Search

Background and Objectives: A anastomotic ring called Circle of Willis, which is formed by the internal carotid and vertebrobasilar systems is one of the greatest anastomosis of human body. It slows down the blood before it reaches the brain and helps in collateral circulation. Anatomic study reveals the variation in the pattern and calibre of vessels which make up the circulus arteriosus. The variations in calibre occurring in the posterior communicating artery and posterior cerebral artery are not uncommon. Methodoloy: A total of 45 brain specimens were collected, cleaned and dissected. A careful examination of the specimens was done to check for variations arterial components of the Circulus Arteriosus. The calibre of the pre communicating (P1) segment of posterior cerebral artery and the posterior communicating artery (PCoA) were carefully recorded. Results: The posterior part of the Circle of Willis was more anomalous and the posterior communicating artery was the most anomalous segment. The fetal configuration of PCoA was found in 20% of the cases. An inverse relationship was found in the components of the posterior part of the circle, between PCoA and P1 segment on the ipsilateral side. Anomalies in the formation of Circulus Arteriosus may predispose to stroke. The neurosurgical importance of this study lies during the exploration of the region for different purposes. Knowledge of the vascular variations will increase the success of the procedure.

Anomalous blood vessels are important from the clinical aspects such as hydronephrosis, Varicocele leading to risk of infarction of kidney during renal transplant surgeries. Here, we report a case series of 30 cadavers of male and female aged between 40- 80 years in the Department of Anatomy of a tertiary care institute in Bangalore, India. In three male cadavers, there was a variation in right testicular artery arising from abdominal aorta above the right renal artery later coursing downward, giving a branch to right kidney (10%). In another two male cadavers, right testicular artery (6.6%) was arising as branch of abdominal aorta above the right renal artery later coursing downward giving branch to right suprarenal gland and also observed right accessory renal artery branch of abdominal aorta arising below superior mesenteric artery and coursing upward to lower pole of right kidney. Observed in two male cadaver, inferior phrenic artery was arising as a common trunk from abdominal aorta above the main renal vessels and coursing laterally upward to diaphragm (6.6%). All the other branches of abdominal aorta and venous drainage were normal in the dissection of cadavers. The knowledge of these variations of arteries are essential before performing any transplantation surgeries, thus one can avoid the complications during uroradiological interventions.

Background Cystic artery is one of the arteries which is of utmost surgical importance, as it originates from the vast range of blood vessels, associated to the coeliac trunk and superior mesenteric artery and its relation to the biliary ducts is variable. Cystic artery is not only difficult to visualize, but difficult to approach during the surgery. This study was undertaken to study the anatomy of arterial variations of cystic artery in the specimens of liver and gallbladder by exploring the extrahepatic duct system, and in addition the relations of cystic artery in the Calot’s triangle were also studied and observed. Materials and Methods The study was conducted on 50 human liver specimens with intact gallbladder and extrahepatic duct system, collected from the Department of Anatomy over a period of 5 years. The specimens obtained were fixed in 10% formalin and were finely dissected. The specimens were observed for parameters like the origin of the cystic artery, its length and diameter, mode and level of termination, relation to the Calot’s triangle, and the extrahepatic duct system. Results Origin of the cystic artery was normal in 92% of cases and variations were seen in approximately 8% cases. The most common origin of the cystic artery was from the right hepatic artery, which was in 92% of the cases. In the present study, in 97% cases the cystic artery terminated by dividing into the superficial and deep branches. In the rest, the artery continued as a superficial branch, the deep branch being replaced by the accessory cystic artery. In 64% cases, the cystic artery was seen within the Calot’s triangle, and in 36% of cases, it was outside the Calot’s triangle. In 67% cases, the cystic artery was medial to the cystic duct, in approximately 63% cases the cystic artery was lateral to the common hepatic duct, and in 30% of the cases the cystic artery passed anterior to the cystic duct. Incidence of accessory cystic arteries in the present study was approximately 4%.

Natural killer (NK) cells are vital innate immune cells that play a crucial role in cancer therapy. They are targeted by therapies designed to modulate, retain, and enhance their antitumor function in vivo. In addition to whole-cell therapy, NK cell-derived exosomes (NDEs) offer high immune safety and are easily subject to chemical, biological, and immunological modifications. This makes them suitable for use in combination with various current cancer therapies to enhance efficacy, treatment outcomes, and reduce side effects in vivo. This review aims to outline summarizes the antitumor potential of NK cells, as well as the current challenges and opportunities in NK cell-based immunotherapies such as allogeneic and autologous NK cell transplantation, CAR NK cell therapy, and the use of cytokines and monoclonal antibodies. The review also explores the dual regulatory effects of tumor exosomes on NK cells, and highlights the potential of NDEs, either alone or in combination with other antitumor therapies, to reprogram the immunosuppressive tumor microenvironment and expedite the therapeutic effects of cancer immunotherapy in future clinical research., (© 2024 Wiley Periodicals LLC.)

The integration of artificial intelligence (AI) into the diagnosis and treatment of autism spectrum disorder (ASD) represents a promising frontier in healthcare. This review explores the current landscape and future prospects of AI technologies in ASD diagnostics and interventions. AI enables early detection and personalized assessment of ASD through the analysis of diverse data sources such as behavioural patterns, neuroimaging, genetics, and electronic health records. Machine learning algorithms exhibit high accuracy in distinguishing ASD from neurotypical development and other developmental disorders, facilitating timely interventions. Furthermore, AI-driven therapeutic interventions, including augmentative communication systems, virtual reality-based training, and robot-assisted therapies, show potential in improving social interactions and communication skills in individuals with ASD. Despite challenges such as data privacy and interpretability, the future of AI in ASD holds promise for refining diagnostic accuracy, deploying telehealth platforms, and tailoring treatment plans. By harnessing AI, clinicians can enhance ASD care delivery, empower patients, and advance our understanding of this complex condition., Competing Interests: Declaration of Competing Interest None Declared, (Copyright © 2024 Elsevier B.V. All rights reserved.)

A highly sensitive, portable, rapid, and accurate colorimetric sensing method is presented. It is based upon exfoliated g-C 3 N 4 nanosheets (E-g-C 3 N 4 NSs), having peroxidase nanozyme-like properties. The as-prepared catalyst (E-g-C 3 N 4 NSs) tends to oxidize the colorless tetramethyl-benzidine (TMB) into oxidized-TMB in the presence of hydrogen peroxide (H 2 O 2 ) generating a dark blue color and corresponding ultraviolet visible-spectral changes following a Michaelis-Menten kinetic. The prepared colorimetric sensor exhibited response within the range 0.001-0.450 μM having R 2 value of 0.999 and a detective limit (LOD) of 0.15 ± 0.04 nM. Furthermore, the sensor also displayed outstanding selectivity, ample stability (10 weeks), and excellent practicability in real sample applications. All these outstanding properties were highly attributed to the large surface area with exposed actives sites, high surface energy, and large conductive structure of E-g-C 3 N 4 NSs. For comparison of the catalytic study, we have also explored the sensing mechanism of B-g-C 3 N 4 , using the same optimized experimental conditions. Resultantly, we concluded that the proposed sensor (E-g-C 3 N 4 NSs) will gain considerable attention for on-site environmental and health monitoring in future endeavor., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Fistulas, abnormal connections between two anatomical structures, significantly impact the quality of life and can result from a variety of causes, including congenital defects, inflammatory conditions, and surgical complications. Stem cell therapy has emerged as a promising alternative due to its potential for regenerative and immunomodulatory effects. This overview of systematic reviews aimed to assess the safety and efficacy of stem cell therapy in managing fistulas, drawing on the evidence available., Methods: This umbrella review was conducted following the Joanna Briggs Institute (JBI) methodology to assess the efficacy and safety of stem cell therapy for treating various types of fistulas. A comprehensive search was performed across multiple electronic databases including PubMed, Embase, Cochrane Register, and Web of Science up to May 5th, 2024. Systematic reviews focusing on stem cell therapy for fistulas were included, with data extracted on study design, stem cell types, administration methods, and outcomes. The quality of the reviews was assessed using the AMSTAR 2 tool, and meta-analyses were conducted using R software version 4.3., Results: Nineteen systematic reviews were included in our umbrella review. The stem cell therapy demonstrated by significant improvements in clinical remission rates, with a relative risk (RR) of 1.299 (95% CI: 1.192 to 1.420). Stem cell therapy enhanced fistula closure rates, both short-term (RR=1.481; 95% CI: 1.036 to 2.116) and long-term (RR=1.422; 95% CI: 1.091 to 1.854). The safety analysis revealed no significant increase in the risk of adverse events with stem cell therapy, showing a pooled RR of 0.972 (95% CI: 0.739 to 1.278) for general adverse events and 1.136 (95% CI: 0.821 to 1.572) for serious adverse events, both of which indicate a safety profile comparable to control treatments. Re-epithelialization rates also improved (RR=1.44; 95% CI: 1.322 to 1.572)., Conclusion: Stem cell therapy shows promise as an effective and safe treatment for fistulas, particularly in inducing remission and promoting closure of complex fistulas. The findings advocate for further high-quality research to confirm these benefits and potentially incorporate stem cell therapy into standard clinical practice for fistula management. Future studies should focus on long-term outcomes and refining stem cell treatment protocols to optimize therapeutic efficacy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The EGF receptors (EGFRs) signaling pathway is essential for tumorigenesis and progression of cancer. Emerging evidence suggests that miRNAs are essential regulators of EGF signaling, influencing various pathway components and tumor behavior. This article discusses the underlying mechanisms and clinical implications of miRNA-mediated regulation of EGF signaling in cancer. miRNAs utilize multiple mechanisms to exert their regulatory effects on EGF signaling. They can target EGF ligands, including EGF and TGF-directly, inhibiting their expression and secretion. In addition, miRNAs can modulate EGF signaling indirectly by targeting EGF receptors, downstream signaling molecules, and transcription factors implicated in regulating the EGF pathway. These miRNAs can disrupt the delicate equilibrium of EGF signaling, resulting in aberrant activation and fostering tumor cell proliferation, survival, angiogenesis, and metastasis. The dysregulation of the expression of specific miRNAs has been linked to clinical outcomes in numerous types of cancer. Specific profiles of miRNA expression have been identified as prognostic markers, reflecting tumor characteristics, invasiveness, metastatic potential, and therapeutic response. These miRNAs can serve as potential therapeutic targets for interventions that modulate EGF signaling and improve patient outcomes. Understanding the intricate relationship between miRNAs and EGF signaling in cancer can transform cancer diagnosis, prognosis, and treatment. The identification of specific miRNAs involved in the regulation of the EGF pathway opens the door to the development of targeted therapies and personalized medicine approaches. In addition, miRNA-based interventions promise to overcome therapeutic resistance and improve the efficacy of existing treatments. miRNAs are crucial regulators of EGF signaling in cancer, affecting tumor behavior and clinical outcomes. Further research is required to decipher the complex network of miRNA-mediated EGF signaling regulation and translate these findings into clinically applicable strategies for enhanced cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Avian influenza, commonly known as bird flu, is a contagious disease that affects both animals and humans, posing a significant threat to public health, animal welfare, and the economy. This study aims to evaluate the knowledge of avian influenza among poultry farmworkers and evaluate the biosecurity practices implemented on their farms., Objective: The study's primary objective was to assess the knowledge regarding avian influenza among poultry farmworkers and the biosecurity practices they follow at the farm., Design: Cross-sectional study., Setting: The study was conducted in a district of South India., Participants: This study included 105 poultry farmworkers across 70 poultry farms in the district., Main Outcome Measures: Assessment of the participants' knowledge related to avian influenza, and the association between knowledge levels, demographic, and farm-related factors such as working experience in the poultry farm, type of poultry farm, type of poultry reared, and biosecurity practices., Results: In the study, 90% of participants were aware of avian influenza, with 36% correctly identifying the virus as its cause, whereas 5% wrongly cited it to be a bacteria. Although 90% knew avian influenza was infectious, only 18% recognized its potential transmission to humans; however, 82% understood prevention methods. Participants with an education level beyond high school displayed significantly higher awareness ( P < .05), emphasizing importance of the education., Conclusions: The study showed diverse awareness levels among poultry farmworkers regarding avian influenza, emphasizing gaps in the knowledge, particularly about its transmission to humans. This underscores the need for targeted awareness campaigns focusing on zoonotic risks to improve the level of understanding and implement effective preventive measures against avian influenza., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) continues to pose a global health concern, necessitating the exploration of innovative therapeutic approaches. In the recent decade, targeting tumor stroma consisting of extracellular matrix (ECM), immune cells, vascular system, hypoxia, and also suppressive mechanisms in HCC has attracted interest in repressing tumor growth and metastasis. Phytochemicals have attained considerable attention because of their manifold biological effects and high capacity for anticancer activities. These chemical agents have shown the capability to modulate different cells and secretions within the stroma of malignancies. In recent years, the development of nanoformulations has further enhanced the therapeutic potential of phytochemicals by improving their solubility, bioavailability, and targeted delivery to tumor tissues. This review aims to provide an encyclopedic overview of the potential of phytochemicals and their nanoformulations as promising therapeutic strategies for targeting HCC. The review initially highlights the broad array of phytochemicals exhibiting potent anticancer properties, including flavonoids, alkaloids, terpenoids, and phenolic compounds, among others. Then, the nanoformulations and modification of these agents will be reviewed. Finally, we will review the latest experiments that have examined the modulation of HCC using adjuvant phytochemicals and their nanoformulations., (© 2024 John Wiley & Sons Ltd.)

The transition from radicle emergence to seedling growth in maize is a crucial phase in the plant's life cycle, where rapid physiological and biochemical changes occur to facilitate successful development. In this study, we conducted a comparative transcriptomic analysis to gain a deeper understanding of the molecular processes driving this critical transition. The early divergence in gene expression patterns highlighted the upregulation of a substantial number of genes during radicle emergence. During radicle emergence, gene ontology (GO) term enrichment analysis unveiled active participation in biological processes such as chromatin assembly, cellular response to abiotic stress, and hormone signaling. This indicates that the initial stages of growth are marked by cellular expansion and adaptation to environmental stimuli. Conversely, in the seedling growth stage, GO analysis demonstrated a shift toward processes such as photosynthesis, nitrogen metabolism, and secondary metabolite biosynthesis, reflecting a transition to energy production and enhanced growth. In contrast, seedling growth was characterized by pathways related to photosynthesis and the production of gibberellins, crucial for robust seedling development. Hormonal regulation and starch metabolism were also prominent during radicle emergence, with various hormones, including auxins, diterpenoids, and brassinosteroids, driving processes like cell enlargement and stem growth. Moreover, starch and sucrose metabolism genes were expressed to mobilize stored reserves for energy during this stage. These findings offer valuable insights into the dynamic regulation of genes and pathways during this critical phase of maize development., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Competing Interests: None

In the wake of changing climatic conditions, plants are frequently exposed to a wide range of biotic and abiotic stresses at various stages of their development, all of which negatively affect their growth, development, and productivity. Drought is one of the most devastating abiotic stresses for most cultivated crops, particularly in arid and semiarid environments. Conventional breeding and biotechnological approaches are used to generate drought-tolerant crop plants. However, these techniques are costly and time-consuming. Plant-colonizing microbes, notably, endophytic fungi, have received increasing attention in recent years since they can boost plant growth and yield and can strengthen plant responses to abiotic stress. In this review, we describe these microorganisms and their relationship with host plants, summarize the current knowledge on how they "reprogram" the plants to promote their growth, productivity, and drought tolerance, and explain why they are promising agents in modern agriculture.

Objective: Assess the impact of introducing a consensus guideline incorporating an adapted Sepsis Risk Calculator (SRC) algorithm, in the management of early onset neonatal sepsis (EONS), on antibiotic usage and patient safety., Design: Multicentre prospective study SETTING: Ten perinatal hospitals in Wales, UK., Patients: All live births ≥34 weeks' gestation over a 12-month period (April 2019-March 2020) compared with infants in the preceding 15-month period (January 2018-March 2019) as a baseline., Methods: The consensus guideline was introduced in clinical practice on 1 April 2019. It incorporated a modified SRC algorithm, enhanced in-hospital surveillance, ongoing quality assurance, standardised staff training and parent education. The main outcome measure was antibiotic usage/1000 live births, balancing this with analysis of harm from delayed diagnosis and treatment, disease severity and readmissions from true sepsis. Outcome measures were analysed using statistical process control charts., Main Outcome Measures: Proportion of antibiotic use in infants ≥34 weeks' gestation., Results: 4304 (14.3%) of the 30 105 live-born infants received antibiotics in the baseline period compared with 1917 (7.7%) of 24 749 infants in the intervention period (45.5% mean reduction). All 19 infants with culture-positive sepsis in the postimplementation phase were identified and treated appropriately. There were no increases in sepsis-related neonatal unit admissions, disease morbidity and late readmissions., Conclusions: This multicentre study provides evidence that a judicious adaptation of the SRC incorporating enhanced surveillance can be safely introduced in the National Health Service and is effective in reducing antibiotic use for EONS without increasing morbidity and mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: None

The conventional curriculum in preclinical medical education has a need for early clinical exposure programs that help in correlation of basic science data with clinical skills. This is helpful to develop clinical reasoning skills, problem-solving abilities, team work, communication skills and overall attitudes and behaviour relevant for a healthcare provider. Preclinical task based learning (TskBL) is an active learning strategy in which the focus for the first year medical student is a real task done by a doctor. In this strategy the student-doctors undergo a standardized patient encounter and discuss the learning issues related to the task in the first year of medical school. The current study is focussed on the student perception of the effectiveness of task based learning module.The TskBL was conducted among first year medical students for nine topics that are commonly encountered in the clinics. After TskBL was planned and implemented the evaluation of the modules was done using focus group discussions. The students highlighted the importance of standardized patients in the TskBL strategy in providing early clinical exposure in preclinical medical education. They reported its usefulness gaining essential knowledge, skills and attitudes for medical learning. They reported positive outcomes of module design and processes and activities in TskBL. Based on the negative aspects of the modules, future improvement was suggested in improving the usefulness of standardized patient encounter. This study showed the novice learners' outlook of the potency of TskBL for several other topics of clinical relevance to provide early clinical exposure in medical schools., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Shenoy R et al.)

Preclinical task-based learning (TskBL) is a simulated learning approach in which the focus for students is a real task done by a medical professional. TskBL includes standardized patient encounters and is helpful to provide early clinical exposure. Our study aimed at planning, implementing, and assessing TskBL among first-year medical students and comparing it to the conventional method of tutorials in the physiology MBBS curriculum. This is a nonequivalent group quasi-experimental study approved by the institutional ethics committee. TskBL was conducted for seven topics among first-year medical students of Kasturba Medical College, Mangalore for three academic years. Participants were divided into a TskBL group and a control group. Both groups attended the theory classes in physiology, practical sessions, and clinical examinations concerning the tasks. After this, the TskBL group underwent TskBL, and the control group underwent tutorials. Pretest and posttest assessments were conducted by using a multiple choice question (MCQ) test and objective structured clinical examinations (OSCEs).The mean TskBL scores for MCQ (exception: hypertension, myasthenia gravis, and chronic obstructive pulmonary disease) and OSCE (exception: anemia and hypertension) were significantly higher than the tutorial group. Pretest and posttest scores revealed significantly higher MCQ and OSCE scores for TskBL (exception: MCQ score for hypertension and chronic obstructive pulmonary disease). The tutorial group did not show a significant improvement in test scores for all the tasks. The TskBL strategy could be used for topics that are likely to be encountered by the students during clinical attachments. Small group teaching can include TskBL in preference to tutorials to provide early clinical exposure in medical schools.

Competing Interests: None

Competing Interests: None

Aspartic proteases are the targets for structure-based drug design for their role in physiological processes and pharmaceutical applications. Structural insights into the thermal inactivation mechanism of an aspartic protease in presence and absence of bound pepstatin A have been obtained by kinetics of thermal inactivation, CD, fluorescence spectroscopy and molecular dynamic simulations. The irreversible thermal inactivation of the aspartic protease comprised of loss of tertiary and secondary structures succeeded by the loss of activity, autolysis and aggregation The enthalpy and entropy of thermal inactivation of the enzyme in presence of pepstatin A increased from 81.2 to 148.5 kcal mol -1 , and from 179 to 359 kcal mol -1  K -1 respectively. Pepstatin A shifted the mid-point of thermal inactivation of the protease from 58 °C to 77 °C. The association constant (K) for pepstatin A with aspartic protease was 2.5 ± 0.3 × 10 5  M -1 and ΔG o value was -8.3 kcal mol -1 . Molecular dynamic simulation studies were able to delineate the role of pepstatin A in stabilizing backbone conformation and side chain interactions. In the Cα-backbone, the short helical segments and the conserved glycines were part of the most unstable segments of the protein. Understanding the mechanism of thermal inactivation has the potential to develop re-engineered thermostable proteases., Competing Interests: Declaration of competing interest All the authors have seen and approved the manuscript and declare no conflicts of interest with the content of this article., (Copyright © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Purpose: To evaluate the clinical outcomes and patient satisfaction after implantation of Optiflex Trio, a new trifocal intraocular lens (IOL) following cataract surgery., Methods: Patients undergoing phacoemulsification for age-related cataracts and who satisfy the eligibility criteria underwent bilateral implantation with Optiflex Trio trifocal IOL. At follow -up visits of 1, 3, 6, and 12 months, binocular uncorrected and corrected distance, intermediate and near visual acuity, reading performance, contrast sensitivity (CS) and patient satisfaction for dysphotopsia and spectacle independence were evaluated using questionnaires., Results: A total of 54 eyes from 27 patients with mean age of 66.30±7.48 years were included in the study. At 12 months, 78% (n = 21) patients had binocular cumulative UDVA of 20/20 or better. Post-op SE refraction accuracy was within ±0.50 D for 93% (n = 50) eyes, and refractive cylinder accuracy was within ≤0.50 D in 94% (n = 51) eyes. The mean binocular UNVA was 0.01±0.05 LogMAR, and the mean UIVA at 60 and 80 cm was 0.07±0.06 and 0.03±0.05 LogMAR, respectively, at 12 months. Reading speeds at 40, 60 and 80 cm showed improvement overtime. No patient had complained of severe dysphotopsia, and none of the patients required glasses for any activity. No eye underwent YAG-laser capsulotomy for significant PCO at the end of mean follow-up., Conclusion: After 12 months, Optiflex Trio trifocal IOL provided a complete visual restoration with good visual quality outcomes in terms of uncorrected distance, intermediate and near visual acuity. The incidence of dysphotopsia was low, and spectacle independence was high, resulting in good patient satisfaction., Trial Registry: CTRI/2019/10/021647 (www.ctri.nic.in)., Competing Interests: Dr Sri Ganesh and Dr Sheetal Brar are consultants to Biotech Vision Care, Ahmedabad, India. The study was supported by a limited grant from Biotech Vision Care Pvt Ltd. The authors reported no other potential conflicts of interest for this work., (© 2021 Brar et al.)

Differentiated Thyroid Cancer (DTC) is increasing in prevalence due to better diagnostic tools and excellent long-term survival. This study is to understand the outcome of twenty-six patients with DTC over a period of 10 years after the initial treatment with surgery and radioiodine therapy. Our study analysis showed no deaths, and indicated that older men were more likely to have persistent disease. Further studies are needed to focus on cost effective long-term management of DTC.

Environment has been contaminated by heavy metals ever since the original magma of earth has solidified. One such toxin is cadmium. Cadmium that has been around since the industrial age, is considered hazardous both to us and to the environment. From time immemorial man is dependent on plants available in nature for several health benefits. Moringa oleifera , has nutritional, pharmacological and antioxidant properties, thus having several medicinal applications. In the present article, we discuss the dose and time dependent damage due to exposure to cadmium on kidneys, liver, testis, lipid profile and haematological parameters in adult Wistar rats and the protective effects of Moringa oleifera (pre-treatment) on cadmium induced damage.

Cancer is a leading cause of death in developed countries and second cause in developing countries. Herein we are reporting the synthesis of novel bisbenzimidazole derivatives and their anticancer properties. Among the newly synthesized bisbenzimidazoles, 3-(4-flurophenylsulfonyl)-1,7-dimethyl-2-propyl-1H,3H-2,5-bibenzo[d]imidazole (FDPB) presented as a potent antiproliferative agent against HeLa, HCT116 and A549 cells with selectivity over normal Vero cells (IC50 >50 μM). Additionally, we evaluated the efficacy of lead compound against Ehrlich ascites tumor (EAT) bearing mice for its antitumor and antiangiogenic properties. Our lead compound significantly reduced the cell viability, body weight, ascites volume and downregulated the formation of neovasculature and production of Vascular Endothelial Growth Factor (VEGF)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this longitudinal study, conducted in women attending antenatal visits at the obstetrics and gynecology clinic of a general hospital in Bangalore, India, we aimed to assess the relationship between prenatal distress in mothers, and maternal report of infant temperament at four months. 100 mothers with normal full term deliveries completed the General Health Questionnaire-28 item version (GHQ) in the third trimester and postnatally. Salivary cortisol and temperament (using the Early Infancy Temperament Questionnaire - EITQ) were assessed in their infants aged 1-4 months. In this study, maternal prenatal psychological distress was not significantly associated with maternal report of difficult temperament in infants. Infants of mothers who were a negative screen for psychological distress (GHQ<7), n=85 had higher scores on the adaptability and approach dimensions of temperament. Infant salivary cortisol was significantly higher in infants with higher intensity scores. These results introduce the possibility of cultural differences in the relationship between prenatal distress in the mother and infant temperament. These could be factors linked to child rearing practices or to the measures employed to study infant temperament. These findings derive from a small sample with few mothers with psychological distress, and need replication in a larger sample., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We present the first evidence for a QTL conditioning an adaptive trait in bulb onion, and the first linkage and population genetics analyses of candidate genes involved in photoperiod and vernalization physiology. Economic production of bulb onion (Allium cepa L.) requires adaptation to photoperiod and temperature such that a bulb is formed in the first year and a flowering umbel in the second. 'Bolting', or premature flowering before bulb maturation, is an undesirable trait strongly selected against by breeders during adaptation of germplasm. To identify genome regions associated with adaptive traits we conducted linkage mapping and population genetic analyses of candidate genes, and QTL analysis of bolting using a low-density linkage map. We performed tagged amplicon sequencing of ten candidate genes, including the FT-like gene family, in eight diverse populations to identify polymorphisms and seek evidence of differentiation. Low nucleotide diversity and negative estimates of Tajima's D were observed for most genes, consistent with purifying selection. Significant population differentiation was observed only in AcFT2 and AcSOC1. Selective genotyping in a large 'Nasik Red × CUDH2150' F2 family revealed genome regions on chromosomes 1, 3 and 6 associated (LOD > 3) with bolting. Validation genotyping of two F2 families grown in two environments confirmed that a QTL on chromosome 1, which we designate AcBlt1, consistently conditions bolting susceptibility in this cross. The chromosome 3 region, which coincides with a functionally characterised acid invertase, was not associated with bolting in other environments, but showed significant association with bulb sucrose content in this and other mapping pedigrees. These putative QTL and candidate genes were placed on the onion map, enabling future comparative studies of adaptive traits.

The study was undertaken to assess nutrient composition, glycemic index and health benefits of barnyard millet in type II diabetics. The millet had 10.5% protein 3.6% fat, 68.8% carbohydrate and 398 kcal/100 g energy. The total dietary fibre content was high (12.6%) including soluble (4.2%) and insoluble (8.4%) fractions. Low glycemic index of the grains both dehulled (50.0) and dehulled and heat treated (41.7) was recorded. The feeding intervention of 28 days revealed a significant reduction in glucose (139.2 to 131.1 mg/dl), LDL-C (from 167.7 to 162.9 mg/dl), VLDL-C (from 24.0 to 23.2 mg/dl), ratio of TC: HDL (from 4.7 to 4.6) and LDL: HDL (from 3.2 to 3.1) in the experimental diabetic groups. Similar, but marginal changes were observed in experimental non diabetics. Marginal decrease of triglycerides and increase of HDL were registered in diabetic groups due to barnyard millet intervention. The study indicated that the dehulled and heat treated barnyard millet is beneficial for type-II diabetics.

Hypertension (HTN) is a leading risk factor for cardiovascular disease (CVD) and continues to affect millions of people in industrialized nations. The increasing prevalence of HTN is closely related to the growing prevalence of obesity. Despite heightened awareness of the disease, a significant percentage of patients are uncontrolled and are at higher risk of heart failure, stroke, and chronic kidney disease. Evidence of the cardiovascular protective role of estrogen in pre-menopausal females has brought attention to estrogen receptor activation as a treatment strategy for HTN. Estrogen promotes vasodilation and decreases inflammation and atherosclerosis. It also controls blood pressure via modulation of the activity of the renin-angiotensin-aldosterone system. The effects of estrogen on the vasculature are partly mediated via membrane receptors. Membrane estrogen receptor α and G-protein-coupled GPER-1 have been studied extensively in the vasculature. This review will describe the available evidence supporting the role of estrogen membrane receptors in blood pressure control and CVD.

Introduction: The development of effective treatments for osteoarthritis (OA) has been hampered by a poor understanding of OA at the cellular and molecular levels. Emerging as a disease of the 'whole joint', the importance of the biochemical contribution of various tissues, including synovium, bone and articular cartilage, has become increasingly significant. Bathing the entire joint structure, the proteomic analysis of synovial fluid (SF) from osteoarthritic shoulders offers a valuable 'snapshot' of the biologic environment throughout disease progression. The purpose of this study was to identify differentially expressed proteins in early and late shoulder osteoarthritic SF in comparison to healthy SF., Methods: A quantitative 18O labeling proteomic approach was employed to identify the dysregulated SF proteins in early (n = 5) and late (n = 4) OA patients compared to control individuals (n = 5). In addition, ELISA was used to quantify six pro-inflammatory and two anti-inflammatory cytokines., Results: Key results include a greater relative abundance of proteins related to the complement system and the extracellular matrix in SF from both early and late OA. Pathway analyses suggests dysregulation of the acute phase response, liver x receptor/retinoid x receptor (LXR/RXR), complement system and coagulation pathways in both early and late OA. The network related to lipid metabolism was down-regulated in both early and late OA. Inflammatory cytokines including interleukin (IL) 6, IL 8 and IL 18 were up-regulated in early and late OA., Conclusions: The results suggest a dysregulation of wound repair pathways in shoulder OA contributing to the presence of a 'chronic wound' that progresses irreversibly from early to later stages of OA. Protease inhibitors were downregulated in late OA suggesting uncontrolled proteolytic activity occurring in late OA. These results contribute to the theory that protease inhibitors represent promising therapeutic agents which could limit proteolytic activity that ultimately leads to cartilage destruction.

Background: Non-structural carbohydrate (NSC; glucose, fructose, sucrose and fructan) composition of onions (Allium cepa L.) varies widely and is a key determinant of market usage. To analyse the physiology and genetics of onion carbohydrate metabolism and to enable selective breeding, an inexpensive, reliable and practicable sugar assay is required to phenotype large numbers of samples., Results: A rapid, reliable and cost-effective microplate-based assay was developed for NSC analysis in onions and used to characterise variation in tissue hexose, sucrose and fructan content in open-pollinated breeding populations and in mapping populations developed from a wide onion cross. Sucrose measured in microplates employing maltase as a hydrolytic enzyme was in agreement with HPLC-PAD results. The method revealed significant variation in bulb fructan content within open-pollinated 'Pukekohe Longkeeper' breeding populations over a threefold range. Very wide segregation from 80 to 600 g kg(-1) in fructan content was observed in bulbs of F2 genetic mapping populations from the wide onion cross 'Nasik Red × CUDH2150'., Conclusion: The microplate enzymatic assay is a reliable and practicable method for onion sugar analysis for genetics, breeding and food technology. Open-pollinated onion populations may harbour extensive within-population variability in carbohydrate content, which may be quantified and exploited using this method. The phenotypic data obtained from genetic mapping populations show that the method is well suited to detailed genetic and physiological analysis., (© 2013 Society of Chemical Industry.)

Objective: The pathophysiology of the most common joint disease, osteoarthritis (OA), remains poorly understood. Since synovial fluid (SF) bathes joint cartilage and synovium, we reasoned that a comparative analysis of its protein constituents in health and OA could identify pathways involved in joint damage. We undertook this study to perform a proteomic analysis of knee SF from OA patients and control subjects and to compare the results to microarray expression data from cartilage and synovium., Methods: Age-matched knee SF samples from 10 control subjects, 10 patients with early-stage OA, and 10 patients with late-stage OA were compared using 2-dimensional difference-in-gel electrophoresis and mass spectrometry (MS). MS with a multiplexed peptide selected reaction monitoring assay was used to confirm differential expression of a subset of proteins in an independent OA patient cohort. Proteomic results were analyzed by Ingenuity Pathways Analysis and compared to published synovial tissue and cartilage messenger RNA profiles., Results: Sixty-six proteins were differentially present in healthy and OA SF. Three major pathways were identified among these proteins: the acute-phase response signaling pathway, the complement pathway, and the coagulation pathway. Differential expression of 5 proteins was confirmed by selected reaction monitoring assay. A focused analysis of transcripts corresponding to the differentially present proteins indicated that both synovial and cartilage tissues may contribute to the OA SF proteome., Conclusion: Proteins involved in the acute-phase response signaling pathway, the complement pathway, and the coagulation pathway are differentially regulated in SF from OA patients, suggesting that they contribute to joint damage. Validation of these pathways and their utility as biomarkers or therapeutic targets in OA is warranted., (Copyright © 2013 by the American College of Rheumatology.)

Immunoglobulins, antigens and complement can assemble to form immune complexes (IC). ICs can be detrimental as they propagate inflammation in autoimmune diseases. Like ICs, submicron extracellular vesicles termed microparticles (MP) are present in the synovial fluid from patients affected with autoimmune arthritis. We examined MPs in rheumatoid arthritis (RA) using high sensitivity flow cytometry and electron microscopy. We find that the MPs in RA synovial fluid are highly heterogeneous in size. The observed larger MPs were in fact MP-containing ICs (mpICs) and account for the majority of the detectable ICs. These mpICs frequently express the integrin CD41, consistent with platelet origin. Despite expression of the Fc receptor FcγRIIa by platelet-derived MPs, we find that the mpICs form independently of this receptor. Rather, mpICs display autoantigens vimentin and fibrinogen, and recognition of these targets by anti-citrullinated peptide antibodies contributes to the production of mpICs. Functionally, platelet mpICs are highly pro-inflammatory, eliciting leukotriene production by neutrophils. Taken together, our data suggest a unique role for platelet MPs as autoantigen-expressing elements capable of perpetuating formation of inflammatory ICs., (Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.)

Background: Although modern sequencing technologies permit the ready detection of numerous DNA sequence variants in any organisms, converting such information to PCR-based genetic markers is hampered by a lack of simple, scalable tools. Onion is an example of an under-researched crop with a complex, heterozygous genome where genome-based research has previously been hindered by limited sequence resources and genetic markers., Results: We report the development of generic tools for large-scale web-based PCR-based marker design in the Galaxy bioinformatics framework, and their application for development of next-generation genetics resources in a wide cross of bulb onion (Allium cepa L.). Transcriptome sequence resources were developed for the homozygous doubled-haploid bulb onion line 'CUDH2150' and the genetically distant Indian landrace 'Nasik Red', using 454™ sequencing of normalised cDNA libraries of leaf and shoot. Read mapping of 'Nasik Red' reads onto 'CUDH2150' assemblies revealed 16836 indel and SNP polymorphisms that were mined for portable PCR-based marker development. Tools for detection of restriction polymorphisms and primer set design were developed in BioPython and adapted for use in the Galaxy workflow environment, enabling large-scale and targeted assay design. Using PCR-based markers designed with these tools, a framework genetic linkage map of over 800cM spanning all chromosomes was developed in a subset of 93 F(2) progeny from a very large F(2) family developed from the 'Nasik Red' x 'CUDH2150' inter-cross. The utility of tools and genetic resources developed was tested by designing markers to transcription factor-like polymorphic sequences. Bin mapping these markers using a subset of 10 progeny confirmed the ability to place markers within 10 cM bins, enabling increased efficiency in marker assignment and targeted map refinement. The major genetic loci conditioning red bulb colour (R) and fructan content (Frc) were located on this map by QTL analysis., Conclusions: The generic tools developed for the Galaxy environment enable rapid development of sets of PCR assays targeting sequence variants identified from Illumina and 454 sequence data. They enable non-specialist users to validate and exploit large volumes of next-generation sequence data using basic equipment.

We have developed NetPath as a resource of curated human signaling pathways. As an initial step, NetPath provides detailed maps of a number of immune signaling pathways, which include approximately 1,600 reactions annotated from the literature and more than 2,800 instances of transcriptionally regulated genes - all linked to over 5,500 published articles. We anticipate NetPath to become a consolidated resource for human signaling pathways that should enable systems biology approaches.

Rationale: The neuropeptide galanin and its receptors are expressed in brain regions implicated in the rewarding effects of natural stimuli and drugs of abuse. Galanin has been shown to attenuate neurochemical, physiological, and behavioral signs of opiate and amphetamine reinforcement., Objective: In the current study, we present evidence that galanin modulates neurochemical and behavioral correlates of cocaine response., Methods: Mice lacking the neuropeptide galanin (Gal -/-) and wild-type (Gal +/+) controls were used to analyze the effects of galanin in an unbiased conditioned place preference paradigm. We then examined cocaine-induced activation of extracellular signal-regulated kinase (ERK) activity as a marker of intracellular signaling in the mesolimbic dopaminergic pathway induced by acute cocaine administration, Results: Gal -/- mice showed significantly greater conditioned place preference at a threshold dose of cocaine (3 mg/kg) than Gal +/+ mice, and this was reversed by administration of the galanin receptor agonist galnon. Consistent with the results of behavioral experiments, there was a significant increase in ERK activation in the ventral tegmental area (VTA) and nucleus accumbens (NAc) of Gal -/- mice but not Gal +/+ mice following acute, systemic cocaine injection at the threshold dose. In the NAc, but not VTA, this effect was reversed by administration of galnon., Conclusions: These data, coupled with previous studies on the effects of morphine and amphetamine, demonstrate that galanin normally attenuates drug reinforcement, potentially via modulation of the mesolimbic dopamine system.

The mechanisms underlying responses to drugs of abuse have been widely investigated; however, less is known about pathways normally protective against the development of drug reinforcement. These pathways are also important since they may regulate individual differences in vulnerability to addiction. The neuropeptide galanin and its binding sites are expressed in brain areas important for drug reward. Previous studies have shown that centrally infused galanin attenuates morphine place preference and peripheral injection of galnon, a galanin agonist, decreases opiate withdrawal signs. The current studies in galanin knockout (GKO) mice examined the hypothesis that galanin is an endogenous negative regulator of opiate reward and identified downstream signaling pathways regulated by galanin. We show that GKO mice demonstrate increased locomotor activation following morphine administration, which is inhibited by acute administration of galnon. GKO mice also show enhanced morphine place preference, supporting the idea that galanin normally antagonizes opiate reward. In addition, morphine-induced ERK1/2 phosphorylation was increased in the VTA of both wild-type and GKO mice, but only the GKO mice showed increases in ERK1/2 and CREB phosphorylation in the amygdala or nucleus accumbens. Furthermore, a single systemic injection of galnon in GKO mice was sufficient to reverse some of the biochemical changes brought about by morphine administration. These data suggest that galanin normally attenuates behavioral and neurochemical effects of opiates; thus, galanin agonists may represent a new class of therapeutic targets for opiate addiction.

The neuropeptide galanin is widely distributed in the central nervous system and plays a role in a number of processes in the adult brain. Galanin also has neurotrophic effects in the developing nervous system and after nerve injury. The current study investigated the mechanism by which galanin promotes neurite outgrowth in the neuronal cell line PC12 and in neurospheres derived from adult hippocampal progenitor cells. We demonstrated that galanin can induce extracellular signal-related kinase (ERK) phosphorylation transiently in a concentration-dependent manner in neurons. Galanin-like peptide, which is thought to signal primarily through the GalR2 receptor subtype, induced ERK phosphorylation with similar kinetics to galanin. In functional studies, the ability of galanin and galanin-like peptide to induce neurite outgrowth was dependent on activation of both protein kinase C and ERK. This study identified a novel physiological role for galanin-induced ERK phosphorylation and identified ERK and protein kinase C as important signaling components in the galanin-mediated modulation of neurite outgrowth.

Repeated morphine administration leads to molecular alterations of the neural circuitry in the locus coeruleus and nucleus accumbens. These changes include increased activity of several components of the cAMP signaling pathway that are thought to be associated with psychological and somatic signs of opiate withdrawal. The neuropeptide galanin has been shown to attenuate cAMP signaling in multiple cell types. The current study demonstrates that acute galanin treatment blocks the consequences of increased cAMP signaling following chronic opiate administration and withdrawal in Cath.a cells and primary cultures of striatal neurons as measured by phosphorylation of the transcription factor cAMP regulatory element-binding protein (CREB). In addition, galanin-mediated attenuation of CREB phosphorylation is independent of galanin-induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in Cath.a cells. These data suggest that galanin receptors may serve as an additional potential therapeutic target for the treatment of opiate withdrawal.