Investigation on ultrasound images for detection of fetal congenital heart defects.

Congenital heart defects (CHD) are one of the serious problems that arise during pregnancy. Early CHD detection reduces death rates and morbidity but is hampered by the relatively low detection rates (i.e., 60%) of current screening technology. The detection rate could be increased by supplementing ultrasound imaging with fetal ultrasound image evaluation (FUSI) using deep learning techniques. As a result, the non-invasive foetal ultrasound image has clear potential in the diagnosis of CHD and should be considered in addition to foetal echocardiography. This review paper highlights cutting-edge technologies for detecting CHD using ultrasound images, which involve pre-processing, localization, segmentation, and classification. Existing technique of preprocessing includes spatial domain filter, non-linear mean filter, transform domain filter, and denoising methods based on Convolutional Neural Network (CNN); segmentation includes thresholding-based techniques, region growing-based techniques, edge detection techniques, Artificial Neural Network (ANN) based segmentation methods, non-deep learning approaches and deep learning approaches. The paper also suggests future research directions for improving current methodologies.

Gallic acid: a polyphenolic compound potentiates the therapeutic efficacy of cisplatin in human breast cancer cells.

Gallic acid (GA) is a natural polyhydroxyphenolic compound with antioxidant, antimutagenic, anti-inflammatory, and antineoplastic activities. Cisplatin (CPT) is a platinum-based chemotherapeutic drug, and it is the treatment of choice for breast, ovarian, testicular, head, and neck cancers. However, the use of anticancer drugs has undesirable effects on patients due to associated toxicities. Thus, it is necessary to search for alternatives that reduce unintended side effects and enhance anticancer potential. The use of natural compounds with the conventional chemotherapeutic drug is a new aspect of cancer therapy. In the present study, we evaluated the ability of GA in the modulation of anticancer effects of CPT in human breast adenocarcinoma cells (MCF-7) by performing MTT, apoptosis, clonogenic cell survival, and micronucleus assays. GA and CPT showed significant cytotoxic activities in MCF-7 cells in a dose-dependent manner. In combination therapy (GA 2.5, 5.0, and 10 µg/mL + CPT10 µg/mL), GA synergistically reduced the MCF-7 cell viability in contrast to the individual therapies. Cancer cells death by GA is through the induction of apoptosis as observed in the acridine orange and ethidium bromide dual staining method. The frequency of micronuclei (MN) was decreased significantly (P < 0.001) in combinational therapy, possibly reducing the risk of chemotherapy-induced MN. Moreover, GA in mono or combinational therapy did not induce any cytotoxic effects in normal breast epithelial cells (MCF-10A). GA did not show any significant difference in colony inhibition compared to CPT. This outcome shows its differential effects in normal and cancerous cells. Hence, the combination GA with chemotherapeutic drugs could represent a promising alternative therapy in cancer treatment with minimal side effects.

Optimization of Oral Posaconazole Step Down Therapy in Management of Rhino-Orbital-Cerebral Mucormycosis (ROCM): Outcome of an Institutional Protocol.

All cases of ROCM received antifungal for a prolong period in step down phase. There is no definite guidelines regarding duration. We have formulated and followed an institutional protocol with good results. To determine the outcome of an institutional protocol and required optimum duration of oral posaconazole therapy to cure ROCM in step down phase, 30 ROCM patients were followed up in step down phase. Oral posaconazole tablet was given for minimum 3, 4 & 1/2 and 6 months to stage-II, III & IV cases respectively, with a provision of extension for another 6 weeks in suspected active diseases. Nasal endoscopy, MRI, histopathology /culture of suspected tissue and hematologic investigations were done routinely to identify the residual active disease or recurrences at earliest. Outcome of this protocol proved excellent as all cases of ROCM were cured. Oral posaconazole step down therapy for a duration according to the stages of disease cured 18 cases (60%) of ROCM. Fourteen patients required extended duration of therapy as per provision of our treatment protocol. Only one patient needed re-debridement. The cases with deformities needed extended period of posaconazole therapy. No one needed posaconazole therapy for more than 7and1/2 months.

Targeting receptor-ligand chemistry for drug delivery across blood-brain barrier in brain diseases.

The blood-brain barrier (BBB) is composed of a layer of endothelial cells that is interspersed with a series of tight junctions and characterized by the absence of fenestrations. The permeability of this barrier is controlled by junctions such as tight junctions and adherent junctions as well as several cells such as astrocytes, pericytes, vascular endothelial cells, neurons, microglia, and efflux transporters with relatively enhanced expression. It plays a major role in maintaining homeostasis in the brain and exerts a protective regulatory control on the influx and efflux of molecules. However, it proves to be a challenge for drug delivery strategies that target brain diseases like Dementia, Parkinson's Disease, Alzheimer's Disease, Brain Cancer or Stroke, Huntington's Disease, Lou Gehrig's Disease, etc. Conventional modes of drug delivery are invasive and have been known to contribute to a "leaky BBB", recent studies have highlighted the efficiency and relative safety of receptor-mediated drug delivery. Several receptors are exhibited on the BBB, and actively participate in nutrient uptake, and recognize specific ligands that modulate the process of endocytosis. The strategy employed in receptor-mediated drug delivery exploits this process of "tricking" the receptors into internalizing ligands that are conjugated to carrier systems like liposomes, nanoparticles, monoclonal antibodies, enzymes etc. These in turn are modified with drug molecules, therefore leading to delivery to desired target cells in brain tissue. This review comprehensively explores each of those receptors that can be modified to serve such purposes as well as the currently employed strategies that have led to increased cellular uptake and transport efficiency.

Cognition, autonomic function, and intellectual outcomes of the paramedical health-care personnel in the hospital settings.

BACKGROUND: In the dedicated intensive care settings, health-care providers need to have higher temporal cognition and sympathovagal balance to optimally deliver critical care interventions. OBJECTIVE: The objective of the study was to estimate the parameters of the temporal cognition and autonomic function of paramedical staffs in acute health-care settings. MATERIALS AND METHODS: In this study on 81 healthy adult paramedical personnel, temporal cognition was assessed using auditory reaction time (ART), visual reaction time (VRT), critical flicker fusion frequency (CFFF), Stroop test (ST), and digits forward test (DFT); Autonomic functions were assessed by heart rate (HR) and blood pressure (BP) variability, and all these outcomes were analyzed with their academic performance. RESULTS: Out of 81 healthy adult nonteaching technical personnel, majority was female; the mean age was 25.10 ± 3.93 years. Age and gender were not significantly related with screen times in terms of smartphone use, playing video games, or regularly using computer; academic performances were also not significantly related with screen times in terms of smartphone use, playing video games, or regularly using computer. In the conventional domains, during analysis of physiological and psychological variables under study, there was no significant relation with screen times when compared with HR, systolic BP, diastolic BP, mean arterial pressure, body mass index, ART, VRT, CFFF, ST, and DFT. Playing video games and regular computer use were significantly correlated with age, gender, AP, CFFF, ST, and DFT. CONCLUSION: This study on paramedical personnel showed a positive relation of temporal cognition and sympathovagal autonomic balance with performing a task or function.

Reviewing the oral carcinogenic potential of E-cigarettes using the Bradford Hill criteria of causation.

The past decade has seen a surge in the use of e-cigarettes, which has prompted the medical community to assess any associated potential health hazards. A major concern was the risk of cancer. Chemical analysis of e-cigarettes has shown the presence of volatile organic compounds with the potential for carcinogenicity. Comparative toxicology analysis has shown e-cigarette to have relatively lower dosages of toxins than conventional combustible cigarettes. Based on comparative analysis, e-cigarettes have been increasingly advocated as a safe alternative to conventional cigarettes. It is vital to recognize that presence of relatively lower toxin level does not preclude carcinogenic potential. The nicotine present in the e-cigarette was presumed to be the major cytotoxic agents, thus nicotine-free e-cigarette was considered as inert. On the contrary, experimental studies on oral cell lines have shown DNA strand breaks on exposure to e-cigarette vapors with or without nicotine. In addition, dysregulations of genes associated with carcinogenic pathways have also been demonstrated in oral tissues exposed to e-cigarette vapors. Despite alarming molecular data, the oral carcinogenic potential of e-cigarette remains unclear, which can be attributed to the lack of long-term prospective and large-scale case-control studies. As e-cigarette users often have other well-established risk factors (conventional cigarette smoking, alcohol, etc.) as associated habits, it is difficult to assess e-cigarette as an independent risk factor for oral cancer. Thus, the present manuscript aims to review the published literature using the Brad Ford Hill criteria of causation to determine the oral carcinogenic potential of e-cigarettes.

Potential Role of Machine Learning in Oncology.

Machine learning (ML) is the ability of computers to learn from data autonomously. It is a core branch of artificial intelligence (AI), which is defined as the ability of a machine to replicate the intellectual processes of humans independently.1,2 The evolution of the microprocessor for home computers resulted in increased computing speed, efficient data collection, storage, and retrieval capacity. Thus AI techniques have evolved, which led to the discovery of artificial neural networks which are computer modeling algorithms mimicking the human brain.3-6 AI has developed to an extent that it can exceed the human brain in board games such as chess, television games, image recognition, and spam e-mail filtering. In addition to engineering, arts, and finance, extensive progress has been made to integrate ML in the field of medicine, especially oncology.

Morbidity Audit of 704 Traumatic Brain Injury Cases in a Dedicated South Indian Trauma Center.

BACKGROUND: In the era of evidence-based health care, protocol of intervention in traumatic brain injury (TBI) cases help decide more easily and safely about patients and prevent unnecessary transfer of patients to other centers. OBJECTIVES: The objective of this study is to provide protocol-based intervention and evaluate the epidemiological, clinical characteristics of TBI cases. METHODS: This prospective study was conducted on 704 patients who were suspected of TBI at the Department of Neurosurgery, Narayana Medical College and Hospital, followed by protocol-based intervention assessed and reassessed repeatedly. RESULTS: Overall, TBI involved 569 (80.82%) adults in the productive age groups (21-60 years); among males 81.47%. Among males, highest (23.15%) cases were in the age group of 31-40 years while in females, majority (27.04%) was among 41-50 years. Road traffic accidents were the most common (54.12%) mechanism of injury followed by fall (21.31%) and two-wheelers (15.20%). More than half sustained mild TBI (51.42%) while 26.28% moderate TBI and 22.30% severe TBI; among males, severe TBI victims 102 (18.82%) were in the productive age group. Loss of consciousness was almost a universal and significant observation (95.45%); vomiting was next common finding (76.42%). Bleeding from the ear-nose-throat (ENT) region was more in males (33.58%) than females (20.75%). Glasgow coma scale was significantly related with loss of consciousness (91.08%), vomiting (63.06%), and ENT bleeding (44.59%) in severe, moderate, and mild injuries. CONCLUSION: A rational clinical acumen with judicious use of diagnostic protocol leads to better management of TBI without unnecessary imaging and thus reduce total health-care costs.

Pharmacological approach to increasing the retention of radiation-induced γ-H2AX foci using phosphatase inhibitors: significance in radiation biodosimetry.

In a scenario of accidental mass radiation exposure transportation and analysis of samples may take some time, resulting in loss of biomarker information over this period. The present study aims to use phosphatase inhibitors for longer retention of focal signals to adopt γ-H2AX as a biodosimetric biomarker for the management of early triage. Peripheral blood lymphocytes isolated from healthy individuals were irradiated in vitro with x-rays and γ-H2AX foci were analysed using fluorescent microscopy and flow cytometric methods. Further, the effect of protein phosphatase 2A inhibitors such as calyculin A, fostriecin and okadiac acid on the retention of foci was studied. Fluorescent microscopy was found to be a more sensitive method than flow cytometry. Calyculin A showed significant retention of focal signals at 6 h with 1.5-fold increased retention compared to radiation alone; this may prove beneficial in early triage management because of a better dose approximation.

T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab.

CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1) specific humanized monoclonal antibody, inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17) have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis. Here, in in vitro experiments we show that by day 3 of human PBMC activation using anti-CD3 and anti-CD28 co-stimulation in a Th17 polarizing milieu, 15-35% of CD4+ T-cells overexpress CD6 and there is an establishment of differentiated Th17 cells. Addition of Itolizumab reduces the activation and differentiation of T cells to Th17 cells and decreases production of IL-17. These effects are associated with the reduction of key transcription factors pSTAT3 and RORγT. Further, transcription analysis studies in these conditions indicate that Itolizumab suppressed T cell activation by primarily reducing cell cycle, DNA transcription and translation associated genes. To understand the mechanism of this inhibition, we evaluated the effect of this anti-human CD6D1 mAb on ALCAM-CD6 as well as TCR-mediated T cell activation. We show that Itolizumab but not its F(ab')2 fragment directly inhibits CD6 receptor hyper-phosphorylation and leads to subsequent decrease in associated ZAP70 kinase and docking protein SLP76. Since Itolizumab binds to CD6 expressed only on human and chimpanzee, we developed an antibody binding specifically to mouse CD6D1. This antibody successfully ameliorated the incidence of experimental autoimmune encephalitis in the mice model. These results position CD6 as a key molecule in sustaining the activation and differentiation of T cells and an important target for modulating autoimmune diseases.

Efficient T3P® mediated synthesis, differential cytotoxicity and apoptosis induction by indolo-triazolo-thiadiazoles in human breast adenocarcinoma cells.

The limited efficacy of marketed anticancer agents demands the design of novel target-specific hybrid molecules incorporating multiple bioactive pharmacores to combat cancer. In the present study, a one-pot simple and efficient T3P® mediated procedure for the preparation of twelve new 3-(substituted- [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazolo)-1H-indoles with short reaction times, easy workup procedure, good yields, and purity of products is described. Cytotoxicity assay (MTT), flow-cytometric univariate cell cycle analysis, Annexin V-FITC staining and DNA fragmentation for cell death mechanism suggested that compound 3d with chloro-substituted phenyl ring induced enhanced cytotoxicity by an apoptotic pathway with high differential toxicity to breast adenocarcinoma cells (MCF-7) when compared with normal human dermal fibroblast cells. Additionally, the interaction between the BH3 domain of anti-apoptotic proteins Bcl-2 and Bcl-xL with the pharmacophore 3d was examined by molecular docking simulations to assess its potential to induce apoptosis. The docking solutions were proposed to explain the observed selectivity of 3d to Bcl-xL protein. From the present findings, the lead compound, 3d exhibited better anticancer activity when related to the other synthesized molecules with specific action on MCF-7 cells and hence can be considered as a plausible candidate chemo-therapeutic agent, although this warrants further experimentation.

Synthesis of silver nanoparticles by endosymbiont Pseudomonas fluorescens CA 417 and their bactericidal activity.

The present study emphasizes on biogenic synthesis of silver nanoparticles and their bactericidal activity against human and phytopathogens. Nanoparticle synthesis was performed using endosymbiont Pseudomonas fluorescens CA 417 inhabiting Coffea arabica L. Synthesized nanoparticles were characterized using hyphenated spectroscopic techniques such as UV-vis spectroscopy which revealed maximum absorption 425nm. Fourier transform infrared spectroscopy (FTIR) analysis revealed the possible functional groups mediating and stabilizing silver nanoparticles with predominant peaks occurring at 3346 corresponding to hydroxyl group, 1635 corresponding carbonyl group and 680 to aromatic group. X-ray diffraction (XRD) analysis revealed the Bragg's diffraction pattern with distinct peaks at 38° 44°, 64° and 78° revealing the face-centered cubic (fcc) metallic crystal corresponding to the (111), (200), (220) and (311) facets of the crystal planes at 2θ angle. The energy dispersive X-ray spectroscopy (EDS) analysis revealed presence of high intense absorption peak at 3keV is a typical characteristic of nano-crystalline silver which confirmed the presence of elemental silver. TEM analysis revealed the size of the nanoparticles to be in the range 5-50nm with polydisperse nature of synthesized nanoparticles bearing myriad shapes. The particle size determined by Dynamic light scattering (DLS) method revealed average size to be 20.66nm. The synthesized silver nanoparticles exhibited significant antibacterial activity against panel of test pathogens. The results showed Klebsiella pneumoniae (MTCC 7407) and Xanthomonas campestris to be more sensitive among the test human pathogen and phyto-pathogen respectively. The study also reports synergistic effect of silver nanoparticles in combination with kanamycin which displayed increased fold activity up to 58.3% against Klebsiella pneumoniae (MTCC 7407). The results of the present investigation are promising enough and attribute towards growing scientific knowledge on development of new antimicrobial agents to combat drug resistant microorganisms. The study provides insight on emerging role of endophytes towards reduction of metal salts to synthesize nanoparticles.

Predicting outcome in traumatic brain injury: Sharing experience of pilot traumatic brain injury registry.

BACKGROUND: A reliable prediction of outcome for the victims of traumatic brain injury (TBI) on admission is possible from concurrent data analysis from any systematic real-time registry. OBJECTIVE: To determine the clinical relevance of the findings from our TBI registry to develop prognostic futuristic models with readily available traditional and novel predictors. MATERIALS AND METHODS: Prospectively collected data using predesigned pro forma were analyzed from the first phase of a trauma registry from a South Indian Trauma Centre, compatible with computerized management system at electronic data entry and web data entry interface on demographics, clinical, management, and discharge status. STATISTICAL ANALYSIS: On univariate analysis, the variables with P < 0.15 were chosen for binary logistic model. On regression model, variables were selected with test of coefficient 0.001 and with Nagelkerke R2 with alpha error of 5%. RESULTS: From 337 cases, predominantly males from rural areas in their productive age, road traffic injuries accounted for two-thirds cases, one-fourths occurred during postmonsoon while two-wheeler was the most common prerequisite. Fifty percent of patients had moderate to severe brain injury; the most common finding was unconsciousness followed by vomiting, ear bleed, seizures, and traumatic amnesia. Fifteen percent required intracranial surgery. Patients with severe Glasgow coma scale score were 4.5 times likely to have the fatal outcome (P = 0.003). Other important clinical variables accountable for fatal outcomes were oral bleeds and cervical spine injury while imperative socio-demographic risk correlates were age and seasons. CONCLUSION: TBI registry helped us finding predictors of clinical relevance for the outcomes in victims of TBI in search of prognostic futuristic models in TBI victims.

Transorbital Orbitocranial Penetrating Injury with an Iron Rod.

Transorbital orbitocranial penetrating injuries (TOPIs) are relatively rare, can be caused by high-speed projectile foreign bodies to low-energy trauma (which is rarer), and account for 24% of penetrating head injuries in adults and approximately 45% in children. We report an uncommon nonfatal case of TOPI where a 16-year-old male child sustained injury due to accidental penetration of metal bar into the forehead. A bicoronal flap was raised to remove the metal bar. The patient recovered well, had normal vision, and doing well at follow-up.

Phase angle measurement in pulmonary tuberculosis patients and control subjects using bio-impedance analysis.

BACKGROUND: Bio-impedance is the measure of impedance of the body. Impedance consists of resistance and reactance. Phase angle (PA) is the tan value of the ratio of reactance versus resistance. PA depends on cell membrane integrity and on body cell mass. Earlier studies have shown a correlation between PA values and body cell mass. Body cell mass varies in chronic diseases like HIV infection, tuberculosis, cancers and chronic renal failure. AIMS: The aim of this study was to compare the PA values of tuberculosis patients (TB) with that of control subjects and to compare the anthropometric values between the groups. MATERIAL AND METHODS: Bioimpedance analysis and PA measurements were done using Bodystat Quadscan 4000 machine on 30 tuberculosis patients and controls between the age group of 18 to 50 years. RESULTS: The PA values were 5.09 +/- 1.11 degrees and 7.2 +/- 1.27 degrees in TB patients and control subjects respectively. PA values were positively correlated with Body mass index (BMI) in TB patients and control (r = 0.42 and 0.011, both p < 0.001). Mean difference and its 95% confidence interval between groups for PA were -2.11 (-2.72, -1.49), for weight -13.9 (-18.1, -9.7), for BMI -5.65 (-7.1, -4.2), for corrected arm muscle area (CAMA) -9.91 (-13.2, -6.6) and for impedance 152.6 (106.6, 198.6). PA, weight, BMI and CAMA were significantly higher in control subjects and impedance was lower in control groups using independent sample t test. CONCLUSIONS: PA and nutritional status were significantly low in TB patients as compared with control subjects.

Evaluation of plasma fibrinogen degradation products and total serum protein concentration in oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSMF) is a potentially malignant disorder with a multifactorial etiology. Malnutrition is a major problem for the inhabitants of most countries where OSMF is prevalent. Recently, a new direction in the etiopathogenesis was provided by the identification of fibrinogen degradation products (FDP) in the plasma of OSMF patients. AIMS AND OBJECTIVES: To assess the role of FDP in the etiology of OSMF and to correlate with the nutritional status by evaluating the total serum protein level. The study also determines to evaluate the correlation between the levels of plasma FDP with respect to the staging and grading of OSMF. Correlation between the levels of Total Serum Protein (TSP) with respect to the staging and grading of OSMF was also evaluated. MATERIALS AND METHODS: The study included 30 cases clinically and histopathologically diagnosed as oral submucous fibrosis. The FDP levels were assessed using both qualitative and semi quantitative method as supplied by 'Tulip Diagnostics (P) Ltd. Total Serum Protein (TSP) estimation was done by Biuret method using Liquixx Protein kit by Erba, Manheim. RESULTS: The study indicates that in qualitative assessment of FDP only 14 subjects showed the presence of FDP levels>200ng/ml. In semiquantitative assessment there is no significant association between varying clinical stages and histopathological grades and FDP levels. Total serum Protein level showed a marginal increase in all subjects. The study revealed a positive correlation between FDP and TSP in all OSMF subjects. CONCLUSION: A larger sample size which would be a better representation of the population and the use of different methods which have higher sensitivities and specificities to evaluate FDP level and detailed fractional analysis of protein along with immunoglobulin profiling would facilitate in attaining more conclusive results.

Preduodenal portal vein in adult with polysplenia syndrome revisited with a case report.

Preduodenal portal vein (PDPV) is a rare developmental anomaly. In infants, this is often associated with duodenal obstruction or biliary atresia. It is generally asymptomatic in adults (Ooshima et al., Hepato-Biliary-Pancreat Surg 5(4):455-458, 1998). Here, we report a singular case of adult PDPV that was discovered accidentally during emergency laparotomy for peritonitis due to gastric perforation in a 38-year-old lady. A plethora of congenital anomalies was uncovered, which is consistent with the reported cases of classical polysplenia syndrome, viz., multiple spleens of equal volume, visceral heterotaxia, right (Rt.)-sided stomach, a left (Lt.)-sided or a large midline liver, malrotation of intestine, a short pancreas, PDPV and IVC abnormalities (Gayer et al., Abdom Imaging 24:178-184, 1999). In addition, abnormalities like anamolous origin of Lt. gastric and splenic arteries from the abdominal aorta with absent celiac trunk, hepatic artery arising from the superior mesenteric artery, hepatic veins draining directly to Rt. atrium, etc. along with hypertrophic and lipomatous interatrial septum have also been detected during further investigations. As of now, we have come across 29 cases of adult PDPV reported in world literature and we are reporting our unique case with a review of literature on anomalies of visceral organs associated with PDPV.