New validated RP-HPLC method for simultaneous estimation of chlorpromazine and trihexyphenidyl HCl in tablets

A simple, specific and precise reverse phase high performance liquid chromatographic method was developed and validated for simultaneous estimation of Chlorpromazine and Trihexyphenidyl HCl in tablets. Quantification was achieved by using a reverse-phase C18 column (Inertsil ODS 3V, 250 mm x 4.6 mm; 5) at 31 o C. The mobile phase consisted of a mixture of ammonium acetate buffer and methanol in the ratio of 15:85 v/v at a flow rate of 1.2 mL/min. The retention times of Chlorpromazine and Trihexyphenidyl HCl were found to be 3.237 min and 5.260 min respectively. The developed method was validated as per ICH Guidelines for linearity, accuracy, precision, detection limit, quantification limit, ruggedness, robustness, specificity and system suitability. The percentage recoveries for both of the drugs from their tablets were found to be 100.34 % and 99.80 % respectively. The method may successfully be employed for the simultaneous determination of Chlorpromazine and Trihexyphenidyl HCl in pharmaceutical tablet dosage forms

Potential screening strategies for early prediction of pre-eclampsia

Background: This study was conducted to evaluate the efficacy of different biochemical and biophysical markers in the early weeks of gestation as screening tools for early prediction of preeclampsia.Methods: This hospital-based prospective observational study conducted on 52 pregnant women, at less than 13 weeks of gestation were recruited. Maternal serum inhibin A and USG uterine artery PI levels were analyzed among the pregnant women who subsequently developed PE and compare with those who did not develop PE. Methods used for the detection of markers were: chemiluminescence immunoassay (CLIA) for serum inhibin A levels, and uterine artery Doppler velocimetry was done by PHILIPS HD11XE transabdominal ultrasound machine using a 4-6 MHz probe with the same sonographer.Results: The present study revealed a significant rise of inhibin A in preeclamptic women when compared to normotensive women (p<0.0001). The mean levels of 1st and 2nd trimester uterine artery PI significantly high in women who subsequently developed PE when compared to those who did not develop preeclampsia (p<0.0001). Study results showed a strong association between gestational age at delivery and neonatal outcome (neonatal birth weight and APGAR) with preeclampsia. The maternal serum inhibin A, and uterine artery PI found to have good sensitivity and specificity for early prediction of PE.Conclusions: Study concluded that the women who are prone to develop PE subsequently, had high levels of MAP, UAPI, inhibin A. In our setting, MAP, UAPI, inhibin A, appeared to be better screening modalities. Combination of the biochemical markers with the biophysical markers, demographic characteristics, and other novel markers will establish the effective screening models for early prediction of PE. Early identification of high-risk cases will offer an opportunity for prophylactic therapy, such as Low- dose Aspirin in selected groups of high-risk women screened in the first trimester, thus improving the maternal and perinatal outcome

POLYPHARMACY INDUCED DRUG INTERACTIONS, ADVERSE DRUG REACTIONS (ADR) AND MEDICATION ERRORS IN TERTIARY CARE SOUTH INDIAN HOSPITAL

Objective: To study the pattern of drug interactions (DI) in our hospital and to identify whether it is associated with polypharmacy. To determine the level of severity of potential drug-drug interactions (PDDI), to detect, monitor and prevention of ADRs in the hospitalized patients and to identify the medication errors (ME). Methods: A prospective interventional study was conducted in a 300 bedded tertiary care South Indian hospital for a period of 6 mo. Prescriptions were analysed for PDDI using Micromedex software 2.2. The causality and severity of ADRs were assessed by using Naranjo’s, WHO UMC Scales and Hart wigs severity scales. ME was identified by review of patient drug charts. Results: Total 190 prescriptions were analyzed, in which 1028 drug interactions were seen. Out of which 718 were DDI, 198 DFI, 100 DEI, and 12 DTI were observed. More number of DI was seen in cardiovascular drugs, antibiotics followed by antacids and antiulcer agents. A total of 52 ADRs were identified in 43 patients. Diuretics, cardiovascular drugs were associated with a higher incidence of ADRs followed by Anti-Diabetic agents. 58 ME was seen in 190 prescriptions, among them omission error, prescribing errors and Wrong dose error was seen. Conclusion: Clinical pharmacist plays a potential role in the health care system in assisting the physician i.e. modifying the number of drugs taken, number of doses taken, medication adherence, identification of drug interactions, preventing, monitoring and detection of ADRs and identifying the medication errors

Wwox deletion leads to reduced GABA-ergic inhibitory interneuron numbers and activation of microglia and astrocytes in mouse hippocampus

The association of WW domain-containing oxidoreductase WWOX gene loss of function with central nervous system (CNS) related pathologies is well documented. These include spinocerebellar ataxia, epilepsy and mental retardation (SCAR12, OMIM: 614322) and early infantile epileptic encephalopathy (EIEE28, OMIM: 616211) syndromes. However, there is complete lack of understanding of the pathophysiological mechanisms at play. In this study, using a Wwox knockout (Wwox KO) mouse model (2 weeks old, both sexes) and stereological studies we observe that Wwox deletion leads to a significant reduction in the number of hippocampal GABA-ergic (γ-aminobutyric acid) interneurons. Wwox KO mice displayed significantly reduced numbers of calcium-binding protein parvalbumin (PV) and neuropeptide Y (NPY) expressing interneurons in different subfields of the hippocampus in comparison to Wwox wild-type (WT) mice. We also detected decreased levels of Glutamic Acid Decarboxylase protein isoforms GAD65/67 expression in Wwox null hippocampi suggesting lower levels of GABA synthesis. In addition, Wwox deficiency was associated with signs of neuroinflammation such as evidence of activated microglia, astrogliosis, and overexpression of inflammatory cytokines Tnf-a and Il6. We also performed comparative transcriptome-wide expression analyses of neural stem cells grown as neurospheres from hippocampi of Wwox KO and WT mice thus identifying 283 genes significantly dysregulated in their expression. Functional annotation of transcriptome profiling differences identified ?neurological disease? and ?CNS development related functions? to be significantly enriched. Several epilepsy-related genes were found differentially expressed in Wwox KO neurospheres. This study provides the first genotype-phenotype observations as well as potential mechanistic clues associated with Wwox loss of function in the brain.Fil: Hussain, Tabish. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Kil, Hyunsuk. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Hattiangady, Bharathi. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Lee, Jaeho. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Kodali, Maheedhar. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Shuai, Bing. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Attaluri, Sahithi. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Takata, Yoko. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Shen, Jianjun. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Shetty, Ashok K.. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Aldaz, Claudio Marcelo. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados Unido

Vascular Malformation Involving the Maxillofacial Region: A Case Report

Vascular anomalies constitute some of the most difficult diagnostic and therapeutic enigmas in the head and neck region and most of the congenital vascular malformations were often misdiagnosed and left untreated. These lesions are the result of an embryonic abnormality of the vascular system. Vascular lesions in the maxillofacial region are rare. These lesions can cause facial asymmetry, loose teeth, tinnitus, headache, and bruits and can be complicated by life threatening conditions such as haemorrhage and heart failure. This article presents a case of 25-year old female patient reported to the Department of Oral Medicine and Radiology with a chief complaint of swelling on the left side of the face. Based on the clinical findings and radiological investigations such as USG with Color Doppler, MR Angiography and CBCT the case was diagnosed as slow flow venous malformation involving the left maxillofacial region. So, the present case report depicts that apart from the clinical findings advanced radiological techniques like contrast enhanced Magnetic Resonance Imaging and CBCT will acts as a useful tool for the accurate diagnosis of Vascular Anamolies (VA)

Computation of the Probabilistic Critical Centers and Reliability Indices of MSW Landfill Slopes Using the Spencer Method of Slices

The shear strength properties of Municipal Solid Waste (MSW) are of special importance when evaluating the stability of landfill slopes. Geoenvironmental engineers are well aware of the existence of many sources of uncertainties associated with shear strength parameters of MSW due to various reasons. The significant uncertainties associated with the shear strength and shear stresses render deterministic modeling potentially misleading. The traditional engineering approaches like method of slices used for evaluating MSW slopes are frequently questionable as they do not adequately account for uncertainties included in analytical modeling and natural variability. In order to quantify the slope stability precisely by taking into account the variability, the Reliability Based Design Optimization (RBDO) framework is presented. The mean and standard deviations associated with unit weight, cohesion and angle of internal friction of the MSW are taken into account in the probabilistic optimization. Reliability analysis is performed using first order reliability method (FORM). A limit state function is formulated against sliding slope failure using Spencer method of slices. The influence of coefficients of variation (COV) of stability number and friction angle on critical center coordinates and reliability index is presented in the form of charts

User Satisfaction and Technology Adoption in Smart Homes: A User Experience Test

Using a mixed-methods approach, we examine the complex link between user happiness and technology adoption in the context of smart homes. Our tests show that user happiness and adoption are highly influenced by the versions of smart home technologies, with Version A producing better user satisfaction (7.2) and adoption rates (68%) than Version B (6.8, 62%). Furthermore, consumers engaging with Features A and C reported the greatest adoption rates (80%) and satisfaction (8.1), indicating that certain features, particularly when paired, have a significant influence on user pleasure. Extended training times resulted in higher user satisfaction and adoption rates of the technology; the 6-hour training group had the greatest adoption rate (84%), and the highest satisfaction (8.3%). Furthermore, user age demographics have a substantial impact on adoption and happiness; young adults have the greatest adoption rate (70%) and contentment (7.6). These results highlight the necessity of developing smart home technologies that are appropriate for various age groups, as well as the significance of feature customization, thorough training, and user-centric design in improving user satisfaction and encouraging technology adoption. Introductio

A single intranasal dose of human mesenchymal stem cell-derived extracellular vesicles after traumatic brain injury eases neurogenesis decline, synapse loss, and BDNF-ERK-CREB signaling

An optimal intranasal (IN) dose of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs), 90 min post-traumatic brain injury (TBI), has been reported to prevent the evolution of acute neuroinflammation into chronic neuroinflammation resulting in the alleviation of long-term cognitive and mood impairments. Since hippocampal neurogenesis decline and synapse loss contribute to TBI-induced long-term cognitive and mood dysfunction, this study investigated whether hMSC-EV treatment after TBI can prevent hippocampal neurogenesis decline and synapse loss in the chronic phase of TBI. C57BL6 mice undergoing unilateral controlled cortical impact injury (CCI) received a single IN administration of different doses of EVs or the vehicle at 90 min post-TBI. Quantifying neurogenesis in the subgranular zone-granule cell layer (SGZ-GCL) through 5′-bromodeoxyuridine and neuron-specific nuclear antigen double labeling at ~2 months post-TBI revealed decreased neurogenesis in TBI mice receiving vehicle. However, in TBI mice receiving EVs (12.8 and 25.6 × 109 EVs), the extent of neurogenesis was matched to naive control levels. A similar trend of decreased neurogenesis was seen when doublecortin-positive newly generated neurons were quantified in the SGZ-GCL at ~3 months post-TBI. The above doses of EVs treatment after TBI also reduced the loss of pre-and post-synaptic marker proteins in the hippocampus and the somatosensory cortex. Moreover, at 48 h post-treatment, brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phosphorylated cyclic AMP response-element binding protein (p-CREB) levels were downregulated in TBI mice receiving the vehicle but were closer to naïve control levels in TBI mice receiving above doses of hMSC-EVs. Notably, improved BDNF concentration observed in TBI mice receiving hMSC-EVs in the acute phase was sustained in the chronic phase of TBI. Thus, a single IN dose of hMSC-EVs at 90 min post-TBI can ease TBI-induced declines in the BDNF-ERK-CREB signaling, hippocampal neurogenesis, and synapses

Observation of tW production in the single-lepton channel in pp collisions at root s=13 TeV

A measurement of the cross section of the associated production of a single top quark and a W boson in final states with a muon or electron and jets in proton-proton collisions at root s = 13 TeV is presented. The data correspond to an integrated luminosity of 36 fb(-1) collected with the CMS detector at the CERN LHC in 2016. A boosted decision tree is used to separate the tW signal from the dominant t (t) over bar background, whilst the subleading W+jets and multijet backgrounds are constrained using data-based estimates. This result is the first observation of the tW process in final states containing a muon or electron and jets, with a significance exceeding 5 standard deviations. The cross section is determined to be 89 +/- 4 (stat) +/- 12 (syst) pb, consistent with the standard model.Peer reviewe