Orofacial Dyskinesia in Uremia in Polycystic Kidney Disease.

Uremic encephalopathy presenting as involuntary movements of the orofacial region is important to recognize because of reversibility seen with resolution of azotaemia though residual neurological dysfunction might persist. Neuroimaging is important part of diagnosis with typical lesions involving basal ganglia seen mostly in diabetic patients. Our case highlights a patient with non-diabetic uremic encephalopathy with facial dyskinesia which is rare with a lesion in unilateral lentiform nucleus and small white matter hyperintensities. Resolution following dialysis pointed to uraemia as aetiology.

Comparison of proposed National Institute of Child Health and Human Development panel recommendations with newborn sepsis risk calculator in term neonates exposed to maternal chorioamnionitis.

BACKGROUND: Maternal chorioamnionitis (MC) is one of the major risk factors for early-onset neonatal sepsis. Kaiser sepsis risk calculator (SRC) is a validated risk assessment tool for such newborns. The National Institute of Child Health and Human Development (NICHD) workshop on MC has proposed a risk assessment algorithm. The objective of the study was to compare the reduction in antibiotic use in newborns treated with SRC and NICHD algorithm and determine the antibiotic use correlation between them. METHODOLOGY: A retrospective chart review was performed on newborns born at ≥ 37 weeks to mothers with MC during the years 2018-2020. The same cohort of newborns was evaluated using SRC and NICHD algorithm to determine whether treatment with antibiotics could have been avoided in some patients. The data were analyzed using a t-test, Chi-square test, and ANOVA. RESULTS: During the study period, 101 newborns were born to mothers with chorioamnionitis and received antibiotics. When the newborns were assessed using the SRC, only 16/101 (15.84%) would have received treatment. When NICHD algorithm was applied to the same cohort 71/101 (70.30%) newborns would have received treatment. The two approaches agreed in their assessment for treatment or observation only in 44/101 (43.56%) of the cases. The NICHD treatment group had a higher incidence of chorioamnionitis as seen in placental pathology (94.37% vs. 75.00% for Kaiser, p-0.015). The SRC treatment group however had newborns with significantly lower Apgar score at 1 min (8.21 vs 6.63, p-0.006) and 5-minute (8.69 vs 8.00, p-0.019) and had significantly higher supplemental oxygen requirements at admission (62.50% vs. 21.13%, p < 0.001). CONCLUSION: Both SRC and NICHD algorithms expose fewer newborns to antibiotics; however, they differ in the number of newborns that would require antibiotics. Ventilation assistance and lower Apgar scores were associated with higher probability of antibiotic administration.

Effectiveness of Parental Preparedness Package among Couples Conceived with Artificial Reproductive Techniques.

Introduction: The problem of infertility is experienced as a crisis or major life stressor with potentially serious negative effects on the couple's relationship and preparation toward the parenthood. According to Sharlip et al., it has been estimated that about 15% of couple would have trouble in conception, and at present, 48.5 million couples experience infertility globally. To decrease the stress among parents to be and to promote healthy parenting for bringing out healthy parent-child relationships, an intervention of Parent Education Program was planned and executed. A study was conducted with the aim to assess the effectiveness of parental preparedness package (PPP) on physical health among couple conceived with artificial reproductive techniques (ART). Materials and Methods: The study was conducted to evaluate the effectiveness of PPP in fifty couples conceived with ART at Dayanand Medical College and Hospital, Ludhiana. Quantitative approach was used to collect the data of couples by doing pre- and postinterventional assessment of physical health of couple using the Structured Physical Health Assessment Scale. Analysis was done with the help of descriptive and inferential statistics. Results: The study revealed that mean score of physical health of couple (both husband and wife) increased significantly after the intervention which infers the effectiveness of PPP (P = 0.001). Conclusion: Our study concludes that PPP should be incorporated in the antenatal care protocol in all couples who conceive using ART.

Artificial Intelligence: A Universal Virtual Tool to Augment Tutoring in Higher Education.

Artificial intelligence is an emerging technology that revolutionizes human lives. Despite the fact that this technology is used in higher education, many professors are unaware of it. In this current scenario, there is a huge need to arise, implement information bridge technology, and enhance communication in the classroom. Through this paper, the authors try to predict the future of higher education with the help of artificial intelligence. This research article throws light on the current education system the problems faced by the subject faculties, students, changing government rules, and regulations in the educational sector. Various arguments and challenges on the implementation of artificial intelligence are prevailing in the educational sector. In this concern, we have built a use case model by using a student assessment data of our students and then built a synthesized using generative adversarial network (GAN). The dataset analyzed, visualized, and fed to different machine learning algorithms such as logistic Regression (LR), linear discriminant analysis (LDA), K-nearest neighbors (KNN), classification and regression trees (CART), naive Bayes (NB), support vector machines (SVM), and finally random forest (RF) algorithm and achieved a maximum accuracy of 58%. This article aims to bridge the gap between human lecturers and the machine. We are also concerned about the psychological emotions of the faculty and the students when artificial intelligence takes control.

COVID-19: Automatic detection from X-ray images by utilizing deep learning methods.

In recent months, a novel virus named Coronavirus has emerged to become a pandemic. The virus is spreading not only humans, but it is also affecting animals. First ever case of Coronavirus was registered in city of Wuhan, Hubei province of China on 31st of December in 2019. Coronavirus infected patients display very similar symptoms like pneumonia, and it attacks the respiratory organs of the body, causing difficulty in breathing. The disease is diagnosed using a Real-Time Reverse Transcriptase Polymerase Chain reaction (RT-PCR) kit and requires time in the laboratory to confirm the presence of the virus. Due to insufficient availability of the kits, the suspected patients cannot be treated in time, which in turn increases the chance of spreading the disease. To overcome this solution, radiologists observed the changes appearing in the radiological images such as X-ray and CT scans. Using deep learning algorithms, the suspected patients' X-ray or Computed Tomography (CT) scan can differentiate between the healthy person and the patient affected by Coronavirus. In this paper, popular deep learning architectures are used to develop a Coronavirus diagnostic systems. The architectures used in this paper are VGG16, DenseNet121, Xception, NASNet, and EfficientNet. Multiclass classification is performed in this paper. The classes considered are COVID-19 positive patients, normal patients, and other class. In other class, chest X-ray images of pneumonia, influenza, and other illnesses related to the chest region are included. The accuracies obtained for VGG16, DenseNet121, Xception, NASNet, and EfficientNet are 79.01%, 89.96%, 88.03%, 85.03% and 93.48% respectively. The need for deep learning with radiologic images is necessary for this critical condition as this will provide a second opinion to the radiologists fast and accurately. These deep learning Coronavirus detection systems can also be useful in the regions where expert physicians and well-equipped clinics are not easily accessible.

Revisiting absent nasal bone in the second trimester.

PURPOSE: To evaluate the outcomes of fetuses diagnosed with absent nasal bone in the second trimester. METHODS: This prospective, observational study included all fetuses who were diagnosed at or referred to our fetal medicine center with an absent nasal bone from 16 weeks onwards from November 2017 to December 2019. Amniocentesis for fetal karyotype and microarray was offered to all women. Women who opted not to undergo invasive testing were also followed up and neonatal outcome noted. RESULTS: 26 fetuses were eligible for inclusion in the study. 8 (30.8%) out of these were diagnosed with aneuploidy: 7 with trisomy 21 and one with trisomy 18. All fetuses with aneuploidy had additional ultrasound abnormality and/or high risk on biochemical screening. CONCLUSIONS: Isolated absent nasal bone in the second trimester with prior low risk on combined screening performed by certified sonographers is unlikely to be associated with Down syndrome.

Recent advances in synthesis and medicinal chemistry of benzodiazepines.

Benzodiazepines (BZDs) represent a diverse class of bicyclic heterocyclic molecules. In the last few years, benzodiazepines have emerged as potential therapeutic agents. As a result, several mild, efficient and high yielding protocols have been developed that offer access to various functionalized benzodiazepines (BZDs). They are known to possess a wide array of biological activities such as anxiolytic, anticancer, anticonvulsant, antipsychotics, muscle relaxant, anti-tuberculosis, and antimicrobial activities. The fascinating spectrum of biological activities exhibited by BZDs in various fields has prompted the medicinal chemist to design and discover novel benzodiazepine-based analogs as potential therapeutic candidates with the desired biological profile. In this review, an attempt has been made by to summarize (1) Recent advances in the synthetic chemistry of benzodiazepines which enable their synthesis with desired substitution pattern; (2) Medicinal chemistry of BZDs as therapeutic candidates with promising biological profile including insight of mechanistic studies; (3) The correlation of biological data with the structure i.e. structure-activity relationship studies were also included to provide an insight into the rational design of more active agents.

Recent advances in the synthetic and medicinal perspective of quinolones: A review.

In the modern scenario, the quinolone scaffold has emerged as a very potent motif considering its clinical significance. Quinolones possess wide range of pharmacological activities such as anticancer, antibacterial, antifungal, antiprotozoal, antiviral, anti-inflammatory, carbonic anhydrase inhibitory and diuretic activity etc. The versatile synthetic approaches have been successfully applied and several of the resulted synthesized compounds exhibit fascinating biological activities in numerous fields. This has prompted to discover quinolone-based analogues among the researchers due to its great diversity in biological activities. In the past few years, various new, efficient and convenient synthetic approaches (including green chemistry and microwave-assisted synthesis) have been designed and developed to synthesize diverse quinolone-based scaffolds which represent a growing area of interest in academic and industry as well as to explore their biological activities. In this review, an attempt has been made by the authors to summarize (1) One of the most comprehensive listings of quinolone-based drugs or agents in the market or under various stages of clinical development; (2) Recent advances in the synthetic strategies for quinolone derivatives as well as their biological implications including insight of mechanistic studies. (3) Further, the biological data is correlated with structure-activity relationship studies to provide an insight into the rational design of more active agents.

Prenatal Presentation of Medulloepithelioma: Case and Literature Review.

Congenital brain tumors (CBTs) are extremely rare and account for only 0.5%-1.9% of all pediatric brain tumors. Medulloepithelioma is one of the rare tumors with an incidence of about 1% among all CBTs with a very dismal prognosis and typically diagnosed at the median age of 24 months. The objective is reporting medulloepithelioma presenting in the intrauterine period with very few prior cases being reported in the prenatal period, and to add to the limited existing literature on medulloepithelioma. We present a rare case of medulloepithelioma referred to us in the antenatal period at 27 weeks and subsequently causing intrauterine fetal demise. Prenatal MRI of the fetal brain and postnatal histopathological findings on autopsy were suggestive of intracranial medulloepithelioma.

Accelerating Lead Identification by High Throughput Virtual Screening: Prospective Case Studies from the Pharmaceutical Industry.

At the onset of a drug discovery program, the goal is to identify novel compounds with appropriate chemical features that can be taken forward as lead series. Here, we describe three prospective case studies, Bruton Tyrosine Kinase (BTK), RAR-Related Orphan Receptor γ t (RORγt), and Human Leukocyte Antigen DR isotype (HLA-DR) to illustrate the positive impact of high throughput virtual screening (HTVS) on the successful identification of novel chemical series. Each case represents a project with a varying degree of difficulty due to the amount of structural and ligand information available internally or in the public domain to utilize in the virtual screens. We show that HTVS can be effectively employed to identify a diverse set of potent hits for each protein system even when the gold standard, high resolution structural data or ligand binding data for benchmarking, is not available.

Business Planning for a Campus-Wide Biobank.

Biobanks are resources that facilitate research. Many biobanks exist around the world, but most tend to focus on a specific disease or research area. BC Children's Hospital and BC Women's Hospital are located on the same campus (Oak Street Campus) in Vancouver, BC, Canada. A campus-wide biobank has been established on the site of these two hospitals to collect specimens and annotated data from children or women seeking medical care at either of the hospitals. Such an initiative requires careful planning and consideration of many factors such as buy in and support of key stakeholders, governance, financial planning, and optimizing specimen collection. We developed a business plan to account for the many aspects associated with integrating the "BC Children's Hospital BioBank." This document describes the approach our business plan took for the implementation of our biobank and the progress, including deviations from the business plan. We also provide a perspective on the current status with a focus on sustainability.

Observational study comparing the performance of first-trimester screening protocols for detecting trisomy 21 in a North Indian population.

OBJECTIVE: To evaluate first-trimester screening protocols for detecting trisomy 21 in an Indian population. METHODS: The present prospective study collected data from women with singleton pregnancies and a crown-to-rump length of 45-84 mm who presented at the fetal medicine unit of a tertiary care center in North India between June 1, 2006, and December 31, 2015, for combined first-trimester screening. Maternal age, nuchal translucency, nasal bone, and maternal serum levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A were assessed for calculating the risk of trisomy 21. Tricuspid regurgitation and qualitative analysis of ductus venosus data were available from June 2010, and were included where available. Trisomy-21 detection rates were calculated for various screening protocols and were compared. RESULTS: There were 4523 women screened and 24 records of trisomy 21. Combined screening with maternal age, nuchal translucency, nasal bone, tricuspid regurgitation, and ductus venosus demonstrated optimal detection and false-positive rates of 93.8% and 1.9%, respectively. Screening using only maternal age yielded a detection rate of 37.5%; using fixed nuchal translucency cut-off values of 2.5 and 3 mm resulted in detection rates of 66.7% and 37.5%, respectively. CONCLUSION: Combined first-trimester screening performed well in an Indian population; combining maternal age, nuchal translucency, nasal bone, ductus venosus, and tricuspid regurgitation yielded the most accurate screening.

Changing trends in use of laparoscopy: a clinical audit.

Aim. To find out the changing trends in indications for use of laparoscopy for diagnostic or operative procedures in gynaecology. Methods. This was a clinical audit of 417 women who underwent laparoscopic procedures over a period of 8 years from January 2005 to December 2012 in the Department of Obstetrics and Gynaecology at a tertiary care centre in Delhi. Results. A total of 417 diagnostic and operative laparoscopic procedures were performed during the period from January 2005 to December 2012. Out of 417 women, 13 women were excluded from the study due to inadequate data. 208 (51.4%) women had only diagnostic laparoscopy whereas 196 (48.6%) patients had operative laparoscopy after the initial diagnostic procedure. Change in trend of diagnostic versus operative procedures was observed from 2005 to 2012. There was increase in operative procedures from 10 (37.03%) women in 2005 as compared to 51 (73.91%) in 2012. The main indication for laparoscopy was infertility throughout the study period (61.38%), followed by chronic pelvic pain (CPP) (11.38%) and abnormal uterine bleeding (AUB) (9.4%). Conclusion. Over the years, there has been a rise in the rate of operative laparoscopy. Though the indications for laparoscopy have remained almost similar during the years, laparoscopy for diagnosis and treatment of CPP and AUB has now increased.

Periodontal infection, impaired fasting glucose and impaired glucose tolerance: results from the Continuous National Health and Nutrition Examination Survey 2009-2010.

AIM: We investigated the relationship between periodontal disease, a clinical manifestation of periodontal infection, and pre-diabetes. METHODS: The National Health and Nutrition Examination Survey, 2009-2010 enrolled 1165 diabetes-free adults (51% female) aged 30-80 years (mean ± SD=50 ± 14) who received a full-mouth periodontal examination and an oral glucose tolerance test. Participants were classified as having none/mild, moderate or severe periodontitis and also according to mean probing depth ≥ 2.19 mm or attachment loss ≥ 1.78 mm, (respective 75th percentiles). Pre-diabetes was defined according to ADA criteria as either: (i) impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). In multivariable logistic regression models, the odds of IFG and IGT were regressed on levels of periodontitis category. RESULTS: The odds ratios and 95% confidence intervals for having IGT among participants with moderate or severe periodontitis, relative to participants with none/mild periodontitis were 1.07 [0.50, 2.25] and 1.93 [1.18, 3.17], p = 0.02. The ORs for having IFG were 1.14 [0.74, 1.77] and 1.12 [0.58, 2.18], p = 0.84. PD ≥ 75 th percentile was related to a 105% increase in the odds of IGT: OR [95% CI] = 2.05 [1.24, 3.39], p = 0.005. CONCLUSIONS: Periodontal infection was positively associated with prevalent impaired glucose tolerance in a cross-sectional study among a nationally representative sample.

3-Amino-pyrazolo[3,4-d]pyrimidines as p38α kinase inhibitors: design and development to a highly selective lead.

Learnings from previous Roche p38-selective inhibitors were applied to a new fragment hit, which was optimized to a potent, exquisitely selective preclinical lead with a good pharmacokinetic profile.

Cyclic amide bioisosterism: strategic application to the design and synthesis of HCV NS5B polymerase inhibitors.

Conformational modeling has been successfully applied to the design of cyclic bioisosteres used to replace a conformationally rigid amide bond in a series of thiophene carboxylate inhibitors of HCV NS5B polymerase. Select compounds were equipotent with the original amide series. Single-point mutant binding studies, in combination with inhibition structure-activity relationships, suggest this new series interacts at the Thumb-II domain of NS5B. Inhibitor binding at the Thumb-II site was ultimately confirmed by solving a crystal structure of 8b complexed with NS5B.

Diphenyl ether non-nucleoside reverse transcriptase inhibitors with excellent potency against resistant mutant viruses and promising pharmacokinetic properties.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are part of the preferred treatment regimens for individuals infected with HIV. These NNRTI-based regimens are efficacious, but the most popular NNRTIs have a low genetic barrier to resistance and have been associated with adverse events. There is therefore still a need for efficacious antiviral medicines that facilitate patient adherence and allow durable suppression of viral replication. As part of an extensive program targeted toward the discovery of NNRTIs that have favorable pharmacokinetic properties, good potency against NNRTI-resistant viruses, and a high genetic barrier to drug resistance, we focused on the optimization of a series of diaryl ether NNRTIs. In the course of this effort, we employed molecular modeling to design a new set of NNRTIs that that are active against wild-type HIV and key NNRTI-resistant mutant viruses. The structure-activity relationships observed in this series of compounds provide insight into the structural features required for NNRTIs that inhibit the replication of a wide range of mutant viruses. Selected compounds have promising pharmacokinetic profiles.

Thermodynamic characterization of pyrazole and azaindole derivatives binding to p38 mitogen-activated protein kinase using Biacore T100 technology and van't Hoff analysis.

Biacore T100 technology was used in conjunction with a van't Hoff analysis to characterize the thermodynamic binding parameters of 85 small-molecule inhibitors of adenosine triphosphate (ATP) binding to p38 mitogen-activated protein (MAP) kinase. The compounds were selected from a large panel of azaindole and pyrazole derivatives for which IC(50) data exist. We showed a strong relationship between the K(D) and IC(50) of a compound, but only a modest relationship between k(off) and IC(50) was detected and an apparent relationship between a compound's k(on) and its IC(50) could not be discerned. Similarly, a correlation between a compound's IC(50) and its thermodynamic parameters DeltaH degrees and DeltaS degrees could not be established. The lack of a predominant kinetic or thermodynamic signature associated with the inhibitory potential of these compounds demonstrates that there exists, even within a single well-defined system, a library of kinetic routes or, alternatively, a library of initial and final enthalpic and entropic states from which to effect inhibition. As a complement to these studies, selected double mutant thermodynamic cycles were performed to probe the energetic coupling, if any, between common sites of fluorination in both the azaindole and pyrazole classes and two different substituents. Although both cycles indicated negligible coupling free energies, both revealed significant coupling enthalpies, an observation made in other similarly dissected systems. The possible significance and caveats associated with these findings along with the advantages of using Biacore technology to derive thermodynamic parameters in drug discovery efforts are discussed.