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The authors report results of the studies relating to the synthesis of nanodot zirconia that has been utilized for the fabrication of electrochemical biosensing platform for the detection of CYFRA-21-1 biomarker, secreted in saliva samples of oral cancer patients. For the synthesis of nanodot zirconia (ndZrO2), the hydrothermal process was used and further functionalized with 3-aminopropyl triethoxysilane (APTES). Electrophoretic deposition technique was employed for its deposition onto the ITO electrode. The EDC-NHS reaction was used for anti-CYFRA-21-1 immobilization and bovine serum albumin (BSA) was used for blocking of the nonspecific binding sites. The fabricated biosensing platform (BSA/anti-CYFRA-21-1/APTES/ndZrO2/ITO) exhibited a wide linear detection range (0.5–50 ng/mL) with excellent sensitivity (0.53 μA mL/ng cm2).
Nipah virus (NiV) outbreak occurred in Kozhikode district, Kerala, India in 2018 with a case fatality rate of 91% (21/23). In 2019, a single case with full recovery occurred in Ernakulam district. We described the response and control measures by the Indian Council of Medical Research and Kerala State Government for the 2019 NiV outbreak. The establishment of Point of Care assays and monoclonal antibodies administration facility for early diagnosis, response and treatment, intensified contact tracing activities, bio-risk management and hospital infection control training of healthcare workers contributed to effective control and containment of NiV outbreak in Ernakulam.
Schizophrenia is a brain disease that has distressed human kind since the beginning of the written history. Firm knowledge about this illness is limited to certain areas including cognitive, risk genes etc. Basic question remains unanswered about the diagnostic heterogeneity and tissue neurochemistry. Several lines of evidence focus on direct involvement of glutamergic system in the pathophysiology of psyhosis.
The pilot study measured the difference between the plasma serine recemase level of normal and schizophrenic patients and estimated the D-isomers excreted in the urine using gas chromatography and Gas chromatography and mass selectivity (GCMS) respectively.
Plasma and urine samples of normal and schizophrenic patients from UAE shows that the level of serine recemase and D-serine respectively is lower in schizophrenic pateints than that of the normal subjects.
The hypofunction of the glutamate N-methyl-D-Aspartate receptor (NMDAR) has been proposed as a model of schizophrenia in humans using molecular marker and also due to evidence suggesting modulation of glutamate cicuitries after antipyschotic administration. In this regard there is increasing evidence from pharmacological and genetic studies that suggest that D-serine an endogenous co agonist to the NMDA subtype glutamate receptor, may be implicated in schizophrenia (SCZ). Although an association of genes for D-serine degradation such as D-amino acid oxidase and G72 has been reported, a role of recemase in SCZ is unclear.
A cross sectional study was conducted to examine the nature of insight in schizophrenia and bipolar disorder as well as compare it between the two disorders. Forty patients with schizophrenia and forty patients with bipolar disorder matched on age, age of onset of illness and duration of illness, were recruited consecutively from the outpatient clinic of a psychiatric hospital. The patients had to be clinically stable on follow-up treatment for at least three months. Insight was measured using Schedule for Assessment of Insight- Extended Version (SAI-E) and Scale of Unawareness of Mental Disorders (SUMD). Both schizophrenia and bipolar disorder had modest level of insight as measured on both the instruments. There was no qualitative difference in insight between the two disorders. However, patients with bipolar disorder had significantly better awareness of illness than patients with schizophrenia. This was evident on both the instruments that showed significant concordance on the items of insight for both the disorders.
Though a number of agents are available to treat acute manic episode but either because of their comparable efficacy to lithium or their dose related side effects, need for better agent is always being felt.
To study the efficacy and side effect profile of lamotrigine and its double blind comparison with lithium in acute mania.
We recruited 50 patients with diagnosis of manic episode according to DSM-IV and were divided into two groups. One group was given lamotrigine 100mg and another lithium 900mg in a double blind fashion. Patints were assessed subsequently on BPRS, CMRS,UKU side effect scale and CGI till next 28 days.
Subjects in lamotrigine group did not show much improvement at the end of 4th week as compared to lithium group. Side effect profile of both groups were in accordance with reported literature except that 61.9% patients in lamotrigine group showed weight loss. Also rash were found in only 3.5% of the lamotrigine group even with such a rapid escalation of the dose.
We found that lamotrigine is ineffective in case of acute manic episode when compared with lithium.
In women, mentalillness is often associated with social burden and inadequate compliance.
Social burden, distress tolerance and medicationadherence among female withmental illness in remission.
Toknow the level of social burden, distresstolerance and its relationship with medicationadherence among Indian female with mental illness in remission.
Fiftyone consecutive asymptomatic female patients were assessed using socio-demographicproforma, The Zarit Burden Interview(ZBI), Distress Tolerance Scale(DTS) and Medication adherence scale(MAS). Seventy five percent of patientsexperienced different levels of burden and 25 %has poor medication adherence. Significant correlationwas observed between social burden and occupation (p<. 05); distress tolerancewith decision making (p<. 05) and knowledge about treatment (p <. 05), andmedication adherence with knowledge about treatment(p<.01). Thetotal scores of ZBI had a significant correlation with DTS scores (p. >01) andMAS score (p<.05).
Social burden is common, and interrelatedwith distress tolerance and medicationadherence in women with mental illness in remission.
Online learning has become an increasingly expected and popular component for education of the modern-day adult learner, including the medical provider. In light of the recent coronavirus pandemic, there has never been more urgency to establish opportunities for supplemental online learning. Heart University aims to be “the go-to online resource” for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of paedagogical material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practising provider. In this manuscript, we review the aims, development, current offerings and standing, and future goals of Heart University.
The Single Ventricle Reconstruction Trial randomised neonates with hypoplastic left heart syndrome to a shunt strategy but otherwise retained standard of care. We aimed to describe centre-level practice variation at Fontan completion.
Centre-level data are reported as median or median frequency across all centres and range of medians or frequencies across centres. Classification and regression tree analysis assessed the association of centre-level factors with length of stay and percentage of patients with prolonged pleural effusion (>7 days).
The median Fontan age (14 centres, 320 patients) was 3.1 years (range from 1.7 to 3.9), and the weight-for-age z-score was −0.56 (−1.35 + 0.44). Extra-cardiac Fontans were performed in 79% (4–100%) of patients at the 13 centres performing this procedure; lateral tunnels were performed in 32% (3–100%) at the 11 centres performing it. Deep hypothermic circulatory arrest (nine centres) ranged from 6 to 100%. Major complications occurred in 17% (7–33%). The length of stay was 9.5 days (9–12); 15% (6–33%) had prolonged pleural effusion. Centres with fewer patients (<6%) with prolonged pleural effusion and fewer (<41%) complications had a shorter length of stay (<10 days; sensitivity 1.0; specificity 0.71; area under the curve 0.96). Avoiding deep hypothermic circulatory arrest and higher weight-for-age z-score were associated with a lower percentage of patients with prolonged effusions (<9.5%; sensitivity 1.0; specificity = 0.86; area under the curve 0.98).
Fontan perioperative practices varied widely among study centres. Strategies to decrease the duration of pleural effusion and minimise complications may decrease the length of stay. Further research regarding deep hypothermic circulatory arrest is needed to understand its association with prolonged pleural effusion.
To assess the effect of tranexamic acid on intra-operative bleeding and surgical field visualisation.
Fifty patients undergoing various endoscopic ear surgical procedures, including endoscopic tympanoplasty, endoscopic atticotomy or mastoidectomy, endoscopic ossiculoplasty, and endoscopic stapedotomy, were randomly assigned to: a study group that received tranexamic acid or a control group which received normal saline. The intra-operative bleeding and operative field visualisation was graded using the Das and Mitra endoscopic ear surgery bleeding and field visibility score, which was separately analysed for the external auditory canal and the middle ear.
The Das and Mitra score was better (p < 0.05) in the group that received tranexamic acid as a haemostat when working in the external auditory canal; with respect to the middle ear, no statistically significant difference was found between the two agents. Mean values for mean arterial pressure, heart rate and surgical time were comparable in both groups, with no statistically significant differences.
Tranexamic acid appears to be an effective haemostat in endoscopic ear surgery, thus improving surgical field visualisation, especially during manipulation of the external auditory canal soft tissues.
The intensity of turbidite sedimentation over long timescales is driven by sea-level change, tectonically driven rock uplift and climatically modulated sediment delivery rates. This study focuses on understanding the effect of sea-level fluctuations and climatic variability on grain-size variations. The grain size and environmental magnetic parameters of Arabian Sea sediments have been documented using 203 samples, spanning the last 200 ka, obtained from International Ocean Discovery Program (IODP) Site U1457. Grain-size end-member modelling suggests that between ~200 and 130 ka there was an increase in the coarse silt fraction caused by sediment transport following reworking of the Indus Fan and development of deep-sea canyons. The sediment size and enhanced magnetic susceptibility indicate a dominant flux of terrestrial sediments. Sedimentation in the distal Indus Fan at c. 200–130 ka was driven by a drop in sea level that lowered the base level in the Indus and Narmada river systems. The low sea-stand caused incision in the Indus delta, canyons and fan area, which resulted in the transportation of coarser sediment at the drilling site. Magnetic susceptibility and other associated magnetic parameters suggest a large fraction of the sediment was supplied by the Narmada River during ~200–130 ka. Since ~130 ka, clay-dominated sedimentation is attributed to the rise in sea level due to warm and wet climate.
Introduction: Abdominal pain is one of the most frequent reasons for an emergency department (ED) visit. Most cases are functional and no therapy has proven effective. Our objective was to determine if hyoscine butylbromide (HBB) (BuscopanTM) is effective for children who present to the ED with functional abdominal pain. Methods: We conducted a randomized, blinded, superiority trial comparing HBB 10 mg plus acetaminophen placebo to oral acetaminophen 15 mg/kg (max 975 mg) plus HBB placebo using a double-dummy approach. We included children 8-17 years presenting to the ED at London Health Sciences Centre with colicky abdominal pain rated >40 mm on a 100 mm visual analog scale (VAS). The primary outcome was VAS pain score at 80 minutes post-administration. Secondary outcomes included adverse effects; caregiver satisfaction with pain management using a five-item Likert scale; recidivism and missed surgical diagnoses within 24-hours of discharge. Analysis was based on intention to treat. Results: We analyzed 225 participants (112 acetaminophen; 113 HBB). The mean (SD) age was 12.4 (3.0) years and 148/225 (65.8%) were females. Prior to enrollment, the median (IQR) duration of pain prior was 2 (4.5) hours and analgesia was provided to 101/225 (44.9%) of participants. The mean (SD) pre-intervention pain scores in the acetaminophen and HBB groups were 62.7 (15.9) mm and 60.3 (17.3) mm, respectively. At 80 minutes, the mean (SD) pain scores in the acetaminophen and HBB groups were 30.1 (28.8) mm and 29.4 (26.4) mm, respectively and there were no significant differences adjusting for pre-intervention scores (p = 0.96). The median (IQR) caregiver satisfaction was high in the acetaminophen [5 (2)] and HBB [5 (1)] groups (p = 0.79). The median (IQR) length of stay between acetaminophen [235 (101)] and HBB [234 (103)] was not significantly different (p = 0.53). The proportion of participants with a return visit for abdominal pain was 4/112 (3.5%) in the acetaminophen group and 6/113 (5.3%) in the HBB group. The most common adverse effect was nausea (9% in each group) and there were no significant differences in adverse effects between acetaminophen (26/112, 23.2%) and HBB (31/113, 27.4%) (p = 0.52). There were no missed surgical diagnoses. Conclusion: For children with presumed functional abdominal pain who present to the ED, both acetaminophen and HBB produce a clinically important (VAS < 30 mm) reduction in pain and should be routinely considered in this clinical setting.
A cross-sectional study on six dairy farms was conducted to ascertain the occurrence of carbapenem-resistant Escherichia coli in calves. Two-hundred and seventy-nine isolates of E. coli were recovered from 90 faecal samples from apparently healthy (45) and diarrhoeal (45) calves. The isolates were screened for phenotypic susceptibility to carbapenems and production of metallo β-lactamase, as well as five carbapenemase resistance genes by PCR, and overexpression of efflux pumps. Eighty-one isolates (29.03%) were resistant to at least one of three carbapenem antibiotics [meropenem (23.30%), imipenem (2.15%) and ertapenem (1.43%)], and one isolate was positive for the blaVIM gene which was located on an Incl1 plasmid of a novel sequence type (ST 297) by multilocus sequence typing. The majority (83.95%) of isolates had an active efflux pump. Calves housed on concrete floors were approximately seven times more likely to acquire meropenem-resistant isolates than those housed on earthen floors (95% CI 1.27–41.54). In India, carbapenem drugs are not used in food animal treatment, hence carbapenem-resistant strains in calves possibly originate from the natural environment or human contact and is of public health importance. To our knowledge, this is the first report of blaVIM carbapenemases gene in calves from India.
The purpose of this study was to evaluate the dosimetric impact of multileaf collimator (MLC) positional errors on dynamic intensity-modulated radiotherapy (IMRT) treatments through planning simulation. Secondly the sensitivity of IMRT MatriXX device for detecting the MLC leaf positional errors was also evaluated.
Materials and methods
In this study five dynamic IMRT plans, each for brain and head–neck (HN), were retrospectively included. An in-house software was used to introduce random errors (uniform distribution between −2·0 and +2·0 mm) and systematic errors [±0·5, ±0·75, ±1·0 and ±2·0 mm (+: open MLC error and −: close MLC error)]. The error-introduced MLC files were imported into the treatment planning system and new dose distributions were calculated. Furthermore, the dose–volume histogram files of all plans were exported to in-house software for equivalent uniform dose (EUD), tumour control probability and normal tissue complication probability calculations. The error-introduced plans were also delivered on LINAC, and the planar fluences were measured by IMRT MatriXX. Further, 3%/3 mm and 2%/2 mm γ-criteria were used for analysis.
In planning simulation study, the impact of random errors was negligible and ΔEUD was <0·5±0·7%, for both brain and HN. The impact of systematic errors was substantial, and on average, the maximum change in EUD for systematic errors (close 2 mm) was −10·7±3·1% for brain and −15·5±2·6% for HN.
It can be concluded that the acceptable systematic error was 0·4 mm for brain and 0·3 mm for HN. Furthermore, IMRT MatriXX device was able to detect the MLC errors ≥2 mm in HN and >3 mm errors in brain with 2%/2 mm γ-criteria.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
Tardive dyskinesia (TD) results from exposure to dopamine-receptor antagonists (DRAs), such as typical and atypical antipsychotics. Clinicians commonly manage TD by reducing the dose of or stopping the causative agent; however, this may cause psychiatric relapse and worsen quality of life. In the 12-week ARM-TD and AIM-TD trials, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores versus placebo and was generally well tolerated, regardless of baseline DRA use or comorbidities.
To evaluate the impact of underlying disease and current DRA use on efficacy and safety of long-term therapy of deutetrabenazine in patients with TD.
Patients with TD who completed ARM-TD or AIM-TD were eligible to enter this open-label, single-arm, long-term extension after completing the 1-week washout period and final evaluation in the blinded portion of the trial. Change in AIMS scores from baseline to Week 54 and patients “Much Improved” or “Very Much Improved” (treatment success) on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC) at Week 54 were analyzed by baseline psychiatric illness type, including mood disorders (bipolar disorder/depression/other) or psychotic disorders (schizophrenia/schizoaffective disorder), and presence or absence of current DRA use.
At Week 54, meaningful improvements from baseline in mean (standard error) AIMS scores were observed for patients with baseline mood disorders (–5.2[0.93]) and psychotic disorders (–5.0[0.63]), and in patients currently using DRAs (–4.6[0.54]) or not using DRAs (–6.4[1.27]). Most patients with mood disorders (73%) and psychotic disorders (71%) were “Much Improved” or “Very Much Improved” on CGIC at Week 54, similar to patients currently using (71%) or not using (74%) DRAs. The majority of patients with mood disorders (62%) and psychotic disorders (57%), as well as patients currently using (58%) or not using (63%) DRAs, were also “Much Improved” or “Very Much Improved” on PGIC at Week 54. Prior treatment in ARM-TD and AIM-TD did not impact the long-term treatment response. Underlying psychiatric disorder and concomitant DRA use did not impact the occurrence of adverse events (AEs). The frequencies of dose reductions, dose suspensions, and withdrawals due to AEs were low, regardless of baseline psychiatric comorbidities and DRAuse.
Long-term deutetrabenazine treatment demonstrated meaningful improvements in abnormal movements in TD patients, which were recognized by clinicians and patients, regardless of underlying psychiatric illness or DRAuse.
Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
Tardive dyskinesia (TD) is an often-irreversible movement disorder that may intensify the stigma of patients with psychiatric disorders and worsen quality of life. In two randomized, double-blind, placebo (PBO)-controlled, 12-week trials, ARM-TD and AIM-TD (‘parent studies’), deutetrabenazine (DTB) demonstrated statistically significant improvements in centrally read Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with PBO and was generally well tolerated.
To evaluate the long-term efficacy of DTB in an open-label safety study following double-blind treatment using site-rated efficacy measures: AIMS, the Clinical Global Impression of Change (CGIC) and the Patient Global Impression of Change (PGIC), which may be used in real-world clinical practice settings.
Patients with TD who completed the parent studies were eligible to enter this open-label, long-term extension (OLE) after completing the 1-week washout period and final evaluation in the blinded portion of the trial. This extension comprised a 6-week titration period followed by a long-term maintenance phase. Patients began DTB at 12mg/day, titrating up to a maximum total dose of 48mg/day based on dyskinesia control and tolerability. Efficacy endpoints included in this analysis are the change in site-rated AIMS score (items 1–7) from parent study baseline, and the proportion of patients who were “Much Improved” or “Very Much Improved” (treatment success) on the CGIC and PGIC from OLE baseline.
At the end of the parent studies (Week 12), patients treated with DTB had experienced greater mean (standard error) improvements in site-rated AIMS score (–5.0[0.40]) than patients given PBO (–3.2[0.47]). With long-term DTB treatment, both groups experienced improvements in site-rated AIMS scores (prior DTB, –7.9[0.62]; prior placebo, –6.6[0.64]) compared with parent study baseline. Similarly, at the end of the parent studies, a greater proportion of patients treated with DTB had treatment success on the CGIC (DTB, 51%; PBO, 32%) and the PGIC (DTB, 46%; PBO: 33%); whereas at Week 54 of the OLE study, treatment success on CGIC and PGIC were similar in both the CGIC (prior DTB: 66%; prior PBO: 68%) and PGIC (prior DTB: 62%; prior PBO: 62%) groups. DTB was generally well tolerated.
Patients treated with DTB showed improvements in abnormal movements, as measured by site-rated AIMS, CGIC, and PGIC scores, which may be used in real-world clinical practice settings. These results corroborate the previously reported efficacy of DTB as observed in the 12-week, double-blind ARM-TD and AIM-TD trials, in which central raters were used to evaluate AIMS scores.
Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
Normal odd-chain SFA (OCSFA), particularly tridecanoic acid (n-13 : 0), pentadecanoic acid (n-15 : 0) and heptadecanoic acid (n-17 : 0), are normal components of dairy products, beef and seafood. The ratio of n-15 : 0:n-17 : 0 in ruminant foods (dairy products and beef) is 2:1, while in seafood and human tissues it is 1:2, and their appearance in plasma is often used as a marker for ruminant fat intake. Human elongases encoded by elongation of very long-chain fatty acid (ELOVL)1, ELOVL3, ELOVL6 and ELOVL7 catalyse biosynthesis of the dominant even-chain SFA; however, there are no reports of elongase function on OCSFA. ELOVL transfected MCF7 cells were treated with n-13 : 0, n-15 : 0 or n-17 : 0 (80 µm) and products analysed. ELOVL6 catalysed elongation of n-13 : 0→n-15 : 0 and n-15 : 0→n-17 : 0; and ELOVL7 had modest activity toward n-15 : 0 (n-15 : 0→n-17 : 0). No elongation activity was detected for n-17 : 0→n-19 : 0. Our data expand ELOVL specificity to OCSFA, providing the first molecular evidence demonstrating ELOVL6 as the major elongase acting on OCSFA n-13 : 0 and n-15 : 0 fatty acids. Studies of food intake relying on OCSFA as a biomarker should consider endogenous human metabolism when relying on OCSFA ratios to indicate specific food intake.