trust. Participants will be randomly allocated to receive standard clinical care (control arm) or standard care plus a glaucoma personal record, detailing the current state of their condition (interventional arm). Participant assessments are designed to test whether provision of a glaucoma personal record 1) improves patient knowledge of glaucoma and 2) contributes to improvements in clinical outcomes, i.e. delay of visual field loss. The primary outcome measure is better client knowledge of glaucoma at the 9-12 month follow-up visit. Secondary outcome measures include the rate of visual field loss and patient-reported outcome measures on visual function (National Eye Institute VFQ - 25) measured at baseline, 9-12 months, 24 months and 36 months. Estimating a 20 % drop-out rate, the study will have 90 % power to detect a mean two-point difference in glaucoma knowledge score between groups at 5 % significance - based on two-sided Mann-Whitney U test. If a glaucoma personal record is found to significantly improve glaucoma patients' knowledge of their condition, this intervention could potentially provide a low-cost, straightforward tool to educate and engage glaucoma patients. Subsequently, this could have the potential to increase patient self-management and therefore allow glaucoma patients to prolong their sight functionality for longer. ISRCTN41306818 , registered on 22 August 2013.


EQ-5D studies in cardiovascular diseases in eight Central and Eastern European countries: a systematic review of the literature.
The measurement of health-related quality of life (HRQoL) by validated generic instruments, such as EQ-5D, has become an increasingly important tool for the assessment of health care in a wide range of diagnoses. We aimed to systematically review EQ-5D literature on cardiovascular diseases in eight Central and Eastern European (CEE) countries. A structured literature search was conducted in MEDLINE, EMBASE, Web of Science, CINAHL, PsycINFO, Cochrane Library, and the EuroQol website up to November 2016. Original cardiovascular-related studies that reported EQ-5D results were included. Of the 36 papers, 17 reported EQ-5D index scores. Most studies were performed in Poland (n = 24, 67%). The most common diagnosis regarding the number of publications and population size was ischaemic heart disease (n = 13, N = 6394), followed by atrial fibrillation (n = 4, N = 1052). The average EQ-5D index scores ranged from 0.61 to 0.88 and from 0.66 to 0.95 for patients before and after cardiac procedure/surgery, respectively (including angioplasty, coronary artery bypass grafting, ablation, surgical correction of septal defects, transcatheter aortic valve implantation [TAVI]). In all studies baseline scores were lower than the repeated assessments after the procedure, with the most substantial improvement of 0.24 in high-risk elderly patients after TAVI. Studies which did not assess invasive treatment reported mean EQ-5D index scores ranging from 0.18 to 0.80. The number of cardiovascular-related studies reporting HRQoL using EQ-5D has consistently increased in CEE countries over the past decade and is outstanding compared with other clinical fields. The EQ-5D index and EQ VAS scores varied based on the disease severity, patient characteristics, and treatment protocol.


The Pfam protein families database.
Pfam is a widely used database of protein families, currently containing more than 13,000 manually curated protein families as of release 26.0. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/). Here, we report on changes that have occurred since our 2010 NAR paper (release 24.0). Over the last 2 years, we have generated 1840 new families and increased coverage of the UniProt Knowledgebase (UniProtKB) to nearly 80%. Notably, we have taken the step of opening up the annotation of our families to the Wikipedia community, by linking Pfam families to relevant Wikipedia pages and encouraging the Pfam and Wikipedia communities to improve and expand those pages. We continue to improve the Pfam website and add new visualizations, such as the 'sunburst' representation of taxonomic distribution of families. In this work we additionally address two topics that will be of particular interest to the Pfam community. First, we explain the definition and use of family-specific, manually curated gathering thresholds. Second, we discuss some of the features of domains of unknown function (also known as DUFs), which constitute a rapidly growing class of families within Pfam.


Behavioural interventions for type 2 diabetes: an evidence-based analysis.
In June 2008, the Medical Advisory Secretariat began work on the Diabetes Strategy Evidence Project, an evidence-based review of the literature surrounding strategies for successful management and treatment of diabetes. This project came about when the Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the Ministry's newly released Diabetes Strategy.After an initial review of the strategy and consultation with experts, the secretariat identified five key areas in which evidence was needed. Evidence-based analyses have been prepared for each of these five areas: insulin pumps, behavioural interventions, bariatric surgery, home telemonitoring, and community based care. For each area, an economic analysis was completed where appropriate and is described in a separate report.To review these titles within the Diabetes Strategy Evidence series, please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html,DIABETES STRATEGY EVIDENCE PLATFORM: Summary of Evidence-Based AnalysesContinuous Subcutaneous Insulin Infusion Pumps for Type 1 and Type 2 Adult Diabetics: An Evidence-Based Analysis Behavioural Interventions for Type 2 Diabetes: An Evidence-Based Analysis BARIATRIC SURGERY FOR PEOPLE WITH DIABETES AND MORBID OBESITY: An Evidence-Based Summary Community-Based Care for the Management of Type 2 Diabetes: An Evidence-Based Analysis Home Telemonitoring for Type 2 Diabetes: An Evidence-Based Analysis Application of the Ontario Diabetes Economic Model (ODEM) to Determine the Cost-effectiveness and Budget Impact of Selected Type 2 Diabetes Interventions in Ontario The objective of this report is to determine whether behavioural interventions are effective in improving glycemic control in adults with type 2 diabetes. Diabetes is a serious chronic condition affecting millions of people worldwide and is the sixth leading cause of death in Canada. In 2005, an estimated 8.8% of Ontario's population had diabetes, representing more than 816,000 Ontarians. The direct health care cost of diabetes was $1.76 billion in the year 2000 and is projected to rise to a total cost of $3.14 billion by 2016. Much of this cost arises from the serious long-term complications associated with the disease including: coronary heart disease, stroke, adult blindness, limb amputations and kidney disease. Type 2 diabetes accounts for 90-95% of diabetes and while type 2 diabetes is more prevalent in people aged 40 years and older, prevalence in younger populations is increasing due to a rise in obesity and physical inactivity in children. Data from the United Kingdom Prospective Diabetes Study (UKPDS) has shown that tight glycemic control can significantly reduce the risk of developing serious complications in type 2 diabetics. Despite physicians' and patients' knowledge of the importance of glycemic control, Canadian data has shown that only 38% of patients with diabetes have HbA1C levels in the optimal range of 7% or less. This statistic highlights the complexities involved in the management of diabetes, which is characterized by extensive patient involvement in addition to the support provided by physicians. An enormous demand is, therefore, placed on patients to self-manage the physical, emotional and psychological aspects of living with a chronic illness. Despite differences in individual needs to cope with diabetes, there is general agreement for the necessity of supportive programs for patient self-management. While traditional programs were didactic models with the goal of improving patients' knowledge of their disease, current models focus on behavioural approaches aimed at providing patients with the skills and strategies required to promote and change their behaviour. Several meta-analyses and systematic reviews have demonstrated improved health outcomes with self-management support programs in type 2 diabetics. They have all, however, either looked at a specific component of self-management support programs (i.e. self-management education) or have been conducted in specific populations. Most reviews are also qualitative and do not clearly define the interventions of interest, making findings difficult to interpret. Moreover, heterogeneity in the interventions has led to conflicting evidence on the components of effective programs. There is thus much uncertainty regarding the optimal design and delivery of these programs by policymakers. EVIDENCE-BASED ANALYSIS OF EFFECTIVENESS: Are behavioural interventions effective in improving glycemic control in adults with type 2 diabetes?Is the effectiveness of the intervention impacted by intervention characteristics (e.g. delivery of intervention, length of intervention, mode of instruction, interventionist etc.)? English Language Published between January 1996 to August 2008 Type 2 diabetic adult population (>18 years)Randomized controlled trials (RCTs)Systematic reviews, or meta-analyses Describing a multi-faceted self-management support intervention as defined by the 2007 Self-Management Mapping Guide (1)Reporting outcomes of glycemic control (HbA1c) with extractable data Studies with a minimum of 6-month follow up Studies with a control group other than usual care Studies with a sample size <30 Studies without a clearly defined intervention glycemic control (HbA1c) systolic blood pressure (SBP) control, lipid control, change in smoking status, weight change, quality of life, knowledge, self-efficacy, managing psychosocial aspects of diabetes, assessing dissatisfaction and readiness to change, and setting and achieving diabetes goals. A search was performed in OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), The Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published between January 1996 and August 2008. Abstracts were reviewed by a single author and studies meeting the inclusion criteria outlined above were obtained. Data on population characteristics, glycemic control outcomes, and study design were extracted. Reference lists were also checked for relevant studies. The quality of the evidence was assessed as being either high, moderate, low, or very low according to the GRADE methodology. The search identified 638 citations published between 1996 and August 2008, of which 12 met the inclusion criteria and one was a meta-analysis (Gary et al. 2003). The remaining 11 studies were RCTs (9 were used in the meta-analysis) and only one was defined as small (total sample size N=47). SUMMARY OF PARTICIPANT DEMOGRAPHICS ACROSS STUDIES: A total of 2,549 participants were included in the 11 identified studies. The mean age of participants reported was approximately 58 years and the mean duration of diabetes was approximately 6 years. Most studies reported gender with a mean percentage of females of approximately 67%. Of the eleven studies, two focused only on women and four included only Hispanic individuals. All studies evaluated type 2 diabetes patients exclusively. STUDY CHARACTERISTICS: The studies were conducted between 2002 and 2008. Approximately six of 11 studies were carried out within the USA, with the remaining studies conducted in the UK, Sweden, and Israel (sample size ranged from 47 to 824 participants). The quality of the studies ranged from moderate to low with four of the studies being of moderate quality and the remaining seven of low quality (based on the Consort Checklist). Differences in quality were mainly due to methodological issues such as inadequate description of randomization, sample size calculation allocation concealment, blinding and uncertainty of the use of intention-to-treat (ITT) analysis. Patients were recruited from several settings: six studies from primary or general medical practices, three studies from the community (e.g. via advertisements), and two from outpatient diabetes clinics. A usual care control group was reported in nine of 11 of the studies and two studies reported some type of minimal diabetes care in addition to usual care for the control group. INTERVENTION CHARACTERISTICS: All of the interventions examined in the studies were mapped to the 2007 Self-management Mapping Guide. The interventions most often focused on problem solving, goal setting and encouraging participants to engage in activities that protect and promote health (e.g. modifying behaviour, change in diet, and increase physical activity). All of the studies examined comprehensive interventions targeted at least two self-care topics (e.g. diet, physical activity, blood glucose monitoring, foot care, etc.). Despite the homogeneity in the aims of the interventions, there was substantial clinical heterogeneity in other intervention characteristics such as duration, intensity, setting, mode of delivery (group vs. individual), interventionist, and outcomes of interest (discussed below). DURATION, INTENSITY AND MODE OF DELIVERY: Intervention durations ranged from 2 days to 1 year, with many falling into the range of 6 to 10 weeks. The rest of the interventions fell into categories of ≤ 2 weeks (2 studies), 6 months (2 studies), or 1 year (3 studies). Intensity of the interventions varied widely from 6 hours over 2 days, to 52 hours over 1 year; however, the majority consisted of interventions of 6 to 15 hours. Both individual and group sessions were used to deliver interventions. Group counselling was used in five studies as a mode of instruction, three studies used both individual and group sessions, and one study used individual sessions as its sole mode of instruction. (ABSTRACT TRUNCATED)


Population-based determinants of radical prostatectomy operative time.
To determine factors that influence radical prostatectomy (RP) operative times. Operative time assessment is inherent to defining surgeon learning curves and evaluating quality of care. Population-based observational cohort study using USA Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data of men diagnosed with prostate cancer during 2003-2007 who underwent robot-assisted radical prostatectomy (RARP, 3458 men) and retropubic RP (RRP, 6993) through to 2009. We obtained median operative time using anaesthesia administrative data for RP and used median regression to assess the contribution of patient, surgeon, and hospital factors to operative times. The median RARP operative time decreased from 315 to 247 min from 2003 to 2008-2009 (P < 0.001), while the median RRP operative time remained similar (195 vs 197 min, P = 0.90). In adjusted analysis, RARP vs RRP (parameter estimate [PE] 70.9; 95% confidence interval [CI] 58, 84; P < 0.001) and obesity (PE 15; 95% CI 7, 23; P < 0.001) were associated with longer operative times while higher surgeon volumes were associated with shorter operative times (P < 0.001). RPs performed by surgeons employed by group (parameter estimate [PE] -22.76; 95% CI -38, -7.49; P = 0.004) and non-government (PE -35.59; 95% CI -68.15, -3.03; P = 0.032) vs government facilities and non-profit vs government hospital ownership (PE -21.85; 95% CI -32.28, -11.42; P < 0.001) were associated with shorter operative times. During our study period, RARP operative times decreased by 68 min while RRP operative times remained stagnant. Higher surgeon volume was associated with shorter operative times, and selective referral or improved efficiency to the level of high-volume surgeons would net almost $15 million (USA dollars) in annual savings.


A mid-infrared biaxial hyperbolic van der Waals crystal.
Hyperbolic media have attracted much attention in the photonics community due to their ability to confine light to arbitrarily small volumes and their potential applications to super-resolution technologies. The two-dimensional counterparts of these media can be achieved with hyperbolic metasurfaces that support in-plane hyperbolic guided modes upon nanopatterning, which, however, poses notable fabrication challenges and limits the achievable confinement. We show that thin flakes of a van der Waals crystal, α-MoO3, can support naturally in-plane hyperbolic polariton guided modes at mid-infrared frequencies without the need for patterning. This is possible because α-MoO3 is a biaxial hyperbolic crystal with three different Reststrahlen bands, each corresponding to a different crystalline axis. These findings can pave the way toward a new paradigm to manipulate and confine light in planar photonic devices.


Identification of histone H2b as a heat-shock protein in Drosophila.
Total cell polypeptides synthesized, in cultured Drosophila cells under control (25 degrees C) and heat-shock (37 degrees C) conditions have been compared in two different two-dimensional polyacrylamide gel electrophoresis systems which, together, resolve polypeptides having a wide range of isoelectric points, including the most basic polypeptides of the cell. The electrophoresis of basic proteins showed that the most prominent basic polypeptide synthesized in heat shock comigrated with histone H2b. This heat-shock polypeptide was identified as histone H2b by two criteria: (a) it comigrated with authentic histone H2b in Triton-urea-acetic acid acrylamide gel electrophoresis after solubilization from nuclei with acid; and (b) partial proteolysis peptide maps of the basic heat-shock protein and histone H2b were identical. The synthesis of histone H2b was induced threefold in heat shock, whereas synthesis of the other histones was reduced from two- to tenfold. The noncoordinate synthesis of histones in Drosophila in heat shock provides an interesting system in which to investigate transcriptional and translational controls of histone synthesis as well as assembly of histones into chromatin.


Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History.
The Consortium on the Genetics of Schizophrenia Family Study evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gating measures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here the authors investigated whether gating measures were more heritable in multiply affected families with a positive family history compared with families with only a single affected proband (singleton). A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons. Both PPI and P50 gating displayed substantially increased heritability in the 97 multiply affected families (47% and 36%, respectively) compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families. PPI and P50 gating measures demonstrate substantially increased heritability in schizophrenia families with a higher genetic vulnerability for illness, providing further support for the commonality of genes underlying both schizophrenia and gating measures.


The flip side of FLIP.
Two major pathways regulate apoptosis induction in mammalian cells. In the extrinsic pathway, apoptosis is induced through specialized surface receptors, whereas in the intrinsic pathway, apoptosis is induced from within the cell, mainly through activation of mitochondria. Shortly after the major mediators of the extrinsic apoptosis pathway, the initiator caspases-8 and -10, were identified, c-FLIP [FLICE-like inhibitory protein; FLICE is FADD (Fas-associated death domain protein)-like interleukin-1beta-converting enzyme], a catalytically inactive caspase-8/-10 homologue, was reported. Whether this structure acts as an inhibitor or promoter of the extrinsic apoptosis pathway has been the subject of much debate. In this issue of the Biochemical Journal, Boatright et al. provide further evidence for the long splice form of c-FLIP (c-FLIP(L)) being an activator of caspase-8/-10, and demonstrate that the resulting heterodimer is enzymically active with a substrate specificity identical with that of the caspase-8 homodimer. Our understanding of the regulators of the extrinsic apoptosis signalling pathway biochemically may provide the means to design drugs to correct the imbalance between apoptosis and proliferation, as found in many diseases.


Lung Nodule with Increasing Fluorodeoxyglucose Uptake in a Patient with a History of Lung Carcinoma and Talc Pleurodesis Evaluated by EBUS-TBNA On-Site Assessment.
Fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan is an indicator of potential malignancy or infection. Patients with a history of talc pleurodesis can develop pleural or lung parenchymal nodules/talcomas. In these patients, talc-associated (non-malignancy-related) FDG uptake may occur over years. A 66-year-old female presented with a past medical history significant for resected non-small-cell lung cancer and was treated with chemotherapy/radiation. The referring physician indicated that she subsequently developed benign pleural effusions and had talc pleurodesis to limit recurrence. The patient was referred to our institution for endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) due to a new left upper lobe nodule with increasing FDG uptake on follow-up interval PET performed at the referring institution. On-site cytologic evaluation showed no evidence of malignancy, but found refractile foreign material, consistent with the presence of talc particles. This case presents the importance of cytologic recognition of talc particles during on-site evaluation and discusses the phenomenon of increasing PET-FDG uptake associated with talc pleurodesis.


Effect of testing for cancer on cancer- or venous thromboembolism (VTE)-related mortality and morbidity in people with unprovoked VTE.
Venous thromboembolism (VTE) is a collective term for two conditions: deep vein thrombosis (DVT) and pulmonary embolism (PE). A proportion of people with VTE have no underlying or immediately predisposing risk factors and the VTE is referred to as unprovoked. Unprovoked VTE can often be the first clinical manifestation of an underlying malignancy. This has raised the question of whether people with an unprovoked VTE should be investigated for an underlying cancer. Treatment for VTE is different in cancer and non-cancer patients and a correct diagnosis would ensure that people received the optimal treatment for VTE to prevent recurrence and further morbidity. Furthermore, an appropriate cancer diagnosis at an earlier stage could avoid the risk of cancer progression and lead to improvements in cancer-related mortality and morbidity. This is an update of a review first published in 2015. To determine whether testing for undiagnosed cancer in people with a first episode of unprovoked VTE (DVT of the lower limb or PE) is effective in reducing cancer or VTE-related mortality and morbidity and to determine which tests for cancer are best at identifying treatable cancers early. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 11 July 2018. We also undertook reference checking to identify additional studies. Randomised and quasi-randomised trials in which people with an unprovoked VTE were allocated to receive specific tests for identifying cancer or clinically indicated tests only were eligible for inclusion. Primary outcomes included all-cause mortality, cancer-related mortality and VTE-related mortality. Two review authors independently selected studies, assessed risk of bias and extracted data. We resolved any disagreements by discussion. No new studies were identified for this 2018 update. In total, four studies with 1644 participants are included. Two studies assessed the effect of extensive tests including computed tomography (CT) scanning versus tests at the physician's discretion, while the other two studies assessed the effect of standard testing plus positron emission tomography (PET)/CT scanning versus standard testing alone. For extensive tests including CT versus tests at the physician's discretion, the quality of the evidence, as assessed according to GRADE, was low due to risk of bias (early termination of the studies). When comparing standard testing plus PET/CT scanning versus standard testing alone, the quality of evidence was moderate due to a risk of detection bias. The quality of the evidence was downgraded further as detection bias was present in one study with a low number of events.When comparing extensive tests including CT versus tests at the physician's discretion, pooled analysis on two studies showed that testing for cancer was consistent with either benefit or no benefit on cancer-related mortality (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.15 to 1.67; 396 participants; 2 studies; P = 0.26; low-quality evidence). One study (201 participants) showed that, overall, malignancies were less advanced at diagnosis in extensively tested participants than in participants in the control group. In total, 9/13 participants diagnosed with cancer in the extensively tested group had a T1 or T2 stage malignancy compared to 2/10 participants diagnosed with cancer in the control group (OR 5.00, 95% CI 1.05 to 23.76; P = 0.04; low-quality evidence). There was no clear difference in detection of advanced stages between extensive tests versus tests at the physician's discretion: one participant in the extensively tested group had stage T3 compared with four participants in the control group (OR 0.25, 95% CI 0.03 to 2.28; P = 0.22; low-quality evidence). In addition, extensively tested participants were diagnosed earlier than control group (mean: 1 month with extensive tests versus 11.6 months with tests at physician's discretion to cancer diagnosis from the time of diagnosis of VTE). Extensive testing did not increase the frequency of an underlying cancer diagnosis (OR 1.32, 95% CI 0.59 to 2.93; 396 participants; 2 studies; P = 0.50; low-quality evidence). Neither study measured all-cause mortality, VTE-related morbidity and mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life.When comparing standard testing plus PET/CT screening versus standard testing alone, standard testing plus PET/CT screening was consistent with either benefit or no benefit on all-cause mortality (OR 1.22, 95% CI 0.49 to 3.04; 1248 participants; 2 studies; P = 0.66; moderate-quality evidence), cancer-related mortality (OR 0.55, 95% CI 0.20 to 1.52; 1248 participants; 2 studies; P = 0.25; moderate-quality evidence) or VTE-related morbidity (OR 1.02, 95% CI 0.48 to 2.17; 854 participants; 1 study; P = 0.96; moderate-quality evidence). Regarding stage of cancer, there was no clear difference for detection of early (OR 1.78, 95% 0.51 to 6.17; 394 participants; 1 study; P = 0.37; low-quality evidence) or advanced (OR 1.00, 95% CI 0.14 to 7.17; 394 participants; 1 study; P = 1.00; low-quality evidence) stages of cancer. There was also no clear difference in the frequency of an underlying cancer diagnosis (OR 1.71, 95% CI 0.91 to 3.20; 1248 participants; 2 studies; P = 0.09; moderate-quality evidence). Time to cancer diagnosis was 4.2 months in the standard testing group and 4.0 months in the standard testing plus PET/CT group (P = 0.88). Neither study measured VTE-related mortality, complications of anticoagulation, adverse effects of cancer tests, participant satisfaction or quality of life. Specific testing for cancer in people with unprovoked VTE may lead to earlier diagnosis of cancer at an earlier stage of the disease. However, there is currently insufficient evidence to draw definitive conclusions concerning the effectiveness of testing for undiagnosed cancer in people with a first episode of unprovoked VTE (DVT or PE) in reducing cancer- or VTE-related morbidity and mortality. The results could be consistent with either benefit or no benefit. Further good-quality large-scale randomised controlled trials are required before firm conclusions can be made.


Stopping Renin-Angiotensin System Inhibitors in Patients with Advanced CKD and Risk of Adverse Outcomes: A Nationwide Study.
It is unknown whether stopping renin-angiotensin system (RAS) inhibitor therapy in patients with advanced CKD affects outcomes. We studied patients referred to nephrologist care, listed on the Swedish Renal Registry during 2007-2017, who developed advanced CKD (eGFR<30 ml/min per 1.73 m2) while on RAS inhibitor therapy. Using target trial emulation techniques on the basis of cloning, censoring, and weighting, we compared the risks of stopping within 6 months and remaining off treatment versus continuing RAS inhibitor therapy. These included risks of subsequent 5-year all-cause mortality, major adverse cardiovascular events, and initiation of kidney replacement therapy (KRT). Of 10,254 prevalent RAS inhibitor users (median age 72 years, 36% female) with new-onset eGFR <30 ml/min per 1.73 m2, 1553 (15%) stopped RAS inhibitor therapy within 6 months. Median eGFR was 23 ml/min per 1.73 m2. Compared with continuing RAS inhibition, stopping this therapy was associated with a higher absolute 5-year risk of death (40.9% versus 54.5%) and major adverse cardiovascular events (47.6% versus 59.5%), but with a lower risk of KRT (36.1% versus 27.9%); these corresponded to absolute risk differences of 13.6 events per 100 patients, 11.9 events per 100 patients, and -8.3 events per 100 patients, respectively. Results were consistent whether patients stopped RAS inhibition at higher or lower eGFR, across prespecified subgroups, after adjustment and stratification for albuminuria and potassium, and when modeling RAS inhibition as a time-dependent exposure using a marginal structural model. In this nationwide observational study of people with advanced CKD, stopping RAS inhibition was associated with higher absolute risks of mortality and major adverse cardiovascular events, but also with a lower absolute risk of initiating KRT.


Influence of Spraying Nano-Curcumin and Nano-Glycyrrhizic Acid on Resistance Enhancement and Some Growth Parameters of Soybean (Glycine max) in Response to Tetranychus urticae Infestation and Drought Stress.
Modern nanotechnology has been credited as one of the most significant inventions of the 21st century. Many agricultural disciplines have been affected by nanotechnology in agriculture. Pest control based on natural compounds needs to be enhanced, and enhancing plant growth under climate change conditions, with increasing periods of drought in many countries, is a very vital aim. Thus, the effect of curcumin nanoparticles (Cu-NPs) and glycyrrhizic acid nanoparticles (GA-NPs) as a foliar application under water deficit on natural infestation with the two-spotted spider mite Tetranychus urticae, plant growth and yield, anatomical and chemical parameters were investigated during this study. The obtained results revealed that drought stress over the two studied seasons significantly increased the population of T. urticae and decreased all morphological and yield characteristics. The application of three mM GA-NPs reduced the mite population average by 39% while using the same concentration of Cu-NPs caused a 33.9% reduction percentage under drought stress. Using 1 mM GA-NPs gave the highest averages of plant height, number of branches, and leaves/plant fresh and dry weight. Moreover, the number of pods, 100 seed weight and seed yield (kg/ha) increased significantly as a result of spraying with GA-NPs under water deficit. From the results, water deficit decreased the values of the leaf and stem anatomical parameters. Treatment with Cu-NPs or GA-NPs under drought stress increased the thickness of mid-vein, xylem, and phloem tissues. Likewise, such treatment increased stem diameter due mainly to the increase in the thickness of cortex, phloem, and xylem tissues compared with the control. Spraying plants with GA-NPs at 1 mM increased the percentages of nitrogen, phosphor, and potassium in seeds in addition to total chlorophyll. Moreover, glutamate, aspartate, leucine, arginine, Lysine, glycine, tyrosine, tryptophan, and methionine concentrations did not differ significantly (p > 0.05) in response to all the studied levels of Cu-NPs or GA-NPs either under normal irrigation or drought condition. In light of these findings, researchers and producers should apply and test both Cu-NPs and GA-NP as nano-fertilizer natural sources on economically viable crops.


Calcium activates two types of potassium channels in rat hippocampal neurons in culture.
Several calcium-dependent potassium currents can contribute to the electrophysiological properties of neurons. In hippocampal pyramidal cells, 2 afterhyperpolarizations (AHPs) are mediated by different calcium-activated potassium currents. First, a rapidly activated current contributes to action-potential repolarization and the fast AHP following individual action potentials. In addition, a slowly developing current underlies the slow AHP, which occurs after a burst of action potentials and contributes substantially to the spike-frequency accommodation observed in these cells during a prolonged depolarizing current pulse. In order to investigate the single Ca2(+)-dependent channels that might underlie these currents, we performed patch-clamp experiments on hippocampal neurons in primary culture. When excised inside-out patches were exposed to 1 microM Ca2+, 2 types of channel activity were observed. In symmetrical bathing solutions containing 140 mM K+, the channels had conductances of 19 pS and 220 pS, and both were permeable mainly to potassium ions. The properties of these 2 channels differed in a number of ways. At negative membrane potentials, the small-conductance channels were more sensitive to Ca2+ than the large channels. At positive potentials, the small-conductance channels displayed a flickery block by Mg2+ ions on the cytoplasmic face of the membrane. Low concentrations of tetraethylammonium (TEA) on the extracellular face of the membrane specifically caused an apparent reduction of the large-channel conductance. The properties of the large- and small-conductance channels are in accord with those of the fast and slow AHP, respectively.


Factors Associated With Initiation of Mechanical Ventilation in Patients With Sepsis: Retrospective Observational Study.
Patients with sepsis are at risk for mechanical ventilation. This study aimed to identify risk factors for initiation of mechanical ventilation in patients with sepsis and assess whether these factors varied with time. Data from the electronic health record were used to model risk factors for initiation of mechanical ventilation after the onset of sepsis. A time-varying Cox model was used to study factors that varied with time. Of 35 020 patients who met sepsis criteria, 28 747 were eligible for inclusion. Mechanical ventilation was initiated within 30 days after sepsis onset in 3891 patients (13.5%). Factors that were independently associated with increased likelihood of receipt of mechanical ventilation were race (White: adjusted hazard ratio [HR], 1.59; 95% CI, 1.39-1.83; other/unknown: adjusted HR, 1.97; 95% CI, 1.54-2.52), systemic inflammatory response syndrome (adjusted HR [per point], 1.23; 95% CI, 1.17-1.28), Sequential Organ Failure Assessment score (adjusted HR [per point], 1.28; 95% CI, 1.26-1.31), and congestive heart failure (adjusted HR, 1.30; 95% CI, 1.17-1.45). Hazard ratios decreased with time for Sequential Organ Failure Assessment score and congestive heart failure and varied with time for 4 comorbidities and 3 culture results. The risk for mechanical ventilation associated with different factors varied with time after sepsis onset, increasing for some factors and decreasing for others. Through a better understanding of risk factors for initiation of mechanical ventilation in patients with sepsis, targeted interventions may be tailored to high-risk patients.


The putative natural killer decoy early gene m04 (gp34) of murine cytomegalovirus encodes an antigenic peptide recognized by protective antiviral CD8 T cells.
Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, the m152 gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the "missing self." The retention, however, is counteracted by the m04 early gene product gp34, which binds to folded MHC-I molecules in the ER and directs the complex to the cell surface. It was thus speculated that gp34 might serve to silence NK cells and thereby complete the immune evasion of MCMV. In light of these current views, we provide here results demonstrating an in vivo role for gp34 in protective antiviral immunity. We have identified an antigenic nonapeptide derived from gp34 and presented by the MHC-I molecule D(d). Besides the immunodominant immediate-early nonapeptide consisting of IE1 amino acids 168-176 (IE1(168-176)), the early nonapeptide m04(243-251) is the second antigenic peptide described for MCMV. The primary immune response to MCMV generates significant m04-specific CD8 T-cell memory. Upon adoptive transfer into immunodeficient recipients, an m04-specific CTL line controls MCMV infection with an efficacy comparable to that of an IE1-specific CTL line. Thus, gp34 is the first noted early protein of MCMV that escapes viral immune evasion mechanisms. These data document that MCMV is held in check by a redundance of protective CD8 T cells recognizing antigenic peptides in different phases of viral gene expression.


Marsh Mallow (Althaea officinalis L.) and Its Potency in the Treatment of Cough.
Althaea officinalis has been traditionally used for management of cough and other respiratory problems. The aim of this review article was to evaluate its efficacy in modern research according to its traditional beliefs. All information was extracted from scientific resources of PubMed Central, ScienceDirect, Wiley, Springer, SID, accessible books, reports, and theses. The results of animal and clinical studies confirmed the efficacy of A. officinalis extracts alone in treatment of dry cough, while combination of A. officinalis with Zataria multiflora, Zingiber officinalis, or Helix hedera increased the efficacy of A. officinalis and improved all kinds of cough. Different mechanisms are involved in expectorant and antitussive effects of A. officinalis in treatment of cough. Therefore, A. officinalis in combination with other plant extracts in different forms of drug could be a good choice for cough, sore throat, and other respiratory ailments.


Association of a functional variant of the nitric oxide synthase 1 gene with personality, anxiety, and depressiveness.
A functional promoter polymorphism of the nitric oxide synthase 1 gene first exon 1f variable number tandem repeat (NOS1 ex1f-VNTR) is associated with impulsivity and related psychopathology. Facets of impulsivity are strongly associated with personality traits; maladaptive impulsivity with neuroticism; and adaptive impulsivity with extraversion. Both high neuroticism and low extraversion predict anxiety and depressive symptoms. The aim of the present study was to evaluate the effect of the NOS1 ex1f-VNTR genotype and possible interaction with environmental factors on personality, anxiety, and depressiveness in a population-representative sample. Short allele carriers had higher neuroticism and anxiety than individuals with the long/long (l/l) genotype. Male short/short homozygotes also had higher extraversion. In the face of environmental adversity, females with a short allele had higher scores of neuroticism, anxiety, and depressiveness compared to the l/l genotype. Males were more sensitive to environmental conditions when they had the l/l genotype and low extraversion. In conclusion, the NOS1 ex1f-VNTR influences personality and emotional regulation dependent on gender and environment. Together with previous findings on the effect of the NOS1 genotype on impulse control, these data suggest that NOS1 should be considered another plasticity gene, because its variants are associated with different coping strategies.


Medication costs to private insurers of diversion of medications for attention-deficit hyperactivity disorder.
The diversion of prescription stimulants for misuse, particularly those used in the treatment of attention-deficit hyperactivity disorder (ADHD), is potentially a significant problem for public health and for healthcare funding and delivery. Most prior research on the diversion of prescription stimulants for misuse, particularly those used in the treatment of ADHD, has focused on the 'end users' of diverted medications rather than the suppliers. Furthermore, little is known about the direct costs of diversion for third-party insurance payers in the US. The objectives of this study were to estimate the prevalence in the US of people whose private insurance paid costs for ADHD prescriptions that they gave or sold to another person (diversion), and to estimate medication costs of diversion to private insurers. Estimates are from a cross-sectional survey of respondents from two Internet survey panels targeting individuals aged 18-49 years in the civilian, noninstitutionalized US population, principally for those who filled prescriptions for ADHD medications in the past 30 days that were covered by private health insurance. Analysis weights were post-stratified to control totals from the Current Population Survey and National Health Interview Survey. Weighted prevalence rates and standard errors for diversion are reported, as are the costs of diverted pills using drug prices reported in the 2008 Thomson Reuters RED BOOK™. Sensitivity analyses were conducted that varied the cost assumptions for medications. Among individuals aged 18-49 years whose private insurance paid some costs for ADHD medications in the past 30 days, 16.6% diverted medications from these prescriptions. Men aged 18-49 years for whom private insurance paid some costs of ADHD drugs in the past 30 days were more than twice as likely as their female counterparts to divert medications from these prescriptions (22.5% vs 9.1%; p = 0.03). After a pro-rated co-payment share was subtracted, the estimated value of diverted medications in a 30-day period was $US8.0 million. Lower- and upper-bound estimates were $US6.9 million to $US17 million, for a range of $US83 million to $US204 million annually. Overall, diversion accounted for about 3.6% of the total costs that private insurers paid for ADHD medications (range: 3.5-4.5%). The percentages varied by medication category, although relative differences were sensitive to inclusion of a pro-rated co-payment. A higher percentage of the costs of extended-release (XR) medications was lost to diversion compared with that for immediate-release (IR) medications. Costs of ADHD medications paid for by private insurers that were lost to diversion were small relative to the total estimated medication costs and relative to total estimated healthcare costs for treating ADHD. Nevertheless, there may be significant cost savings for insurers if diversion can be reduced, particularly for XR medications. These findings represent a first step to informing policies to reduce diversion both in the interest of public health and for direct and indirect cost savings to insurers.


Documentation Practices for Transgender Youth Admitted to an Inpatient Psychiatric Unit.
Population-based surveys estimate that 0.7% of youth (13 to 17 y of age) in the United States identifies as transgender. Transgender youth are at an increased risk of anxiety, depression, and suicide attempts that often require inpatient care. Unfortunately, because of perceived insensitivity to gender identity from their providers, which includes incorrect use of names and/or pronouns, they may delay seeking necessary care. To date, there have been no specific documentation practice guidelines published by the International Association of Child and Adolescent Psychiatry and Allied Professions, American Academy of Child and Adolescent Psychiatry (AACAP), or other professional associations. The main goal of this study was to review documentation practices among multidisciplinary teams caring for hospitalized transgender youth on a child and adolescent inpatient psychiatry unit. Retrospective chart reviews were completed for 44 transgender patients who were hospitalized between 2008 and 2017. The charts were reviewed for consistency in the documentation of name and gender by the multidisciplinary team. Members included child and adolescent staff psychiatrists, residents, fellows, nurses, nurse practitioners, physician assistants, and social workers. Inconsistency was defined as at least 2 members of the team referring to a patient by a different name and/or gender pronoun in separate notes or >2 interchanges of name and/or gender pronoun in a single note. Kappa coefficient was calculated between each team member role to estimate exact agreement statistics. In 43.2% (n=19) of cases, team members did not have a consistent approach to documenting a patient's name and/or gender pronoun and 18% (n=8) of discharge summaries were also inconsistent in this documentation. The greatest agreement in documentation practices was noted between the team and the staff psychiatrist (κ=0.446). Findings from this study suggest that inpatient treatment teams show inconsistency in documentation practices for youth transgender inpatients. Further work is necessary to understand the implications of these findings for patient satisfaction and clinical outcomes.


Essential Roles of the sppRA Fructose-Phosphate Phosphohydrolase Operon in Carbohydrate Metabolism and Virulence Expression by Streptococcus mutans.
The dental caries pathogen Streptococcus mutans can ferment a variety of sugars to produce organic acids. Exposure of S. mutans to certain nonmetabolizable carbohydrates, such as xylitol, impairs growth and can cause cell death. Recently, the presence of a sugar-phosphate stress in S. mutans was demonstrated using a mutant lacking 1-phosphofructokinase (FruK) that accumulates fructose-1-phosphate (F-1-P). Here, we studied an operon in S. mutans, sppRA, which was highly expressed in the fruK mutant. Biochemical characterization of a recombinant SppA protein indicated that it possessed hexose-phosphate phosphohydrolase activity, with preferences for F-1-P and, to a lesser degree, fructose-6-phosphate (F-6-P). SppA activity was stimulated by Mg2+ and Mn2+ but inhibited by NaF. SppR, a DeoR family regulator, repressed the expression of the sppRA operon to minimum levels in the absence of the fructose-derived metabolite F-1-P and likely also F-6-P. The accumulation of F-1-P, as a result of growth on fructose, not only induced sppA expression, but it significantly altered biofilm maturation through increased cell lysis and enhanced extracellular DNA release. Constitutive expression of sppA, via a plasmid or by deleting sppR, greatly alleviated fructose-induced stress in a fruK mutant, enhanced resistance to xylitol, and reversed the effects of fructose on biofilm formation. Finally, by identifying three additional putative phosphatases that are capable of promoting sugar-phosphate tolerance, we show that S. mutans is capable of mounting a sugar-phosphate stress response by modulating the levels of certain glycolytic intermediates, functions that are interconnected with the ability of the organism to manifest key virulence behaviors.IMPORTANCEStreptococcus mutans is a major etiologic agent for dental caries, primarily due to its ability to form biofilms on the tooth surface and to convert carbohydrates into organic acids. We have discovered a two-gene operon in S. mutans that regulates fructose metabolism by controlling the levels of fructose-1-phosphate, a potential signaling compound that affects bacterial behaviors. With fructose becoming increasingly common and abundant in the human diet, we reveal the ways that fructose may alter bacterial development, stress tolerance, and microbial ecology in the oral cavity to promote oral diseases.


Distinct effects of contraction-induced injury in vivo on four different murine models of dysferlinopathy.
Mutations in the DYSF gene, encoding dysferlin, cause muscular dystrophies in man. We compared 4 dysferlinopathic mouse strains: SJL/J and B10.SJL-Dysf(im)/AwaJ (B10.SJL), and A/J and B6.A-Dysf(prmd)/GeneJ (B6.A/J). The former but not the latter two are overtly myopathic and weaker at 3 months of age. Following repetitive large-strain injury (LSI) caused by lengthening contractions, all except B6.A/J showed ~40% loss in contractile torque. Three days later, torque in SJL/J, B10.SJL and controls, but not A/J, recovered nearly completely. B6.A/J showed ~30% torque loss post-LSI and more variable recovery. Pre-injury, all dysferlinopathic strains had more centrally nucleated fibers (CNFs) and all but A/J showed more inflammation than controls. At D3, all dysferlinopathic strains showed increased necrosis and inflammation, but not more CNFs; controls were unchanged. Dystrophin-null DMD(mdx) mice showed more necrosis and inflammation than all dysferlin-nulls. Torque loss and inflammation on D3 across all strains were linearly related to necrosis. Our results suggest that (1) dysferlin is not required for functional recovery 3 days after LSI; (2) B6.A/J mice recover from LSI erratically; (3) SJL/J and B10.SJL muscles recover rapidly, perhaps due to ongoing myopathy; (4) although they recover function to different levels, all 4 dysferlinopathic strains show increased inflammation and necrosis 3 days after LSI.


Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety.
For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.


Toxic effect of high concentration of sonochemically synthesized polyvinylpyrrolidone-coated silver nanoparticles on Citrobacter sp. A1 and Enterococcus sp. C1.
Currently, silver nanoparticles (AgNPs) have gained importance in various industrial applications. However, their impact upon release into the environment on microorganisms remains unclear. The aim of this study was to analyze the effect of polyvinylpyrrolidone-capped AgNPs synthesized in this laboratory on two bacterial strains isolated from the environment, Gram-negative Citrobacter sp. A1 and Gram-positive Enterococcus sp. C1. Polyvinylpyrrolidone-capped AgNPs were synthesized by ultrasound-assisted chemical reduction. Characterization of the AgNPs involved UV-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, and energy dispersive X-ray spectroscopy. Citrobacter sp. A1 and Enterococcus sp. C1 were exposed to varying concentrations of AgNPs, and cell viability was determined. Scanning electron microscopy was performed to evaluate the morphological alteration of both species upon exposure to AgNPs at 1000 mg/L. The synthesized AgNPs were spherical in shape, with an average particle size of 15 nm. The AgNPs had different but prominent effects on either Citrobacter sp. A1 or Enterococcus sp. C1. At an AgNP concentration of 1000 mg/L, Citrobacter sp. A1 retained viability for 6 hours, while Enterococcus sp. C1 retained viability only for 3 hours. Citrobacter sp. A1 appeared to be more resistant to AgNPs than Enterococcus sp. C1. The cell wall of both strains was found to be morphologically altered at that concentration. Minute and spherical AgNPs significantly affected the viability of the two bacterial strains selected from the environment. Enterococcus sp. C1 was more vulnerable to AgNPs, probably due to its cell wall architecture and the absence of silver resistance-related genes.


Community monitoring for youth violence surveillance: testing a prediction model.
Predictive epidemiology is an embryonic field that involves developing informative signatures for disorder and tracking them using surveillance methods. Through such efforts assistance can be provided to the planning and implementation of preventive interventions. Believing that certain minor crimes indicative of gang activity are informative signatures for the emergence of serious youth violence in communities, in this study we aim to predict outbreaks of violence in neighborhoods from pre-existing levels and changes in reports of minor offenses. We develop a prediction equation that uses publicly available neighborhood-level data on disorderly conduct, vandalism, and weapons violations to predict neighborhoods likely to have increases in serious violent crime. Data for this study were taken from the Chicago Police Department ClearMap reporting system, which provided data on index and non-index crimes for each of the 844 Chicago census tracts. Data were available in three month segments for a single year (fall 2009, winter, spring, and summer 2010). Predicted change in aggravated battery and overall violent crime correlated significantly with actual change. The model was evaluated by comparing alternative models using randomly selected training and test samples, producing favorable results with reference to overfitting, seasonal variation, and spatial autocorrelation. A prediction equation based on winter and spring levels of the predictors had area under the curve ranging from .65 to .71 for aggravated battery, and .58 to .69 for overall violent crime. We discuss future development of such a model and its potential usefulness in violence prevention and community policing.


Development of a short term assay for lymphoblastic transformation in man.
Blastic stimulation of lymphocytes by antigens or mitogens is usually measured by 3H-TdR labelling of DNA synthesis in 4 to 7 days. However, it has been recently shown, first in mice and guinea pigs, then in men, that it is possible to detect an earlier event by measurement of protein synthesis with 3H-Leucine in a few hours. The work presented here is devoted to determine the optimal conditions of such a short term assay in man. The technique we propose is described. Preliminary clinical results in lymphomas patients, compared to "in vitro" skin tests, are encouraging.


The structure of foot-and-mouth disease virus: implications for its physical and biological properties.
The structure of foot-and-mouth disease virus has been solved at a resolution of 2.9 A by X-ray diffraction techniques. The overall structural organisation of the particle is similar to that seen in other picornaviruses but there are several unique features. Many of these help to explain its characteristic physical and biological properties. In particular the canyon or pit found at the surface of other picornaviruses is lacking, which has important implications for cell attachment and the process of infection. Also there are 60 large disordered protrusions at the surface corresponding to the major antigenic site. This disorder is of particular interest in relation to the striking ability of linear synthetic peptides to induce protective immunity against foot-and-mouth disease.


Society of pediatric liver transplantation: Current registry status 2011-2018.
SPLIT was founded in 1995 in order to collect comprehensive prospective data on pediatric liver transplantation, including waiting list data, transplant, and early and late outcomes. Since 2011, data collection of the current registry has been refined to focus on prospective data and outcomes only after transplant to serve as a foundation for the future development of targeted clinical studies. To report the outcomes of the SPLIT registry from 2011 to 2018. This is a multicenter, cross-sectional analysis characterizing patients transplanted and enrolled in the SPLIT registry between 2011 and 2018. All patients, <18 years of age, received a first liver-only, a combined liver-kidney, or a combined liver-pancreas transplant during this study period. A total of 1911 recipients from 39 participating centers in North America were registered. Indications included biliary atresia (38.5%), metabolic disease (19.1%), tumors (11.7%), and fulminant liver failure (11.5%). Greater than 50% of recipients were transplanted as either Status 1A/1B or with a MELD/PELD exception score. Incompatible transplants were performed in 4.1%. Kaplan-Meier estimates of 1-year patient and graft survival were 97.3% and 96.6%. First 30 days of surgical complications included reoperation (31.7%), hepatic artery thrombosis (6.3%), and portal vein thrombosis (3.2%). In the first 90 days, biliary tract complications were reported in 13.6%. Acute cellular rejection during first year was 34.7%. At 1 and 2 years of follow-up, 39.2% and 50.6% had normal liver tests on monotherapy (tacrolimus or sirolimus). Further surgical, survival, allograft function, and complications are detailed.


Neurotrophin-4 is more potent than brain-derived neurotrophic factor in promoting, attracting and suppressing geniculate ganglion neurite outgrowth.
The geniculate ganglion, which provides innervation to taste buds in the anterior tongue and palate, is unique among sensory ganglia in that its neurons depend on both neurotrophin-4 (NT4) and brain-derived neurotrophic factor (BDNF) for survival. Whereas BDNF is additionally implicated in taste axon guidance at targeting stages, much less is known about the guidance role of NT4 during targeting, or about either neurotrophin during initial pathfinding. NT4 and BDNF have distinct expression patterns in vivo, raising the possibility of distinct roles. We characterized the influence of NT4 and BDNF on geniculate neurites in collagen I gels at early embryonic through postnatal stages. During early pathfinding to the tongue (embryonic days 12-13; E12-13), NT4 and BDNF promote significantly longer outgrowth than during intralingual targeting (E15-18). NT4 is more potent than BDNF at stimulating neurite outgrowth and both factors exhibit concentration optima, i.e. intermediate concentrations (0.25 ng/ml NT4 or 25 ng/ml BDNF) promote maximal neurite extension and high concentrations (10 ng/ml NT4 or 200 ng/ml BDNF) suppress it. Only partial suppression was seen at E12 (when axons first emerge from the ganglion in vivo) and postnatally, but nearly complete suppression occurred from E13 to E18. We show that cell death is not responsible for suppression. Although blocking the p75 receptor reduces outgrowth at the optimum concentrations of NT4 and BDNF, it did not reduce suppression of outgrowth. We also report that NT4, like BDNF, can act as a chemoattractant for geniculate neurites, and that the tropic influence is strongest during intralingual targeting (E15-18). NT4 does not appear to act as an attractant in vivo, but it may prevent premature invasion of the epithelium by suppressing axon growth.


Ta3N5/Co(OH)x composites as photocatalysts for photoelectrochemical water splitting.
Ta3N5 nanotubes (NTs) were obtained from nitridation of Ta2O5 NTs, which were grown directly on Ta foil through a 2-step anodization procedure. With Co(OH)x decoration, a photocurrent density as high as 2.3 mA cm-2 (1.23 V vs. NHE) was reached under AM1.5G simulated solar light; however, the electrode suffered from photocorrosion. More stable photoelectrochemical (PEC) performance was achieved by first loading Co(OH)x, followed by loading cobalt phosphate (Co-Pi) as double co-catalysts. The Co(OH)x/Co-Pi double co-catalysts may act as a hole storage layer that slows down the photocorrosion caused by the accumulated holes on the surface of the electrode. A "waggling" appearance close to the "mouth" of Ta2O5 NTs was observed, and may indicate structural instability of the "mouth" region, which breaks into segments after nitridation and forms a top layer of broken Ta3N5 NTs. A unique mesoporous structure of the walls of the Ta3N5 NTs, which is reported here the first time, is also a result of the nitridation process. We believe that the mesoporous structure makes it difficult for the nanotubes to be fully covered by the co-catalyst layer, hence rationalizing the remaining degradation by photocorrosion.


Observational analysis of feeding induced by Delta9-THC and anandamide.
Endogenous cannabinoid systems have been implicated in the physiological regulation of appetite by the ability of cannabinoid receptor agonists to induce hyperphagia. Both the exogenous cannabinoid Delta9-THC and the endocannabinoid arachidonoyl ethanolamide (anandamide) stimulate eating in rats. However, there has been no detailed analysis of the adjustments to feeding behaviour underlying this action. We used observational methods to determine the specific components of feeding affected by these compounds. Two groups (n=6) of presatiated, male, Lister hooded rats received either Delta9-THC (0, 0.5, 1.0 or 2.0 mg/kg) or anandamide (0, 1.0, 5.0 or 10.0 mg/kg sc), and their behaviour in an open field was recorded for 45 min. Behaviour (eating, drinking, rearing, grooming, sniffing, locomotion, resting/inactivity, sleeping) was continuously monitored to provide data on the latency, temporal distribution, duration and frequency of each category. Under control conditions, a minority of animals ate small quantities of lab chow, with feeding beginning only after a long latency. Both Delta9-THC and anandamide selectively stimulated feeding, with a marked reduction in latency. Apart from its rapid onset, cannabinoid-induced eating retained the normal, species-typical sequence, characteristic of untreated, free-feeding rats. Our data suggest that exogenously administered cannabinoids promote eating by increasing the incentive value of food and support a role for endocannabinoids in the regulation of the appetitive aspects of feeding motivation.


MicroRNA-155 Controls T Helper Cell Activation During Viral Infection.
MicroRNA (miR) 155 has been implicated in the regulation of innate and adaptive immunity as well as autoimmune processes. Importantly, it has been shown to regulate several antiviral responses, but its contribution to the immune response against cytopathic viruses such as vesicular stomatitis virus (VSV) infections is not known. Using transgenic/recombinant VSV expressing ovalbumin, we show that miR-155 is crucially involved in regulating the T helper cell response against this virus. Our experiments indicate that miR-155 in CD4+ T cells controls their activation, proliferation, and cytokine production in vitro and in vivo upon immunization with OVA as well as during VSV viral infection. Using intravital multiphoton microscopy we analyzed the interaction of antigen presenting cells (APCs) and T cells after OVA immunization and found impaired complex formation when using miR-155 deficient CD4+ T cells compared to wildtype CD4+ T cells ex vivo. In contrast, miR-155 was dispensable for the maturation of myeloid APCs and for their T cell stimulatory capacity. Our data provide the first evidence that miR-155 is required for efficient CD4+ T cell activation during anti-viral defense by allowing robust APC-T cell interaction required for activation and cytokine production of virus specific T cells.


Affiliative behavior, ultrasonic communication and social reward are influenced by genetic variation in adolescent mice.
Social approach is crucial for establishing relationships among individuals. In rodents, social approach has been studied primarily within the context of behavioral phenomena related to sexual reproduction, such as mating, territory defense and parental care. However, many forms of social interaction occur before the onset of reproductive maturity, which suggests that some processes underlying social approach among juvenile animals are probably distinct from those in adults. We conducted a longitudinal study of social investigation (SI) in mice from two inbred strains to assess the extent to which genetic factors influence the motivation for young mice to approach one another. Early-adolescent C57BL/6J (B6) mice, tested 4-6 days after weaning, investigated former cage mates to a greater degree than BALB/cJ (BALB) mice, irrespective of the sex composition within an interacting pair. This strain difference was not due to variation in maternal care, the phenotypic characteristics of stimulus mice or sensitivity to the length of isolation prior to testing, nor was it attributable to a general difference in appetitive motivation. Ultrasonic vocalization (USV) production was positively correlated with the SI responses of mice from both strains. Interestingly, several USV characteristics segregated with the genetic background of young mice, including a higher average frequency and shorter duration for the USVs emitted by B6 mice. An assessment of conditioned place preference responses indicated that there was a strain-dependent difference in the rewarding nature of social contact. As adolescent mice aged, SI responses gradually became less sensitive to genetic background and more responsive to the particular sex of individuals within an interacting pair. We have thus identified a specific, genetic influence on the motivation of early-adolescent mice to approach one another. Consistent with classical theories of motivation, which propose a functional relationship between behavioral approach and reward, our findings indicate that reward is a proximal mechanism through which genetic factors affect social motivation during early adolescence.


Dinuclear NHC-palladium complexes containing phosphine spacers: synthesis, X-ray structures and their catalytic activities towards the Hiyama coupling reaction.
Six dinuclear N-heterocyclic carbene (NHC) palladium complexes, [PdCl2(IMes)]2(μ-dppe) (1), [PdCl2(IPr)]2(μ-dppe) (2), [PdCl2(IMes)]2(μ-dppb) (3), [PdCl2(IPr)]2(μ-dppb) (4), [PdCl2(IMes)]2(μ-dpph) (5), and [PdCl2(IPr)]2(μ-dpph) (6) [IMes = N,N'-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene; IPr = N,N'-bis-(2,6-di(iso-propyl)phenyl)imidazol-2-ylidene; dppe = 1,2-bis(diphenylphosphino)ethane, dppb = 1,4-bis(diphenylphosphino)butane; and dpph = 1,6-bis(diphenylphosphino)hexane], have been synthesized through bridge-cleavage reactions of chloro-bridged dimeric compounds, [Pd(μ-Cl)(Cl)(NHC)]2, with the corresponding diphosphine ligands. The obtained compounds were fully characterized by (1)H NMR, (13)C NMR and (31)P NMR spectroscopy, FT-IR, elemental analysis and single-crystal X-ray crystallography. Moreover, further explorations of the catalytic potential of the dinuclear carbene palladium complexes as catalysts for the Pd-catalyzed transformations have been performed under microwave irradiation conditions, and the complexes exhibited moderate to good catalytic activity in the Hiyama coupling reaction of trimethoxyphenylsilane with aryl chlorides.


Damage to white matter pathways in subacute and chronic spatial neglect: a group study and 2 single-case studies with complete virtual "in vivo" tractography dissection.
The exact anatomical localization of right hemisphere lesions that lead to left spatial neglect is still debated. The effect of confounding factors such as acute diaschisis and hypoperfusion, visual field defects, and lesion size may account for conflicting results that have been reported in the literature. Here, we present a comprehensive anatomical investigation of the gray- and white matter lesion correlates of left spatial neglect, which was run in a sample 58 patients with subacute or chronic vascular strokes in the territory of the right middle cerebral artery. Standard voxel-based correlates confirmed the role played by lesions in the posterior parietal cortex (supramarginal gyrus, angular gyrus, and temporal-parietal junction), in the frontal cortex (frontal eye field, middle and inferior frontal gyrus), and in the underlying parietal-frontal white matter. Using a new diffusion tensor imaging-based atlas of the human brain, we were able to run, for the first time, a detailed analysis of the lesion involvement of subcortical white matter pathways. The results of this analysis revealed that, among the different pathways linking parietal with frontal areas, damage to the second branch of the superior longitudinal fasciculus (SLF II) was the best predictor of left spatial neglect. The group study also revealed a subsample of patients with neglect due to focal lesion in the lateral-dorsal portion of the thalamus, which connects the premotor cortex with the inferior parietal lobule. The relevance of fronto-parietal disconnection was further supported by complete in vivo tractography dissection of white matter pathways in 2 patients, one with and the other without signs of neglect. These 2 patients were studied both in the acute phase and 1 year after stroke and were perfectly matched for age, handedness, stroke onset, lesion size, and for cortical lesion involvement. Taken together, the results of the present study support the hypothesis that anatomical disconnections leading to a functional breakdown of parietal-frontal networks are an important pathophysiological factor leading to chronic left spatial neglect. Here, we propose that different loci of SLF disconnection on the rostro-caudal axis can also be associated with disconnection of short-range white matter pathways within the frontal or parietal areas. Such different local disconnection patterns can play a role in the important clinical variability of the neglect syndrome.


Parvalbumin in most gamma-aminobutyric acid-containing neurons of the rat cerebral cortex.
gamma-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. In the cerebral cortex, GABA-containing cells represent a subpopulation of interneurons. With semithin frozen sections, it is possible to demonstrate that most GABA neurons in the rat somatosensory cortex contain the calcium-binding protein parvalbumin and that parvalbumin is found virtually only in GABA neurons. Parvalbumin seems to influence the electrical properties and enzymatic machinery to modulate neuronal excitability and activity. The specific role of parvalbumin in GABA-containing cortical cells may be related to controlling the effectiveness of their inhibitory action.


Current and future treatment options for gonorrhoea.
The delivery of effective antimicrobial therapy is essential for public health control of gonorrhoea, in the absence of a suitable vaccine. The antimicrobial agent chosen should have high efficacy and quality, lack toxicity and give >95% success when given empirically. Guidelines, which are informed by surveillance data, are used to aid clinicians in their choice of appropriate agent. Historically, gonorrhoea treatment has been delivered as a single, directly observed dose but this has resulted in failure of successive antimicrobial agents which have been replaced by a new antimicrobial to which resistance has been rare or non-existing. Following the drift towards decreased susceptibility and treatment failure to the extended spectrum cephalosporins, and the lack of 'new' alternative antimicrobials, the threat of difficult to treat or untreatable gonorrhoea has emerged. The challenge of maintaining gonorrhoea as a treatable infection has resulted in national, regional and global response or action plans. This review discusses different approaches to the future treatment of gonorrhoea including; use of ceftriaxone, the injectable cephalosporin at increased dosage; dual antimicrobial therapy; use of drugs developed for other infections and use of older agents, directed by rapid point of care tests, to susceptible infections. Finally, it is considered whether the time is right to readdress the possibility of developing an effective gonococcal vaccine, given the major advances in our understanding of natural infection, molecular pathogenesis and the revolution in molecular biology techniques.


Development of an osteoblast-based 3D continuous-perfusion microfluidic system for drug screening.
In this work, we demonstrated that biological cells could be cultured in a continuous-perfusion glass microchip system for drug screening. We used mouse Col1a1GFP MC-3T3 E1 osteoblastic cells, which have a marker gene system expressing green fluorescent protein (GFP) under the control of osteoblast-specific promoters. With our microchip-based cell culture system, we realized automated long-term monitoring of cells and sampling of the culture supernatant system for osteoblast differentiation assay using a small number of cells. The system successfully monitored cells for 10 days. Under the 3D microchannel condition, shear stress (0.07 dyne/cm(2) at a flow rate of 0.2 microL/min) was applied to the cells and it enhanced the GFP expression and differentiation of the osteoblasts. Analysis of alkaline phosphatase (ALP), which is an enzyme marker of osteoblasts, supported the results of GFP expression. In the case of differentiation medium containing bone morphogenetic protein 2, we found that ALP activity in the culture supernatant was enhanced 10 times in the microchannel compared with the static condition in 48-well dishes. A combined system of a microchip and a cell-based sensor might allow us to monitor osteogenic differentiation easily, precisely, and noninvasively. Our system can be applied in high-throughput drug screening assay for discovering osteogenic compounds.


Pinpointing disulfide connectivities in cysteine-rich proteins.
A simple MD-based protocol is presented to accurately predict both the sequence and order of disulfide bond formation in proteins containing multiple cysteine residues. It provides a detailed description of their dynamical and structural features, which can be used to perform ensemble-averaged ECD calculations. Plant cyclotides are used as model compounds.


Thromboembolic phenomena after arthroscopic shoulder surgery.
The purpose of this study was to review a series of patients who experienced thromboembolic events after shoulder arthroscopy and attempt to identify possible risk factors or associations with thromboembolic phenomena after shoulder arthroscopy. After institutional review board approval, a retrospective database review from 2 fellowship-trained surgeons over a 5-year consecutive period was conducted to identify all patients who underwent shoulder arthroscopy (N = 1,908). Six patients were identified as sustaining thromboembolic events after shoulder arthroscopy (5 deep vein thromboses [DVTs] and 4 pulmonary embolisms [PEs]), but there were no deaths. Patient demographics (age, gender, significant medical history, and body mass index), operative detail (concomitant procedures, positioning, and DVT prophylaxis), and diagnosis and treatment of the thromboembolic events (Doppler ultrasound/chest computed tomography, hypercoagulability testing, and treatment with Coumadin [Bristol-Myers Squibb, New York, NY]) were recorded. Over a 5-year period, from 2002 to 2006, there were 6 patients known to have had thromboembolic events (5 documented DVTs and 4 PEs) after shoulder arthroscopy at the 2 institutions participating in the study. The total number of shoulder arthroscopies performed was 1,908. The mean patient age was 47 years (range, 18 to 71 years). All patients were evaluated with Doppler ultrasound, chest radiography, and chest computed tomography. Patients were treated with Coumadin, after bridging with low-molecular weight heparin. For the 5 documented DVTs, all lesions occurred on the same side as the operated extremity. There were 3 upper extremity lesions and 2 lower extremity lesions. Postoperative DVT and PE are unusual and potentially fatal consequences of arthroscopic shoulder surgery. We report a low prevalence (0.31%), but all patients in this series required hospitalization and subsequent anticoagulation. All patients who had arthroscopic shoulder surgery during this study period-those with and without thromboembolic events-were in the lateral decubitus position with arm traction. Thromboembolic complications included both ipsilateral upper and lower extremity DVTs, as well as a high percentage of PEs (4 of 6 patients). A wide age range was seen in the patients with thromboembolic complications, and 3 of the patients had known identifiable risk factors. Level IV, therapeutic case series.