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The use of intrathecal (IT) dexamethasone during subarachnoid block (SAB) has not been evaluated. There are no pooled data available to decide on the optimal regimen of IT dexamethasone during SAB, irrespective of the type of surgery. There is uncertainty about its dosage, effectiveness, and safety, and a need to establish clear guidelines on its use. Our objective was to evaluate the effectiveness and safety of use of IT dexamethasone during SAB. We performed a meta-analysis (PROSPERO, CRD42022304944) of trials that included patients who underwent a variety of surgical procedures under SAB. Patients received concomitant IT dexamethasone as an adjuvant to spinal local anesthetics. The analyzed outcomes included sensory and motor effects as well as adverse and/or beneficial side effects. Subgroup analysis was planned based on different doses used. Trial sequential analysis (TSA) was used to estimate the required sample size information (RIS) for each outcome. Eighteen studies (2531 participants) were included in this analysis. Addition of IT dexamethasone (4-8 mg) to heavy bupivacaine effectively prolonged the duration of sensory blockade (mean difference, MD = 63.8 minutes; [95% confidence interval, CI, 33.1-94.5], P < 0.0001), two-segment regression time (MD = 20.1[95% CI, 0.96-39.2], P = 0.04) and first rescue analgesic time (MD = 143.3 [95% CI, 90.3-196.0], P = 0.001). Subgroup analyses revealed superior effects of 8 mg dose over 4 mg for sensory and analgesic effects. The effect of dexamethasone on duration of motor blockade was inconclusive. Additionally, lower risk ratios (RRs) were recorded for spinal anesthesia-related hypotension (RR = 0.74 [95% CI, 0.6-0.9], P = 0.0003) and nausea/vomiting (RR = 0.62 [95% CI, 0.41-0.93], P = 0.02) in the dexamethasone group. For outcomes such as sensory blockade, analgesia, and hypotension, the required information size was reached during TSA. In conclusion, IT dexamethasone, used as an adjuvant to spinal local anesthetic, especially at the dose of 8 mg, increases sensory blockade duration and the time for request of the first rescue analgesic. SAB-induced side effects such as hypotension, nausea, and vomiting are lesser with the use of IT dexamethasone. However, further studies are necessary to draw meaningful conclusions on its safety profile., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Saudi Journal of Anesthesia.)

Background or Purpose: The prognosis of m ixed cardiomyopathy (CMP) in patients with implanted cardioverter-defibrillators (ICDs) has not been investigated. We aim to study the demographic, clinical, device therapies and survival characteristics of mixed CMP in a cohort of patients implanted with a defibrillator., Methods: The term mixed CMP was used to categorise patients with impaired left ventricular ejection fraction attributed to documented non-ischemic triggers with concomitant moderate coronary artery disease. This is a single center observational cohort of 526 patients with a mean follow-up of 8.7 ± 3.5 years., Results: There were 42.5% patients with ischemic cardiomyopathy (ICM), 26.9% with non-ischemic cardiomyopathy (NICM) and 30.6% with mixed CMP. Mixed CMP, compared to NICM, was associated with higher mean age (69.1 ± 9.6 years), atrial fibrillation (55.3%) and greater incidence of comorbidities. The proportion of patients with mixed CMP receiving device shocks was 23.6%, compared to 18.4% in NICM and 27% in ICM. The VT cycle length recorded in mixed CMP (281.6 ± 43.1 ms) was comparable with ICM (282.5 ± 44 ms; p = 0.9) and lesser than NICM (297.7 ± 48.7 ms; p = 0.1). All-cause mortality in mixed CMP (21.1%) was similar to ICM (20.1%; p = 0.8) and higher than NICM (15.6%; p = 0.2). The Kaplan-Meier curves revealed hazards of 1.57 (95% CI: 0.91, 2.68) for mixed CMP compared to NICM., Conclusion: In a cohort of patients with ICD, the group with mixed CMP represents a phenotype predominantly comprised of the elderly with a higher incidence of comorbidities. Mixed CMP resembles ICM in terms of number of device shocks and VT cycle length. Trends of long-term prognosis of patients with mixed CMP are worse than NICM and similar to ICM., (© 2023. Crown.)

Introduction: LANDMARC (CTRI/2017/05/008452), a prospective, observational real-world study, evaluated the occurrence of diabetes complications, glycemic control and treatment patterns in people with type 2 diabetes mellitus (T2DM) from pan-India regions over a period of 3 years., Methods: Participants with T2DM (≥25 to ≤60 years old at diagnosis, diabetes duration ≥2 years at the time of enrollment, with/without glycemic control and on ≥2 antidiabetic therapies) were included. The proportion of participants with macrovascular and microvascular complications, glycemic control and time to treatment adaptation over 36 months were assessed., Results: Of the 6234 participants enrolled, 5273 completed 3 years follow-up. At the end of 3-years, 205 (3.3%) and 1121 (18.0%) participants reported macrovascular and microvascular complications, respectively. Nonfatal myocardial infarction (40.0%) and neuropathy (82.0%) were the most common complications. At baseline and 3-years, 25.1% (1119/4466) and 36.6% (1356/3700) of participants had HbA1c <7%, respectively. At 3-years, population with macrovascular and microvascular complications had higher proportion of participants with uncontrolled glycemia (78.2% [79/101] and 70.3% [463/659], respectively) than those without complications (61.6% [1839/2985]). Over 3-years, majority (67.7%-73.9%) of the participants were taking only OADs (biguanides [92.2%], sulfonylureas [77.2%] and DPP-IV inhibitors [62.4%]). Addition of insulin was preferred in participants who were only on OADs at baseline, and insulin use gradually increased from 25.5% to 36.7% at the end of 3 years., Conclusion: These 3-year trends highlight the burden of uncontrolled glycemia and cumulative diabetes-related complications, emphasizing the importance of optimizing diabetes management in India., (© 2023 Sanofi and The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Introduction: There are limited data on the real-world management of diabetes in the Indian population. In this 2-year analysis of the LANDMARC study, the management of type 2 diabetes mellitus (T2DM) and related complications were assessed., Method: This multicenter, observational, prospective study included adults aged ≥25 to ≤60 years diagnosed with T2DM (duration ≥2 years at enrollment) and controlled/uncontrolled on ≥2 anti-diabetic agents. This interim analysis at 2 years reports the status of glycaemic control, diabetic complications, cardiovascular (CV) risks and therapy, pan-India including metropolitan and non-metropolitan cities., Results: Of the 6234 evaluable patients, 5318 patients completed 2 years in the study. Microvascular complications were observed in 17.6% of patients (1096/6234); macrovascular complications were observed in 3.1% of patients (195/6234). Higher number of microvascular complications were noted in patients from non-metropolitan than in metropolitan cities (p < .0001). In 2 years, an improvement of 0.6% from baseline (8.1%) in mean glycated haemoglobin (HbA1c) was noted; 20.8% of patients met optimum glycaemic control (HbA1c < 7%). Hypertension (2679/3438, 77.9%) and dyslipidaemia (1776/3438, 51.7%) were the predominant CV risk factors in 2 years. The number of patients taking oral anti-diabetic drugs in combination with insulin increased in 2 years (baseline: 1498/6234 [24.0%] vs. 2 years: 1917/5763 [33.3%]). While biguanides and sulfonylureas were the most commonly prescribed, there was an evident increase in the use of dipeptidyl peptidase-IV inhibitors (baseline: 3049/6234, 48.9% vs. 2 years: 3526/5763, 61.2%)., Conclusion: This longitudinal study represents the control of T2DM, its management and development of complications in Indian population., Clinical Trial Registration Number: CTRI/2017/05/008452., (© 2023 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Air pollution is a known environmental health hazard. A major source of air pollution includes diesel exhaust (DE). Initially, research on DE focused on respiratory morbidities; however, more recently, exposures to DE have been associated with neurological developmental disorders and neurodegeneration. In this study, we investigated the effects of sub-chronic inhalation exposure to DE on neuroinflammatory markers in two inbred mouse strains and both sexes, including whole transcriptome examination of the medial prefrontal cortex. We exposed aged male and female C57BL/6J (B6) and DBA/2J (D2) mice to DE, which was cooled and diluted with HEPA-filtered compressed air for 2 h per day, 5 days a week, for 4 weeks. Control animals were exposed to HEPA-filtered air on the same schedule as DE-exposed animals. The prefrontal cortex was harvested and analyzed for proinflammatory cytokine gene expression ( Il1β , Il6 , Tnfα ) and transcriptome-wide response by RNA-seq. We observed differential cytokine gene expression between strains and sexes in the DE-exposed vs. control-exposed groups for Il1β , Tnfα , and Il6 . For RNA-seq, we identified 150 differentially expressed genes between air and DE treatment related to natural killer cell-mediated cytotoxicity per Kyoto Encyclopedia of Genes and Genomes pathways. Overall, our data show differential strain-related effects of DE on neuroinflammation and neurotoxicity and demonstrate that B6 are more susceptible than D2 to gene expression changes due to DE exposures than D2. These results are important because B6 mice are often used as the default mouse model for DE studies and strain-related effects of DE neurotoxicity warrant expanded studies.

Two-component signal transduction systems (TCSs), consisting of a sensor histidine kinase (HK) and a response regulator (RR), sense environmental stimuli and then modulate cellular responses, typically through changes in gene expression. Our previous work identified the DNA binding motif of CD1586, an RR implicated in Clostridioides difficile strain R20291 sporulation. To determine the role of this RR in the sporulation pathway in C. difficile, we generated a deletion strain of cd1688 in the historical 630 strain, the homolog of cd1586 . The C. difficile Δcd1688 strain exhibited a hypersporulation phenotype, suggesting that CD1688 negatively regulates sporulation. Complementation of the C. difficile Δcd1688 strain restored sporulation. In contrast, a nonphosphorylatable copy of cd1688 did not restore sporulation to wild-type (WT) levels, indicating that CD1688 must be phosphorylated to properly modulate sporulation. Expression of the master regulator spo0A , the sporulation-specific sigma factors sigF , sigE , sigG , and sigK , and a signaling protein encoded by spoIIR was increased in the C. difficile Δcd1688 strain compared to WT. In line with the increased spoIIR expression, we detected an increase in mature SigE at an earlier time point, which arises from SpoIIR-mediated processing of pro-SigE. Taken together, our data suggest that CD1688 is a novel negative modulator of sporulation in C. difficile and contributes to mediating progression through the spore developmental pathway. These results add to our growing understanding of the complex regulatory events involved in C. difficile sporulation, insight that could be exploited for novel therapeutic development. IMPORTANCE Clostridioides difficile causes severe gastrointestinal illness and is a leading cause of nosocomial infections in the United States. This pathogen produces metabolically dormant spores that are the major vehicle of transmission between hosts. The sporulation pathway involves an intricate regulatory network that controls a succession of morphological changes necessary to produce spores. The environmental signals inducing the sporulation pathway are not well understood in C. difficile. This work identified a response regulator, CD1688, that, when deleted, led to a hypersporulation phenotype, indicating that it typically acts to repress sporulation. Improving our understanding of the regulatory mechanisms modulating sporulation in C. difficile could provide novel strategies to eliminate or reduce spore production, thus decreasing transmission and disease relapse.

A strong evidence of the effects of radiation absorption on the living community together with a better solution to reduce the radiation intensity without compromising the usage of wireless communication systems is presented. This study analyses the radiation effects on living things and validates the proposed techniques for specific absorption rate (SAR) value reduction at 2.45 GHz. To reduce these radiation impacts on the living community, proper shielding from the radiation and effectively reorienting antenna radiation patterns are the solutions suggested. An analogous antenna configuration in wireless communication systems - a coplanar waveguide fed loop antenna is considered and an open loop resonator (OLR) optimized in ANSYS HFSS at 2.45 GHz is incorporated on the back side of the proposed antenna for achieving SAR value reduction. Theoretical and experimental validation is carried out by measuring the variation in absorption power on each vegetable sample using vector network analyzer E5080A. The existence of OLR on the back side of the antenna reduces the absorption power upto 2 dB. From experimental validation, the proposed technique provides 88% to 98% reduction in SAR value when tested in each sample. Along with this OLR exhibits the capability to enhance the shielding characteristics to the controlled environment of experimental setup for analyzing the stages of seed germination, which helps in reducing the reported radiation effects and growth retardation. The proposed method of EMR reduction with miniaturized planar resonator can be effectively used in the communication systems operating at 2.45 GHz for creating a reduced radiation environment.

Introduction: Longitudinal data on management and progression of type 2 diabetes mellitus (T2DM) in India are scarce. LANDMARC (CTRI/2017/05/008452), first-of-its-kind, pan-India, prospective, observational study aimed to evaluate real-world patterns and management of T2DM over 3 years., Methods: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrolment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. The first-year trends for glycaemic control, therapy and diabetic complications, including those from metropolitan and non-metropolitan cities are reported here., Results: Of 6236 enrolled participants, 5654 completed 1 year in the study. Although the overall mean glycated haemoglobin (HbA1c) improved by 0.5% (baseline: 8.1%) at 1 year, only 20% of the participants achieved HbA1c <7%. Participants from metropolitan and non- metropolitan cities showed similar decrease in glycaemic levels (mean change in HbA1c: -0.5% vs. -0.5%; p = .8613). Among diabetic complications, neuropathy was the predominant complication (815/6236, 13.1% participants). Microvascular complications (neuropathy, nephropathy and retinopathy) were significantly (p < .0001) higher in non-metropolitan than metropolitan cities. Hypertension (2623/6236, 78.2%) and dyslipidaemia (1696/6236, 50.6%) continued to be the most commonly reported cardiovascular risks at 1 year. After 1 year, majority of the participants were taking only oral anti-diabetic drugs (OADs) (baseline: 4642/6236 [74.4%]; 1 year: 4045/6013 [67.3%]), while the proportion of those taking insulin along with OADs increased (baseline: 1498/6236 [24.0%] vs. 1 year: 1844/6013 [30.7%]). Biguanides and sulfonylureas were the most used OADs. The highest increase in use was seen for dipeptidyl peptidase-IV inhibitors (baseline: 3047/6236 [48.9%]; 1 year: 3529/6013 [58.7%]). Improvement in all glycaemic parameters was significantly (p < .0001) higher in the insulin vs. the insulin-naïve subgroups; in the insulin-naïve subgroup, no statistical difference was noted in those who received >3 vs. ≤3 OADs., Conclusions: First-year trends of the LANDMARC study offer insights into real-world disease progression, suggesting the need for controlling risk factors and timely treatment intensification in people with T2DM., (© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Somatosensory-evoked potential and motor-evoked potential (MEP) are used during complex spinal surgeries to ensure the neurological integrity of the patient. Here, we report a case of a patient with type 3 thoracolumbar scoliosis whose surgery was stopped due to loss of signal in the neuromonitoring over the right lower limb in the exposure stage, before instrumentation and manipulation. The patient had right lower limb weakness and hence the surgery was abandoned. The same abnormality was present when we tried surgery for the second time. Surgery was aborted and the potentials recovered and the patient woke up without disability. In summary, this case illustrates that changes in MEPs can occur even at early stages in more vulnerable cases and is to be looked for to avoid disability., Competing Interests: None

In this work, a compact dielectric sensor for the detection of adulteration in solid and liquid samples using planar resonators is presented. Six types of filter prototypes operating at 2.4 GHz are presented, optimized, numerically assessed, fabricated and experimentally validated. The obtained experimental results provided an error less than 6% with respect to the simulated results. Moreover, a size reduction of about 69% was achieved for the band stop filter and a 75% reduction for band pass filter compared to standard sensors realized using open/short circuited stub microstrip lines. From the designed filters, the miniaturised filter with Q of 95 at 2.4 GHz and size of 35 mm × 35 mm is formulated as a sensor and is validated theoretically and experimentally. The designed sensor shows better sensitivity, and it depends upon the dielectric property of the sample to be tested. Simulation and experimental validation of the designed sensor is carried out by loading different samples onto the sensor. The adulteration detection of various food samples using the designed sensor is experimentally validated and shows excellent sensing on adding adulterants to the original sample. The sensitivity of the sensor is analyzed by studying the variations in resonant frequency, scattering parameters, phase and Q factor with variation in the dielectric property of the sample loaded onto the sensor.

Introduction: Longitudinal data on progression, complications, and management of type 2 diabetes mellitus (T2DM) across India are scarce. LANDMARC (CTRI/2017/05/008452), the first pan -India, longitudinal, prospective, observational study, aims to understand the management and real-world outcomes of T2DM over 3 years., Methods: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrollment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. Baseline characteristics were analyzed using descriptive statistics., Results: Of the 6279 recruited participants, 6236 were eligible for baseline assessment (56.6% [ n / N  = 3528/6236] men; mean ± SD age: 52.1 ± 9.2 years, diabetes duration: 8.6 ± 5.6 years). mean ± SD HbA1c, fasting plasma glucose, and postprandial glucose values were 64 ± 17 mmol/mol (8.1 ± 1.6%), 142.8 ± 50.4 mg/dl, and 205.7 ± 72.3 mg/dl, respectively. Only 25.1% ( n / N  = 1122/6236) participants had controlled glycemia (HbA1c < 53 mmol/mol, <7%). Macrovascular and microvascular complications were prevalent in 2.3% ( n / N  = 145/6236) and 14.5% ( n / N  = 902/6236) participants, respectively. Among those with complications, non-fatal myocardial infarction ( n / N  = 74/145, 51.0%) and neuropathy ( n / N  = 737/902, 81.7%) were the most reported macrovascular and microvascular complication, respectively. Hypertension ( n / N  = 2566/3281, 78.2%) and dyslipidemia ( n / N  = 1635/3281, 49.8%) were the most reported cardiovascular risks. Majority (74.5%; n / N  = 4643/6236) were taking oral anti-diabetic drugs (OADs) only, while 24.4% ( n / N  = 1522/6236) participants were taking OADs+insulin. Biguanides ( n / N  = 5796/6236, 92.9%) and sulfonylureas ( n / N  = 4757/6236, 76.3%) were the most reported OADs. Basal ( n / N  = 837/6236, 13.4%) and premix ( n / N  = 684/6236, 11.0%) insulins were the most reported insulins., Conclusions: Baseline data from LANDMARC help understand the clinical/medical profile of study participants and underscore the extent of suboptimal glycemic control and prevalence of associated complications in a vast majority of Indians with T2DM., Competing Interests: AKD, AM, AGU, and NR received honoraria from Sanofi and other pharmaceutical companies. KMPK is on the advisory board of Sanofi and received honorarium for his talks. SJ received speaker/advisory/research grants from Abbott, Astrazeneca, Biocon, Boehringer Ingelheim, Eli Lilly, Franco Indian, Glenmark, Lupin, Marico, MSD, Novartis, Novo Nordisk, Roche, Sanofi, Serdia, Twinhealth, and Zydus. SK received honoraria/ speaker fees from Eli Lilly, Novo Nordisk, and Sanofi. HT received honoraria from MSD, Novartis, Sanofi and from other companies for advice and lectures. BS received honorarium from Aventis, Novo Nordisk, Eli Lilly, Boehringer Ingelheim (BI), and MSD. RG, AN, SM, SKM, VK, DC, VS, CT, and GC are employees of Sanofi. SC received honoraria/grants from Biocon, BI, Intas, Novartis, Sanofi, and Serdia. SKW has nothing to declare. AHZ received honoraria from Novo Nordisk, Eli Lilly, Johnson & Johnson, AstraZeneca, BI, and Sanofi., (© 2021 Sanofi. Published by John Wiley & Sons Ltd.)

Aim: India contributes towards a large part of the worldwide epidemic of diabetes and its associated complications. However, there are limited longitudinal studies available in India to understand the occurrence of diabetes complications over time. This pan-India longitudinal study was initiated to assess the real-world outcomes of diabetes across the country., Methods: The LANDMARC study is the first prospective, multicentre, longitudinal, observational study investigating a large cohort of people with type 2 diabetes mellitus across India over a period of 3 years. The primary objective of this ongoing study is to determine the proportion of people developing macrovascular diabetes complications over the duration of the study (36 months ± 45 days) distributed over seven visits; the secondary objective is to evaluate microvascular diabetes complications, glycaemic control and time-to-treatment adaptation or intensification. Overall, 6300 participants (aged 25-60 years) diagnosed with type 2 diabetes for at least 2 years will be included from 450 centres across India. Data will be recorded for baseline demographics, comorbidities, glycaemic measurements, use of anti-hyperglycaemic medications and any cardiovascular or other diabetes-related events occurring during the observational study period., Conclusions: The LANDMARC study is expected to reveal the trends in complications associated with diabetes, treatment strategies used by physicians, and correlation among treatment, control and complications of diabetes within the Indian context. The findings of this study will help to identify the disease burden, emergence of early-onset complications and dose titration patterns, and eventually develop person-centred care and facilitate public health agencies to invest appropriate resources in the management of diabetes. (Trial Registration No: CTRI/2017/05/008452)., (© 2019 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Two-component signaling systems are the primary means by which bacteria, archaea, and certain plants and fungi react to their environments. The model yeast, Saccharomyces cerevisiae, uses the Sln1 signaling pathway to respond to hyperosmotic stress. This pathway contains a hybrid histidine kinase (Sln1) that autophosphorylates and transfers a phosphoryl group to its own receiver domain (R1). The phosphoryl group is then transferred to a histidine phosphotransfer protein (Ypd1) that finally passes it to the receiver domain (R2) of a downstream response regulator (Ssk1). Under normal conditions, Ssk1 is constitutively and preferentially phosphorylated in the phosphorelay. Upon detecting hyperosmotic stress, Ssk1 rapidly dephosphorylates and activates the high-osmolarity glycerol (HOG) pathway, initiating a response. Despite their distinct physiological roles, both Sln1 and Ssk1 bind to Ypd1 at a common docking site. Co-crystal structures of response regulators in complex with their phosphorelay partners are scarce, leaving many mechanistic and structural details uncharacterized for systems like the Sln1 pathway. In this work, we present the co-crystal structure of Ypd1 and a near wild-type variant of the receiver domain of Ssk1 (Ssk1-R2-W638A) at a resolution of 2.80 Å. Our structural analyses of Ypd1-receiver domain complexes, biochemical determination of binding affinities for Ssk1-R2 variants, in silico free energy estimates, and sequence comparisons reveal distinctive electrostatic properties of the Ypd1/Ssk1-R2-W638A complex that may provide insight into the regulation of the Sln1 pathway as a function of dynamic osmolyte concentration., (© 2019 The Authors. Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.)

This study is conducted to review the literature systematically to determine most reliable outcome measures, important clinical and radiological variables affecting the prognosis in cervical spondylotic myelopathy patients. A literature search was performed for articles published during the last 10 years. As functional outcome measures we recommend to use modified Japanese Orthopaedic Association scale, Nurick's grade, and Myelopathy Disability Index. Three clinical variables that affect the outcomes are age, duration of symptoms, and severity of the myelopathy. Examination findings require more detailed study to validate their effect on the outcomes. The predictive variables affecting the outcomes are hand atrophy, leg spasticity, clonus, and Babinski's sign. Among the radiological variables, the curvature of the cervical spine is the most important predictor of prognosis. Patients with instability are expected to have a poor surgical outcome. Spinal cord compression ratio is a critical factor for prognosis. High signal intensity on T2-weighted magnetic resonance images is a negative predictor for prognosis. The most important predictors of outcome are preoperative severity and duration of symptoms. T2 hyperintensity and cord compression ratio can also predict outcomes. New radiological tests may give promising results in the future.

Objectives: Reports exist in the literature on the relationship between comorbid conditions and recurrence of lumbar disc herniation. Meanwhile, documented evidence abound on microdiscectomy and posterior lumbar interbody fusion (PLIF) as techniques of managing recurrent disc prolapse. Some surgeons would choose to perform PLIF instead of microdiscectomy for a first time re-herniation, because of the possibility of higher chances of further recurrence as well as increased likelihood of spinal instability following treatment with microdiscectomy. In this study, the authors sought to determine whether PLIF is better than microdiscectomy for first-time recurrent single-level lumbar disc prolapse and to compare the impact of comorbidities on outcome following revision., Patients and Methods: This was retrospective review of surgical treatment of patients with recurrent single-level disc prolapse with either microdiscectomy or PLIF at a tertiary health institution in India., Results: A total of 26 patients were evaluated. There was no statistically significant correlation between the presence of comorbidity and outcome in terms of improvement of pain ( P > 0.05 at 95% degree of confidence; Spearman's ρ =0.239). Patients who had PLIF were neither more nor less likely to have a better outcome compared to those who had microdiscectomy, though this finding was not statistically significant (odds ratio = 0.263; P = 0.284)., Conclusion: There was no significant relationship between the presence of comorbidity and outcome following revision. Microdiscectomy did not prove to be a better option than PLIF for surgical management of recurrent single-level disc prolapse. A quality randomized controlled study would help to validate these findings., Competing Interests: There are no conflicts of interest.

Background: Many bacteria and certain eukaryotes utilize multi-step His-to-Asp phosphorelays for adaptive responses to their extracellular environments. Histidine phosphotransfer (HPt) proteins function as key components of these pathways. HPt proteins are genetically diverse, but share a common tertiary fold with conserved residues near the active site. A surface-exposed glycine at the H + 4 position relative to the phosphorylatable histidine is found in a significant number of annotated HPt protein sequences. Previous reports demonstrated that substitutions at this position result in diminished phosphotransfer activity between HPt proteins and their cognate signaling partners., Results: We report the analysis of partner binding interactions and phosphotransfer activity of the prototypical HPt protein Ypd1 from Saccharomyces cerevisiae using a set of H + 4 (G68) substituted proteins. Substitutions at this position with large, hydrophobic, or charged amino acids nearly abolished phospho-acceptance from the receiver domain of its upstream signaling partner, Sln1 (Sln1-R1). An in vitro binding assay indicated that G68 substitutions caused only modest decreases in affinity between Ypd1 and Sln1-R1, and these differences did not appear to be large enough to account for the observed decrease in phosphotransfer activity. The crystal structure of one of these H + 4 mutants, Ypd1-G68Q, which exhibited a diminished ability to participate in phosphotransfer, shows a similar overall structure to that of wild-type. Molecular modelling suggests that the highly conserved active site residues within the receiver domain of Sln1 must undergo rearrangement to accommodate larger H + 4 substitutions in Ypd1., Conclusions: Phosphotransfer reactions require precise arrangement of active site elements to align the donor-acceptor atoms and stabilize the transition state during the reaction. Any changes likely result in an inability to form a viable transition state during phosphotransfer. Our data suggest that the high degree of evolutionary conservation of residues with small side chains at the H + 4 position in HPt proteins is required for optimal activity and that the presence of larger residues at the H + 4 position would cause alterations in the positioning of active site residues in the partner response regulator.

The Clostridioides difficile R20291 genome encodes 57 response regulator proteins that, as part of two-component signaling pathways, regulate adaptation to environmental conditions. Genomic and transcriptomic studies in C. difficile have been limited, due to technical challenges, to the analysis of either high-throughput screens or high-priority targets, such as primary regulators of toxins or spore biology. We present the use of several technically accessible and generally applicable techniques to elucidate the putative regulatory targets of a response regulator, RR&#95;1586, involved in sporulation of the hypervirulent C. difficile strain R20291. A DNA-binding specificity motif for RR&#95;1586 was determined using a bacterial one-hybrid assay originally developed for Drosophila transcription factors. Comparative bioinformatics approaches identified and in vitro experiments confirmed RR&#95;1586 binding sites upstream of putative target genes, including those that encode phosphate ion transporters, spermidine/putrescine biosynthesis and transport pathways, ABC type transport systems, known regulators of sporulation, and genes encoding spore structural proteins. Representative examples of these regulatory interactions have been tested and confirmed in Escherichia coli -based reporter assays. Finally, evidence of possible regulatory mechanisms is also presented. A working model includes self-regulation by RR&#95;1586 and phosphorylation-dependent and -independent DNA binding at low- and high-fidelity binding sites, respectively. Broad application of this and similar approaches is anticipated to be an important catalyst for the study of gene regulation by two-component systems from pathogenic or technically challenging bacteria. IMPORTANCE Clostridioides difficile spores survive under harsh conditions and can germinate into actively dividing cells capable of causing disease. An understanding of the regulatory networks controlling sporulation and germination in C. difficile could be exploited for therapeutic advantage. However, such studies are hindered by the challenges of working with an anaerobic pathogen recalcitrant to genetic manipulation. Although two-component response regulators can be identified from genetic sequences, identification of their downstream regulatory networks requires further development. This work integrates experimental and bioinformatic approaches, which provide practical advantages over traditional transcriptomic analyses, to identify the putative regulon of the C. difficile response regulator RR&#95;1586 by first screening for protein-DNA interactions in E. coli and then predicting regulatory outputs in C. difficile ., (Copyright © 2018 Hebdon et al.)

Background: Previous comparative studies have shown that apart from lack of any significant difference in neurologic outcomes between laminoplasty and laminectomy following resection of intradural spinal tumours, spinal column issues such as postoperative deformities, malalignment, and adjacent level disease have also been clearly demonstrated to be quite similar for both techniques. However, there is no study yet that describes any difference in neurologic outcomes for long-segment intradural lesions as a rare subset of these lesions (in terms of number of spinal segments involved) following surgical management between these two techniques., Materials and Methods: This is a retrospective review of surgical treatment with either laminectomy or laminoplasty done for patients with long-segment intradural tumors at a tertiary health-care institution in India., Results: Out of over 167 patients surgically treated for intradural tumors during the study period, a total of 60 patients were included in the evaluation. The long-segment tumors were intramedullary in 22 (36.7%) patients and intradural-extramedullary in the remaining 38 (63.3%) patients. No patient in both cohorts had any revisional surgery after initial resection or any serious complications. The incidence of neurologic function remaining unchanged at the end of follow-up was similar between laminoplasty and laminectomy (12.5% vs. 11.1%). There was no significant correlation between the preoperative McCormick score and postoperative McCormick score ( P > 0.05 at 95% degree of confidence; Spearman's rho = 0.028), suggesting that functional outcomes were not dependent on the initial neurologic status. Multivariate logistic regression analysis showed that : the two independent variables (Extent of surgery and Choice of procedure) were not significant predictors of the dependent variable (Functional outcome following surgery) (odds ratio = 3.836; p = 0.071)., Conclusion: This retrospective evaluation demonstrates laminoplasty not to be more or less likely to have any better functional outcome or need for revision compared to laminectomy in the resection of long-segment intradural lesions. A quality randomized controlled study on a much larger scale will be required to validate this finding., Competing Interests: There are no conflicts of interest.

Perfluoropolyether tetraol (PFPE tetraol) possesses a hydrophobic perfluoropolyether chain in the backbone and two hydroxyl groups at each chain terminal, which facilitates the formation of hydrogen bonds with water molecules resulting in the formation an extended physical network. About 3 wt% water was required for the formation of the microphase separated physical network of PFPE tetraol. The mechanism responsible for the microphase separation of water clusters in the physical network was studied using a combination of techniques such as NMR spectroscopy, molecular dynamics (MD) simulations and DSC. MD simulation studies provided evidence for the formation of clusters in the PFPE tetraol physical network and the size of these clusters increased gradually with an increase in the extent of hydration. Both MD simulations and NMR spectroscopy studies revealed that these clusters position themselves away from the hydrophobic backbone or vice versa. The presence of intra- and inter-chain aggregation possibility among hydrophilic groups was evident. DSC results demonstrated the presence of tightly and loosely bound water molecules to the terminal hydroxyl groups of PFPE tetraol through hydrogen bonding. The data from all the three techniques established the formation of a physical network driven by hydrogen bonding between the hydrophilic end groups of PFPE tetraol and water molecules. The flexible nature of the PFPE tetraol backbone and its low solubility parameter favour clustering of water molecules at the terminal groups and result in the formation of a gel.

Background: Though different techniques have been successfully employed in the treatment of recurrent lumbar disc herniation, the one which should be considered most ideal has remained a controversy, particularly since there are currently no generally accepted guidelines for surgical care., Objective: To review previous publications comparing the available operative options, with the aim of determining if any of the available interventions gives better outcomes compared to others., Methods: A systematic literature review of previous publications comparing various techniques employed in the surgical treatment of recurrent disc herniation., Results: All publications investigated in this review clearly demonstrated quite comparable outcomes, with no superiority of one method over the other., Conclusion: In view of the currently available data and evidence, minimally invasive techniques for revision of recurrent disc herniation do not really appear to be superior to the conventional open surgical approaches and vice-versa. We suggest the management strategy for surgical treatment of each case of recurrence to be simply based on the experience of the surgeon, the available facilities and equipment. Fusion should not be undertaken in all recurrences but should only be considered as an option for revision when spinal instability, spinal deformity or associated radiculopathy is present.

OBJECTIVE Neurogenic kyphoscoliosis in pediatric patients has varied causes and diverse management options. The most common management strategy is to stage the orthopedic and neurosurgical aspects of the correction at an interval of 3-6 months from each other. The aim of this study was to report the authors' experience with correction of deformity in children with associated neurological abnormalities requiring intervention as a single-stage surgical treatment. METHODS Of 591 pediatric patients with scoliosis treated at the Amrita Institute of Medical Sciences and Research Centre between January 2001 and January 2011, the authors identified all patients with neurogenic kyphoscoliosis who underwent deformity correction and a neurosurgical procedure in the same surgical session when they were younger than 15 years. Data regarding the demographic details, preoperative Cobb angle/kyphotic angle, surgical details, postoperative complications, cost of the procedure, and long-term neurological outcome were collected for each case and analyzed. Based on the results of this analysis, the authors propose a 2-category risk stratification system for the timing of deformity correction depending on the primary neurogenic etiology. RESULTS Ten cases involving patients with neurogenic kyphoscoliosis requiring both deformity correction and neurosurgical procedure met the criteria and were included in the analysis. All 10 patients were younger than 15 years; their mean age was 10.8 years. The average Cobb angle was 59.5°. Five patients underwent foramen magnum decompression, 5 patients underwent spinal cord detethering, and 1 patient had intraspinal intradural tumor excision. The mean estimated blood loss was 1177 ml (range 700-1550 ml), and the mean operative time was 4.4 hours (range 3-5.5 hours). There were no intraoperative complications. None of the patients had any new postoperative neurological deficits. The mean postoperative Cobb angle of the main thoracic curve was 12.6°. CONCLUSIONS Simultaneous deformity correction along with a definitive neurosurgical procedure in patients with neurogenic kyphoscoliosis can be performed without added morbidity and avoids both the added costs and the risk of complications associated with a second surgery. The risk stratification system proposed in this paper may serve as a guideline for case selection and help to optimize outcome.

Determination of time since death (TSD) plays very important role in forensic examination as it narrows down field of suspects and aids in deceased identification. This study utilizes the fluorescence property of vitreous humor (VH) tryptophan to determine TSD using o-phthalaldehyde (OPA). The detection limit of these fluorometric studies was found to be 8 ppb indicating sensitivity and high accuracy in TSD determination. The study was performed on selected 76 cadaver with known TSD ranging from 3 to 90 h. Excellent correlation between VH tryptophan and TSD was obtained with a coefficient of correlation R 2 = 0.9590. Results showed statistically significant increase in vitreous tryptophan with TSD up to 90 h, and the proposed method was efficaciously applied for prediction of TSD as no systematic error exist. The regression equation obtained from the study is [Trp] = 2.21 + 2.98 * TSD., (© 2017 American Academy of Forensic Sciences.)

Mortality and morbidity attributed to asthma remains to be the biggest nightmare worldwide. Hence, the study was aimed to compare the cardio metabolic risk factors as assessed by Body mass index (BMI), waist hip ratio (WHR), serum triacylglycerol and uric acid in well controlled and poorly controlled asthmatics and to correlate these parameters with the severity of asthma. A case control study was conducted on 90 subjects who were segregated into well controlled asthmatics (n = 30) and poorly controlled asthmatics (n = 30) who were diagnosed based on Global initiative for Asthma management guidelines and healthy volunteers (n = 30). Centrifuged fasting venous blood samples were used for biochemical analysis, pulmonary function test, BMI, and waist hip ratio (WHR) were measured. The statistical analysis was done using SPSS version 17. There was a significant increase in BMI, WHR, lipid profile, serum uric acid and decrease in forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC in poorly controlled asthmatics. There was a significant association between FEV1 and serum uric acid, BMI and Triacylgycerol in poorly controlled asthmatics. Poorly controlled asthmatics have greater risk of developing cardiometabolic problems. Serum uric acid can be used as one of the severity markers in asthma to assess cardio metabolic risk.

Context: Asthma is a chronic inflammatory disorder of the airway with involvement of various cellular populations and release of many inflammatory mediators. Eosinophils and serum immunoglobulin E (IgE) are considered a good marker of airway inflammation in asthma. The correlation of clinical assessment with various markers of airway inflammation in asthma is not well established in the Indian population., Aims: This study aims to study the correlation of serum IgE, sputum eosinophil count, and peripheral eosinophil count with clinical severity of Asthma., Methods: This is a cross-sectional study involving 76 stable asthmatic patients of 18-60 years of age attending the pulmonary medicine OPD. Spirometry measured at baseline. Participants were categorized according to the GINA criteria based on clinical symptoms and pulmonary function test. Blood samples were collected for peripheral eosinophil count, serum IgE levels, and sputum samples for eosinophil count. All three parameters were compared with severity of asthma. The correlation of sputum eosinophil count, peripheral eosinophil count, and serum IgE with severity of asthma was analyzed by Pearson's Chi-square test, Fisher's exact test, and the correlation coefficient was reported together with standard error of the estimate., Results: The mean age of patients in our study was 37.42 years and 56.6% were male. There was a significant inverse correlation between serum IgE levels and predicted forced expiratory volume 1 s (FEV1). Sputum eosinophilia was significantly seen in severe persistent asthma patients (19.7%). There was a significant inverse correlation between sputum eosinophil count and predicted FEV1and forced vital capacity. We also found there was a significant association between peripheral eosinophil count, sputum eosinophil count, and elevated serum IgE (g100 IU/mL) with severe persistent asthma., Conclusions: The assessment of sputum eosinophil count is simple, inexpensive, noninvasive, and direct measurement of airway inflammation. It could be the preferred method in monitoring airway inflammation and guided management in day-to-day practice.

Introduction: Hypothyroidism is a silent epidemic of our times. In India, the prevalence of hypothyroidism is 11%. The effect of hypothyroidism on respiratory system is debatable with studies suggesting both obstructive and restrictive disease patterns. The symptoms range from mild dyspnoea to life-threatening respiratory failure. This study emphasizes the effect of hypothyroidism on dynamic respiratory functions., Aim: To find out the changes in dynamic respiratory functions (FVC, FEV1, FEV1% and PEFR) in both male and female hypothyroid patients within age group of 18-45 years., Materials and Methods: This cross-sectional study was conducted in Jubilee Mission Medical College, Thrissur, Kerala, India. Total number of 60 newly detected cases of both sexes in 18-45 years age group attending endocrinology outpatient department were enrolled. Patients with previous respiratory diseases and history of smoking were excluded. Proforma was filled up followed by clinical examination. Spirometry was performed using a computerised spirometer 'microQuark'. The data was analysed by paired t-test and Analysis of Variance (ANOVA) test., Results: The mean of the observed values in all the dynamic pulmonary parameters showed highly significant difference from the predicted mean of the parameters (p<0.001). They also decreased considerably with age, gender and BMI which were statistically significant (p<0.05)., Conclusion: The above findings suggest that respiratory abnormality in newly detected cases of hypothyroidism shows a mixed pattern. This highlights that while investigating a patient with respiratory disorder, the thyroid status should always be probed into, as the effects of hypothyroidism can be reversed with proper treatment.

Present study represents a novel approach of PCR ready-human DNA extraction method from skeletal remains using copper nanoparticles (CuNPs) for personnel identification. To achieve rapid, cost effective, sensitive and non-hazardous method for DNA extraction we utilized CuNPs synthesized using microwave. The applicability of this approach was first tested in blood samples and afterwards, this system was extended to skeletal remains' samples also. This method yields good quality DNA that are ready for PCR reactions from small quantities of blood and skeletal remains. Consequently, even small quantities of nanoparticles could be potentially utilized for a highly efficient isolation of DNA from skeletal remains as well as from ancient archaeological samples. The present method has the advantages that it is quick with high yield, inexpensive, robust, environment friendly and does not require use of hazardous organic solvents., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In this work, we report the smart application of AgNPs based sensors for determination of time since death (TSD) via recognition and quantification of vitreous humor (VH) cystine as well as provide the portability for on spot determination of TSD. The lower detection limit was found to be 7.0ng/ml with prominent selectivity. It was found that there is a linear correlation between the VH cystine concentration and TSD as the concentration of cystine increases up to 96h±3.9h. Further for the first time TSD determination is given a smart approach and it proves to have a great utility up to 24h±2.6h. The linear regression equation between TSD (the dependent variable), RGB intensity of cystine concentration till 24h (the independent variable) was found to be TSD=26.69+-0.05*x. The proposed method gives the smart detection, portability, rapidity, sensitivity, selectivity as well as cost effectiveness for determination of time since death., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Clostridium difficile is a spore-forming obligate anaerobe that can remain viable for extended periods, even in the presence of antibiotics, which contributes to the persistence of this bacterium as a human pathogen during host-to-host transmission and in hospital environments. We examined the structure and function of a gene product with the locus tag CDR20291&#95;0991 (cdPadR1) as part of our broader goal aimed at elucidating transcription regulatory mechanisms involved in virulence and antibiotic resistance of the recently emergent hypervirulent C. difficile strain R20291. cdPadR1 is genomically positioned near genes that are involved in stress response and virulence. In addition, it was previously reported that cdPadR1 and a homologue from the historical C. difficile strain 630 (CD630&#95;1154) were differentially expressed when exposed to stressors, including antibiotics., Results: The crystal structure of cdPadR1 was determined to 1.9 Å resolution, which revealed that it belongs to the PadR-s2 subfamily of PadR transcriptional regulators. cdPadR1 binds its own promoter and other promoter regions from within the C. difficile R20291 genome. DNA binding experiments demonstrated that cdPadR1 binds a region comprised of inverted repeats and an AT-rich core with the predicted specific binding motif, GTACTAT(N 2 )ATTATA(N)AGTA, within its own promoter that is also present in 200 other regions in the C. difficile R20291 genome. Mutation of the highly conserved W in α4 of the effector binding/oligomerization domain, which is predicted to be involved in multi-drug recognition and dimerization in other PadR-s2 proteins, resulted in alterations of cdPadR1 binding to the predicted binding motif, potentially due to loss of higher order oligomerization., Conclusions: Our results indicate that cdPadR1 binds a region within its own promoter consisting of the binding motif GTACTAT(N 2 )ATTATA(N)AGTA and seems to associate non-specifically with longer DNA fragments in vitro, which may facilitate promoter and motif searching. This suggests that cdPadR1 acts as a transcriptional auto-regulator, binding specific sites within its own promoter, and is part of a broad gene regulatory network involved, in part, with environmental stress response, antibiotic resistance and virulence.

Rapid response to external stimuli is crucial for survival and proliferation of microorganisms. Pathogenic fungi employ histidine-to-aspartate multistep phosphorelay systems to respond to environmental stress, progress through developmental stages and to produce virulence factors. Because these His-to-Asp phosphorelay systems are not found in humans, they are potential targets for the development of new antifungal therapies. Here we report the characterization of the histidine phosphotransfer (HPt) protein Ypd1 from the human fungal pathogen Cryptococcus neoformans Results from this study demonstrate that CnYpd1 indeed functions as a phosphorelay protein in vitro, and that H138 is confirmed as the site of phosphorylation. We found that CnYpd1 exhibits unique characteristics in comparison to other histidine phosphotransfer proteins, such as an extended N-terminal amino acid sequence, which we find contributes to structural integrity, a longer phosphorylated life time and the ability to bind calcium ions., (© FEMS 2016.)

Creatinine is the most important parameter to be determined in the diagnosis of renal, muscular and thyroid function. The most common method for the determination of creatinine is Jaffe's reaction, a routine practice for blood and urine analysis. However, in cases of icteric and haemolyzed blood samples, interference occurs during the estimation of creatinine by other constituents present in the blood like bilirubin, creatine, and urea, which lead to wrong diagnosis. To overcome such difficulty, we have developed a silver nanoparticle (Ag NPs) based sensor for the selective determination of creatinine. In this study, a new approach has been given to the traditional Jaffe's reaction, by coating Ag NPs with picric acid (PA) to form an assembly that can selectively detect creatinine. The Ag NPs based sensor proficiently and selectively recognizes creatinine due to the ability of picric acid to bind with it and form a complex. The nanoassembly and the interactions were investigated by transmission electron microscopy (TEM), dynamic light scattering (DLS) analysis, UV-Vis spectroscopy, FT-IR spectroscopy and ESI-MS, which demonstrated the binding affinity of creatinine with PA-capped Ag NPs. A linear correlation was obtained in the range of 0.01 μM-1 μM with an R(2) value of 0.9998 and a lower detection limit of 8.4 nM. The sensor was successfully applied to different types of blood and CSF samples for the determination of creatinine, and the results were compared to that of the Jaffe's method. With the advantages of high sensitivity, selectivity and low sample volume, this method is potentially suitable for the on-site monitoring of creatinine.

A new, simple, ultra-sensitive and selective approach has been reported for the "on spot" colorimetric detection of creatinine based on calix[4]arene functionalized gold nanoparticles (AuNPs) with excellent discrimination in the presence of other biomolecules. The lower detection limit of the method is 2.16nM. The gold nanoparticles and p-tert-butylcalix[4]arene were synthesized by microwave assisted method. Specifically, in our study, we used dynamic light scattering (DLS) which is a powerful method for the determination of small changes in particle size, improved selectivity and sensitivity of the creatinine detection system over colorimetric method. The nanoassembly is characterized by Transmission electron microscopy (TEM), DLS, UV-vis and ESI-MS spectroscopy, which demonstrates the binding affinity due its ability of hydrogen bonding and electrostatic interaction between -NH group of creatinine and pSDSC4. It exhibits fast response time (<60s) to creatinine and has long shelf-life (>5 weeks). The developed pSDSC4-AuNPs based creatinine biosensor will be established as simple, reliable and accurate tool for the determination of creatinine in human urine samples., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Estimation of postmortem interval is a very important question in some medicolegal investigations. For the precise estimation of postmortem interval, there is a need of a method which can give accurate estimation. Bromocresol green (BCG) is a simple dye binding method and widely used in routine practice. Application of this method in forensic practice may bring revolutionary changes. In this study, cerebrospinal fluid was aspirated from cisternal puncture from 100 autopsies. A study was carried out on concentration of albumin with respect to postmortem interval. After death, albumin present in CSF undergoes changes, after 72 h of death, concentration of albumin has become 0.012 mM, and this decrease was linear from 2 h to 72 h. An important relationship was found between albumin concentration and postmortem interval with an error of ± 1-4h. The study concludes that CSF albumin can be a useful and significant parameter in estimation of postmortem interval., (Copyright © 2015 The Chartered Society of Forensic Sciences. Published by Elsevier Ireland Ltd. All rights reserved.)

Cerebrospinal fluid (CSF) leak is a common complication of surgery involving the lumbar spine. Over the past decades, there has been significant advancement in understanding the basis, management and techniques of treatment for post-operative CSF leak following lumbar spine surgery. In this article, we review previous work in the literature on the various factors and technical errors during or after lumbar spine surgery that may lead to this feared complication, the available options of management with focus on the various techniques employed, the outcomes and also to highlight on the current trends. We also discuss the presentation, factors contributing to its development, basic concepts and practical aspects of the management with emphasis on the different techniques of treatment. Different outcomes following various techniques of managing post-operative CSF leak after lumbar spine surgery have been well described in the literature. However, there is currently no most ideal technique among the available options. The choice of which technique to be applied in each case is dependent on each surgeon's cumulative experience as well as a clear understanding of the contributory underlying factors in each patient, the nature and site of the leak, the available facilities and equipment., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The National Heart Foundation (NHF) and Cardiac Society of Australia and New Zealand (CSANZ) Acute Coronary Syndrome (ACS) guidelines recommend the use of a high sensitivity troponin assay (hsTrop) in the assessment of patients presenting with ACS. A troponin delta of 50% compared with the previously recommended 20% is advocated by the guidelines to aid in the clinical diagnosis of ACS. We sought to determine the clinical impact of the updated recommendation to use 50% troponin delta for patients presenting with chest pain to the emergency department., Method: We retrospectively collected data for all patients >18 years presenting with chest or abdominal pain with a hsTrop test performed between January-June 2012. Patients with a STEMI, lacked serial hsTrop, were on dialysis or had trauma-related pain were excluded., Results: Of the 1054 eligible patients, 422 (40%) with serial hsTrop had at least one abnormal troponin (>14 ng/ml). 73 (6.9%) fell within 20-50%. Twenty-seven had clinical or ECG evidence suggestive of ACS and were referred for further cardiac investigations. Of the remainder, five patients were medically managed for ACS, 38 patients with non-cardiac chest pain had no further tests. At 1 year follow-up, of the patients that did not undergo further investigations, 6 patients represented with ACS; there was no cardiac mortality., Conclusion: Our data showed a number of patients that would be potentially missed with the implementation of a 50% troponin. However, this loss of sensitivity was mitigated by the use of clinical acumen., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

A novel photoinduced electron transfer (PET) based substituted calix[4]arene fluoroionophore has been used for the selective recognition of tryptophan (L-Trp) and histidine (L-His) by emission spectroscopy. The detection limit of the synthesized receptor was found to be 0.00826 nM for L-Trp and 0.00158 nM for L-His. Moreover, this probe has been applied for the recognition of L-Trp and L-His from blood serum.

Neurofibromatosis type 1 (NF-1) is a heterogeneous autosomal dominant disease with an incidence ranging from 1 in 2500 to 1 in 3000. Rare intrathoracic vascular disorders resulting in massive spontaneous hemothorax with fatal consequences may occur in these patients, so also are various types of skeletal dysplasia which may result in dramatic presentations, posing management challenges to the attending physicians. We report the case of a 43-year-old woman with NF-1 who developed spontaneous massive hemothorax and was discovered to have a concurrent giant intrathoracic meningocele and thoracic kyphoscoliosis with severe vertebral dysplastic changes. Surgical treatment via a right thoracotomy with primary repair of the meningocele and spinal fusion with fibula graft resulted in good outcome. This case represents an extreme manifestation of this otherwise indolent disease in clinical practice.

Pruritic patches on the patient's trunk and extremities prompted his visit, but it was the "birthmark" on his back that was far more worrisome.

Inexpensive, rapid, and reliable methods of detection are crucial to the control of toxicological investigations. Here we report a highly sensitive, selective and cost effective method for the detection of trace amounts of clonazepam based on gold nanoparticles (AuNPs) in the presence of melamine. Hydrogen bonding interactions between clonazepam and melamine resulted in the aggregation of AuNPs and a consequent color change of AuNPs from wine red to blue. The results showed that the absorption ratio (A636/A552) was linear for clonazepam concentrations in the range of 10 × 10(-8) to 1.0 × 10(-9) M (R(2) = 0.999). The detection limit was 8.9 × 10(-10) M (S/N = 3), which was much lower than that of most existing methods. Coexisting substances including alprazolam, diazepam, nitrazepam and lorazepam did not affect the determination of clonazepam. The sensor developed by this new approach could be used as a spot test and a good alternative means for on-site and real time screening of clonazepam. This proposed scheme was also supported by the use of real samples such as skeletal remains and blood to illustrate the applicability of the developed nanosensor by a series of experiments.

The present work reports a series of novel cationic fullerene derivatives bearing a substituted-quinazolinone moiety as a side arm. Fullerene-quinazolinone conjugates synthesized using the 1,3-dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinone were characterized by elemental analysis, FT-IR, (1)H NMR, (13)C NMR and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H 37 Rv strain). All the compounds exhibited significant activity with the most effective having MIC in the range of 1.562-3.125 μg/mL. Compound 9f exhibited good biological activity compared to standard drugs. We developed a computational strategy based on the modeled M. tuberculosis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) using homology modeling techniques and studied its binding pattern with synthesized fullerene derivatives. We then explored the surface geometry of the protein to place the cage adjacent to the active site while optimizing its quinazolinone side arm to establish H bonding with active site residues.

A novel PET with ICT based substituted calix[4]arene fluroionophore was synthesized and used for detection of Cu(2+) and F(-) by emission spectra. The detection limit of the synthesized receptor was found to be 4.16 nM for Cu(2+) and 2.15 nM for F(-). Moreover, this probe has been applied for recognition of Cu(2+) in blood serum and F(-) from waste water.

A novel PET (photoinduced electron transfer) based substituted calix[4]arene fluoroionophore has been synthesized and used for the selective recognition of Cd(2+) and Sr(2+) by emission spectra. The detection limit of the synthesized receptor was found to be 0.94 pM for Cd(2+) and 1.04 pM for Sr(2+). Moreover, this probe has been applied to the recognition of Cd(2+) and Sr(2+) in waste water.

We developed a new, advanced, simple and non enzymatic approach for the colorimetric detection of glucose based on calix[4]arene/phenyl boronic acid (CX-PBA)functionalized gold nanoparticles (AuNPs). This molecular receptor proficiently and selectively recognizes glucose due to its ability to reversibly bind diol-containing compounds. The assembly was characterized by transmission electron micrograph (TEM), dynamic light scattering (DLS), UV-Vis, FT-IR, ESI-MS and (1)H NMR spectrometry, which demonstrates the binding affinity for glucose via a boronic acid-diol interaction. The linear range for glucose was found to be 5-100 nM with phosphate buffer pH 10, with a lower detection limit of 4.3 nM. Interference by other saccharides was negligible. The biosensor has been successfully applied to estimate the glucose in human blood serum samples and the results compared well to an automatic analyzer. With the advantages of high sensitivity, selectivity and low sample volume, this method is potentially suitable for the on-site monitoring of glucose.

A high concern for human health and safety has motivated dynamic research on the potential impact of transition metal ions and their toxic effects, thus it is very challenging to design transition-metal ion detection devices that are cost-effective, rapid and applicable to the biological milieus. Driven by the need to detect trace amounts of Fe(3+) from blood samples, we report a highly selective and ultrasensitive calix[4]arene modified silver nanoprobe for Fe(3+) recognition at the 9.4 nM level from aqueous solution with excellent discrimination against other heavy metals and biomolecules. The assembly was characterized by TEM (transmission electron microscopy), DLS (dynamic light scattering), UV-Vis, FT-IR, ESI-MS and (1)H NMR spectrometry, which demonstrate the higher binding affinity for Fe(3+). The biosensor has been successfully applied to estimate the ferric ion in human blood serum as well as in human hemoglobin.

A series of novel cationic fullerene derivatives bearing a substituted-quinazolin-4(3H)-one moiety as a side arm were synthesized using the 1,3-dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinones. The synthesized compounds 5a-f were characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR, and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H37RV) and antimicrobial activity against selected Gram-positive (Staphylococcus aureus and S. pyogenes) and Gram-negative (Pseudomonas aeruginosa, Klebsiella pneumonia and Escherichia coli) bacterial and fungal strains (Candida albicans, Aspergillus clavatus, and A. niger), respectively. All the compounds exhibited significant activity, with the most effective compounds having MIC values and zones of inhibition comparable to those of standard drugs., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel structurally simple calix[4]arene appended 8-amidoquinoline linked conjugate was synthesized and has been used as a turn-on fluorescence probe for Zn(2+) and turn off fluorescence probe for F(-). Moreover, this probe has been applied for Zn(2+) detection in blood serum upto 8.7 μM and fluoride detection upto 22 nM in waste water samples, using emission spectra.