Circadian genes in the medial accumbal shell (mNAcSh) region regulate binge alcohol consumption. Here, we investigated if antisense‐induced knockdown of major circadian genes (Per1, Per2, and NPAS2) ...in the mNAcSh of mice exposed to intermittent access two‐bottle choice (IA2BC) paradigm modulates the expression of histone deacetylase‐2 (HDAC‐2) and CREB‐binding protein (CBP), key epigenetic modifiers associated with withdrawal‐associated behaviors such as anxiety. Adult male C57BL/6J mice (N = 28), surgically implanted with bilateral guide cannulas above the mNAcSh, were chronically (4 weeks) exposed to alcohol (20% v/v) or saccharin (0.03%) via IA2BC paradigm. In the fourth week, a mixture of antisense (AS‐ODNs; N = 14/group) or nonsense (NS‐ODNs; N = 14/group) oligodeoxynucleotides against circadian genes were bilaterally infused into the mNAcSh. Subsequently, alcohol/saccharin consumption and preference were measured followed by euthanization of animals and verification of microinjection sites by visual inspection and the expression of HDAC‐2 and CBP by using RT‐PCR along with the verification of antisense‐induced downregulation of circadian genes in the mNAcSh. As compared with NS‐ODNs, AS‐ODNs infusion significantly attenuated the alcohol‐induced increase in HDAC‐2 and reduction in CBP expression in the mNAcSh along with a significant reduction in alcohol consumption and preference. No significant effect was observed on either saccharin consumption or preference. Our results suggest that circadian genes in the mNAcSh may have a causal to play in mediating epigenetic changes observed after chronic alcohol consumption.
The present study used the intermittent access two‐bottle choice (IA2BC) paradigm, a model of alcohol abuse that mimics alcohol use disorder in humans and investigated the role of circadian genes in the modulation of epigenetic regulators, CREB‐binding protein (CBP), and histone deacetylase‐2 (HDAC2) in the medial accumbal shell (mNAcSh) of mice exposed to excessive alcohol consumption. We found that local antisense‐induced knockdown of major circadian genes normalized epigenetic mechanisms by reducing HDAC‐2 and increasing CBP in the mNAcSh, thereby reducing excessive alcohol consumption.
Introduction
We recently showed that circadian genes expressed in the shell region of nucleus accumbens (NAcSh) play a key role in alcohol consumption, though, the molecular mechanism of those ...effects is unclear. Because CREB‐binding protein (CBP) promotes Per1 gene expression, we hypothesized that alcohol consumption would increase CBP expression in the NAcSh and antisense‐induced knockdown of CBP would reduce Per1 expression and result in a reduction in alcohol consumption.
Methods
To test our hypothesis, we performed two experiments. The Drinking‐in‐the‐dark (DID) paradigm was used to evaluate alcohol consumption in male C57BL/6J mice. In Experiment 1 we examined the effects of alcohol consumption on CBP gene expression in the NAcSh. Control animals were exposed to, sucrose 10% (w/v) taste and calorie and water (consummatory behavior). In Experiment 2 examined the effects of CBP gene silencing on the expression of the Per1 gene in the NAcSh and alcohol consumption in mice exposed to alcohol using the DID paradigm. CBP gene silencing was achieved by local infusion of two doses of either CBP antisense oligodeoxynucleotides (AS‐ODNs; Antisense group) or nonsense ODNs (NS‐ODNs; Nonsense group) bilaterally microinjected into the NAcSh within 24 h before alcohol consumption on Day 4 of the DID paradigm. The microinfusion sites were verified by cresyl violet staining.
Results
Compared to sucrose, alcohol consumption, under the DID paradigm, significantly increased the expression of CBP in the NAcSh. Compared to Controls, bilateral infusion of CBP AS‐ODNs significantly reduced the expression of Per1 in the NAcSh and alcohol consumption without affecting the amount of sucrose consumed.
Conclusions
Our results suggest that CBP is an upstream regulator of Per1 expression in the NAcSh and may act via Per1 to modulate alcohol consumption.
The CREB‐binding protein (CBP), a transcriptional co‐activator with histone acetyltransferase activity, is associated with alcohol consumption; however, the exact neuroanatomical substrate is not known. In this study, we have shown that mice exposed to binge alcohol consumption display a significant increase in CBP expression in the nucleus accumbens shell region. Antisense‐induced knockdown of CBP in this region significantly reduced alcohol consumption and Per1 gene expression suggesting that CBP acts via accumbal shell region to increase alcohol consumption and Per1 expression.
Orthogonal frequency division multiplexing (OFDM) is a prominent standard for 4G and next generation wireless communication systems. The main disadvantage of OFDM is its high sensitivity to carrier ...frequency offsets (CFO) caused due to the inaccuracies in the frequencies of the local oscillators and the Doppler shift due to mobility. This gives rise to inter-carrier interference. Therefore, frequency offset compensation must be accomplished with high fidelity. The effect of CFO is observed with respect to signal to noise ratio and bit error rate. The system performance can be improved by using estimation techniques like maximum likelihood estimation (MLE), least square estimation, minimum mean square error estimation and other estimation techniques. In this paper, MLE is used as a frequency offset estimation and correction scheme. The presence CFO affects the orthogonality of the subcarriers, which deteriorates the performance of the system, hence the estimation and correction of the above is of great importance in the OFDM system.
India ranks among the top countries experiencing worst traffic congestion in the world. According to the reports, in India it takes more than 400 minutes to reach a hospital for every second heart ...attack patient which is almost 13 times more than the ideal time of 30 minutes. The primary aim of this proposed solution is to minimize the response time of ambulances approaching the needy. Our proposed approach of the 'One-Tap-Button' emergency response app provides just one 'SOS' (Save Our Souls) button which sends the location of the user to the nearest hospital or medical center within a definite range set in the app via a library called socket.io. The location with the notification mentioning the details of the patient/victim is viewed in the integrated Google Maps app interface. A GPS (Global Positioning System) modem fitted in the ambulance which is responsible for keeping live track of their location by the servers i.e., the hospital's portal. WebRTC (Web Real-Time Communications) live video streaming feature enables direct patient-doctor communication during emergencies, facilitating real-time audio and video transmission. This seamless integration enhances emergency response and prompt healthcare communication.
Today, recommendation systems are widely used to solve the problem of finding the most relevant information from the abundant amount of data present. The literature findings suggest that there have ...been studies in various domains of recommendation systems such as skin care recommendations, movie recommendations, course recommendations, and others. However, limited studies exist on recommending products such as laptops which are a necessity these days and have become an important part of day-to-day life. From office workers to homemakers to undergraduate students this product is required by all. The undergraduate community faces challenges in identifying the right laptop due to lack of knowledge and expertise. Purchasing a laptop that matches the desired specifications for a particular specialization is tedious. The question in hand is "Do online reviews aid their decision-making for product (laptop) purchase?". They all use different methods and approaches in order to form recommendations best suit their problem at hand. This study reviews the extant literature on product recommendation systems and proposes a Laptop Recommendation System based on a hybrid model, combining both Content-Based Filtering and Collaborative Filtering. The study captures data through the use of an online survey administered to undergraduate engineering respondents. The factors considered were processor, operating system, graphic card, and RAM (Random Access Memory). The data is analyzed through panda's library of python programming. The proposed specialization-based laptop recommendation system would be of benefit to engineering undergraduates to make an informed decision.
Optical spatial modulation (OSM) is a multiple-input-multiple-output technique wherein the overall information is transferred through spatial and signal domains simultaneously. A problem in OSM is ...the necessity for channel state information at receiver (CSIR) that is obtained by complex channel estimation procedure. Apart from this, a small error in CSIR can cause a significant loss in the error performance of the OSM scheme. In this paper, in order to avoid the requirement of CSIR, a new scheme named as differential OSM (DOSM) is proposed; the average symbol error rate for the DOSM scheme with pulse-amplitude modulation is assessed under negative exponential and gamma-gamma channel models. A special and simplified version of DOSM, called as differential optical space shift keying is also discussed. It is noticed from the analysis that bypassing the requirement of CSIR leads to a small degradation in the error performance of DOSM scheme as compared to its traditional counterpart scheme with perfect CSIR. On the other hand, the proposed scheme outperforms OSM scheme with imperfect CSIR. Further investigations thoroughly examine the interplay between the error performance and spectral efficiency of the proposed scheme.
•Contribution of home injuries (29% in hospital admissions) to the overall trauma burden of tertiary care hospitals is substantial and needs to be looked upon seriously.•There is no significant ...difference in the overall mortality in patients sustaining injuries at home or sustaining injuries outside the home.•Mortality in pediatric (<15 years) and the elderly (>64 years) patients are significantly higher if they are injured at home compared with outside the home.•Most home injuries are preventable with simple and cost-effective strategies. The study highlights an urgent need for a public health policy for sustainable prevention strategies to lessen domestic/home injuries, especially in children and the elderly.
‘In-home injuries’ are those that occur within the house or its immediate surroundings. The literature on the prevalence and magnitude of home injuries is sparse. This study was designed to characterize the mechanisms of ‘in-home’ injuries and compare their outcomes with ‘outside home injuries’.
The Australia-India Trauma Systems Collaboration (AITSC) Project created a multicentric registry consisting of trauma patients admitted at four urban tertiary care hospitals in India from April 2016 to March 2018. This registry data was analysed for this study. All admitted patients except for dead on arrival were included. Patients were categorised into ‘in-home’ and ‘outside home’ cohorts based on the place where the trauma occurred. The outcome measures were 30 day in-hospital mortality and the length of hospital stay. Two subgroup analyses were performed, the first comprised pediatric patients (<15 years) and the second elderly patients >64 years).
Among 9354 patients in the AITSC data registry, 8398 patients were included in the study. Out of these, 29 percent were in-home injuries, whereas the rest occurred outside home. The 30 day in-hospital mortality was 10.6 percent in the ‘in-home’ cohort, as compared to 13.7 percent in the ‘outside home’ cohort. This difference although significant on univariable analysis (p <0.01), there was no significant difference on multivariable regression analysis, after adjusting for age and injury severity score (OR = 0.88, 95% CI = 0.73–1.04; p = 0.15). The length of hospital stay was shorter in the home injuries group (median = 5 days; IQR = 3–12 days) compared to the outside-home group (median = 7 days; IQR = 4–14 days) (p < 0.01). In the pediatric and the elderly, on multivariable regression analysis, in-home injuries were associated with higher mortality than outside home injuries.
There was no significant difference in the 30 day in-hospital mortality amongst admitted trauma patients sustaining injuries at home or outside the home. However, in pediatric and elderly patients the chances of mortality was significantly higher when injured at home.
Background: Thalassemia and hemoglobinopathies are a group of inherited conditions characterized by abnormalities in the synthesis or structure of hemoglobin (Hb). According to estimates, ...approximately 7% of the world population is a carrier of Hb disorders, leading to high morbidity and mortality. To reduce the burden of these highly prevalent monogenic disorders, detecting them in the carrier stage is crucial to prevent disease progression. Aim: We aimed to estimate the prevalence and spectrum of hemoglobinopathies in females in the reproductive (20-40 years) age group. Settings and Design: It was a retrospective observational study carried out for 2.5 years (from January 2018 till June 2020). Materials and Methods: All the females in the age group of 20-40 years age whose blood samples were received in the department for High-Performance Liquid Chromatography (HPLC) were included. The cases with abnormal HPLC findings were analyzed for hematological parameters including hemoglobin, RBC count, and RBC indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), & red cell distribution width - coefficient of variation (RDW-CV). Statistical Analysis: Statistical package for social science (SPSS) statistics 21 version for Microsoft Windows (Chicago, USA) was used for statistical analysis of data. The data were described in terms of range, mean ± standard deviation (SD), frequencies (number of cases), and relative frequencies (percentage) as appropriate. Results: During the study period, 72.2% of the females were affected with β-thalassemia trait, followed by HbD Punjab trait (17.8%), HbQ India trait (2.9%), β-thalassemia major (1.8%), and two cases (1.2%) each of HbS trait, HbD Iran trait, and compound heterozygous of HbD Punjab and β-thalassaemia, whereas HbE trait, compound heterozygous of HbQ and β-thalassemia, compound heterozygous of HbJ-variant and β-thalassemia had one case each (0.6%). Conclusion: Preventive strategies are cost-effective and include population screening, premarital screening, screening of spouses, genetic counseling, and prenatal diagnosis. Educating the carrier females about the potential risk and various screening methods may help in controlling the disease.
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