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Pharmacogenetic studies in obsessive-compulsive disorder (OCD) primarily focussing on serotonergic and dopaminergic polymorphisms, provided inconsistent findings. There is recent evidence for glutamatergic abnormalities in OCD.
Examine the association glutamatergic genes with serotonin reuptake inhibitor (SRI) response in OCD.
To study pharmacogenetic association between SLC1A1 and GRIN2B polymorphisms with SRI response in OCD.
DSM-IV OCD patients were recruited from a specialty OCD clinic and evaluated using the Yale-Brown obsessive compulsive scale (YBOCS), Mini International Neuropsychiatric Interview (MINI) plus, Clinical Global Impression scale (CGI). They were subsequently reassessed with YBOCS and CGI. To study extreme phenotypes, we included only full responders (> 35% YBOCS improvement and CGI-I score of 1 or 2) to any SRI (n = 191) and non-responders (< 25% YBOCS improvement and CGI-I score ≥ 4) to adequate trial of at least two SRIs (n = 84). Partial responders were excluded. Genotyping was performed using an ABI9700 PCR machine.
Genotype frequencies did not deviate significantly from the values predicted by the Hardy-Weinberg equation. Case-control association analyses revealed no significant association between genotype/allele frequencies with SRI response.
Our data does not show any association between polymorphisms in glutamatergic genes and SRI response in OCD though such associations have been found in other studies. More SNP's in the same gene could be responsible for the pharmacogenetic associations. More homogenous sample considering symptom dimensions and other phenotypic variables may be needed. It may be critical to go beyond “usual suspect” candidate gene research. In this regard, a novel approach to identify SRI response biomarkers is the use of cellular models.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Contemporary treatment guidelines recommend use of second-generation antipsychotics (SGAs) either as mono therapy or in combination with mood stabilizers as first-line treatment. While these drugs have been established to have superior efficacy compared to placebo, there is very less data comparing these antipsychotics with one another. We sought to study differences in the five-year outcome of first episode of mania (FEM) treated with olanzapine or risperidone, either alone or in combination with mood stabilizer.
We conducted a retrospective chart review of patients diagnosed with FEM (ICD-10) in the year 2008 (n = 88) at our centre. We selected the data of patients prescribed either olanzapine or risperidone for the purpose of this analysis. We extracted data about time to recovery and recurrence after FEM, total episodes, drug compliance and response, and number of follow-up visits from 2008 to 2013. The study was approved by the Institute Ethics Committee.
A total of 88 patients received diagnosis of FEM in the year 2008, of which 50 (56.8%) received risperidone and 35 (39.8%) received olanzapine. The two groups were comparable in socio-demographic and clinical symptomatology of FEM (all P > 0.08). Complete recovery was significantly more in the olanzapine group than the risperidone group (χ2 = 4.84, P < 0.05).
Our study indicates that risperidone and olanzapine, either alone or in combination with mood stabilizers have a similar impact on the five-year course of BD following a first manic episode. However, olanzapine is associated with more complete recovery from FEM than risperidone.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
To evaluate the feasibility, efficacy, and safety of Amplatzer vascular plug II in large and elongated ducts in infants.
Patent arterial duct device closure is technically challenging in infants with large and elongated ducts because Amplatzer duct occluder and Amplatzer duct occluder II have high chances of causing aortic coarctation and left pulmonary artery stenosis, respectively. The Amplatzer vascular plug II being soft with no retention discs on either sides helps in mitigating these problems.
This is a prospective, observational study involving infants with clinical, echocardiographic and angiographic evidence of large left to right shunt. All the children underwent duct closure using Amplatzer vascular plug II.
Eighteen infants qualified for the study. Mean age and weight were 8.63 ± 3.84 months and 6.3 ± 1.7 kg, respectively. The angiographic mean duct diameter at the pulmonary artery end was 4.66 ± 0.92 mm, and the mean duct length was 9.4 ± 2.48 mm. The size of Amplatzer vascular plug II used varied from 6 mm to 10 mm. Technical success was achieved in 16/18 cases. One patient had device embolisation, and in the other, the device was found to be unstable. The ratio of Amplatzer vascular plug II size to the duct diameter was 1.65 ± 0.27, while the ratio of ductal length to device length was 1.48 ± 0.46 in those with successful outcome.
Amplatzer vascular plug II is a safe and effective option in appropriately selected infants with elongated ducts. Diameter and length of Amplatzer vascular plug II vis-a-vis those of the ductus are important determinants of the successful outcome.
To study 2D and 3D dosimetric values for bladder and rectum, and the influence of bladder volume on bladder dose in high dose rate (HDR) intracavitary brachytherapy (ICBT). The large patient data incorporated in this study would better represent the inherent variations in many parameters affecting dosimetry in HDR-ICBT.
Material and Methods:
We prospectively collected data for 103 consecutive cervical cancer patients (over 310 HDR fractions) undergoing CT-based HDR-ICBT at our centre. Correlation among bladder and rectum maximum volume doses and corresponding International Commission on Radiation Units and Measurement (ICRU) point doses were estimated and analysed. Impact of bladder volume on bladder maximum dose was assessed.
The ICRU point doses to bladder and rectum varied from the volumetric doses to these organs. Further, bladder volume poorly correlated with bladder maximum dose for volume variations encountered in the clinical practice at our centre.
ICRU point doses to bladder and rectum are less likely to correlate with long-term toxicities to these organs. Further, in clinical practice where inter-fraction bladder volume does not vary widely there is no correlation between bladder volume and bladder dose.
Our ability to describe crystal structure features is of crucial importance when attempting to understand structure–property relationships in the solid state. In this paper, the authors introduce robocrystallographer, an open-source toolkit for analyzing crystal structures. This package combines new and existing open-source analysis tools to provide structural information, including the local coordination and polyhedral type, polyhedral connectivity, octahedral tilt angles, component-dimensionality, and molecule-within-crystal and fuzzy prototype identification. Using this information, robocrystallographer can generate text-based descriptions of crystal structures that resemble descriptions written by human crystallographers. The authors use robocrystallographer to investigate the dimensionalities of all compounds in the Materials Project database and highlight its potential in machine learning studies.
Background: Seizures are rare in REM sleep. To our knowledge, the effects of different sleep stages in anti-NMDA encephalitis have not been studied. Methods: Case report. Results: 32 year-old healthy female presented with acute fluctuating level of consciousness with episodic impulsivity, disorientation, and emotional outbursts following 3 days of headache. Her temperature was 37.8°C and she was started on ceftriaxone, vancomycin, and acyclovir. CSF only showed a total nuclear cell count of 182 and pleocytosis. MRI revealed increased T2 hyperintense right lateral temporal and parietal cortical thickening. EEG revealed right frontotemporal seizures with left sided rhythmic jerking, and an extreme delta brush pattern. Interestingly, seizures and extreme delta brush disappeared in REM sleep. After HSV PCR was negative, she was immunosuppressed with corticosteroids, IVIG, rituximab, and cyclophosphamide, given the extreme delta brush pattern. Repeat CSF analysis eventually yielded highly positive anti-NMDA antibodies. Ten weeks later, she became seizure free. Conclusions: For the first time, we report REM sleep in a case of anti-NMDA encephalitis during which there was absence of extreme delta brush and ictal EEG patterns. This observation may provide insight into the ongoing debate over whether extreme delta brush is an ictal EEG pattern.
Dicationic cobalt(II) complexes of the type [Co(fterpy)2]c(X)2·nH2O·mCH3OH (fterpy = 4′-(2-furyl)-2,2′:6′,2″-terpyridine; 1: X = PF6-, n = 1.5, m = 0; 2: X = ClO4-, n = 1, m = 1) have been isolated using self-assembly method and characterized by various spectroscopic techniques. In crystalline states both compounds exhibit gradual and incomplete spin crossover (SCO) behaviour in the temperature range 2-320 K. Various spin states of cobalt(II) in 1 have been confirmed by crystallographic evidences at 150 K and 293 K. A variation in counter anions and solvent molecules from 1 to 2 substantially improves the cooperativity among the spin active metal centres and thereby changing the nature of SCO behaviour.
Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test–retest reliability was assessed using intra-class correlation coefficients (ICC), Bland–Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland–Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test–retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=−2·30+0·17x) (95 % CI −0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.
In this work, we present an oxygen-releasing insole to treat diabetic foot ulcers. The insole consists of two layers of polydimethylsiloxane: the top layer has selective laser-machined areas (to tune oxygen permeability) targeting the ulcerated foot region, while the bottom layer provides structural support and incorporates a chamber for oxygen storage. When loaded with a pressure of 150 kPa (average value for standing/walking), the insole is able to release oxygen at a rate of 1.8 mmHg/min/cm2. At lower sitting pressures, the delivery rate persists at 0.092 mmHg/min/cm2, raising the oxygen level to an optimal healing value (50 mmHg) for a 2 × 2 cm2 wound within 150 min.
Background: Gliomas demonstrate epigenetic dysregulation highlighted by the Glioma CpG-Island Methylator Phenotype (G-CIMP) seen in IDH1 mutant tumors. IDH1 mutation perturbs the balance between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) by inhibiting TET-mediated active demethylation. The role 5hmC plays in IDH1 mutant tumors remains poorly understood. Methods: We profiled 5hmC in high grade IDH1 mutant (n = 12) and wild-type (n = 9) tumors on the Illumina MethylationEPIC Beadchip. We examined regions with high 5hmC abundance (top 1% probes), and differentially hydroxymethylated regions (DHMR). 5hmC profiles were correlated with gene expression. Results: Mean 5hmC b-values were 4.6%% and 3.8% for IDH1 mutant and wild-type tumors, respectively. Top 1% and DHMR probes demonstrated increased 5hmC among IDH1 mutants. 5hmC enriched for enhancer and super-enhancers. Among G-CIMP target genes, 22/50 were hydroxymethylated in our IDH1 mutant cohort, suggesting that 5hmC contributes to their overall methylation. Gene expression was associated with gene body 5hmC. 48 genes differentially expressed between IDH1 cohorts showed a positive Spearman correlation between 5hmC and gene expression, in particular for genes upregulated in IDH1 mutants. Conclusions: Locus-specific gain of 5hmC, targeting regulatory regions and associated with over-expressed genes, suggests a significant role for 5hmC in IDH1 mutant HGG.
Introduction: Situational awareness (SA) is essential for maintenance of scene safety and effective resource allocation in mass casualty incidents (MCI). Unmanned aerial vehicles (UAV) can potentially enhance SA with real-time visual feedback during chaotic and evolving or inaccessible events. The purpose of this study was to test the ability of paramedics to use UAV video from a simulated MCI to identify scene hazards, initiate patient triage, and designate key operational locations. Methods: A simulated MCI, including fifteen patients of varying acuity (blast type injuries), plus four hazards, was created on a college campus. The scene was surveyed by UAV capturing video of all patients, hazards, surrounding buildings and streets. Attendees of a provincial paramedic meeting were invited to participate. Participants received a lecture on SALT Triage and the principles of MCI scene management. Next, they watched the UAV video footage. Participants were directed to sort patients according to SALT Triage step one, identify injuries, and localize the patients within the campus. Additionally, they were asked to select a start point for SALT Triage step two, identify and locate hazards, and designate locations for an Incident Command Post, Treatment Area, Transport Area and Access/Egress routes. Summary statistics were performed and a linear regression model was used to assess relationships between demographic variables and both patient triage and localization. Results: Ninety-six individuals participated. Mean age was 35 years (SD 11), 46% (44) were female, and 49% (47) were Primary Care Paramedics. Most participants (80 (84%)) correctly sorted at least 12 of 15 patients. Increased age was associated with decreased triage accuracy [-0.04(-0.07,-0.01);p=0.031]. Fifty-two (54%) were able to localize 12 or more of the 15 patients to a 27x 20m grid area. Advanced paramedic certification, and local residency were associated with improved patient localization [2.47(0.23,4.72);p=0.031], [-3.36(-5.61,-1.1);p=0.004]. The majority of participants (78 (81%)) chose an acceptable location to start SALT triage step two and 84% (80) identified at least three of four hazards. Approximately half (53 (55%)) of participants designated four or more of five key operational areas in appropriate locations. Conclusion: This study demonstrates the potential of UAV technology to remotely provide emergency responders with SA in a MCI. Additional research is required to further investigate optimal strategies to deploy UAVs in this context.
We examined vancomycin-resistant enterococci (VRE)-directed antimicrobial use and VRE bacteremia in a cohort of allogeneic hematopoietic cell transplantation patients from a center where VRE screening is standard prior to transplant. In this cohort, VRE bacteremia (VREB) was infrequent. In patients without VREB, colonized patients received VRE therapy more often than noncolonized patients.
Background: Recent advances in neurophysiological techniques have contributed to our understanding of the pathophysiology of Huntington’s disease (HD). Studies of the motor cortical excitability and central motor pathways have shown variable results. Objectives: Our aims were to evaluate the cortical excitability changes in HD using transcranial magnetic stimulation (TMS) and correlate the changes with cognitive impairment. Methods: The study included 32 HD patients and 30 age- and gender-matched controls. The demographic and clinical profiles of the patients were recorded. All subjects were evaluated by TMS and resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI), and intracortical facilitation were determined. A battery of neuropsychological tests was administered to all subjects. Results: The mean age of the patients was 42.1±14.1 years, and that of controls 39.4±12.4 years (p=0.61). There was no significant difference in RMT and CMCT between the two groups. There was a mild prolongation of the contralateral SP in HD, but it was not significant. SICI was significantly reduced in HD (p<0.0001). A significant impairment in attention, verbal fluency, executive function, visuospatial function, learning, and memory was observed in HD patients. However, there was no correlation between cortical excitability changes and cognitive impairment. Conclusions: TMS is a valuable method of evaluating cortical excitability changes in HD. These patients have reduced SICI and significant impairment of cognition in multiple domains.
The burden of dengue virus infections increased globally during recent years. Though India is considered as dengue hyper-endemic country, limited data are available on disease epidemiology. The present study includes molecular characterization of dengue virus strains occurred in Hyderabad, India, during the year 2014. A total of 120 febrile cases were recruited for this study, which includes only children and 41 were serologically confirmed for dengue positive infections using non-structural (NS1) and/or IgG/IgM ELISA tests. RT-PCR, nucleotide sequencing and evolutionary analyses were carried out to identify the circulating serotypes/genotypes. The data indicated a high percent of severe dengue (63%) in primary infections. Simultaneous circulation of all four serotypes and co-infections were observed for the first time in Hyderabad, India. In total, 15 patients were co-infected with more than one dengue serotype and 12 (80%) of them had severe dengue. One of the striking findings of the present study is the identification of serotype Den-1 as the first report from this region and this strain showed close relatedness to the Thailand 1980 strains but not to any of the strains reported from India until now. Phylogenetically, all four strains of the present study showed close relatedness to the strains, which are reported to be high virulent.
This study compared the therapeutic efficacy of steroidal and non-steroidal agents for treating oral lichen planus.
Forty patients with clinical and/or histologically proven oral lichen planus were randomly placed into four groups and treated with topical triamcinolone, oral dapsone, topical tacrolimus or topical retinoid for three months. Pre- and post-treatment symptoms and signs were scored for each patient.
Patients in all treatment groups showed significant clinical improvement after three months (p < 0.05), with steroidal and non-steroidal agents having equal efficacy. Furthermore, of the non-steroidal drugs, oral dapsone had greater efficacy than topical retinoid (p < 0.05). However, no significant differences in outcome were recorded for oral dapsone vs topical tacrolimus (p > 0.05) and for topical retinoid vs topical tacrolimus (p > 0.05).
Non-steroidal drugs such as dapsone, tacrolimus and retinoid are as efficacious as steroidal drugs for treating oral lichen planus, and avoid the side effects associated with steroids.
Introduction: Multiples barriers to appropriate analgesia are reported in the paediatric emergency department (PED), including limited accessibility to effective strategies. Our objective: was to evaluate the improvement in the accessibility of pain and anxiety management strategies in Canadian PEDs, after the creation of a national pediatric pain Quality Improvement Collaborative (QIC), through Pediatric Emergency Research Canada (PERC). Methods: In 2013, the TRAPPED 1 survey was administered to Canadian PEDs, in order to evaluate what resources were in place for pain and anxiety management. A pain QIC was then created to stimulate the implementation of new strategies, through information sharing between PEDs. In 2015, the TRAPPED 2 cross sectional survey was administered. Its focus was to evaluate the improvement in the accessibility of specific strategies reported by each centre, after participating in this QIC, and working to implement change within their own PEDs. Results: All 15/15 Canadian PEDs responded to the TRAPPED 1 survey in 2013 and 11 agreed to participate in the national pain QIC. In-person, phone meetings, follow up surveys and email communications were employed for information sharing. Strategies identified by the QIC to be newly introduced in individual centres were educational initiatives, distraction options, nurse-initiated protocols and intranasal (IN) medications. All 15 PEDs completed the TRAPPED 2 survey. Compared to 2013, an increased number of PEDs used face-based pain scales (14/15 vs 6/15) and behavioural scales (5/15 vs 1/15) for pain assessment in 2015. Use of reminder posters on pain management at triage increased from 4/15 to 6/15 PEDs. Availability of tablets for distraction increased from 4/15 to 10/15 PEDs. Nurse-initiated protocols for topical anesthetic and oral sucrose (for needle procedures) increased from 10/15 to 12/15 sites and from 12/15 to 14/15 sites respectively. Availability of IN medications increased; fentanyl from 9/15 to 14/15 sites and midazolam from 8/15 to 10/15 sites. Ten of the 11 PEDs involved in the QIC strategy reported the implementation of at least one of their own identified strategies. Conclusion: This study suggests that the use of a QIC may improve the introduction of new strategies to reduce pain and anxiety in EDs. QICs may also be helpful to other centres when introducing new strategies.