Multiple Early Life Stressors as Risk Factors for Neurodevelopmental Abnormalities in the F1 Wistar Rats.

Cumulative exposure to multiple early life stressors is expected to affect behavioral development, causing increased susceptibility to neuropsychiatric disorders. The present study was designed to mimic such conditions in a rat model to study behavioral impairments during adolescence and adulthood. Female Wistar rats (n = 32; 140-150 gm) were switched to a low protein (LP; 8% protein) or control (20% protein) diet 15 days prior to conception, and then the diet regime was maintained throughout the experimental period. Pups born to control and LP dams were intraperitoneally injected with deltamethrin (DLT-pyrethroid insecticide; 0.7 mg/kg body weight; PND 1 to 7), lipopolysaccharide (LPS-bacterial endotoxin; 0.3 mg/kg body weight; PND 3 and 5), or DLT+LPS, on designated days forming eight experimental groups (Control, LP, Control+LPS, LP+LPS, Control+DLT, LP+DLT, Control+DLT+LPS and LP+DLT+LPS). Neurobehavioral assessments were performed in F1 rats (1, 3, 6 months) by open field, elevated plus maze, light and dark box, and rotarod tests. LP rats were found to be highly susceptible to either singular or cumulative exposure as compared to their age-matched control counterparts, showing significantly severe behavioral abnormalities, such as hyperactivity, attention deficits and low anxiety, the hallmark symptoms of neuropsychiatric disorders like schizophrenia and ADHD, suggesting thereby that early life multi-hit exposure may predispose individuals to developmental disorders.

Lithium-based perovskites materials for photovoltaic solar cell and protective rays window applications: a first-principle calculations.

Perovskites are the key enabler materials for the solar cell applications in the achievement of high performance and low production costs. In this article, the structural, mechanical, electronic, and optical properties of rubidium-based cubic nature perovskite LiHfO3 and LiZnO3 are investigated. These properties are investigated using density-functional theory with the aid of CASTEP software by introducing ultrasoft pseudo-potential plane-wave (USPPPW) and GG-approximation-PB-Ernzerhof exchange-correlation functionals. It is investigated that the proposed compounds exhibit stable cubic phase and meet the criteria of mechanical stability by the estimated elastic properties. Also, according to Pugh's criterion, it is noted that LiHfO3 is ductile and LiZnO3 is brittle. Furthermore, the electronic band structure investigation of LiHfO3 and LiZnO3 shows that they have indirect bandgap (BG). Moreover, the BG analysis of the proposed materials shows that these are easily accessible. Also, the results for partial density of states (DOS) and total DOS confirm the degree of a localized electron in the distinct band. In addition, the optical transitions in the compounds are examined by fitting the damping ratio for the notional dielectric functions scaling to the appropriate peaks. At absolute zero temperature, the materials are observed as semiconductors. Therefore, it is evident from the analysis that the proposed compounds are excellent candidates for solar cells and protective rays applications.

Zirconium-based cubic-perovskite materials for photocatalytic solar cell applications: a DFT study.

The structural, electronic, optical, and mechanical characteristics of the cubic inorganic perovskites XZrO3 (X = Rb and K) based on Rb and K were studied using Cambridge Serial Total Energy Package (CASTEP)-based density functional theory (DFT) via the ultrasoft pseudo-potential (USP) plane wave and generalized gradient approximation (GGA)-Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional. The measured lattice parameters are 3.55 Å and 4.23 Å, and the band gaps of RbZrO3 and KZrO3 are 3.57 eV and 3.78 eV, respectively. Our results indicate that the compounds have indirect and wide bandgaps, making them useful for improving conductivity. It is observed that the compounds have anisotropic, ductile, and brittle natures. The anisotropic factor values of RbZrO3 and KZrO3 are 0.67067 and 0.87224, and their Poisson's ratios are 0.27356 and 0.25853, respectively. In terms of optical properties, they exhibited high optical absorption and conductivity and were active in the visible region for solar cell applications. These results indicate that they could be highly useful for light-emitting diodes (LEDs) and other reflection purposes owing to their indirect bandgap. The results of our investigation of RbZrO3 and KZrO3 present them as favorable materials for solar cell and LED applications.

Oxidative-Stress-Induced Cellular Toxicity and Glycoxidation of Biomolecules by Cosmetic Products under Sunlight Exposure.

Cosmetics, commonly known as 'makeup' are products that can enhance the appearance of the human body. Cosmetic products include hair dyes, shampoos, skincare, sunscreens, kajal, and other makeup products. Cosmetics are generally applied throughout the face and over the neck region. Sunlight has different wavelengths of light, which include UV-A, UV-B, UV-C, and other radiations. Most cosmetic products have absorption maxima (λmax) in the range of visible light and UV-R. The effect of light-induced photosensitization of cosmetic products, which results in the production of free radicals through type-I and type-II photosensitization mechanisms. Free-radicals-mediated DNA damage and oxidative stress are common consequences of cosmetic phototoxicity. Cosmetic phototoxicity may include percutaneous absorption, skin irritation, eye irritation, photosensitization, mutagenicity, and genotoxicity. Oxidative stress induces membrane lipid peroxidation, glycoxidation, and protein covalent modifications, resulting in their dysfunction. Natural antioxidants inhibit oxidative-stress-induced cosmetic toxicity. Sunlight-induced photodegradation and accumulation of cosmetic photoproducts are also a matter of serious concern. India has tropical weather conditions throughout the year and generally, a majority of human activities such as commerce, agriculture, sports, etc. are performed under bright sunlight conditions. Thus, more focused and dedicated research is warranted to explore the effects of cosmetics on oxidative stress, glycoxidation of biomolecules, and photoproducts accumulation for its total human safety.

Pre-hospital Delay and Its Reasons in Patients With Acute Myocardial Infarction Presenting to a Primary Percutaneous Coronary Intervention-Capable Center.

Objective This study aimed to assess the duration of pre-hospital delay among ST-Segment Elevation Myocardial Infarction (STEMI) patients and its contributing factors. Methodology A cross-sectional study was conducted at Rural Satellite Center in Larkana, Pakistan from May to September 2020. A total of 240 STEMI patients who underwent primary percutaneous coronary intervention (P-PCI) were included. The patients' demographic characteristics, index event characteristics, mode of transportation, misinterpretations, misdiagnoses, and financial problems were recorded. Data were analyzed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Results The observed pre-hospital time was 120 minutes; 229 (median; interquartile range [IQR]). It was found that 33.3% of patients arrived within one hour of the symptom onset, while 20.4% of patients delayed hospital arrival for more than six hours. The delay rate was highest among patients aged 41 to 65 years. Moreover, delayed admissions were more common among females as compared to males (p=0.008). Among the causes of delay in hospital arrival were misinterpretation, misdiagnosis, and transportation and financial issues. Of these, misdiagnosis significantly influenced the delay rate, i.e., more than 50% of the misdiagnosed patients arrived hospital after six hours of symptom onset (p<0.05). Conclusion The P-PCI rural satellite center had a positive impact as the observed pre-hospital delay rate was considerably less as compared to that reported in the existing literature. Moreover, the confounding factors were misdiagnosis and misinterpretations. We need to develop the concept of immediate appropriate help-seeking among patients.

Optimization of metronidazole SR buccal tablet for gingivitis using genetic algorithm.

Gingivitis is a condition that needs sustained concentration of antibiotic locally over extended period of time. The current study aimed to formulate and evaluate the sustained and localized release of metronidazole (MTZ) as mucoadhesive buccal tablet containing hydroxypropylmethyl cellulose (HPMC), Carbopol 940® (CP), carboxymethylcellulose (CMC) and ethyl cellulose (EC) as mucoadhesive polymers. Tablets were directly compressed with proportions of polymeric blends (F1-F16). The results indicated that weight variation (249±2.10mg) and friability (0.21%) were within USP compendial limits. Maximum mucoadhesive strength and time were depicted by F1 and F14 which were 28.47g and 12hr respectively. Formulations, except F4, were within physiological pH limit. Maximum swellability index (261.9%) was exhibited by F16, at 8 hr, containing highest concentration of CP, HPMC and additional CMC. For in vitro release, the pre-set 8 hr complete release were shown by formulations, F15 and F16 which were 100% and 97%, respectively. Genetic algorithm was applied on the attributes to optimize polymeric response in accordance with desirability. The software predicted composition (F17) was tested which revealed that physical characteristics were in accordance with the compendial standards. The release kinetics, evaluated through DDsolver⌖, suggested that release of MTZ followed non-Fickian diffusion type in Korsmeyer-Peppas model. Therefore, MTZ, if delivered as mucoadhesive buccal formulation (F17) containing amounts (mg) of CP (16.4), HPMC (78.7), CMC (8.3) and EC (10.5) will simulate satisfactory release i.e. 96% at 8 hr in simulated buccal fluid.

Depression and Anxiety in patients undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome.

BACKGROUND AND OBJECTIVE: Depression and anxiety are very common in patients with cardiac diseases. Percutaneous coronary intervention (PCI) has not only decreased mortality but angina, heart failure and recurrent hospitalization all are improved. Therefore, anxiety and depression associated with fibrinolytic therapy in acute coronary syndrome (ACS) are expected to be decreased in the patient undergoing PCI. Therefore, the aim of this study was to determine prevalence of depression and anxiety in patients undergoing percutaneous coronary intervention for acute coronary syndrome. METHODS: This study was conducted at Larkana Satellite Center of National Institute of Cardiovascular Diseases (NICVD), Pakistan from August 2018 to December 2018. Patients who underwent cardiac intervention within one month were enrolled in this study. Patients were interviewed regarding their basic demographics, indication for intervention and procedure details. Symptoms of anxiety were assessed using the translation of inventory of SAS (Zung's Self-Rating Anxiety Scale). Patients were interviewed for depression by using Becks depression inventory (BDI). RESULTS: A total of 153 patients were included in this study out of which 118 (77.1%) were males and 35 (22.5%) were females. All were married except one. Diabetes mellitus (DM) was present in 61 (39.9%), hypertension (HTN) in 69 (45.15%), obesity in 15 (9.8%), and 40 (26.1%) were smokers. Depression was present in 16 (10.5%) patients and anxiety was present in 12 (7.5%) of patients. On analysis of the association of various factor with depression; non-diabetics, housewives, laborers and uneducated were found to be more depressed. While those who smoke or earn more than 50 thousand were found less likely to be depressed. CONCLUSION: Both depression and anxiety were present in only 10.5% and 7.5% of the patients after percutaneous coronary intervention for acute coronary syndrome.

Outcome at Six Months After Primary Percutaneous Coronary Interventions Performed at a Rural Satellite Center of Sindh Province of Pakistan.

Introduction Primary percutaneous coronary intervention (PPCI) is now a well-established treatment of acute ST-elevation myocardial infarction (STEMI). For the first time in Pakistan, various off-site satellite centers are established to perform PPCI 24-hours. Our population mainly resides in the rural area with low literacy rate and poor socioeconomic conditions. The majority of the patients who are presented in the satellite center had either never received any long-term treatment plan or were non-compliant to their medication. The objective of this study was to determine the outcome of patients at six months who underwent primary PCI at a rural satellite center of Sindh, Pakistan. Methods This study was conducted at Larkana satellite center of National Institute of Cardiovascular Diseases, Karachi. Patients who underwent PPCI for STEMI from October 2017 to March 2018 were enrolled in the study. In case of death of the patient, data were obtained from the attendant of the deceased. Patients, on follow-up visits, were interrogated for post-procedure symptoms. Results A total of 271 patients were enrolled in the study. The mean age ± standard deviation of patients was 54.84 ± 10.64 years. The most common culprit artery was left anterior descending (LAD) artery with 161 (59.4%) patients, followed by right coronary artery (RCA) with 98 (36.2%) patients. Only 41 (15%) patients had a three-vessel disease, while 141 (52%) patients had single-vessel disease. On follow-up, 70 (25.8%) patients complained of chest pain grade II, 20 (7.4%) complained of shortness of breath (SOB) grade II, 44 (16.2%) complained of vertigo, and 16 (5.9%) complained of nonspecific weakness. The mortality rate of 6.3% (17) was observed after six months of PPCI. The mortality rate was found to be lower for patients with LAD disease (p = 0.036) and higher among patients with RCA as the culprit artery (p = 0.045). The mortality rate was significantly associated with the number of diseased vessels and the type of stent deployed. Conclusion Primary PCI, at a rural satellite center, has an overall positive outcome. Steps should be taken to provide free medication along with encouragement towards compliance of dual antiplatelet medication. Furthermore, the facility for subsequent procedures should be provided at the same set-up.

Oxidative stress-mediated photoactivation of carbazole inhibits human skin cell physiology.

Prolonged exposure of the earth's surface to the sun's ultraviolet radiation may result in various skin diseases and cataract. Carbazole (CBZ), as a polycyclic-aromatic hydrocarbon (PAH), is blended with a five-member nitrogen-containing ring. It is found in cigarette smoke, coal, eye kohl, tattoo ink, and wood combustion and affects various types of flora and fauna. Our findings suggest that CBZ generates reactive oxygen species (ROS) like O2•- through type-I photodynamic reaction and causes phototoxicity in the human keratinocyte cell line (HaCaT), which has been proved by mitochondrial dehydrogenase and neutral red uptake assays. CBZ induces single strand DNA damage. We have investigated the involvement of the apoptotic pattern of cell death and confirmed it by cytochrome C release from mitochondria and caspase-9 activation. Similarly, photo-micronuclei formation was associated to CBZ-induced phototoxicity. The results of this study strongly support that the upregulation of bax, cyto-C, apaf-1, casp-9 and down regulation of bcl2, keap-1, nrf-2, and hmox-1 genes cause apoptopic cell death. Downregulation of antioxidant genes showed a significant amount of ROS generation by photosensitized CBZ. Therefore, the current study will be a step forward to safeguard human beings from sunlight-induced photosensitive CBZ prolonged exposure.

Sunscreen-induced expression and identification of photosensitive marker proteins in human keratinocytes under UV radiation.

Solar ultraviolet (UV) radiation is the main factor of photocarcinogenesis, photoaging, and photosensitivity; thus protection from biological damaging UV radiation is a concern. Sunscreens containing UV filters are the most preferred means of photoprotection but the safety and efficacy of UV filters are in question. Benzophenone (BP) and its derivatives, namely, benzophenone 1 (BP1), is commonly used in sunscreens as a UV blocker. The aim of this study was to assess the effects of BP and BP1 on the differential expression of proteins in human keratinocytes (HaCaT cells) under exposure to ultraviolet A radiation. Photosensitive proteins were screened from HaCaT cells by two-dimensional (2-D) gel electrophoresis, and identification of these differentially expressed proteins was performed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF)/TOF mass spectrometry. Protein identification was performed using the search program MASCOT and a database made of SUMO and GhJMJ12 amino acid sequences. Our results showed that the proteins involved directly or indirectly in apoptosis are 70 kDa heat shock protein, long-chain specific acyl-CoA dehydrogenase, serine/threonine-protein kinase, and FAM78A protein, which were upregulated in comparison to control HaCaT cells. The expressions of binding immunoglobulin protein, podocalyxin-like protein, actin, cytoplasmic, and calreticulin precursors were downregulated. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity and genotoxicity of BPs. The results of 2-D gel electrophoresis followed by mass spectrometry showed expression of novel proteins involved in promoting or initiating apoptotic pathways. Hence, we conclude that BPs should be avoided as a UV blocker from sunscreens because of its potential to promote apoptotic proteins in human skin keratinocytes.

Procedural determinants of fluoroscopy time in patients undergoing cardiac catheterization.

BACKGROUND & OBJECTIVE: Due to increase in number of cardiac catheterization procedures safety concerns is an issue nowadays. Multiple diagnostic modalities use radiations, which also put a patient at higher cumulative radiation exposure. Therefore steps should be taken to minimize radiation exposure during cardiac catheterization. Hence determination of factors which prolong FT will result in better understanding of problem. This retrospective study was undertaken to determine factors responsible for prolong fluoroscopy time in patients undergoing coronary artery catheterization. METHODS: This retrospective study was conducted at catheterization Laboratory National Institute of Cardiovascular Diseases, Karachi from June 2014 to June 2015. Patients of either gender, aged between 18 to 90 years undergoing cardiac catheterization procedures were included. Radiation exposure time was measured in terms of fluoroscopy time. RESULTS: A total of 957 patients were included in this study out of which 731 were of diagnostic Coronary Angiograms (CA) and 226 were of Percutaneous Coronary Intervention (PCI). The mean age of the study participants was 54.12±10.89 years and majority 734(76.6%) were male. Mean fluoroscopy time (FT) in the patients subjected to PCI was 9.61±6.07 minutes while in cases for CA 4.17±4.13 minutes. FT for CA was observed significantly dependent on procedural access, operator's experience, and LV angiogram. While FT for PCI was found dependent on number of stents deployed during the procedure. CONCLUSION: For invasive coronary angiographic procedures radial route increased fluoroscopy time. For percutaneous coronary intervention femoral and radial route fluoroscopy time were not significantly different.

Comparison of qSOFA and SOFA score for predicting mortality in severe sepsis and septic shock patients in the emergency department of a low middle income country.

OBJECTIVE: We aimed to determine a comparison between the Quick Sequential Organ Failure Assessment (qSOFA) score and existing Sequential Organ Failure Assessment (SOFA) score when applied to severe sepsis & septic shock patients in the Emergency Department (ED) for prediction of in-hospital mortality in the setting of a tertiary care hospital ED in a low-middle income country. METHOD: We conducted a prospective observational cohort study on 760 subjects. The qSOFA, SOFA score and in-hospital mortality were assessed by area under the receiver operating curve (AUROC). We calculated sensitivity and specificity for each score for outcomes at cut-offs of 0.92 and 0.63 for qSOFA and SOFA in Severe Sepsis respectively and 0.89 and 0.63 for qSOFA and SOFA in Septic shock respectively. RESULTS: In patients with severe sepsis, the AUROC of qSOFA for predicting mortality in subjects was 0.92 (95% CI; 0.89-0.94) with 96% sensitivity and 87% specificity in comparison to the AUROC of SOFA score which was 0.63 (95% CI; 0.55-0.70 with 71% sensitivity and 57% specificity. In patients with septic shock, the AUROC of qSOFA for predicting mortality in subjects was 0.89 (95% CI; 0.85-0.92) with 92% sensitivity and 85% specificity in comparison to the AUROC of SOFA score which was 0.63 (95% CI; 0.55-0.70 with 70% sensitivity and 59% specificity. CONCLUSION: Our study concludes that qSOFA score is an effective tool at predicting in hospital mortality in comparison to SOFA score when applied to severe sepsis and septic shock patients in the setting of a tertiary care hospital ED of a low-middle income country however, further studies are needed before application for this purpose.

Quadruple Valve Replacement for Carcinoid Heart Disease.

INTRODUCTION: Carcinoid heart disease most frequently involves the tricuspid or, more rarely, the pulmonary valve and presents with right heart failure as 5-HT is metabolized by the lung. Left-sided valve involvement is quite rare. We describe our experience of 3 patients presenting with heart failure secondary to carcinoid heart disease affecting all four cardiac valves. There are only four previous isolated case reports in the literature. METHODS: All three patients underwent quadruple valve replacement during a single operation. Right ventricular outflow tract reconstruction with a pericardial patch was performed in all patients. For 24 hours prior to surgery, all patients received intravenous octreotide, which continued in intensive care for at least 24 hours. RESULTS: Mean cross-clamp and bypass times were 175 (range 164-197 minutes) and 210 (range 195-229 minutes) minutes, respectively. Mean intensive treatment unit (ITU) and inpatient stays were 2.3 (range 2-3 days) and 12 (range 9-16 days) days, respectively. One patient was reopened for bleeding 4 hours postoperatively from a ventricular pacing wire site. None required a permanent pacemaker postoperatively. There were no other complications in any patient. The quality of life was excellent at 6-16 months clinic follow-up as they were in NYHA 1. Postoperative echocardiography showed no paravalvular leaks and well-functioning prostheses in all cases. CONCLUSION: Surgery to replace all four valves is feasible with excellent medium-term survival and a very low rate of complications. Patients with carcinoid heart disease should always be considered for surgery irrespective of the extent of valvular involvement.

Author Correction: Intensified summer monsoon and the urbanization of Indus Civilization in northwest India.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Quadruple valve replacement for carcinoid heart disease

Abstract Introduction: Carcinoid heart disease most frequently involves the tricuspid or, more rarely, the pulmonary valve and presents with right heart failure as 5-HT is metabolized by the lung. Left-sided valve involvement is quite rare. We describe our experience of 3 patients presenting with heart failure secondary to carcinoid heart disease affecting all four cardiac valves. There are only four previous isolated case reports in the literature. Methods: All three patients underwent quadruple valve replacement during a single operation. Right ventricular outflow tract reconstruction with a pericardial patch was performed in all patients. For 24 hours prior to surgery, all patients received intravenous octreotide, which continued in intensive care for at least 24 hours. Results: Mean cross-clamp and bypass times were 175 (range 164-197 minutes) and 210 (range 195-229 minutes) minutes, respectively. Mean intensive treatment unit (ITU) and inpatient stays were 2.3 (range 2-3 days) and 12 (range 9-16 days) days, respectively. One patient was reopened for bleeding 4 hours postoperatively from a ventricular pacing wire site. None required a permanent pacemaker postoperatively. There were no other complications in any patient. The quality of life was excellent at 6-16 months clinic follow-up as they were in NYHA 1. Postoperative echocardiography showed no paravalvular leaks and well-functioning prostheses in all cases. Conclusion: Surgery to replace all four valves is feasible with excellent medium-term survival and a very low rate of complications. Patients with carcinoid heart disease should always be considered for surgery irrespective of the extent of valvular involvement.