Innovative educational methods and technologies applicable to continuing professional development in periodontology.
Continuous professional development (CPD) in Periodontology refers to the overall framework of opportunities that facilitate a life-long learning practice, driven by the learner-practitioner and supported by a variety of institutions and individuals. CPD must address different needs for a great diversity of practitioners. It is clear that no particular methodology or technology is able to successfully accommodate the entire spectrum of CPD in Periodontology. Course designers must choose from and combine a wide array of methodologies and technologies, depending upon the needs of the learners and the objectives of the intended education. Research suggests that 'interactivity', 'flexibility', 'continuity' and 'relevance to learners' practice' are major characteristics of successful CPD. Various methods of mentoring, peer-learning environments and work-based learning have been combined with reflective practice and self-study to form the methodological backbone of CPD courses. Blended learning encompasses a wide array of technologies and methodologies and has been successfully used in CPD courses. Internet-based content learning management systems, portable Internet devices, powerful databases and search engines, together with initiatives such as 'open access' and 'open courseware' provide an array of effective instructional and communication tools. Assessment remains a key issue in CPD, providing learners with valuable feedback and it ensures the credibility and effectiveness of the learning process. Assessment is a multi-level process using different methods for different learning outcomes, as directed by current evidence and best practices. Finally, quality assurance of the education provided must follow CPD courses at all times through a structured and credible process.


Elasmobranch bycatch in the demersal prawn trawl fishery in the Gulf of Papua, Papua New Guinea.
The elasmobranch bycatch of the Gulf of Papua Prawn Fishery is investigated in detail for the first time. Fisheries observers collected data on the elasmobranch bycatch from a total of 403 trawl sets (1,273 hrs) in the Gulf of Papua. A total of 40 species of elasmobranchs were recorded ranging in size from a 12 cm disc width stingray to a 350 cm total length sawfish. High mortality rates were recorded (>80%), attributed to the long trawl durations (up to 4 hours). The future inclusion of bycatch reduction devices would likely reduce the number of larger elasmobranchs being caught, based on evidence from the prawn trawl fisheries of northern Australia, and is being investigated by the PNG National Fisheries Authority. Differences in catch compositions were detected across the management zones as well as between the two monsoonal seasons (SE Monsoon and NW Monsoon). Increased monitoring and additional research is required and management plans should address the elasmobranch bycatch and in particular their high mortality rate.


A plasma membrane-localized small peptide is involved in rice aluminum tolerance.
A transcription factor for Al tolerance, ART1, regulates the expression of at least 30 genes in rice. Here we functionally characterized one of the downstream genes, OsCDT3, which encodes a predicted peptide of only 53 amino acid residues rich in cysteine. Knockdown of this gene resulted in decreased tolerance to Al, but did not affect the tolerance to Cd. The aluminum (Al) content in the root residues including cell wall and the plasma membrane of knockdown lines decreased, but the Al concentration in the root cell sap increased compared with those of the wild-type rice. OsCDT3 was mainly expressed in the roots and its expression was specifically induced by Al exposure, not by low pH and other metals. There was a small genotypic variation in OsCDT3 expression level, but no correlation between Al tolerance and the OsCDT3 variation was found among 17 rice cultivars. Analysis of pOsCDT3::GFP transgenic rice showed that OsCDT3 was expressed at all cells in the root tips. Transient expression of OsCDT3 fused with GFP at both N- and C-termini showed that OsCDT3 was anchored to the plasma membrane. Expression of OsCDT3 in yeast conferred tolerance to Al, but not to Cd. Furthermore, OsCDT3 did not show transport activity for Al in yeast, but was able to directly bind Al in vitro. Taken together, our results indicate that OsCDT3 anchoring to the plasma membrane may play a role in stopping entry of Al into the root cells by binding Al, therefore, contributing to high Al tolerance in rice.


Primary leukocyte screens for innate immune agonists.
The innate immune system of mammals is a key defense mechanism against invading foreign pathogens. Innate immune stimulants may have applications as vaccine adjuvants as well as in the treatment of cancer and some viral diseases, and clinical studies have been performed using agonists of Toll-like receptors (TLRs) 7, 8, and 9. The high-throughput screens for such agonists have typically relied on the overexpression of a single TLR gene in an immortalized cell line and are inherently artificial systems that are restricted to the identification of agonists for a single receptor. The authors describe 2 assays for the identification of immunostimulants that employ primary human leukocytes cocultured with hepatitis C virus (HCV) replicon-expressing cells. In these assays, stimulation of innate immune pathways in leukocytes induces interferon (IFN) expression, which acts to inhibit HCV replication, providing a high-throughput and low-cost readout for leukocyte activation. These assays are highly sensitive and provide a physiologically relevant system for the identification of a broad range of immunostimulant agents.


Expertise and the spatio-temporal characteristics of anticipatory information pick-up from complex movement patterns.
Groups of high- (n = 14), intermediate- (n = 12), and low-skilled (n = 15) cricket batsmen participated in two experiments to examine expertise-related differences in anticipatory information pick-up that combined temporal and spatial occlusion methodologies. In experiment 1 participants were shown video displays of a bowler delivering one of three different types of delivery with the display manipulated so that only selected local features of the bowler's movement pattern (bowling hand, bowling hand and arm, trunk, lower body, or whole body) were visible and then only for specific time periods prior to ball release. Only the highly-skilled players were able to produce better-than-chance predictions of ball type and then only under a limited set of display conditions. Information from bowling hand and arm cues was particularly critical although continuous visibility of these cues was apparently not essential for information pick-up. In experiment 2 the order in which particular features were made visible throughout the bowler's movement pattern was varied in an attempt to find the sequence of cues that was most favourable for effective information pick-up. The necessity in this experiment to switch vision between different features eliminated the highly-skilled players' capability to anticipate. Expert anticipation is dependent on sensitivity to information arising from a select set of local cues, and forced attentional switches between different cues negate effective information pick-up and, with it, the expert advantage.


Shark Related Injuries: A Case Series of Emergency Department Patients.
Shark-related-injuries (SRIs) are not thoroughly evaluated in the medical literature given their rare occurrence. Previous studies involve the utilization of large-independent databases and have demonstrated that shark attacks appear to be increasing, even though mortality of SRIs has decreased from 51% in 1958 to 8.3% in 2001. We performed a retrospective chart review on patients presenting to 10 emergency departments (ED) in southeastern Virginia from February 22, 2008 through December 31, 2016. We used a free-text search feature to identify patients documented to have the word "shark" in the record. We reported descriptive statistics for patient demographics, disposition, mortality, time of injury, body injury location, activity during injury, injury severity score (ISS), antibiotic use, and if the patient was in the International Shark Attack File(ISAF) or the Global Shark Attack File(GSAF). We identified 11 patients. Most patients were male (81.8%) and Caucasian (90.9%) with a mean age of 35 years old (SD = 13.4, range17-55). Most patients (72.7%) arrived to the ED by private vehicle. Seventy-eight percent of patients were safely discharged from the ED. There were no deaths. There was a bimodal distribution of the time of injury around noon and early evening. Only 1 of our patients was present in the GSAF and 4 were present in the ISAF. Most SRIs can be safely evaluated, treated, and discharged from the ED. Utilization of large databases for shark related research may underestimate its prevalence in the US. Further research is needed into the care of SRIs in the ED.


3,4-Methylenedioxy-N-methamphetamine (ecstasy) promotes the survival of fetal dopamine neurons in culture.
The current study examined whether modest concentrations of MDMA could increase the survival and/or neurite outgrowth of fetal midbrain dopamine (DA) neurons in vitro since increased DA neurite outgrowth has been previously observed in vivo from prenatal exposure. MDMA concentrations in fetal brain were quantified to determine relevant in vivo concentrations to employ in vitro. A dose response study in vitro demonstrated that MDMA, at concentrations observed in vivo, resulted in increased, DA-specific, neuron survival. Higher doses resulted in non-specific neurotoxicity. MDMA application immediately after culture establishment resulted in greater survival than delayed application, however both were superior to control. MDMA significantly increased the expression of the slc6a3 gene (dopamine transporter; DAT) in culture. Co-application of the DAT reuptake inhibitor methylphenidate (MPH) with MDMA attenuated this effect. Progressive reductions in MPH concentrations restored the MDMA-induced survival effect. This suggests that MDMA's action at DAT mediates the survival effect. Neurite density per neuron was unaffected by MDMA in vitro suggesting that MDMA promotes DA neuron survival but not neurite outgrowth in culture. Finally, animals prenatally exposed to MDMA and examined on postnatal day 35 showed an increase in tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra but not in the ventral tegmental area. These data suggest that during development, MDMA can increase the survival of DA neurons through its action at its transporter. Understanding how MDMA increases DA neuron survival may provide insight into normal DA neuron loss during development.


Studies of serum C-reactive protein in systemic lupus erythematosus.
To examine the relationship of serum C-reactive protein (CRP) levels to other indicators of disease activity during the course of systemic lupus erythematosus (SLE). In 124 patients serum CRP was measured retrospectively by ELISA and in some instances by radial immunodiffusion. Serum CRP levels were compared to laboratory, clinical, and radiographic assessments of disease activity. In many patients, serial CRP levels were measured over months or years to determine whether elevations of serum CRP reflected apparent changes in other disease activity variables. CRP was also measured in lyophilized aliquots of 24 h urine samples from SLE patients and controls with other renal disorders. Parallel determinations of interleukin 6 (IL-6) were made by ELISA in healthy controls and SLE patients. Of the 124 SLE patients studied, most showed elevations in serum CRP levels in the course of their disease. No inverse or direct correlation was noted between serum CRP and levels of nucleosome antigen or serum IgM or IgG anti-DNA antibody. In patients with renal involvement and proteinuria, CRP was often detected in 24-h urine samples. A strong correlation (p < 0.001) was noted between CRP and IL-6 levels in healthy subjects, but no correlation was recorded between serum CRP and IL-6 in SLE. Contrary to previous reports, most patients with SLE in our study showed elevations of serum CRP during the course of their illness, and extremely high serum CRP was recorded in some patients. CRP was also found in concentrated urine samples from patients with renal involvement and often paralleled elevated serum levels. In patients, no correlation was seen between CRP serum levels and serum IL-6, whereas a strong correlation between CRP level and IL-6 was recorded in healthy subjects.


Antiviral resistance testing.
Current genotypic resistance tests fail to amplify drug-resistant minority variants when they are present below 20% of the total virus population. Next-generation sequencing (NGS) addresses this issue and is being introduced into diagnostic laboratories. This review gives an overview of the resistance tests currently used and explores the opportunities and challenges that NGS genotypic resistance tests will bring. The technical challenges of NGS, such as PCR and sequence-related errors, are being addressed and various assays are currently undergoing technical validation for clinical use. Although not conclusive, the data seem to suggest that NGS will be valuable for low genetic barrier drugs and certain types of tests such as the HIV-1 tropism test. Clinical validation of the reporting and interpretation of minority variant results are essential when laboratories start reporting these results. The first wave of NGS technology is being rolled out in diagnostic laboratories. Antiviral test benefits include increased sensitivity and eventually cheaper antiviral resistance tests. There is a risk that low percentage minority variants may be over interpreted. This could result in antiviral drugs, which may have been effective, being possibly denied to patients if proper clinical validation studies are not performed.


Migration of Type III Secretion System Transcriptional Regulators Links Gene Expression to Secretion.
Many plant-pathogenic bacteria of considerable economic importance rely on type III secretion systems (T3SSs) of the Hrc-Hrp 1 family to subvert their plant hosts. T3SS gene expression is regulated through the HrpG and HrpV proteins, while secretion is controlled by the gatekeeper HrpJ. A link between the two mechanisms was so far unknown. Here, we show that a mechanistic coupling exists between the expression and secretion cascades through the direct binding of the HrpG/HrpV heterodimer, acting as a T3SS chaperone, to HrpJ. The ternary complex is docked to the cytoplasmic side of the inner bacterial membrane and orchestrates intermediate substrate secretion, without affecting early substrate secretion. The anchoring of the ternary complex to the membranes potentially keeps HrpG/HrpV away from DNA. In their multiple roles as transcriptional regulators and gatekeeper chaperones, HrpV/HrpG provide along with HrpJ potentially attractive targets for antibacterial strategies.IMPORTANCE On the basis of scientific/economic importance, Pseudomonas syringae and Erwinia amylovora are considered among the top 10 plant-pathogenic bacteria in molecular plant pathology. Both employ type III secretion systems (T3SSs) of the Hrc-Hrp 1 family to subvert their plant hosts. For Hrc-Hrp 1, no functional link was known between the key processes of T3SS gene expression and secretion. Here, we show that a mechanistic coupling exists between expression and secretion cascades, through formation of a ternary complex involving the T3SS proteins HrpG, HrpV, and HrpJ. Our results highlight the functional and structural properties of a hitherto-unknown complex which orchestrates intermediate T3SS substrate secretion and may lead to better pathogen control through novel targets for antibacterial strategies.


Periurethral gland abscess: aetiology and treatment.
To establish some characteristics of patients with periurethral gland abscess, its microbiological profile, and response to treatment. The patients were seen at the Khami Road Clinic, Bulawayo, a municipal STD referral clinic, serving an urban population. Twenty consecutive men with periurethral abscesses were studied. Demographic data and a sexual history were obtained from each patient. Aspirates from the abscess cavities and urethral swabs were collected for microbiology, and blood samples taken for syphilis and HIV serology. The patients were treated by aspiration of the abscess cavities, followed by a single injection of kanamycin 2.0 g followed by a 1 week course of oral doxycycline 100 mg twice daily. Neisseria gonorrhoeae was cultured from three aspirates and five urethral specimens. Chlamydia trachomatis was found in two aspirates and three urethral specimens. Other organisms isolated included Gram negative and anaerobic bacilli. HIV antibody was detected in 13 of 18 patients tested. The response to initial treatment was good, but the abscesses ruptured in two patients, one of whom developed a urinary fistula. One patient required treatment with an alternative antimicrobial regimen. This study demonstrated a role for N gonorrhoeae and possibly for C trachomatis in the aetiology of periurethral abscess. The prevalence of HIV infection in these patients was high. The results of treatment of periurethral abscess by aspiration of pus and followed by antimicrobial therapy covering both N gonorrhoeae and C trachomatis were acceptable.


Hemorrhagic transformation after cerebral infarction: current concepts and challenges.
Hemorrhagic transformation (HT) is a frequent complication of acute ischemic stroke that is especially common after thrombolytic therapy. The risk of HT limits the applicability of tissue plasminogen activator (tPA). Here, we sought to review the rate, classification, predictors, possible mechanism, and clinical outcomes of HT, as well as existing therapeutic approaches, in order to call attention to the current challenges in the treatment of this complication.


[Anthrax meningoencephalitis: a case report and review of Turkish literature].
The incidence of anthrax is decreasing in Turkey, however, it is still endemic in some regions of the country. Although central nervous system involvement is rare in cases with anthrax, high mortality rates are significant. Here, we report a 46-years old woman who was anthrax meningoencephalitis. The patient was from Yozgat located in Central Anatolia, Turkey. Her history revealed that following peeling the skin of sheeps and consuming their meat a week ago, a lesion developed in her left forearm and she had been treated with penicilin G with the diagnosis of cutaneous anthrax in a local health center. The patient was admitted to the emergency room of our hospital due to increased headache and loss of conciousness and diagnosed as anthrax meningitis. Crytallized penicilin G (24 MU/day IV) and vancomycin (2 g/day IV) were initiated. The macroscopy of cerebrospinal fluid (CSF) sample was haemorrhagic, white blood cell count was 40/mm3 (80% of neutrophil) and Gram staining of CSF yielded abundant gram-positive bacilli. The diagnosis was confirmed by the isolation of Bacillus anthracis from CSF culture. Although the isolate was susceptible to penicillin and dexamethasone was added to the treatment, the patient died. Review of the Turkish literature revealed seven cases of anthrax with central nervous system involvement between 1980-2008. One of the patients was an 11-years old boy and the others were adults aged between 19 and 64 years. The source of the infection was skin in four patients and inhalation in one patient. The most common findings in all of the patients were inhabitance in rural area, haemorrhagic CSF and loss of all patients despite appropriate antibiotic therapy. In conclusion, anthrax meningitis and meningoencephalitis should be considered in the differential diagnosis of haemorrhagic meningitis in areas where anthrax is endemic and high rate of mortality despite appropriate therapy should always be kept in mind.


Differential expression of CD133 based on microsatellite instability status in human colorectal cancer.
The association between the types of genomic instability and cancer stem cell (CSC) has not been elucidated. We aimed to investigate the expressions of CSC markers with respect to microsatellite instability (MSI) status in human colorectal cancer (CRC). Immunostainings for CD133, CD44, and CD166, and K-ras mutation analysis were performed on 50 MSI-high (MSI-H), and 50 microsatellite stable (MSS) CRC tissues. In 11 MSS and MSI-H CRC cell lines, CD133 expression and DNA methylation statuses of the CD133 promoter were determined. The proportion of CD133 positive cells and the ability of colosphere formation were compared between HCT116 cells and HCT116 + Chr3 cells (hMLH1-restored HCT116 cells). Immunohistochemistry for CSC markers revealed that high CD133 expression was more frequent in MSS cancers than in MSI-H (P < 0.001, 74.0% vs. 28.0%, respectively), and related with short disease-free survival. Neither CD44 nor CD166 expression differed significantly with respect to MSI status. K-ras mutation showed no association with expressions of CD133, CD44, or CD166. CD133 expression was relatively high in the MSS cell lines compared to those in MSI-H, and showed a reverse correlation with DNA methylation of the CD133 promoter. hMLH1-restored HCT116 cells increased proportions of CD133 positive cells and colosphere forming ability, compared to those in HCT116 cells. In conclusion, high levels of CD133 expression were observed more frequently in MSS CRC than in MSI-H, suggesting that differential expression of colon CSC markers may be linked to tumor characteristics dependent on MSI status.


Calcium citrate for vulvar vestibulitis. A case report.
A woman had suffered from vulvar vestibulitis (vulvodynia) for four years. Pain from the disorder had disrupted her ability to function at work and home as well as sexually. An initial full range of treatments, including multiple operations, had produced no relief. Examination of the urine for evidence of excess oxalate, which has been shown to cause epithelial reactions similar to those found in vulvodynia, showed periodic hyperoxaluria and pH elevations related to the symptoms. Calcium citrate was given to modify the oxalate crystalluria. The symptoms were significantly reduced in three months, and the patient was pain free after one year. She was able to resume normal work, family, sexual and recreational activities. Withdrawal of the calcium citrate resulted in a return of the symptoms; reinstitution alleviated them. These findings suggest that further study of individualized metabolic factors that may underlie vulvodynia is warranted.


Spatiotemporal expression of bone morphogenetic protein family ligands and receptors in the zebrafish ovary: a potential paracrine-signaling mechanism for oocyte-follicle cell communication.
The bone morphogenetic proteins (BMPs), originally identified by their abilities to induce bone and/or cartilage formation, have been reported to be involved in various growth and differentiation processes, including reproduction. Although mammalian models are more frequently used to study the BMP system in reproduction, we have extended the study to the zebrafish, an excellent model for studying female reproduction in teleosts. Reverse transcription-PCR analysis revealed the expression of the Bmp ligands (bmp2a, bmp2b, bmp4, bmp6, and bmp7a) and the type II Bmp receptors (bmpr2a and bmpr2b) in various tissues, including the ovary. Spatiotemporal distribution of these Bmp ligands and receptors in the ovary was then investigated in this study. Reverse transcription-PCR on isolated follicle layers and denuded oocytes demonstrated that all Bmp ligands examined were exclusively or abundantly expressed in the oocyte, whereas the two receptors were expressed exclusively in the follicle layers, strongly suggesting a potential paracrine signaling from the oocyte towards the follicle layer by various Bmp ligands. This supports the current view that instead of being passively controlled and nurtured by the follicle layer for its growth and development, the oocyte may play an active role by releasing various growth differentiation factors to regulate follicle layer function. Quantitative analysis of temporal expression profiles during folliculogenesis revealed an increased expression of bmp2a, bmp2b, bmp4, and bmp6 from primary growth (stage I) to previtellogenic (stage II) stages, followed by steady declines toward the end of folliculogenesis when the follicles became fully grown. On the contrast, the BMP receptors (bmpr2a and bmpr2b) consistently showed an increase in expression during folliculogenesis, with the peak levels reached at the full-grown stage prior to final oocyte maturation. The spatiotemporal expression patterns of the Bmp family in the zebrafish follicles provide important insights into potential roles for Bmps during follicle development as oocyte-derived factors. Further experiments using recombinant zebrafish Bmp4 showed that Bmp4 had an inhibitory effect on spontaneous oocyte maturation in vitro, but not 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP)-induced oocyte maturation in vitro.


The effectiveness of citalopram for idiopathic chronic fatigue.
Chronic fatigue greatly affects quality of life and is a common reason for physician visits. Patients with chronic fatigue are often treated with antidepressants. Prior to enrollment, all subjects had substantial fatigue for 6 months or more that was not explained by depression, organic illness, or lifestyle behaviors. Patients already taking an antidepressant were excluded from the study. Two designs were used. (1) Thirty-one subjects were given placebo for 1 week and then citalopram, 20 to 40 mg/day, for 2 months. Statistical testing evaluated whether fatigue (measured with the Rand Vitality Index) was reduced after citalopram was started. (2) Fatigue changes for subjects taking citalopram were compared with fatigue changes after 1 month and 2 months for 76 similar subjects taking an ineffective treatment. In design 1, fatigue for subjects taking citalopram was significantly and substantially reduced when subjects were switched from placebo to citalopram, p <.05. Benefits at 2 months were greatest for subjects who had fatigue less than 5 years, p <.01, and women, p <.01. In design 2, fatigue scores for subjects taking citalopram were not significantly better than the comparison group for all subjects but were significantly better at 2 months for subjects with less severe fatigue at baseline, p =.005, and for women, p =.08. Depression scores were not significantly better for citalopram subjects overall (p >.10) but were for certain subgroups. For all subjects, citalopram was associated with greater decrease in headaches and muscle aches at 1 month, p <.01. Citalopram may improve fatigue and symptoms associated with fatigue for some patients.


Lowered cardiac sympathetic nerve performance in response to exercise in Parkinson's disease.
We examined whether cardiac sympathetic denervation influences the cardiovascular response to exercise in Parkinson's disease (PD). Sixteen patients with PD were divided into two groups, according to their cardiac uptake of (123)I-metaiodobenzylguanidine (denervated group, 10 patients with heart to mediastinum (H/M) ratio < 1.7; innervated group, six patients with H/M ratio > 1.7) and compared changes in blood pressure (BP), heart rate (HR), and cardiac contractility with 13 control subjects during ergometric exercise stress. Velocity index (VI), an indicator of cardiac contractility, was measured using impedance cardiography and recorded every minute. Exercise began at a power output of 20 W for the first 2 min and increased 10 W every 2 min to a maximal intensity of 60 W. All control subjects accomplished the procedure while six patients with PD could not continue after the first minute of 50 W loading. There were no significant differences in BP or HR change between the three groups. However, a significant reduction in VI was observed from the first minute of the 30 W workload in the denervated group compared to the control group. This lowered response continued till 50 W loading and was significantly different to the innervated group at 50 W loading. No significant VI changes were observed between the control and innervated groups throughout the exercise test. Patients with PD with reduced MIBG uptake had a lowered cardiac contractility than innervated subjects during exercise, suggesting that this response represents the impaired exercise capacity of patients with PD with cardiac sympathetic denervation.


Atypical cortical representation of peripheral visual space in children with an autism spectrum disorder.
A key feature of early visual cortical regions is that they contain discretely organized retinotopic maps. Titration of these maps must occur through experience, and the fidelity of their spatial tuning will depend on the consistency and accuracy of the eye movement system. Anomalies in fixation patterns and the ballistics of eye movements are well documented in autism spectrum disorder (ASD), with off-center fixations a hallmark of the phenotype. We hypothesized that these atypicalities might affect the development of visuo-spatial maps and specifically that peripheral inputs might receive altered processing in ASD. Using high-density recordings of visual evoked potentials (VEPs) and a novel system-identification approach known as VESPA (visual evoked spread spectrum analysis), we assessed sensory responses to centrally and peripherally presented stimuli. Additionally, input luminance was varied to bias responsiveness to the magnocellular system, given previous suggestions of magnocellular-specific deficits in ASD. Participants were 22 ASD children (7-17 years of age) and 31 age- and performance-IQ-matched neurotypical controls. Both VEP and VESPA responses to central presentations were indistinguishable between groups. In contrast, peripheral presentations resulted in significantly greater early VEP and VESPA amplitudes in the ASD cohort. We found no evidence that anomalous enhancement was restricted to magnocellular-biased responses. The extent of peripheral response enhancement was related to the severity of stereotyped behaviors and restricted interests, cardinal symptoms of ASD. The current results point to differential visuo-spatial cortical mapping in ASD, shedding light on the consequences of peculiarities in gaze and stereotyped visual behaviors often reported by clinicians working with this population.


Cigarette smoking reduction and changes in nicotine dependence.
The relationship of nicotine dependence (ND) to smoking behavior and cessation has been well characterized. However, little is known about the association between smoking reduction (SR) and ND. We retrospectively evaluated the lifetime prevalence and extent of SR and whether ND as assessed by a modified Fagerström Test for Nicotine Dependence (FTND) score without cigarettes per day (CPD) and time-to-first cigarette changed with reductions in CPD. As part of the Collaborative Study of the Genetics of Nicotine Dependence (COGEND), 47,777 individuals from 2 mid-Western metropolitan areas were identified for a community-based telephone screening, yielding 6,955 current daily smokers ages 25-44 years (European-American, n = 5,135 and Black, n = 1,820). The FTND was administered to measure current ND and peak ND in respondents whose current daily CPD is lower than their reported lifetime peak. About 44% (n = 3,077) of the sample reported reducing their smoking from their lifetime peak, with a mean reduction of 14.4 CPD (SD = 8.9) or a 54.0% reduction compared with peak smoking. Controlling for peak smoking and years smoked, the magnitude of SR was associated with declines in ND excluding the direct contribution of CPD. Self-reported SR was associated with reduced levels of ND. The impact of this reduction on smoking cessation and health risks and smoking cessation requires further study, particularly given the retrospective nature of the present dataset.


Treatment of Depression in Patients with Concomitant Cardiac Disease.
Depressed patients are at increased risk of cardiovascular (CV) disease (CVD) and those with concomitant depression and CVD are at increased risk of death. The safety and efficacy of antidepressants in patients with CVD varies greatly between the agent used and type of disease. This review will summarize the CV adverse effect and drug interaction profile of antidepressants and discuss the use of antidepressants in CVD patients. We searched MEDLINE, PubMed, CINAHL, Web of Science, PsycINFO, and The Cochrane Library from inception to June 2014 to identify studies relevant to antidepressant use in patients with CVD. Primary references from the identified articles were also evaluated for inclusion. Descriptive analysis was performed for the included studies in this review. Orthostatic hypotension was more common with tricyclic antidepressants (TCAs), trazodone and monoamine oxidase inhibitors (MAOIs). Hypertension can be significant with serotonin norepinephrine reuptake inhibitors (SNRIs) and MAOIs. The potential for QT prolongation is present with TCAs, certain selective serotonin reuptake inhibitors (SSRIs), certain SNRIs and mirtazapine. Due to its low risk of drug-drug interactions, adverse effect profile and potential for beneficial antiplatelet activity, sertraline could be considered the choice antidepressant for patients with ischemic heart disease. SSRIs and potentially SNRIs are relatively safe and effective options for patients with heart failure. In patients at high risk for ventricular arrhythmias, bupropion has the overall lowest risk for QT prolongation. TCAs and MAOIs should be avoided in patients with concomitant CVD. In conclusion, due to the increased morbidity and mortality associated with comorbid CVD and depression, practitioners should readily assess and initiate management of depression in such patients. The choice of antidepressant should take into account the potential CV impact of the various agents balancing safety and efficacy.


Prolactin-induced expression of intercellular adhesion molecule-1 and the accumulation of monocytes/macrophages during regression of the rat corpus luteum.
Intercellular adhesion molecule-1 (ICAM-1) is thought to facilitate the recruitment and migration of monocytes/macrophages to sites of inflammation. Here we investigated whether the luteolytic effect of prolactin in the hypophysectomized rat is associated with the expression of ICAM-1. In addition, we examined the effect of exogenous testosterone (or its potential conversion to estradiol endogenously) on the corpus luteum to address recent speculation that ovarian steroids might augment luteal regression. Immature, 30-day-old rats were ovulated with eCG and hCG and then hypophysectomized; this resulted in a single cohort of persistent corpora lutea. The rats were assigned randomly into four treatment groups: vehicle treatment without or with testosterone (VEH-T4, VEH+T4) and prolactin treatment without or with testosterone (PRL-T4, PRL+T4). Corpora lutea of control rats exhibited minimal ICAM-1 staining and contained relatively few monocytes/macrophages. In contrast, corpora lutea of prolactin-treated rats exhibited prominent ICAM-1 staining and contained numerous monocytes/macrophages. Testosterone did not overtly affect ICAM-1 staining, numbers of monocytes/macrophages, or concentrations of plasma progestins (progesterone and 20alpha-dihydroprogesterone) in either VEH or prolactin treatment groups; notwithstanding, luteal weights increased significantly in response to testosterone in VEH+T4 rats compared to VEH-T4 rats and prolactin-treated rats. We conclude that ICAM-1 expression and monocyte/macrophage accumulation are associated with prolactin-induced luteal regression in the rat and that these aspects are not influenced by testosterone.


Distribution of intracortical renal blood flow induced by bumetanide in the dog.
Experiments were performed in hydropenic, anesthetized dogs to investigate the effect of two dose levels of bumetanide on sodium excretion, urinary concentration, total renal blood flow and intracortical distribution of blood flow using the radioactive microsphere technique. Intravenous administration of bumetanide (0.025 mg/kg followed by 0.025 mg/min) did not alter blood flow within the kidney. A higher dose of bumetanide (0.1 mg/kg followed by 0.1 mg/min) significantly increased total renal blood flow and lowered renal vascular resistance. The rise in renal blood flow after bumetanide was due entirely to an increase in perfusion to the midcortical and juxtamedullary regions. A transient rise in plasma renin activity was measured only after the higher dose of bumetanide. Both doses of bumetanide increased sodium excretion and depressed solute free water reabsorption, although natriuresis was greater in response to the high dose. The results indicate that higher dose levels of bumetanide can increase total renal blood flow to the inner cortex. However, changes in renal blood flow were apparently not essential for the diuretic action of bumetanide because a significant natriuresis was observed in a setting where no change in intrarenal hemodynamics could be detected.


First Report of "Candidatus Liberibacter solanacearum" on Tobacco in Honduras.
In April of 2012, tobacco (Nicotiana tabacum L.) plants with symptoms resembling those associated with viral infection were observed in commercial fields in the Department of El-Paraíso, Honduras. Symptoms on affected plants included apical leaf curling and stunting, overall chlorosis and plant stunting, young plant deformation with cabbage-like leaves, wilting, and internal vascular necrosis of stems and leaf petioles. All cultivars grown were affected, with disease incidence ranging from 5 to 80% of symptomatic plants per field. The fields were also heavily infested with the psyllid Bactericera cockerelli. This psyllid is a serious pest of solanaceous crops in the United States, Mexico, Central America, and New Zealand and has been shown to transmit the bacterium "Candidatus Liberibacter solanacearum" to potato, tomato, and other solanaceous species (2,3). Tobacco (cv. Habano criollo) plant samples were collected from one field in the municipality of Trojes. Initial testing of the plant samples for viruses, including Tobacco mosaic virus, Impatiens necrotic spot virus, Cucumber mosaic virus, and Potato virus Y, using Immunostrips (Agdia, Elkhart, IN) were negative. Total DNA was then extracted from leaf tissues of a total of 13 plants, including eight symptomatic plants and five asymptomatic plants with the cetyltrimethylammonium bromide (CTAB) buffer extraction method (2,4). The DNA samples were tested by PCR using specific PCR primer pairs OA2/OI2c and OMB 1482f/2086r, to amplify a portion of 16S rDNA and the outer membrane protein (OMB) gene of "Ca. L. solanacearum," respectively (2). All eight (100%) symptomatic plant samples were positive for "Ca. L. solanacearum" with both sets of primer pairs. "Ca. L. solanacearum" was not detected in the asymptomatic plants. The 16S rDNA and OMB gene amplicons of two plant samples each were cloned and four clones of each of the four amplicons were sequenced. BLASTn analysis of the consensus sequences confirmed "Ca. L. solanaeacrum" in the tobacco samples. The 16S rDNA consensus sequences (1,168 bp) of all amplicons were identical and showed 100% identity with several 16S rDNA sequences of "Ca. L. solanacearum" in GenBank (e.g., Accession Nos. HM245242, JF811596, and JX559779). The consensus sequence of the OMB amplicon (605 bp) showed 97 to 100% homology with a number of "Ca. L. solanacearum" OMB sequences in GenBank, including Accession Nos. CP002371, FJ914617, JN848754 and JN848752. The tobacco-associated consensus 16S rDNA and OMB sequences from this study were deposited in GenBank as Accession Nos. KC768320 and KC768328, respectively. To our knowledge, this is the first report of "Ca. L. solanacearum" associated with tobacco in Honduras, where this cash crop is economically important. This bacterium has also caused millions of dollars in losses to potato, tomato, and several other solanaceous crops in North and Central America and New Zealand, particularly in regions where B. cockerelli is present (3). Furthermore, "Ca. L. solanacearum" has caused significant economic damage to carrot crops in Europe, where it is transmitted by the psyllids Trioza apicalis in northern Europe (4) and B. trigonica in the Mediterranean region (1). References: (1) A. Alfaro-Fernandez et al. Plant Dis. 96:581, 2012. (2) J. M. Crosslin. Southwest. Entomol. 36:125, 2011. (3) J. E. Munyaneza. Am. J. Pot. Res. 89:329, 2012. (4) J. E. Munyaneza et al. J. Econ. Entomol. 103:1060, 2010.


The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and meta-analysis of randomized controlled trials.
This systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to determine the effect of melatonin supplementation on the inflammatory markers among individuals with metabolic syndrome (MetS) and related disorders. We searched the following databases up to March 2018: PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. Three reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias of included primary studies. Statistical heterogeneity was assessed using Cochran's Q test and I-square (I2) statistic. Data were pooled using the random effect model and standardized mean difference (SMD) was considered as the summary effect size. Six trials of 317 potential reports were identified to be suitable for our meta-analysis. The pooled results using random effects model indicated that melatonin supplementation significantly reduced C-reactive protein (CRP) (SMD = - 1.80; 95% CI - 3.27, - 0.32; P = 0.01; I2: 95.2) and interleukin 6 (IL-6) concentrations (SMD = - 2.02; 95% CI - 3.57, - 0.47; P = 0.01; I2: 91.2) among patients with MetS and related disorders; however, it did not affect tumor necrosis factor-α (TNF-α) concentrations (SMD = - 1.87; 95% CI - 3.81, 0.07; P = 0.05; I2: 94.4). In summary, the current meta-analysis showed the promising effect of melatonin administration on reducing CRP and IL-6, but not TNF-α levels among patients with MetS and related disorders. Additional prospective studies are recommended using higher supplementation doses and longer intervention period.


Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli.
Substitution therapies for orphan genetic diseases, including enzyme replacement methods, are frequently hampered by the limited availability of the required therapeutic substance. We describe the isolation of a pterin intermediate from bacteria that was successfully used for the therapy of a hitherto incurable and lethal disease. Molybdenum cofactor (Moco) deficiency is a pleiotropic genetic disorder characterized by the loss of the molybdenum-dependent enzymes sulphite oxidase, xanthine oxidoreductase and aldehyde oxidase due to mutations in Moco biosynthesis genes. An intermediate of this pathway-'precursor Z'-is more stable than the cofactor itself and has an identical structure in all phyla. Thus, it was overproduced in the bacterium Escherichia coli, purified and used to inject precursor Z-deficient knockout mice that display a phenotype which resembles that of the human deficiency state. Precursor Z-substituted mice reach adulthood and fertility. Biochemical analyses further suggest that the described treatment can lead to the alleviation of most symptoms associated with human Moco deficiency.


Elements upstream of the AAUAAA within the human immunodeficiency virus polyadenylation signal are required for efficient polyadenylation in vitro.
Recent in vivo studies have identified specific sequences between 56 and 93 nucleotides upstream of a polyadenylation [poly(A)] consensus sequence, AAUAAA, in human immunodeficiency virus type 1 (HIV-1) that affect the efficiency of 3'-end processing at this site (A. Valsamakis, S. Zeichner, S. Carswell, and J. C. Alwine, Proc. Natl. Acad. Sci. USA 88:2108-2112, 1991). We have used HeLa cell nuclear extracts and precursor RNAs bearing the HIV-1 poly(A) signal to study the role of upstream sequences in vitro. Precursor RNAs containing the HIV-1 AAUAAA and necessary upstream (U3 region) and downstream (U5 region) sequences directed accurate cleavage and polyadenylation in vitro. The in vitro requirement for upstream sequences was demonstrated by using deletion and linker substitution mutations. The data showed that sequences between 56 and 93 nucleotides upstream of AAUAAA, which were required for efficient polyadenylation in vivo, were also required for efficient cleavage and polyadenylation in vitro. This is the first demonstration of the function of upstream sequences in vitro. Previous in vivo studies suggested that efficient polyadenylation at the HIV-1 poly(A) signal requires a spacing of at least 250 nucleotides between the 5' cap site and the AAUAAA. Our in vitro analyses indicated that a precursor containing the defined upstream and downstream sequences was efficiently cleaved at the polyadenylation site when the distance between the 5' cap and the AAUAAA was reduced to at least 140 nucleotides, which is less than the distance predicted from in vivo studies. This cleavage was dependent on the presence of the upstream element.


TGF-beta1 causes airway fibrosis and increased collagen I and III mRNA in mice.
Subepithelial collagen and extracellular matrix protein deposition are important pathophysiological components of airway remodelling in chronic asthma. Animal models based on the local reaction to antigens show structural alterations in the airway submucosal region and provide important information regarding disease pathophysiology. We describe a murine model of peribronchial fibrosis using intratracheally instilled transforming growth factor (TGF)-beta(1) in BALB/C mice that facilitates a mechanistic approach to understanding the cellular and molecular pathways leading to airway fibrosis. BALB/C mice were intratracheally instilled with either TGF-beta(1) or buffered saline. Airway fibrosis was assessed by light microscopy, hydroxyproline content, and polymerase chain reaction (PCR) for collagen I and III on microdissected airway samples. The lysyl oxidase inhibitor beta-aminoproprionitrile (BAPN) was administered to TGF-beta(1) treated mice to block airway collagen deposition. Airway hyperresponsiveness was also measured after treatment with TGF-beta(1). During the 7 days after administration of TGF-beta(1) the mice developed increased subepithelial collagen which could be blocked by BAPN. Increased mRNAs for collagen types I and III were seen in microdissected airways 1 week after TGF-beta(1), and significantly increased total collagen was found in the airways 4 weeks after TGF-beta(1). A detectable increase in airway hyperreactivity occurred. This new model should facilitate detailed study of airway remodelling that occurs in the absence of detectable cellular inflammation, and allow examination of the functional consequences of a major structural alteration in the conducting airways uncomplicated by inflammatory cell influx.


Raman intensity enhancement of molecules adsorbed onto HfS2 flakes up to 200 layers.
Newly emerging two-dimensional transition metal dichalcogenide HfS2 has received considerable attention recently due to its ultrahigh photoresponsivity, well-balanced carrier mobility and an appropriate band gap which offer potential in electronic and optoelectronic devices. In this work, HfS2 flakes up to 200 layers with varying color contrasts are fabricated and transferred on a SiO2/Si substrate. The Raman intensities of HfS2 flakes and Raman intensities of molecules adsorbed on HfS2 flakes are quantitatively studied both theoretically and experimentally by considering an optical interference effect. The effects of the main experimental factors: thickness of SiO2 and excitation wavelength on Raman intensities are also theoretically investigated. Due to the low absorption of HfS2, many strong high-order interference-induced enhancement peaks are observed which are different from high absorption materials like graphene and MoS2, in which only 2-4 interference-induced enhancement peaks exist. Due to the environmental instability of single layer HfS2 under ambient conditions, multi-layer HfS2 is a better choice than single layer HfS2 as a Raman scattering substrate which has a stronger Raman enhancement and a better environmental stability. The discovery here will expand the application of HfS2 flakes in molecular detection.


Ascertainment, classification, and impact of neoplasm detection during prolonged treatment with dual antiplatelet therapy with prasugrel vs. clopidogrel following acute coronary syndrome.
Studies have suggested increased cancer incidence associated with long-term dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). We evaluated cancer incidence and treatment-related differences in an analysis of DAPT for ACS. The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial enrolled 9326 participants with ACS, who received aspirin plus clopidogrel or prasugrel. Median treatment exposure was 15 months. Cancer history and screening procedures were collected. Suspected non-benign neoplasm events were reported and adjudicated. The primary outcome was detection of new, non-benign neoplasm. Factors associated with neoplasm events, the relationship of these events to cardiovascular and bleeding endpoints, and treatment-related differences in neoplasm detection were studied. Among 9240 participants who received ≥1 dose of study drug, 1.8% had a confirmed neoplasm event. The efficacy composite of cardiovascular death, myocardial infarction, or stroke occurred more frequently among those with a neoplasm event vs. those without (18.2 vs. 13.5%) as did Global Use of Strategies to Open Occluded Coronary Arteries severe/moderate bleeding (11.2 vs. 1.5%). Screening rates were substantially higher in North America and Western Europe/Scandinavia vs. other regions. Factors most strongly associated with detection of neoplasm events were older age, region, male sex, and current/recent smoking. Among the pre-specified population without a history of neoplasm or previous curative treatment for neoplasm (n = 9105), the incidence of neoplasm events was similar with prasugrel vs. clopidogrel (1.8 vs. 1.7%; HR = 1.04; 95% CI 0.77-1.42; P = 0.79). Neoplasm events were infrequent during long-term DAPT after ACS, were associated with differential cancer-screening practices across regions, and the frequency of neoplasm detection was similar with prasugrel vs. clopidogrel. ClinicalTrials.gov identifier: NCT00699998.


How the baby learns to see: Donald O. Hebb Award Lecture, Canadian Society for Brain, Behaviour, and Cognitive Science, Ottawa, June 2015.
Hebb's (1949) book The Organisation of Behaviour presented a novel hypothesis about how the baby learns to see. This article summarizes the results of my research program that evaluated Hebb's hypothesis: first, by studying infants' eye movements and initial perceptual abilities and second, by studying the effect of visual deprivation (e.g., congenital cataracts) on later perceptual development. Collectively, the results support Hebb's hypothesis that the baby does indeed learn to see. Early visual experience not only drives the baby's initial scanning of objects, but also sets up the neural architecture that will come to underlie adults' perception. (PsycINFO Database Record


Dynamic mitochondrial transcription and translation in B cells control germinal center entry and lymphomagenesis.
Germinal center (GC) B cells undergo proliferation at very high rates in a hypoxic microenvironment but the cellular processes driving this are incompletely understood. Here we show that the mitochondria of GC B cells are highly dynamic, with significantly upregulated transcription and translation rates associated with the activity of transcription factor A, mitochondrial (TFAM). TFAM, while also necessary for normal B cell development, is required for entry of activated GC precursor B cells into the germinal center reaction; deletion of Tfam significantly impairs GC formation, function and output. Loss of TFAM in B cells compromises the actin cytoskeleton and impairs cellular motility of GC B cells in response to chemokine signaling, leading to their spatial disorganization. We show that B cell lymphoma substantially increases mitochondrial translation and that deletion of Tfam in B cells is protective against the development of lymphoma in a c-Myc transgenic mouse model. Finally, we show that pharmacological inhibition of mitochondrial transcription and translation inhibits growth of GC-derived human lymphoma cells and induces similar defects in the actin cytoskeleton.


Synthetic torso for training in and evaluation of urologic laparoscopic skills.
The expanding use of advanced minimally invasive surgical techniques demands more advanced training methods, objective measures of resident performance, and more realistic and anatomically correct training models. A new synthetic torso for urologic laparoscopy training was developed and assessed. The trainer, Lapman, was based on the Visible Human Model and has the exact shape of a human torso. The torso models the outer shape of the body and the abdominal and pulmonary cavities. Animal or synthetic models of the abdominal organs may be placed in the abdominal cavity. An abdominal wall provides access and seals the cavity and can be replaced after repeated punctures with laparoscopic instruments. The thoracic cavity connects to a pneumatic pump to simulate breathing. In order to render realistic mechanic properties, the torso is cast of materials with elastic properties similar to those of soft tissue and incorporates a synthetic skeleton. These similar mechanical properties and the thoracic insufflation create realistic ventilatory motion simulation. Twenty-five individuals--medical students, residents, and attending urologists--participated in a study comparing Lapman with a standard training box. Lapman presented several advantages over the traditional training box, specifically with regard to internal and external views and the incorporation of a realistically shaped abdominal wall. A significant and recurrent theme was the value of the synthetic wall as a tool to gain a greater appreciation of the importance of port placement. Study participants at all levels of training appreciated that Lapman gives a more realistic approximation of the operative procedure. The novelty of the trainer consists in its anatomic shape, realistic mechanical properties, and ventilatory simulation. This paper reports on its design, construction, and preliminary tests.


Habitat restoration promotes pollinator persistence and colonization in intensively managed agriculture.
Widespread evidence of pollinator declines has led to policies supporting habitat restoration including in agricultural landscapes. Yet, little is yet known about the effectiveness of these restoration techniques for promoting stable populations and communities of pollinators, especially in intensively managed agricultural landscapes. Introducing floral resources, such as flowering hedgerows, to enhance intensively cultivated agricultural landscapes is known to increase the abundances of native insect pollinators in and around restored areas. Whether this is a result of local short-term concentration at flowers or indicative of true increases in the persistence and species richness of these communities remains unclear. It is also unknown whether this practice supports species of conservation concern (e.g., those with more specialized dietary requirements). Analyzing occupancies of native bees and syrphid flies from 330 surveys across 15 sites over eight years, we found that hedgerow restoration promotes rates of between-season persistence and colonization as compared with unrestored field edges. Enhanced persistence and colonization, in turn, led to the formation of more species-rich communities. We also find that hedgerows benefit floral resource specialists more than generalists, emphasizing the value of this restoration technique for conservation in agricultural landscapes.


Beating the superparamagnetic limit with exchange bias.
Interest in magnetic nanoparticles has increased in the past few years by virtue of their potential for applications in fields such as ultrahigh-density recording and medicine. Most applications rely on the magnetic order of the nanoparticles being stable with time. However, with decreasing particle size the magnetic anisotropy energy per particle responsible for holding the magnetic moment along certain directions becomes comparable to the thermal energy. When this happens, the thermal fluctuations induce random flipping of the magnetic moment with time, and the nanoparticles lose their stable magnetic order and become superparamagnetic. Thus, the demand for further miniaturization comes into conflict with the superparamagnetism caused by the reduction of the anisotropy energy per particle: this constitutes the so-called 'superparamagnetic limit' in recording media. Here we show that magnetic exchange coupling induced at the interface between ferromagnetic and antiferromagnetic systems can provide an extra source of anisotropy, leading to magnetization stability. We demonstrate this principle for ferromagnetic cobalt nanoparticles of about 4 nm in diameter that are embedded in either a paramagnetic or an antiferromagnetic matrix. Whereas the cobalt cores lose their magnetic moment at 10 K in the first system, they remain ferromagnetic up to about 290 K in the second. This behaviour is ascribed to the specific way ferromagnetic nanoparticles couple to an antiferromagnetic matrix.


Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation.
N-methyl-d-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B receptor in the absence or presence of the GluN2B-specific allosteric modulator Ro 25-6981 (Ro), determined by cryogenic electron microscopy (cryo-EM). In the absence of Ro, the GluN2A and GluN2B amino-terminal domains (ATDs) adopt "closed" and "open" clefts, respectively. Upon binding Ro, the GluN2B ATD clamshell transitions from an open to a closed conformation. Consistent with a predominance of the GluN2A subunit in ion channel gating, the GluN2A subunit interacts more extensively with GluN1 subunits throughout the receptor, in comparison with the GluN2B subunit. Differences in the conformation of the pseudo-2-fold-related GluN1 subunits further reflect receptor asymmetry. The triheteromeric NMDAR structures provide the first view of the most common NMDA receptor assembly and show how incorporation of two different GluN2 subunits modifies receptor symmetry and subunit interactions, allowing each subunit to uniquely influence receptor structure and function, thus increasing receptor complexity.


The geographical distribution and prevalence of Echinococcus multilocularis in animals in the European Union and adjacent countries: a systematic review and meta-analysis.
This study aimed to provide a systematic review on the geographical distribution of Echinococcus multilocularis in definitive and intermediate hosts in the European Union (EU) and adjacent countries (AC). The relative importance of the different host species in the life-cycle of this parasite was highlighted and gaps in our knowledge regarding these hosts were identified. Six databases were searched for primary research studies published from 1900 to 2015. From a total of 2,805 identified scientific papers, 244 publications were used for meta-analyses. Studies in 21 countries reported the presence of E. multilocularis in red foxes, with the following pooled prevalence (PP): low (≤ 1 %; Denmark, Slovenia and Sweden); medium (> 1 % to < 10 %; Austria, Belgium, Croatia, Hungary, Italy, the Netherlands, Romania and the Ukraine); and high (> 10 %; Czech Republic, Estonia, France, Germany, Latvia, Lithuania, Poland, Slovakia, Liechtenstein and Switzerland). Studies from Finland, Ireland, the United Kingdom and Norway reported the absence of E. multilocularis in red foxes. However, E. multilocularis was detected in Arctic foxes from the Arctic Archipelago of Svalbard in Norway. Raccoon dogs (PP 2.2 %), golden jackals (PP 4.7 %) and wolves (PP 1.4 %) showed a higher E. multilocularis PP than dogs (PP 0.3 %) and cats (PP 0.5 %). High E. multilocularis PP in raccoon dogs and golden jackals correlated with high PP in foxes. For intermediate hosts (IHs), muskrats (PP 4.2 %) and arvicolids (PP 6.0 %) showed similar E. multilocularis PP as sylvatic definitive hosts (DHs), excluding foxes. Nutrias (PP 1.0 %) and murids (PP 1.1 %) could play a role in the life-cycle of E. multilocularis in areas with medium to high PP in red foxes. In areas with low PP in foxes, no other DH was found infected with E. multilocularis. When fox E. multilocularis PP was >3 %, raccoon dogs and golden jackals could play a similar role as foxes. In areas with high E. multilocularis fox PP, the wolf emerged as a potentially important DH. Dogs and cats could be irrelevant in the life-cycle of the parasite in Europe, although dogs could be important for parasite introduction into non-endemic areas. Muskrats and arvicolids are important IHs. Swine, insectivores, murids and nutrias seem to play a minor or no role in the life-cycle of the parasite within the EU and ACs.


Practical example of the correction of Fourier-transform spectra for detector nonlinearity.
HgCdTe photoconductive detectors can display a nonlinear response when illuminated. In interferometric applications, this behavior must be accounted for in the data transformation process to avoid errors in the measurement of the spectral distribution of the incident radiation. A model for the distortion of the interferogram is proposed and applied to solar observations made by the Atmospheric Trace Molecule Spectroscopy (ATMOS) Fourier-transform spectrometer during orbital sunrise and sunset from the Space Shuttle. Empirical estimation of the dc current level is necessary for this instrument, and satisfactory nonlinearity correction is obtained for several of the primary ATMOS optical filters. For ATMOS broadband optical filters that cover more than one half the alias bandwidth, the model is inadequate because of the presence of antialiasing electronic filters within the instrument, and it is necessary to resort to estimation and subtraction of the residual baseline offset. In either case the remaining base line offsets are typically smaller than 1%, which is satisfactory, although offset remains a significant systematic source of error in the estimation of the abundance of telluric and solar constituents from the spectra.


Folate status and health: challenges and opportunities.
Each year approximately 2400 pregnancies develop folic acid-preventable spina bifida and anencephaly in Europe. Currently, 70% of all affected pregnancies are terminated after prenatal diagnosis. The prevalence of neural tube defects (NTDs) has been significantly lowered in more than 70 countries worldwide by applying fortification with folic acid. Periconceptional supplementation of folic acid also reduces the risk of congenital heart diseases, preterm birth, low birth weight, and health problems associated with child mortality and morbidity. All European governments failed to issue folic acid fortification of centrally processed and widely eaten foods in order to prevent NTDs and other unwanted birth outcomes. The estimated average dietary intake of folate in Germany is 200 μg dietary folate equivalents (DFE)/day. More than half of German women of reproductive age do not consume sufficient dietary folate to achieve optimal serum or red blood cell folate concentrations (>18 or 1000 nmol/L, respectively) necessary to prevent spina bifida and anencephaly. To date, targeted supplementation is recommended in Europe, but this approach failed to reduce the rate of NTDs during the last 10 years. Public health centers for prenatal care and fortification with folic acid in Europe are urgently needed. Only such an action will sufficiently improve folate status, prevent at least 50% of the NTD cases, reduce child mortality and morbidity, and alleviate other health problems associated with low folate such as anemia.


Effect of information and telephone-guided access to community support for people with chronic kidney disease: randomised controlled trial.
Implementation of self-management support in traditional primary care settings has proved difficult, encouraging the development of alternative models which actively link to community resources. Chronic kidney disease (CKD) is a common condition usually diagnosed in the presence of other co-morbidities. This trial aimed to determine the effectiveness of an intervention to provide information and telephone-guided access to community support versus usual care for patients with stage 3 CKD. In a pragmatic, two-arm, patient level randomised controlled trial 436 patients with a diagnosis of stage 3 CKD were recruited from 24 general practices in Greater Manchester. Patients were randomised to intervention (215) or usual care (221). Primary outcome measures were health related quality of life (EQ-5D health questionnaire), blood pressure control, and positive and active engagement in life (heiQ) at 6 months. At 6 months, mean health related quality of life was significantly higher for the intervention group (adjusted mean difference = 0.05; 95% CI = 0.01, 0.08) and blood pressure was controlled for a significantly greater proportion of patients in the intervention group (adjusted odds-ratio = 1.85; 95% CI = 1.25, 2.72). Patients did not differ significantly in positive and active engagement in life. The intervention group reported a reduction in costs compared with control. An intervention to provide tailored information and telephone-guided access to community resources was associated with modest but significant improvements in health related quality of life and better maintenance of blood pressure control for patients with stage 3 CKD compared with usual care. However, further research is required to identify the mechanisms of action of the intervention. Controlled-Trials.com ISRCTN45433299.


Timing and sequence of brain activity in top-down control of visual-spatial attention.
Recent brain imaging studies using functional magnetic resonance imaging (fMRI) have implicated a frontal-parietal network in the top-down control of attention. However, little is known about the timing and sequence of activations within this network. To investigate these timing questions, we used event-related electrical brain potentials (ERPs) and a specially designed visual-spatial attentional-cueing paradigm, which were applied as part of a multi-methodological approach that included a closely corresponding event-related fMRI study using an identical paradigm. In the first 400 ms post cue, attention-directing and control cues elicited similar general cue-processing activity, corresponding to the more lateral subregions of the frontal-parietal network identified with the fMRI. Following this, the attention-directing cues elicited a sustained negative-polarity brain wave that was absent for control cues. This activity could be linked to the more medial frontal-parietal subregions similarly identified in the fMRI as specifically involved in attentional orienting. Critically, both the scalp ERPs and the fMRI-seeded source modeling for this orienting-related activity indicated an earlier onset of frontal versus parietal contribution ( approximately 400 versus approximately 700 ms). This was then followed ( approximately 800-900 ms) by pretarget biasing activity in the region-specific visual-sensory occipital cortex. These results indicate an activation sequence of key components of the attentional-control brain network, providing insight into their functional roles. More specifically, these results suggest that voluntary attentional orienting is initiated by medial portions of frontal cortex, which then recruit medial parietal areas. Together, these areas then implement biasing of region-specific visual-sensory cortex to facilitate the processing of upcoming visual stimuli.


Surgical Correction of Diplopia in Orbital Fracture: Influence of Material and Design.
The purpose of this study is to compare the association of diplopia after orbital fracture repair using titanium mesh and high-density polyethylene-coated titanium mesh. Retrospective review of records of consecutive patients who presented for primary/secondary correction of orbital fracture attending author's institute was done. Patients attending the institution between January 2013 and December 2017 (5 years' period) fulfilling the inclusion and exclusion criteria were included for this study. In all, 44 patients, who fulfilled the inclusion and exclusion criteria, were included in the study. The mean age was 31.86 ± 9.1 years and the mean period of follow-up was 9.37 ± 2.1 months postoperatively, with a range of 6.5-24 months. There were 65.91% males, and the most common etiology was road traffic accident (50%). In all, 11 (25%) cases had postoperative diplopia. Of the 11 cases that had diplopia, 6 had Class 1 and 5 had Class 2 diplopia. Of these 11 cases, 8 cases had completion or partial resolution of diplopia by the end of 8 weeks' period, and in 3 cases, it persisted even after 3 months of care. The occurrence of diplopia was compared by demographic factor using Chi-square test, and the mesh type was only statistically significant (P = 0.026). The present study indicates that both types of mesh provide reliable, clinically better results. However, with passage of time, it was clinically observed that removing uncoated mesh poses extreme difficulty by the adherences and growth penetrating the meshes. In certain instances, clinically, it was observed that such adhesions may be a cause of compromise of eyeball movement. Noncoated titanium orbital implants may lead to the adherence of orbital and periorbital structures, resulting in restrictive diplopia. High-density polyethylene-coated titanium mesh shows better performance as compared to noncoated mesh in preventing adherence situations.


Climate change and the optimal arrival of migratory birds.
Recent climate change has sparked an interest in the timing of biological events, which is a general problem in life-history evolution. Reproduction in many organisms breeding in seasonal environments, e.g. migratory birds, is dependent on the exploitation of a short but rich food supply. If the seasonal timing of the food peak advances owing to climate change, then one would expect the bird to track those changes, hence, initiate migration and breeding earlier. However, when there is competition for territories and a risk of pre-breeding mortality, the optimal response to a shifting food distribution is no longer obvious. We develop a theoretical model to study how the optimal arrival time depends on the mean and variance of the food distribution, the degree of competition for territories and the risk of mortality. In general, the optimal shift in arrival date should never be as extreme as the shift in food peak date. Our results also show that we should expect the high variation of trends in arrival date observed among migratory birds, even if migration and information about climate change were unconstrained.


Duration of first admission and its relation to the readmission rate in a psychiatry hospital.
Most psychiatric illnesses have a chronic relapsing course. It is estimated that the readmission rate for discharged patients is approximately 40-50% within one year of their discharge from the hospital. The current emphasis in mental health service is on brief hospitalization and providing community-based services. To understand the relationship between the duration of first hospital admission and the rates of readmission in a psychiatry hospital. All the patients admitted at Asha hospital, Hyderabad for the first time between16 September, 2003 to 15 March, 2004, were included in the study. The hospital records of these patients were examined and the data was collected on various variables, which included demographic variables, duration of hospital stay, diagnosis, and the number of readmissions for a period of approximately three-and-a-half years. The duration of the first hospital stay was divided into four categories, Group 1:1-7 days, Group 2:8 to 14 days, Group 3:15 to 30 days, and Group 4: More than 30 days. The sample consisted of 516 patients, out of whom 17 were excluded because of insufficient data. Two hundred and fifty patients belonged to Group 1 (1 to 7 days), 206 patients in Group 2 (8 to 14 days), Group 3 (15 to 30 days) constituted 35 patients, and eight patients were in Group 4 ( > 30 days). The length of the initial hospital stay is important to prevent future hospitalization. There are no definite predictors for readmission that could be detected, except for the length of the initial admission in the study.


Structure of the Human cGAS-DNA Complex Reveals Enhanced Control of Immune Surveillance.
Cyclic GMP-AMP synthase (cGAS) recognition of cytosolic DNA is critical for immune responses to pathogen replication, cellular stress, and cancer. Existing structures of the mouse cGAS-DNA complex provide a model for enzyme activation but do not explain why human cGAS exhibits severely reduced levels of cyclic GMP-AMP (cGAMP) synthesis compared to other mammals. Here, we discover that enhanced DNA-length specificity restrains human cGAS activation. Using reconstitution of cGAMP signaling in bacteria, we mapped the determinant of human cGAS regulation to two amino acid substitutions in the DNA-binding surface. Human-specific substitutions are necessary and sufficient to direct preferential detection of long DNA. Crystal structures reveal why removal of human substitutions relaxes DNA-length specificity and explain how human-specific DNA interactions favor cGAS oligomerization. These results define how DNA-sensing in humans adapted for enhanced specificity and provide a model of the active human cGAS-DNA complex to enable structure-guided design of cGAS therapeutics.


Relative abilities of young sheep and goats to self-medicate with tannin-rich sainfoin when infected with gastrointestinal nematodes.
Plant secondary metabolites (PSM) are one of the promising options to control gastrointestinal nematodes in sheep and goats. The objective of this study was to assess the abilities of sheep and goats to self-medicate with tannin-rich sainfoin (Onobrychis viciifolia) (SF) when infected with gastrointestinal nematodes, using a cafeteria and an operant conditioning trial. Hypotheses were that parasitized (P) lambs and goat kids would show greater intake and preference for SF than their non-parasitized (NP) counterparts, that kids would eat more SF than lambs (due to their lower resistance against parasites and their greater ability to consume PSM), and that SF intake would increase over time for P animals. We used 20 female kids and 20 ewe lambs aged 3 months. Half of the animals per species (n = 10) were experimentally infected with 170 L3 larvae of Haemonchus contortus/kg of BW (P). The other half were free from parasites throughout the study (NP). Five weeks after infection, animals were exposed to a 24-day cafeteria trial (three 8-day periods) offering a free choice between two legume pellets: SF (3.8% condensed tannins) and alfalfa (ALF, Medicago sativa; no tannin). Subsequently, animals were involved in an operant conditioning trial of two 4-day long sessions, to assess in short-term tests their motivation to walk for a SF reward when offered in choice with freely available ALF. In the cafeteria trial, SF preference was greater in kids than in lambs, particularly in the first two periods. We did not observe a greater preference for SF in P animals, which was even greater in NP animals for periods 1 and 2. Sainfoin intake increased through periods for P animals, which led to similar SF preferences for all groups during period 3. In the operant-conditioning trial, motivation to get the SF reward was similar between P and NP animals. These results support the hypotheses that goats are more willing to consume tanniferous feeds than sheep, and that P animals increased SF intake through time. However, the emergence of a curative self-medicative behaviour was not supported, as P individuals did not show greater SF intake, preference, nor a greater motivation to get SF than NP animals, regardless of animal species. These findings are discussed with previous results and some explanations are presented.


EZSCAN for undiagnosed type 2 diabetes mellitus: A systematic review and meta-analysis.
The EZSCAN is a non-invasive device that, by evaluating sweat gland function, may detect subjects with type 2 diabetes mellitus (T2DM). The aim of the study was to conduct a systematic review and meta-analysis including studies assessing the performance of the EZSCAN for detecting cases of undiagnosed T2DM. We searched for observational studies including diagnostic accuracy and performance results assessing EZSCAN for detecting cases of undiagnosed T2DM. OVID (Medline, Embase, Global Health), CINAHL and SCOPUS databases, plus secondary resources, were searched until March 29, 2017. The following keywords were utilized for the systematic searching: type 2 diabetes mellitus, hyperglycemia, EZSCAN, SUDOSCAN, and sudomotor function. Two investigators extracted the information for meta-analysis and assessed the quality of the data using the Revised Version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Pooled estimates were obtained by fitting the logistic-normal random-effects model without covariates but random intercepts and using the Freeman-Tukey Arcsine Transformation to stabilize variances. Heterogeneity was also assessed using the I2 measure. Four studies (n = 7,720) were included, three of them used oral glucose tolerance test as the gold standard. Using Hierarchical Summary Receiver Operating Characteristic model, summary sensitivity was 72.0% (95%CI: 60.0%- 83.0%), whereas specificity was 56.0% (95%CI: 38.0%- 74.0%). Studies were very heterogeneous (I2 for sensitivity: 79.2% and for specificity: 99.1%) regarding the inclusion criteria and bias was present mainly due to participants selection. The sensitivity of EZSCAN for detecting cases of undiagnosed T2DM seems to be acceptable, but evidence of high heterogeneity and participant selection bias was detected in most of the studies included. More studies are needed to evaluate the performance of the EZSCAN for undiagnosed T2DM screening, especially at the population level.


A novel role of the interferon-inducible protein IFI16 as inducer of proinflammatory molecules in endothelial cells.
The human IFI16 gene is an interferon-inducible gene implicated in the regulation of endothelial cell proliferation and tube morphogenesis. Immunohistochemical analysis has demonstrated that this gene is highly expressed in endothelial cells in addition to hematopoietic tissues. In this study, gene array analysis of human umbilical vein endothelial cells overexpressing IFI16 revealed an increased expression of genes involved in immunomodulation, cell growth, and apoptosis. Consistent with these observations, IFI16 triggered expression of adhesion molecules such as ICAM-1 and E-selectin or chemokines such as interleukin-8 or MCP-1. Treatment of cells with short hairpin RNA targeting IFI16 significantly inhibited ICAM-1 induction by interferon (IFN)-gamma demonstrating that IFI16 is required for proinflammatory gene stimulation. Moreover, functional analysis of the ICAM-1 promoter by deletion- or site-specific mutation demonstrated that NF-kappaB is the main mediator of IFI16-driven gene induction. NF-kappaB activation appears to be triggered by IFI16 through a novel mechanism involving suppression of IkappaBalpha mRNA and protein expression. Support for this finding comes from the observation that IFI16 targeting with specific short hairpin RNA down-regulates NF-kappaB binding activity to its cognate DNA and inhibits ICAM-1 expression induced by IFN-gamma. Using transient transfection and luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation, we demonstrate indeed that activation of the NF-kappaB response is mediated by IFI16-induced block of Sp1-like factor recruitment to the promoter of the IkappaBalpha gene, encoding the main NF-kappaB inhibitor. Activation of NF-kappaB accompanied by induction of proinflammatory molecules was also observed when IkappaBalpha expression was down-regulated by specific small interfering RNA, resulting in an outcome similar to that observed with IFI16 overexpression. Taken together, these data implicate IFI16 as a novel regulator of endothelial proinflammatory activity and provide new insights into the physiological functions of the IFN-inducible gene IFI16.


Alcohol policies and highway vehicle fatalities.
This study investigates the impact of beer taxes and a variety of alcohol-control policies on motor vehicle fatality rates. Special attention is paid to omitted variables biases resulting from failing to adequately control for grassroots efforts to reduce drunk driving, the enactment of other laws which simultaneously operate to reduce highway fatalities, and the economic conditions existing at the time the legislation is passed. In the preferred models, most of the regulations have little or no impact on traffic mortality. By contrast, higher beer taxes are associated with reductions in crash deaths and this result is relatively robust across specifications.


Trephine epilepsy surgery: the inferior temporal gyrus approach.
To describe our technique for temporal lobe epilepsy surgery using a minimal-access approach. Our epilepsy surgery registry was reviewed, and all patients with at least 2 years follow-up were queried. Clinical data included age, sex, side of lesion, presence of mesial temporal sclerosis, surgical complications, and Engel class outcome. Our operation was performed through a 6- to 8-cm linear vertical incision extending upward from just anterior to the tragus. An oval trephine (2 x 3 cm) craniotomy was performed flush with the middle fossa floor. Resection of part of the inferior temporal gyrus provided a corridor to the mesial temporal lobe. Identification of the temporal horn of the lateral ventricle was followed by resection of the parahippocampal gyrus, the amygdala, and the uncus. Segregation of the hippocampus and its subsequent resection in subpial fashion preserved perimesencephalic vasculature. Use of a fine suture for skin closure produced a cosmetic result. In our 8-year series of 201 patients with a minimum follow-up duration of 2 years, we have observed a low number (1.5%) of complications and a 78% rate of Engel Class I seizure-free outcome. Surgery times were short (average, 2-5 h; range, 2 h 20 min-4 h 10 min) and hospital stays brief (<3 d; range, 1-4 d). Our results suggest that the trephine craniotomy with the inferior temporal gyrus approach has the advantage of minimal invasiveness, including brief operative times and postoperative stays, and also effectively reduces or eradicates medically intractable seizures.


Mesophase structure and behaviour in bulk and restricted geometry of a dimeric compound exhibiting a nematic-nematic transition.
We present structural studies of a dimeric compound composed of a central heptyl spacer linking two mesogens consisting of terphenyl units at which two adjacent fluoro groups are attached to each central ring. The terminal rings are linked to pentyl chains as terminal groups. The material exhibits a nematic-nematic transition and a low temperature modulated phase. The higher temperature nematic phase was found to exhibit an anomaly of the bend elastic constant similar to that of the dimers with N-Ntb phase sequence, and the physical properties of the low-temperature nematic phase are similar to those of the known Ntb materials. The structure of the low-temperature modulated smectic/columnar phase is described together with its ability to form freely suspended films and fibres. The relation of the modulated structure to the fibre formation and to the appearance of the labyrinthine instability in freely-suspended films is discussed.


Eicosapentaenoic Acid as a Potential Therapeutic Approach to Reduce Cardiovascular Risk in Patients with End-Stage Renal Disease on Hemodialysis: A Review.
Patients with end-stage renal disease on hemodialysis have excess cardiovascular disease (CVD) burden with substantially increased CV event rates compared with the general population. Traditional interventions that, according to standard clinical guidelines, reduce CV risk such as antihypertensive therapy, diet, exercise, and statins are not similarly effective in the hemodialysis population. This raises the question of whether additional risk factors, such as enhanced inflammation and oxidative stress, may drive the increased CVD burden in hemodialysis patients. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into the atherosclerotic plaque as well as membrane phospholipid bilayers and produces beneficial effects on inflammatory and oxidative mechanisms involved in atherosclerotic plaque formation and progression. EPA levels and the ratio of EPA to the omega-6 polyunsaturated fatty acid arachidonic acid (AA) are reduced in hemodialysis patients. Serum EPA levels have been inversely correlated with proinflammatory cytokines, and the EPA/AA ratio has been inversely associated with CV events in hemodialysis cohorts. Three recent studies involving over 800 hemodialysis patients and follow-up of 2-3 years suggest that EPA therapy may improve clinical outcomes in this patient population as evidenced by significant reductions in cardiovascular mortality, all-cause mortality, and/or CV events. Further studies with high-purity EPA are warranted in patients on hemodialysis, especially given the fact that other interventions including antihypertensives, diet, exercise, and statins have not provided meaningful benefit.


Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer.
Efforts to reduce the late toxicity associated with chemoradiation (CRT) for locally advanced head and neck squamous cell cancer (LA-HNSCC) have focused on radiotherapy (RT) dose de-escalation. In this phase I/II protocol investigating the addition of everolimus to induction chemotherapy (IC), we incorporated a novel response-adapted volume de-escalation (RAVD) approach using IC response to guide the extent of RT volume reduction. Patients with measurable LA-HNSCC received two cycles of IC (cisplatin, paclitaxel, cetuximab ± everolimus). Patients with ≥50% reduction in the sum of tumor diameters [good response (GR)] received TFHX (paclitaxel, fluorouracil, hydroxyurea, and 1.5 Gy twice daily RT every other week) to a dose of 75 Gy with the single planning target volume (PTV1) encompassing exclusively gross disease. Patients with <50% response [non-response (NR)] were treated with TFHX encompassing PTV1 and the next nodal station at risk (PTV2) to a dose of 45 Gy followed by a sequential boost to PTV1 to a dose of 75 Gy. Ninety-four patients were enrolled. Randomization to everolimus was discontinued on interim analysis after 50 patients due to futility. IC response was evaluable in 89 patients. Thirty-seven patients (41.6%) had GR and 52 (58.4%) had NR. There was a trend for improved progression-free (P = 0.086) but not overall survival (P = 0.94) for GR versus NR. The 2-year PFS and OS were 86.0% and 83.5% for GR and 68.7% and 85.4% for NR, respectively. NR were significantly more likely to undergo G-tube placement during treatment (50.0% GR versus 73.5% NR, P = 0.040) and be G-tube dependent at 6-month follow-up (5.7% GR versus 32.6% NR, P = 0.005). The addition of everolimus to IC was not beneficial. The elimination of elective nodal coverage in patients with GR to IC did not appear to compromise outcomes and resulted in significantly decreased late toxicity. Further investigation of RAVD is warranted. NCT01133678.


Gender Differences in Food Choice: Effects of Superior Temporal Sulcus Stimulation.
The easy availability of food has caused a shift from eating for survival to hedonic eating. Women, compared to men, have shown to respond differently to food cues in the environment on a behavioral and a neural level, in particular to energy rich (compared to low energy) foods. It has been demonstrated that the right posterior superior temporal sulcus (STS) is the only region exhibiting greater activation for high vs. low calorie food choices. In order to test for a possible causal role of STS in food choice, we applied high frequency transcranial random noise stimulation (tRNS) on STS assuming a different response pattern between males and females. Our participants (18 females, 17 males) performed a forced choice task between food pairs matched for individual liking but differed in calorie, during the left STS, right STS stimulation and sham condition. Male participants showed a general preference for low calorie (LC) foods compared to females. In addition, we observed in males, but not in females, an increase of high calorie (HC) food choice during right STS tRNS compared to sham condition and left STS tRNS. Finally, we found an increase of missed choices during right STS stimulation compared to sham condition and left STS stimulation. In conclusion, thanks to tRNS evidence, we both confirm the involvement and suggest a causal role of right posterior STS in feeding behavior. Moreover, we suggest that gender differences exist in STS mechanisms underlying food choice.


The perceived effects of parent-led support groups for parents of children with disabilities.
Parent-led support groups for parents who have children with disabilities are voluntary organizations with goals to provide social support and information and to foster advocacy. The purpose of this study was to explore parents' perceptions of the effect of parent-led support groups in providing parents with support and knowledge and in improving parents' ability to deal with childhood disability issues. Qualitative methods were used to examine the experiences of members of nine parent-run support groups. From these groups, 20 parents were interviewed about the benefits and limitations of participation in support group. Information was also collected by observing support group meetings and reviewing group documents. Interview, observation, and document data were analysed to identify emerging themes. Results of the study indicated that the effects of belonging to a parent-led parent support group were substantial. Through these groups, parents gain increased skills, an increased sense of power and a sense of belonging. Participants are able to connect with each other and provide support and skills to deal with the day-to-day issues of raising a child with disabilities.


The association between retinal vessel diameter and retinal nerve fiber layer thickness in asymmetric normal tension glaucoma patients.
The aim of this study was to evaluate the associations between retinal vessel diameter and retinal nerve fiber layer (RNFL) thickness in patients with normal tension glaucoma (NTG). This study included 67 untreated patients with asymmetric NTG, with no evidence of glaucoma in the contralateral eyes, and 48 age- and sex-matched normal control subjects. We included patients from 20 to 70 years of age who had no history of hypertension, diabetes, or other vascular diseases. All subjects underwent detailed eye examinations that included red-free photography, stereoscopic optic disc photography, automated perimetry, and measurement of RNFL thickness with optical coherence tomography. We compared RNFL thicknesses, temporal retinal arteriolar diameters (TRAD), and temporal retinal venular diameters (between quadrants with and without RNFL defects) with computer-assisted imaging software. The mean diameter of the temporal retinal vessels in the quadrants with RNFL defects were significantly smaller in patients with NTG than in those with quadrants without RNFL defects (P < 0.001) and in control subjects (P < 0.001). TRADs were correlated with RNFL defects and RNFL thicknesses (P < 0.05) in binary logistic regression analysis and in multiple linear regression analysis (P < 0.001). There were no statistically significant differences between vessel diameters in control subjects and those in nondefective quadrants of the affected NTG eyes or the unaffected eyes of patients with NTG. Our results show that narrower retinal vessels are found in areas of RNFL defects. Considering previous reports and our analysis, this is likely due to the decreased demand for retinal blood flow in damaged areas of the retina.


Tyrosine kinase inhibitors targeting FLT3 in the treatment of acute myeloid leukemia.
Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells. Although significant progress has been made in treating many types of cancers during recent years, AML remains a deadly disease with survival rate lagging behind other blood cancers. A combination of toxic chemotherapies has been the standard AML treatment for more than 40 years. With intensive efforts to define the pathogenesis of AML, novel therapeutic drugs targeting key molecular defects in AML are being developed. Mutated in nearly 30% of AML, FMS-like tyrosine kinase 3 (FLT3) represents one of the most attractive targets. FLT3 mutants resulted from either internal tandem duplication (ITD) or point mutations possess enhanced kinase activity and cause constitutive activation of signaling. To date, several small molecule inhibitors of FLT3 have been developed but their clinical efficacy is limited due to a lack of potency and the generation of drug resistance. Therefore, next-generation FLT3 inhibitors overcoming these limitations are urgently in need. This review focuses on the pathological role of mutant FLT3 in the development of AML, the current status of FLT3 inhibitor development, and mechanisms underlining the development of resistance to existing FLT3 inhibitors.


Observational study of buprenorphine treatment of opioid-dependent pregnant women in a family medicine residency: reports on maternal and infant outcomes.
Within a family medicine residency, an outpatient buprenorphine treatment program was provided for pregnant women who were dependent on opioids. The purpose of this study was to investigate the outcomes of infants who were exposed to a range of doses of buprenorphine in utero and to determine how closely observed maternal/fetal outcomes (eg, method of delivery and infants requiring treatment for neonatal abstinence syndrome [NAS]) match those previously reported in the literature. This study consists of a retrospective case series of 23 infants born to 22 pregnant women who were dependent on opioids and who were treated with buprenorphine during a 31-month period. Thirty-five percent of infants (8 of 23) required treatment for NAS. There was no significant relationship between maternal dose of buprenorphine and birth weight, NAS severity (ie, peak NAS score), or time to first peak NAS score. Infants born to tobacco users had a significantly lower birth weight (P = .0136) than infants born to nonusers. Seventy percent of infants (16 of 23) were breastfeeding at the time of discharge from the hospital. The observations made in this case series are consistent with data previously reported in the literature. Infants in this study were more likely to be breastfed than those previously described by others, but further analysis is necessary to determine whether this finding is significant.


Reproductive health decision making among Ghanaian women.
Women's reproductive health decision-making and choices, including engaging in sexual intercourse and condom use, are essential for good reproductive health. However, issues concerning sexual intercourse and condom use are shrouded in secrecy in many sub-Saharan African countries. This study investigates factors that affect decision making on engaging in sexual intercourse and use of condom among women aged 15-49. A nationally representative sample (N = 3124) data collected in the 2008 Ghana Demographic and Health Survey was used. Multivariate logistic regression was used to study the association between women's economic and socio-demographic characteristics and their decision making on engaging in sexual intercourse and use of condom. One out of five women reported that they could not refuse their partners' request for sexual intercourse while one out of four indicated that they could not demand the use of condoms by their partners. Women aged 35-49 were more likely to make decision on engaging in sexual intercourse (OR = 1.35) compared to those aged 15-24. Furthermore, the higher a woman's education, the more likely that she would make decision regarding condom use. Also, if a woman had primary (OR = 1.37) or secondary (OR = 1.55) education, she is more likely to make decision regarding engaging in sexual intercourse compared to a woman who had no formal education. Compared to women in the Greater Accra region (the capital city region), women in the Western region (OR = 2.10), Central region (OR = 2.35), Brong Ahafo (OR = 1.70), Upper East (OR = 7.71) and Upper West (OR = 3.56) were more likely to make decision regarding the use of condom. Women who were in the richest, rich and middle wealth index categories were more likely to make decision regarding engaging in sexual intercourse as well as condom use compared to the poorest. Interventions and policies geared at empowering women to take charge of their reproductive health should focus particularly on women from less wealthy backgrounds and those with low educational attainments.