Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy

Blood biomarkers have been explored for their potential to provide objective measures in the assessment of traumatic brain injury (TBI). However, it is not clear which biomarkers are best for diagnosis and prognosis in different severities of TBI. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mild TBI (mTBI), predicting delayed recovery after mTBI, and predicting adverse outcome after severe TBI (sTBI). We conducted a literature search of publications on biomarkers in TBI published up until July 2018. Operating characteristics were pooled for each biomarker for comparison. For detecting concussion, 4 biomarker panels and creatine kinase B type had excellent discriminative ability. For detecting intracranial injury and the need for a head CT scan after mTBI, 2 biomarker panels, and hyperphosphorylated tau had excellent operating characteristics. For predicting delayed recovery after mTBI, top candidates included calpain-derived αII-spectrin N-terminal fragment, tau A, neurofilament light, and ghrelin. For predicting adverse outcome following sTBI, no biomarker had excellent performance, but several had good performance, including markers of coagulation and inflammation, structural proteins in the brain, and proteins involved in homeostasis. The highest-performing biomarkers in each of these categories may provide insight into the pathophysiologies underlying mild and severe TBI. With further study, these biomarkers have the potential to be used alongside clinical and radiological data to improve TBI diagnostics, prognostics, and evidence-based medical management

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, <scp>genotype–phenotype</scp> correlations and common mechanisms

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (&gt;60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS‐like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or “DTRs”). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype–phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population

Artificial Intelligence in Self Driving Cars: Applications, Implications and Challenges

Artificial intelligence (AI) being integrated in almost every field of endeavour. The autonomous vehicles market is one of the fascinating sector which encouraging regulators, consumers and policy makers to understand its need, problems it is solving and how it is being applied. The study focuses on applications of AI in Self-Driving Cars. Big Data collected using sensors and IoT devices allows AI to analyse the surroundings and make appropriate decisions for the movement of the car in the following steps: Data Collection, Data Processing, Path Planning and Action. The problems of conventional cars like poor road safety, lesser independence for the disabled, high costs, less productivity, traffic congestion, high travel time, and environmental pollution can be prevented with self-driving cars via the application of AI. However, challenges like social acceptability, road conditions, traffic conditions, weather conditions, data privacy and cybersecurity are faced by AI powered self-driving cars. The study also covers similar challenges specific to India. This paper also includes future possibilities of Level 5 self-driving

Management of Ectodermal Dysplasia in A 7 Year Old Child

Background: Ectodermal dysplasia is a hereditary group of disorders which are manifested as X-linked recessive trait and has a full expression in males, whereas females show little or no signs of the disorder. This disorder leads to disturbances in the ectoderm of the developing embryo. It has many evident general and oral features which makes its rehabilitation of utmost importance. Correction of the presenting clinical oral disorders may help improve the quality of life for the patient. A multidisciplinary approach has to be adopted for such cases and it becomes a challenge in pediatric patients. In this report, etiology, clinical presentation, diagnosis and treatment plan of a 7-year-old male patient suffering from ectodermal dysplasia has been discussed

Understanding the Relationship between Glutathione, TGF-β, and Vitamin D in Combating Mycobacterium tuberculosis Infections

Tuberculosis (TB) remains a pervasive global health threat. A significant proportion of the world&rsquo;s population that is affected by latent tuberculosis infection (LTBI) is at risk for reactivation and subsequent transmission to close contacts. Despite sustained efforts in eradication, the rise of multidrug-resistant strains of Mycobacteriumtuberculosis (M. tb) has rendered traditional antibiotic therapy less effective at mitigating the morbidity and mortality of the disease. Management of TB is further complicated by medications with various off-target effects and poor compliance. Immunocompromised patients are the most at-risk in reactivation of a LTBI, due to impairment in effector immune responses. Our laboratory has previously reported that individuals suffering from Type 2 Diabetes Mellitus (T2DM) and HIV exhibited compromised levels of the antioxidant glutathione (GSH). Restoring the levels of GSH resulted in improved control of M. tb infection. The goal of this review is to provide insights on the diverse roles of TGF- &beta; and vitamin D in altering the levels of GSH, granuloma formation, and clearance of M. tb infection. We propose that these pathways represent a potential avenue for future investigation and development of new TB treatment modalities

Differential weight loss with intermittent fasting or daily calorie restriction in low‐ and high‐fitness phenotypes

Recent interest has focused on the benefits of time‐restricted feeding strategies, including intermittent fasting, for weight loss. It is not yet known whether intermittent fasting is more effective than daily caloric restriction at stimulating weight loss and how each is subject to individual differences. Here, rat models of leanness and obesity, artificially selected for intrinsically high (HCR) and low (LCR) aerobic capacity, were subjected to intermittent fasting and 50% calorie restrictive diets in two separate experiments using male rats. The lean, high‐fitness HCR and obesity‐prone, low‐fitness LCR rats underwent 50% caloric restriction while body weight and composition were monitored. The low‐fitness LCR rats were better able to retain lean mass than the high‐fitness HCR rats, without significantly different proportional loss of weight or fat. In a separate experiment using intermittent fasting in male HCR and LCR rats, alternate‐day fasting induced significantly greater loss of weight and fat mass in LCR compared with HCR rats, although the HCR rats had a more marked reduction in ad libitum daily food intake. Altogether, this suggests that intermittent fasting is an effective weight‐loss strategy for those with low intrinsic aerobic fitness; however, direct comparison of caloric restriction and intermittent fasting is warranted to determine any differential effects on energy expenditure in lean and obesity‐prone phenotypes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168438/1/eph13033_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168438/2/eph13033.pd

Risks of hypertension and thromboembolism in patients receiving bevacizumab with chemotherapy for colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Guidelines show that for metastatic colorectal cancer (mCRC), a combination of three-drug regimens, fluorouracil, leucovorin, and oxaliplatin and bevacizumab (BVZ), is one of the first-line standard therapies. BVZ is generally well tolerated; however, it is associated with infrequent, life-threatening side effects such as severe hypertension (HTN) (5%-18%), Grade ≥3 arterial thromboembolism (ATE) (2.6%), Grade ≥3 hemorrhagic events (1.2%-4.6%), and gastrointestinal perforation (0.3%-2.4%). This meta-analysis aims to evaluate the additive risk of BVZ-induced severe HTN and thromboembolism when BVZ is combined with a standard chemotherapy regime in patients with mCRC. METHODS: Our search was conducted from January 29, 2022, to February 22, 2022, through databases of PubMed, clinicaltrial.gov, EMBASE, Web of Science, and Cochrane Library. Data analysis from randomized controlled trials (RCTs) and clinical trials was conducted using Review Manager V.5.4, comparing BVZ-chemotherapy to chemotherapy only, focusing on cardiovascular AE such as HTN and arterial and venous thromboembolism. RESULTS: The analysis from 26 clinical trials and RCTs showed that the odds of HTN were about four times higher, and ATE subgroup analysis of 11 studies showed over two times higher odds of ATE in patients being treated with BVZ compared to the chemotherapy-only group. CONCLUSION: BVZ, when added to the standard chemotherapy regimen for mCRC, was associated with higher odds of developing HTN and thromboembolism, specifically ATE, than the chemotherapy-only group. Our findings are significant as they provide vital information in analyzing the risk-benefit ratio of adding BVZ to the standard chemotherapy regime in patients with mCRC, especially in patients with vascular comorbidities

Differential weight loss with intermittent fasting or daily calorie restriction in low‐ and high‐fitness phenotypes

Recent interest has focused on the benefits of time‐restricted feeding strategies, including intermittent fasting, for weight loss. It is not yet known whether intermittent fasting is more effective than daily caloric restriction at stimulating weight loss and how each is subject to individual differences. Here, rat models of leanness and obesity, artificially selected for intrinsically high (HCR) and low (LCR) aerobic capacity, were subjected to intermittent fasting and 50% calorie restrictive diets in two separate experiments using male rats. The lean, high‐fitness HCR and obesity‐prone, low‐fitness LCR rats underwent 50% caloric restriction while body weight and composition were monitored. The low‐fitness LCR rats were better able to retain lean mass than the high‐fitness HCR rats, without significantly different proportional loss of weight or fat. In a separate experiment using intermittent fasting in male HCR and LCR rats, alternate‐day fasting induced significantly greater loss of weight and fat mass in LCR compared with HCR rats, although the HCR rats had a more marked reduction in ad libitum daily food intake. Altogether, this suggests that intermittent fasting is an effective weight‐loss strategy for those with low intrinsic aerobic fitness; however, direct comparison of caloric restriction and intermittent fasting is warranted to determine any differential effects on energy expenditure in lean and obesity‐prone phenotypes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168438/1/eph13033_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168438/2/eph13033.pd

Risks of hypertension and thromboembolism in patients receiving bevacizumab with chemotherapy for colorectal cancer: A systematic review and meta‐analysis

Abstract Background Guidelines show that for metastatic colorectal cancer (mCRC), a combination of three‐drug regimens, fluorouracil, leucovorin, and oxaliplatin and bevacizumab (BVZ), is one of the first‐line standard therapies. BVZ is generally well tolerated; however, it is associated with infrequent, life‐threatening side effects such as severe hypertension (HTN) (5%–18%), Grade ≥3 arterial thromboembolism (ATE) (2.6%), Grade ≥3 hemorrhagic events (1.2%–4.6%), and gastrointestinal perforation (0.3%–2.4%). This meta‐analysis aims to evaluate the additive risk of BVZ‐induced severe HTN and thromboembolism when BVZ is combined with a standard chemotherapy regime in patients with mCRC. Methods Our search was conducted from January 29, 2022, to February 22, 2022, through databases of PubMed, clinicaltrial.gov, EMBASE, Web of Science, and Cochrane Library. Data analysis from randomized controlled trials (RCTs) and clinical trials was conducted using Review Manager V.5.4, comparing BVZ‐chemotherapy to chemotherapy only, focusing on cardiovascular AE such as HTN and arterial and venous thromboembolism. Results The analysis from 26 clinical trials and RCTs showed that the odds of HTN were about four times higher, and ATE subgroup analysis of 11 studies showed over two times higher odds of ATE in patients being treated with BVZ compared to the chemotherapy‐only group. Conclusion BVZ, when added to the standard chemotherapy regimen for mCRC, was associated with higher odds of developing HTN and thromboembolism, specifically ATE, than the chemotherapy‐only group. Our findings are significant as they provide vital information in analyzing the risk–benefit ratio of adding BVZ to the standard chemotherapy regime in patients with mCRC, especially in patients with vascular comorbidities