Search

Essential oils (EOs) are volatile secondary plant metabolites, which provide characteristic aroma and flavour, specific to many plants. They are mainly derived from herbs and spices, and used traditionally by humans for many centuries for their antimicrobial and preservative properties. The term ‘’essential oil’’ is misleading as neither they are ‘’essential’’ for nutrition and metabolism nor ‘’oils’’ as glycerol based lipids. They are aromatic compounds with oily appearance. The phrase “essential” derives from “essence,” which means smell or taste, and relates to the property of these substances of providing specific flavours and odours to many plants. EOs and their components reduce entric methane and ammonia emission by modulating rumen microbial community structure and could be used as phytogenic feed additive. However, their effects need to be studied by long term in vivo experimentation, as adaptation of rumen microbes could lead to ineffectiveness. Optimum dose of bioactive essential oil components and their appropriate combinations needs to be standardized in relation to dietary composition of animals to achieve consistent benefit of their feeding for livestock health and performance before their application in large scale livestock production systems.

Silent estrus results in spread-out kidding and extended inter-kidding interval in goats. Progesterone (P4) priming for 12-14 days could be one of the approaches for estrus induction with optimum fertility. The present work was carried to comparatively assess the duration of P4 priming on estrus and fertility in silent estrus goats. Sirohi does (n=18) with a history of anestrus and high basal P4 in paired samples were equally divided into three groups. Does in P-0 d group received 200 IU of equine chorionic gonadotropin by intramuscular route. Does in group second and third were subjected to per-vaginal P4 sponges for 7 (P-7 d) and 14 (P-14 d) days, respectively and were given 200 IU equine chorionic gonadotropin following sponge withdrawal. Estrus was monitored for 72 h at 12 h intervals using teaser buck to record estrus per cent, induction time and duration. Estrus induction was highest in P-14 d (6/6) than P-0 d and P-7 d (4/6 and 5/6), respectively. Estrus induction time was shorter in P-7 d and P-14 d than P-0 d. The estrus duration was shortest in P-14 d group. The conception and pregnancy rate did not differ significantly among the groups, though all the does in P-14 d conceived. The fertility was non-significantly higher in P-14 d (6/6) and P-7 d group (5/5) than P-0 d (3/4). It could be concluded that P4 priming for 7-14 days in silent estrus does results in improved reproductive performances.

Small ruminants are important components of smallholder production systems in dry regions of the country and require technological transformation for bringing the farmers out of the vicious cycle of poverty. There is huge scope of improving the income and livelihood of farmers in these harsh topographies because of expanding market and demand for small ruminant products. Live animal sale is the main source of income from small ruminants contribute up to three-fourths-of total income. Milk of sheep is produced in negligible amount and consumed in households while goat milk is well in demand but small portion is sold by farmers and mostly used in households. The price of wool is depressed, whereas carpet wool produced in some regions receives prime price in the market. The main factors affecting small ruminant production in dry areas are feed scarcity, poor genetic make of animals, poor health cover facilities, lack of proximity to market and climate change effects. The technological adoption for enhancing productivity of small ruminants in dry areas has been discussed in this overview. The genetic improvement of small ruminant resources, valuation of breeds, exploring value addition/alternative uses of wool and goat milk, improvement of range management, feed base, use of unconventional feeds, flock health management, reproduction management, improving feed efficiency, value addition, quality issues, creating farmers' organisations, improving market access are some of the issues that need priority in research and development for improving productivity of small ruminants for better livelihood security and income generation of farmers in dryland regions. With the concerted efforts of research, extension and development workers, living conditions of small ruminants farmers can be improved which will alleviate poverty, create employment opportunity in rural areas and reduce migration of younger generation to the cities.

Surge of demand for meat from diverse sources in a time of decling land and other natural resources shifted the trend of producing more sheep per sheep. Prolificacy aspect in sheep can be used as an important arsenal to fulfil this objective. FecB gene mutation perhaps spread from Garole microsheep of India, has been widely used for introduction of prolificacy in monotocus sheep worldwide. The ovulation rate and litter size are two most important reproductive parameters influenced by FecB gene besides small influences on other sheep production parameters. While implementing the FecB introgression programmes precaution needs to be observed to avoid lamb mortality. The results of the experiments conducted worldwide on FecB introgression programmes suggest that high prolificacy is economically beneficial under intensive and semi-intensive management system of sheep rearing. There were variable effects of FecB genotype documented from different parts of the world. With goal oriented research efforts, the prolificacy in FecB carrier Avishaan sheep, a triple breed cross developed from Garole, Malpura and Patanwadi at ICAR-CSWRI are showing promising sheep for future. There are several challenges for using FecB gene in the future using assisted reproductive and genome editing technology. The effect of FecB gene on different sheep production parameters as reported in the literature are summarized in present work.

Competing Interests: Disclosure The authors are employees of Bristol Myers Squibb.

Conformity of tumour volumes and dose plans in prostate brachytherapy (BT) can be constrained by unwanted needle deflections, needle access restrictions and visualisation limitations. This work validates the feasibility of teleoperated robotic control of an active steerable needle using magnetic resonance (MR) for guidance. With this system, perturbations can be counteracted and critical structures can be circumvented to access currently inaccessible areas. The system comprises of (1) a novel steerable needle, (2) the minimally invasive robotics in an MR environment (MIRIAM) system, and (3) the daVinci Research Kit (dVRK). MR scans provide visual feedback to the operator controlling the dVRK. Needle steering is performed along curved trajectories to avoid the urethra towards targets (representing tumour tissue) in a prostate phantom with a targeting error of 1.2 ± 1.0 mm. This work shows the potential clinical applicability of active needle steering for prostate BT with a teleoperated robotic system in an MR environment., (© 2023. The Author(s).)

Background: Night eating syndrome (NES) is described as a disordered eating pattern relative to sleep, where consumption of food occurs in the evening and night. Numerous studies had been conducted in various populations but studies on (NES) among call centre employees are limited. Aim: This study aimed to determine the prevalence of NES and its determinants among selected inbound call centre employees in Kuala Lumpur, Malaysia. Methods: In this cross-sectional study, a total of 217 inbound call centre employees were recruited through random sampling. A self-administered socio-demographic and work-related questionnaire was used to collect data on the background of the respondents. Information on NES and well-being was obtained by using the Night Eating Questionnaire (NEQ) and World Health Organisation-Five Well-Being Index (WHO-5) respectively. Data on dietary intakes, smoking habits, alcohol intakes and life stress were acquired using a Simple Lifestyle Indicator Questionnaire (SLIQ) while eating behaviour of the respondents was studied using the Three-Factor Eating Questionnaire (TFEQ-18). Results: The mean age of the respondents was 24.1 ± 6.0 years. The prevalence of NES was 12.0% (95% CI = 8.12-17.24). The binary logistic regression identified that NES is significantly associated with adequate exercise (AOR = 4.250, p  = 0.012) and emotional eating (AOR = 6.510, p  = 0.014). Conclusion: This study showed that the prevalence of NES was high in the call centre and repeated nocturnal eating can have multiple adverse health effects. Therefore, promoting healthy eating habits are crucial to reduce the impacts of NES.

Introduction: Congenital unilateral sensorineural hearing loss (cuSNHL) carries potentially significant social, educational, and developmental consequences. Early diagnosis enables investigation, and consideration of options for management and early intervention, helping to mitigate the effects of hearing loss. Cochlear nerve dysplasia (CND) is a prominent cause of cuSNHL and may affect candidacy for cochlear implantation. Socioeconomic disadvantage may impact on a patient's family's capacity to participate in necessary intervention and follow-up., Methods: Infants with severe-profound cuSNHL referred to a large Australian quaternary pediatric center between October 2004 and December 2020 were retrospectively included. Audiometric and clinical data, and the presence of hearing loss risk factors were obtained from a prospectively collated database. In Australia MRI scans are provided free-of-charge to citizens and residents. MRI scans were reviewed to determine the status of the nerves within the internal acoustic meatus (IAM grade) along with attendance rates. Travel distance to the hospital was also calculated. Reasons for non-attendance at MRI were obtained from patient medical records and correspondence. Socioeconomic, educational, and occupational indices, and travel distances were obtained using patient residential postcodes with reference to Australian Bureau of Statistics data., Results: A total of 98 patients were reviewed, 64.3% (n = 63) of whom underwent MRI. The median age at diagnosis was 40 days (IQR 27). The prevalence of CND was 75% (n = 47). Importantly, there was no significant difference in the degree of hearing loss between IAM grades (F(4,57) = 1.029, p = 0.405). Socioeconomic indices were significantly lower in patients not attending MRI investigations compared with patients who did attend. Travel distance was not significantly different between the two groups., Conclusion: CND is a prominent cause of cuSNHL in Australian infants. MRI at a young age allows parent education regarding management options and timely intervention where indicated. Socioeconomic disadvantage significantly impacts on participation in further routine assessment of cuSNHL, potentially limiting management options for these children long term., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ageing is a multi-factorial phenomenon which is considered as a major risk factor for the development of neurodegeneration, osteoporosis, cardiovascular disease, dementia, cancer, and other chronic diseases. Phenotypically, ageing is related with a combination of molecular, cellular, and physiological levels like genomic and epi-genomic alterations, loss of proteostasis, deregulation of cellular and subcellular function and mitochondrial dysfunction. Though, no single molecular mechanism accounts for the functional decline of different organ systems in older humans but accumulation of DNA damage or mutations is a dominant theory which contributes largely to the development of ageing and age-related diseases. However, mechanistic, and hierarchical order of these features of ageing has not been clarified yet. Scientific community now focus on the effect of obesity on accelerated ageing process. Obesity is a complex chronic disease that affects multiple organs and tissues. It can not only lead to various health conditions such as diabetes, cancer, and cardiovascular disease but also can decrease life expectancy which shows similar phenotype of ageing. Higher loads of DNA damage were also observed in the genome of obese people. Thus, inability of DNA damage repair may contribute to both ageing and obesity apart from cancer predisposition. The present review emphasizes on the involvement of molecular phenomenon of DNA metabolism in development of obesity and how it accelerates ageing in mammals., Competing Interests: All authors declare that they have no competing interests.

In an on-going investigation of bioactive metabolites producing potential endophytic fungi, the strain Lasiodiplodia theobromae (SJF-1) was isolated from a medicinal plant Syzygium cumini. The cultural, morphological and molecular identification was done with the SJF-1 strain. The obtained gene sequence was deposited in NCBI with accession number MG 938644. The methanolic extract of SJF-1 strain possessed one major bioactive fraction, and it was purified by column chromatography. Further, it was identified as Mellein by various spectroscopic studies ( 1 H, 13 C, DEPT-135°, FT-IR, ESI-HR-MS and 2D NMR). Biologically, Mellein showed potent anti-Xanthomonas activity with minimum inhibitory concentration (MIC) values ranging from 1·9 to 62·5 μg ml -1 against 11 Xanthomonas strains, a broad-spectrum antimicrobial activity with MIC 7·8-31·25 μg ml -1 and 1·9-31·25 μg ml -1 towards both bacterial and fungal strains, respectively. The scanning electron microscope analysis proved the antimicrobial efficacy of a Mellein by rupturing the cell walls of Xanthomonas sp. Molecular docking studies further supported that the Mellein showed good binding interactions with the proteins of Xanthomonas sp. to reduce pathogenicity. Further, in silico pharmacological studies showed that this metabolite exhibited high gastrointestinal absorption properties and promising oral drug bioavailability. We report, anti-Xanthomonas, in silico docking and pharmacological studies of Mellein from (SJF-1) strain for the first time., (© 2022 Society for Applied Microbiology.)

Background: Carotid plaque morphology plays an important role in determining outcome of carotid artery stenting (CAS). Intravascular ultrasound (IVUS) and its extension VH (Virtual Histology)-IVUS evaluate plaque characteristics in real time and guide decision making during stenting. To date, there is no consensus about indications of IVUS and its validated methods. This systematic review and meta-analysis aims to evaluate the clinical utility of IVUS in carotid artery interventions (CAS) and develop a future consensus for research and practice parameters., Methods: A systematic review and meta-analysis was performed of the English literature articles published till February 2021. Studies reporting on IVUS parameters and findings and also its performance compared with other imaging modalities were included in review. Pooled prevalence with 95% confidence intervals (CI) was calculated. The statistical analysis was conducted in R version 3.6.2., Results: A total of 2015 patients from 29 studies were included. Proportional meta-analysis was performed on 1566 patients from 11 studies. In 9 studies, stroke/transient ischemic attack (TIA) had a pooled prevalence of 4% (95% CI 3%-5%) while asymptomatic stroke had a pooled prevalence of 46% (95% CI 31%-62%) in 4 studies following IVUS. Two studies reported that IVUS detected more plaque protrusion compared with angiography (n=33/396 vs 11/396). IVUS led to stent type or size change in 8 of 48 cases which were missed on angiography in 3 other studies. Concordance between VH-IVUS and true histology was good at 80% to 85% reported in 2 studies., Conclusions: This systematic review and meta-analysis showed, though IVUS fared better to computed tomography (CT)/magnetic resonance (MR) angiography for better stent selection during CAS, with low to moderate risk of bias in the studies included. However, large scale, preferably randomized controlled studies are needed to predict its role in determining clinical outcome.

Background: Tracheostomy, being a high aerosol-generating procedure, poses a great challenge to surgeons, especially during the coronavirus disease 2019 pandemic. It is important to preserve staff numbers as this fight may go on for a long time. Personal protective equipment plays a key role in the protection of healthcare workers. Barrier enclosure has been attempted in procedures such as intubation and tracheostomy. The use of boxes became popularised for intubation and they have been utilised in many centres., Methods: This paper describes the box designed by our team and presents our surgical experience with the box. The box is made of transparent acrylic. It is sealed at all ends, with a negative-pressure environment. The hand ports were designed to allow maximum manoeuvrability for surgeons, without restricting hand movements., Conclusion: The proposed box will provide more protection to healthcare workers during tracheostomy. However, the box is yet to be validated.

Steerable instruments allow for precise access to deeply-seated targets while sparing sensitive tissues and avoiding anatomical structures. In this study we present a novel omnidirectional steerable instrument for prostate high-dose-rate (HDR) brachytherapy (BT). The instrument utilizes a needle with internal compliant mechanism, which enables distal tip steering through proximal instrument bending while retaining high axial and flexural rigidity. Finite element analysis evaluated the design and the prototype was validated in experiments involving tissue simulants and ex-vivo bovine tissue. Ultrasound (US) images were used to provide visualization and shape-reconstruction of the instrument during the insertions. In the experiments lateral tip steering up to 20 mm was found. Manually controlled active needle tip steering in inhomogeneous tissue simulants and ex-vivo tissue resulted in mean targeting errors of 1.4 mm and 2 mm in 3D position, respectively. The experiments show that steering response of the instrument is history-independent. The results indicate that the endpoint accuracy of the steerable instrument is similar to that of the conventional rigid HDR BT needle while adding the ability to steer along curved paths. Due to the design of the steerable needle sufficient axial and flexural rigidity is preserved to enable puncturing and path control within various heterogeneous tissues. The developed instrument has the potential to overcome problems currently unavoidable with conventional instruments, such as pubic arch interference in HDR BT, without major changes to the clinical workflow., Competing Interests: The authors have declared that no competing interests exist.

Jupiter’s atmosphere has a system of zones and belts punctuated by small and large vortices, the largest being the Great Red Spot. How these features change with depth is unknown, with theories of their structure ranging from shallow meteorological features to surface expressions of deep-seated convection. We present observations of atmospheric vortices using the Juno spacecraft’s Microwave Radiometer. We found vortex roots that extend deeper than the altitude at which water is expected to condense, and we identified density inversion layers. Our results constrain the three-dimensional structure of Jupiter’s vortices and their extension below the clouds.

Donor-type aplasia (DTA) is a condition where an individual continues to be aplastic even after a successful engraftment of a hematopoeitic stem cell transplant with a majority of donor type cells in the bone marrow. This entity has been seen with varying frequency around the world, especially in Southeast Asia. However, its incidence in the Indian subcontinent remains fairly low. Here is a case of a 17-year-old child with DTA who had a 89% population of donor cells after a successful transplant and presented with recurrent severe aplastic anemia later. The patient eventually succumbed to his condition before a second transplant could be performed. The awareness about the seriousness of this relatively rare condition, therefore, needs to be emphasized., Competing Interests: None

Atomically precise ultradoping of silicon is possible with atomic resists, area-selective surface chemistry, and a limited set of hydride and halide precursor molecules, in a process known as atomic precision advanced manufacturing (APAM). It is desirable to expand this set of precursors to include dopants with organic functional groups and here we consider aluminium alkyls, to expand the applicability of APAM. We explore the impurity content and selectivity that results from using trimethyl aluminium and triethyl aluminium precursors on Si(001) to ultradope with aluminium through a hydrogen mask. Comparison of the methylated and ethylated precursors helps us understand the impact of hydrocarbon ligand selection on incorporation surface chemistry. Combining scanning tunneling microscopy and density functional theory calculations, we assess the limitations of both classes of precursor and extract general principles relevant to each., (© 2021 IOP Publishing Ltd.)

Atomic precision advanced manufacturing (APAM) leverages the highly reactive nature of Si dangling bonds relative to H- or Cl-passivated Si to selectively adsorb precursor molecules into lithographically defined areas with sub-nanometer resolution. Due to the high reactivity of dangling bonds, this process is confined to ultra-high vacuum (UHV) environments, which currently limits its commercialization and broad-based appeal. In this work, we explore the use of halogen adatoms to preserve APAM-derived lithographic patterns outside of UHV to enable facile transfer into real-world commercial processes. Specifically, we examine the stability of H-, Cl-, Br-, and I-passivated Si(100) in inert N 2 and ambient environments. Characterization with scanning tunneling microscopy and x-ray photoelectron spectroscopy (XPS) confirmed that each of the fully passivated surfaces were resistant to oxidation in 1 atm of N 2 for up to 44 h. Varying levels of surface degradation and contamination were observed upon exposure to the laboratory ambient environment. Characterization by ex situ XPS after ambient exposures ranging from 15 min to 8 h indicated the Br- and I-passivated Si surfaces were highly resistant to degradation, while Cl-passivated Si showed signs of oxidation within minutes of ambient exposure. As a proof-of-principle demonstration of pattern preservation, a H-passivated Si sample patterned and passivated with independent Cl, Br, I, and bare Si regions was shown to maintain its integrity in all but the bare Si region post-exposure to an N 2 environment. The successful demonstration of the preservation of APAM patterns outside of UHV environments opens new possibilities for transporting atomically-precise devices outside of UHV for integrating with non-UHV processes, such as other chemistries and commercial semiconductor device processes., (© 2021 IOP Publishing Ltd.)

The COVID-19 pandemic gave an opportunity to adopt many appropriate changes in the behavior of the people in India. The major gears of those behavior changes were the enforcement by the government, fear, motivation (self and induced), and self-experiences or realizations with time. If those changes are fitted in the Trans-Theoretical Model, Indian people have passed through the "Pre-Contemplation" to "Action" stage of behavior changes during different phases of this pandemic. Frequent hand hygiene, maintaining physical distancing, use of face mask, cough etiquettes, avoid greetings through physical contacts, fear in spitting and urination at public places, refrain from gatherings and avoiding outside food are some of the examples of those appropriate behaviors which were enforced or learnt during the COVID pandemic. The continuous lockdown made people understand the difference between "want" and "need," the importance of local production, and the significance of social media and technology in routine life. The work-from-home strategy gave a chance to appreciate the work--life balance in a more applied way. The first-ever lifetime experience of unbelievable rejuvenating nature because of lack of human play taught people to appreciate nature. Although the current focus is on responding to the pandemic and on coping with its immediate effects, yet this is the time when there is an urgent need to create an enabling environment to support and sustain these COVID-19 appropriate behaviors (maintenance stage) to reap the maximum benefits out of them. Sustaining these appropriate behaviors is also important considering the bimodal distribution of the COVID-19 and possibility of advent of the second wave of COVID-19 in near future., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Family Medicine and Primary Care.)

Background: Duration of persistence of SARS-CoV-2 in the upper respiratory tract of infected individuals has important clinical and epidemiological implications., Aim: We aimed to establish the duration and risk factors for persistence of SARS-CoV-2 in the upper respiratory tract of asymptomatic infected individuals., Methods: Data of repeat rRT-PCR (real-time reverse transcription-polymerase chain reaction) test done for SARS-CoV-2 infected individuals at our institute at Jodhpur, India were analysed from 19 March to 21 May 2020. Duration of virus persistence was estimated with parametric regression models based on weibull, log-normal, log-logistic, gamma and generalized gamma distributions. Factors associated with prolonged viral persistence were analysed with the best-fitting model., Results: Fifty-one SARS-CoV-2 infected individuals with repeat rRT-PCR test were identified with 44 asymptomatics. The asymptomatic individuals had median virus persistence duration of 8.87 days (95% CI: 7.65-10.27) and 95 percentile duration of 20.70 days (95% CI: 16.08-28.20). The overall median virus persistence including both symptomatic and asymptomatic individuals was found to be 9.18 days (95% CI: 8.04-10.48). Around one-fourth asymptomatics (10/44) demonstrated SARS-CoV-2 persistence beyond 2 weeks. Age <60 years and local transmission were found to be significantly associated with longer virus persistence among asymptomatic individuals on univariate regression but not in multivariate analysis., Conclusion: Recommended home isolation duration for SARS-CoV-2 infected individuals in India should be extended from 17 days to at least 3 weeks. Prolonged persistence of SARS-CoV-2 in a considerable proportion of asymptomatic individuals merits attention with regard to ensuring universal infection prevention precautions irrespective of symptomatic status., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Nitrogen (N) fertilizer represents a significant cost for the grower and may also have environmental impacts through nitrate leaching and N 2 O (a greenhouse gas) emissions associated with denitrification. The objectives of this study were to quantify the genetic variability in N partitioning and N remobilization in Indian spring wheat cultivars and identify traits for improved grain yield and grain protein content for application in breeding N-efficient cultivars. Twenty-eight bread wheat cultivars and two durum wheat cultivars were tested in field experiments in two years in Maharashtra, India. Growth analysis was conducted at anthesis and harvest to assess above-ground dry matter (DM) and dry matter and N partitioning. Flag-leaf photosynthesis rate (A max ), flag-leaf senescence rate and canopy normalized difference vegetation index (NDVI) were also assessed. Significant N × genotype level interaction was observed for grain yield and N-use efficiency. There was a positive linear association between post-anthesis flag-leaf A max and grain yield amongst the 30 genotypes under high N (HN) conditions. Flag-leaf A max was positively associated with N uptake at anthesis (AGN A ). Under both HN and low N (LN) conditions, higher N uptake at anthesis was associated with delayed onset of flag-leaf senescence and higher grain yield. Under N limitation, there was a genetic negative correlation between grain yield and grain protein concentration. Deviation from this negative relationship (grain protein deviation or GPD) was related to genotypic differences in post-anthesis N uptake. It is concluded that N uptake at anthesis was an important determinant of flag-leaf photosynthesis rate and grain yield under high N conditions; while post-anthesis N uptake was an important determinant of GPD of wheat grown under low to moderate N conditions in India., Competing Interests: None., (© 2020 The Authors.)

Achieving optimal blood glucose control in Type 1 diabetes is a delicate balance between ensuring tight glycaemic control and achieving this without the expense of hypoglycaemia and weight gain, two major factors impacting quality of life. This is a real challenge for people with Type 1 diabetes and underpins many of the struggles they face in self-managing on a day-to-day basis. The main goals of insulin delivery are to try to simulate the physiology of β-cell insulin secretion as closely as possible and to overcome the challenges of peripheral insulin administration by achieving rapidity of onset with mealtime insulins and stability of the glucose-lowering effects of long-acting insulins. Since the early days of human insulin use, there have been many developments in insulin formulations that aim to achieve these goals as much as possible, thus contributing to better glycaemic control whilst minimizing hypoglycaemia. In the present review we discuss the currently available insulin analogues and the challenges of achieving glucose control using current analogues in those on multiple daily injections, and appraise the evidence base for newer-generation insulin analogues, such as insulin degludec, glargine U300, faster-acting insulin aspart and BioChaperone lispro. We also highlight new insulins in development and unmet needs in people with Type 1 diabetes., (© 2018 Diabetes UK.)

Amebiasis caused by protozoa Entamoeba histolytica (EH) is the third leading parasitic cause of human mortality. Although amebiasis is endemic in India, only about 10% of the infected individuals manifest disease. Clinical spectrum of amebiasis ranges from asymptomatic colonization to amebic colitis to hemorrhagic and fulminant colitis. Factors causing an invasive infection are not completely understood. Pathogen virulence, host immunity, and ability of the pathogen to evade host immune response play vital role in determining the disease course. Host factors such as immunocompromised states may make an individual susceptible to develop symptomatic infection. Malignancies usually result in chronic debilitation which may make the individual prone to develop invasive amebiasis with rapid progression. We report two cases of invasive amebiasis which developed a fulminant course in the immediate postoperative period after abdominal surgeries for visceral malignancies., Competing Interests: None

Our aim was to evaluate the feasibility and role of sentinel lymph node (SLN) biopsy using methylene blue dye alone in identifying occult lymph node metastases in early oral cancer (cT1, T2, and cN0). The study was done from 2013-15 in 94 patients in a large cancer centre. The blue nodes were dissected and sent for frozen section, routine histopathological examination, and immunohistochemical testing for cytokeratin, and was followed by elective neck dissection in all patients. The identification rate was 93.61%. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for frozen section and haematoxylin and eosin (H&E) staining were 84.6%, 100%, 100%, 93.9% and 95.5%, respectively. Occult lymph node metastasis was seen in 27.6% cases. Biopsy of SLN with blue dye alone might be used successfully with good sensitivity and negative predictive value in countries with limited resources in the developing world. Immunohistochemistry contributes to it by increasing the sensitivity and NPV, and thereby improves the diagnostic value., (Copyright © 2019. Published by Elsevier Ltd.)

Nitrogen (N) fertilizer represents a significant cost for the grower and may also have environmental impacts through nitrate leaching and N 2 O (a greenhouse gas) emissions associated with denitrification. The objectives of this study were to quantify the genetic variability in N-use efficiency (NUE) in Indian spring wheat cultivars and identify traits for improved NUE for application in breeding. Twenty eight bread wheat cultivars and two durum wheat cultivars were tested in field experiments in two years in Maharashtra, India. Detailed growth analysis was conducted at anthesis and harvest including dry matter (DM) and N partitioning. Senescence of the flag leaf was assessed from a visual score every 3-4 days from anthesis to complete flag-leaf senescence and fitted against thermal time to estimate the onset and end of post-anthesis senescence. Grain yield (GY) was reduced under low N (LN) by an average of 1.46 t ha -1 (-28%). Significant N × genotype level interaction was observed for grain yield and NUE. Above-ground N uptake at harvest was reduced from 162 kg N ha -1 under high N (HN) to 85 kg N ha -1 under low N (LN) conditions, while N-utilization efficiency (grain DM yield per unit crop N uptake at harvest; NUtE) increased from 32.7 to 44.6 kg DM kg -1 N. Genetic variation in GY under LN related mainly to variation in N uptake at harvest rather than NUtE; and the N × genotype effect for GY was mainly explained by the interaction for N uptake at harvest. Averaging across years, the linear regression of onset of flag-leaf senescence on GY amongst cultivars was significant under both HN (R 2 0.16. p  < 0.05) and LN (R 2 0.21, p  < 0.05) conditions. Onset of flag-leaf senescence was positively associated with N uptake at anthesis under HN (R 2 0.34, p < 0.001) and LN (R 2 0.22, p < 0.01) conditions. Flag-leaf senescence timing was not associated with post-anthesis N uptake. It is concluded that increased N accumulation at anthesis was correlated with flag-leaf senescence timing and that N accumulation at anthesis is an important trait for enhancing grain yield and NUE of wheat grown under low to moderate N supply in India.

Background: Permanent neonatal diabetes caused by mutations in the KCNJ11 gene may be managed with high-dose sulfonylureas. Complete transfer to sulfonylureas is not successful in all cases and can result in insulin monotherapy. In such cases, the outcomes of combining sulfonylureas with insulin have not been fully explored. We present the case of a woman with diabetes due to a KCNJ11 mutation, in whom combination therapy led to clinically meaningful improvements., Case: A 22-year-old woman was found to have a KCNJ11 mutation (G334V) following diagnosis with diabetes at 3 weeks. She was treated with insulin-pump therapy, had hypoglycaemia unawareness and suboptimal glycaemic control. We assessed the in vitro response of the mutant channel to tolbutamide in Xenopus oocytes and undertook sulfonylurea dose-titration with C-peptide assessment and continuous glucose monitoring. In vitro studies predicted the G334V mutation would be sensitive to sulfonylurea therapy [91 ± 2% block (n = 6) with 0.5 mM tolbutamide]. C-peptide increased following a glibenclamide test dose (from 5 to 410 pmol/l). Glibenclamide dose-titration was undertaken: a lower glibenclamide dose did not reduce blood glucose levels, but at 1.2 mg/kg/day insulin delivery was reduced to 0.1 units/h. However, when insulin was stopped, hyperglycaemia ensued. Glibenclamide was further increased (2 mg/kg/day), but once-daily long-acting insulin was still required to maintain glycaemia. This resulted in improved HbA 1c of 52 mmol/mol (6.9%), restoration of hypoglycaemia awareness and reduced glycaemic variability., Conclusion: In people with KCNJ11 mutations causing permanent neonatal diabetes, and where complete transfer is not possible, consideration should be given to dual insulin and sulfonylurea therapy. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Untethered miniature robotics have recently shown promising results in several scenarios at the microscale, such as targeted drug delivery, microassembly, and biopsy procedures. However, the vast majority of these small-scale robots have very limited manipulation capabilities, and none of the steering systems currently available enable humans to intuitively and effectively control dexterous miniaturized robots in a remote environment. In this paper, we present an innovative micro teleoperation system with haptic assistance for the intuitive steering and control of miniaturized self-folding soft magnetic grippers in 2-D space. The soft grippers can be wirelessly positioned using weak magnetic fields and opened/closed by changing their temperature. An image-guided algorithm tracks the position of the controlled miniaturized gripper in the remote environment. A haptic interface provides the human operator with compelling haptic sensations about the interaction between the gripper and the environment, as well as enables the operator to intuitively control the target position and grasping configuration of the gripper. Finally, magnetic and thermal control systems regulate the position and grasping configuration of the gripper. The viability of the proposed approach is demonstrated through two experiments involving 26 human subjects. Providing haptic stimuli elicited statistically significant improvements in the performance of the considered navigation and micromanipulation tasks. Note to Practitioners -The ability to accurately and intuitively control the motion of miniaturized grippers in remote environments can open new exciting possibilities in the fields of minimally-invasive surgery, micromanipulation, biopsy, and drug delivery. This paper presents a micro teleoperation system with haptic assistance through which a clinician can easily control the motion and open/close capability of miniaturized wireless soft grippers. It introduces the underlying autonomous magnetic and thermal control systems, their interconnection with the master haptic interface, and an extensive evaluation in two real-world scenarios: following of a predetermined trajectory, and pick-and-place of a microscopic object.

Background: Recent literature suggests that neonatal adiposity is predictive of later metabolic health, while neonatal lean mass is predictive of later cognitive function amongst preterm infants. Anthropometric indices that accurately reflect neonatal body composition could improve clinical care and aid future research, but their validity has not been systematically tested in preterm infants., Objective: To determine the weight/length indices that best reflect neonatal body composition in preterm infants., Methods: Weight and length were measured, and body composition (fat-free mass (FFM), fat mass (FM) and percent body fat (%BF)) was assessed using air-displacement plethysmography within 72 h of birth in 218 preterm infants. The best weight/length proxy for FFM, FM and %BF were those with the highest proportion variance explained (R 2 ) and lowest root mean square error (RMSE) in linear regression models., Results: Among all of the weight/length indices tested, weight/length 2 was the best proxy for %BF, but nonetheless exhibited very low variance explained (R 2  = 0.27) and high prediction error (RMSE = 3.5% fat). Body weight unadjusted for length was strongly associated with FFM (R 2  = 0.97)., Conclusions: No weight/length index accurately reflected %BF. Weight/length indices are not appropriate for assessment of relative adiposity in preterm infants near birth. What's known on this subject: Compared with term infants, preterm infants have increased fat mass and diminished fat-free mass upon hospital discharge. Early adiposity predicts later metabolic health, while early lean mass is predictive of later neurodevelopmental outcomes. Optimal anthropometric proxies for preterm body composition at birth are not established., What This Study Adds: Weight is an adequate surrogate for lean mass at birth in preterm infants. There are no weight/length indices that accurately reflect neonatal adiposity at birth., (© 2016 World Obesity Federation.)

Background: Sinonasal lymphomas are the commonest nonepithelial malignancies of the nasal cavity and paranasal sinuses. They may spread from their site of origin in nasal cavity and invade adjacent structures including orbits leading to varying presentation and a diagnostic dilemma., Case: A-77- year old Nepalese male presented with swelling of left eye since 1 month and pain in the same eye since 2 days., Observation: Examination revealed axial proptosis, swelling of lids, restricted extraocular movement, diffuse conjunctival and ciliary congestion with chemosis. Visual acuity was grossly decreased. The case was diagnosed as left orbital cellulitis and treated with broad spectrum intravenous antibiotics and oral steriods. There was no response despite 3 days of antibiotics and steroids therefore a computed tomography was planned which showed features of Sinonasal malignancy invading the orbit. Repeated biopsy was suggestive of malignant small round cell tumour. In the view of unclear preoperative biopsy indicating further details on the histologic type of tumor and extensive erosion of maxilla with complete loss of vision in the eye the patient was planned for Total Maxillectomy with Orbital extenteration of the left orbit. Post-operative histopathological and Immunohistochemical report were suggestive of High grade Lymphoma. The patient was advised for Adjuvant Chemotherapy and Radiotherapy, which the patient refused due to financial constraints. He is on occasional follow up since the last 6 months., Conclusions: The diagnosis of maxillary sinus lymphoma needs to be borne in mind when a clinician encounters a case of Orbital Cellulitis. It may be difficult to diagnose clinically and require radio-pathological correlation., (© NEPjOPH.)

Bone marrow mononuclear cell (BM-MNC) therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review of published studies using BM-MNC therapy in patients with ischaemic stroke (IS). Literature was searched using MEDLINE, PubMed, EMBASE, Trip Database, Cochrane library and clinicaltrial.gov to identify studies on BM-MNC therapy in IS till June, 2016. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta-analysis. We included non-randomized open-label, single-arm and non-randomized comparative studies or randomized controlled trials (RCTs) if BM-MNCs were used to treat patients with IS in any phase after the index stroke. One randomized trial, two non-randomized comparative trials and four single-arm open-label trials (total seven studies) involving 227 subjects (137 patients and 90 controls) were included in the systematic review and meta-analysis. The pooled proportion for favourable clinical outcome (modified Rankin Scale score ≤2) in six studies involving 122 subjects was 29% (95% CI 0.16-0.43) who were exposed to BM-MNCs and pooled proportion for favourable clinical outcome of 69 subjects (taken from two trials) who did not receive BM-MNCs was 20% (95% CI 0.12-0.32). The pooled difference in the safety outcomes was not significant between both the groups. Our systematic review suggests that BM-MNC therapy is safe up to 1 year post-intervention and is feasible; however, its efficacy in the case of IS patients is debatable. Well-designed randomized controlled trials are required to provide more information on the efficacy of BM-MNC transplantation in patients with IS., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Majority of patients of lung cancer present with locally advanced or metastatic disease, where systemic therapy is the treatment of choice. Many of these patients have local symptoms due to thoracic disease, wherein radiotherapy is proven to be an effective modality for alleviation of symptoms. However, the optimal dose of radiotherapy for adequate palliation remains debatable. The purpose of this retrospective study was to assess the efficacy of two different schedules of thoracic radiotherapy (TRT) with respect to symptom palliation., Materials and Methods: A total of 100 consecutively treated patients with stages III-IV lung cancer treated with two different fractionation regimens of palliative TRT, either protracted course 20 Gy/5# over 1 week or short course of 17 Gy/2# over 8 days were assessed for symptom relief and survival. Impact of patient, tumor and treatment-related factors on response and overall survival (OS) was done by univariate analysis using log-rank test., Results: Median age of the entire cohort was 60 years, majority being males, smokers with low Eastern Cooperative Oncology Group performance status (performance score ≥2). Predominant symptoms were chest pain (68) followed by cough (21) and dyspnea (15). Palliative TRT was offered as either protracted course 20 Gy/5# over 1 week or short course of 17 Gy/2# over 8 days in 21 and 79 patients respectively. Median duration of symptom relief was 2 months, no differences in OS at 1 year with either regimen., Conclusions: TRT is an effective means of palliation having similar symptom relief and outcomes with weekly (17 Gy/2# over 8 days) or protracted radiotherapy regimens (20 Gy/5#over 1 week). Short TRT schedules are convenient and economical for patients as well as resource sparing for high volume centers.

COX-2 inhibitors exhibit anticancer effects in various cancer models but due to the adverse side effects associated with these inhibitors, targeting molecules downstream of COX-2 (such as mPGES-1) has been suggested. Even after calls for mPGES-1 inhibitor design, to date there are only a few published inhibitors targeting the enzyme and displaying anticancer activity. In the present study, we have deployed both ligand and structure-based drug design approaches to hunt novel drug-like candidates as mPGES-1 inhibitors. Fifty-four compounds with tested mPGES-1 inhibitory value were used to develop a model with four pharmacophoric features. 3D-QSAR studies were undertaken to check the robustness of the model. Statistical parameters such as r 2 = 0.9924, q 2 = 0.5761 and F test = 1139.7 indicated significant predictive ability of the proposed model. Our QSAR model exhibits sites where a hydrogen bond donor, hydrophobic group and the aromatic ring can be substituted so as to enhance the efficacy of the inhibitor. Furthermore, we used our validated pharmacophore model as a three-dimensional query to screen the FDA-approved Lopac database. Finally, five compounds were selected as potent mPGES-1 inhibitors on the basis of their docking energy and pharmacokinetic properties such as ADME and Lipinski rule of five.

Milk-derived bioactive peptides have been identified as potential ingredients of health-promoting functional foods. These bioactive peptides are targeted at diet-related chronic diseases especially the non-communicable diseases viz., obesity, cardiovascular diseases and diabetes. Peptides derived from the milk of cow, goat, sheep, buffalo and camel exert multifunctional properties, including anti-microbial, immune modulatory, anti-oxidant, inhibitory effect on enzymes, anti-thrombotic, and antagonistic activities against various toxic agents. Majority of those regulate immunological, gastrointestinal, hormonal and neurological responses, thereby playing a vital role in the prevention of cancer, osteoporosis, hypertension and other disorders as discussed in this review. For the commercial production of such novel bioactive peptides large scale technologies based on membrane separation and ion exchange chromatography methods have been developed. Separation and identification of those peptides and their pharmacodynamic parameters are necessary to transfer their potent functional properties into food applications. The present review summarizes the preliminary classes of bioactive milk-derived peptides along with their physiological functions, general characteristics and potential applications in health-care.

Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

NF-κB has been implicated in mechanisms promoting inflammation in tumor microenvironment leading to breast cancer metastasis. Owing to critical role of CCL2 during metastasis, particularly in its capacity to act as a chemoattractant for macrophages and their precursors i.e monocytes, we decided to explore if pro-metastatic function of NF-κB could be attributable to CCL2 and/or macrophage infiltration. Through our study we provide experimental and clinical evidence in support of co-ordinated expression of chemokines CCL2, NF-κB and intratumoral macrophage content particularly with respect to breast cancer, with an additional evidence of these three variables being key determinant for poor prognosis and diminished survival amongst breast cancer patients both independently as well in a coordinated manner. The mean fold increase in mRNA expression level of NF-κB and CCL2 indicated that it was over expressed 13.57 and 13.18 fold respectively in tumor tissue as compared to adjacent normal tissue. Among these Immunohistochemistry expression of CD68 marker showed that 62 patients (66.7%) had low/moderate CD68 expression while 31 patients (33.3%) had strong expression. All three variables viz.NF-κB, CCL2 and CD68 showed significant (p<0.05 or p<0.01 or p<0.001) respectively associations with both clinicopathological (except CD68 with stage) and hormone receptors (ER, PR and Her2/neu) and their co-expressions indicating these as predictors of breast cancer. In this study we decipher the possible molecular mechanism by way of which NF-κB may promote breast cancer metastasis. Our study has clinical relevance as it establishes significance of these three variables as potential predictive markers to be employed in breast cancer.

Background: Lung cancer most commonly presents in advanced stages in developing countries, where combined modality treatment using chemo-radiotherapy (CTRT) is the standard of care., Materials and Methods: A retrospective audit of patients of nonsmall cell lung cancer (NSCLC) treated at a single Institute from January 2008 to December 2012 was conducted. Various prognostic factors affecting disease-free survival (DFS) and overall survival (OS) were studied by univariate and multivariate analysis. All patients were meticulously followed-up clinically and telephonic contacts., Results: Overall 171 patients of NSCLC were treated with definitive CTRT using concurrent chemotherapy in 66% patients and sequential therapy in 28% patients. The actuarial 2 years DFS was 17.5% and 2 years OS was 61.5%. Complete response to treatment resulted in significantly better DFS and OS. Definitive CTRT was very well-tolerated in these patients with good compliance., Conclusion: Definitive CTRT, sequence being individualized depending on performance status and disease stage at presentation, is a feasible and effective treatment modality for locally advanced NSCLC patients in the developing world. Response to treatment is an important prognostic factor for treatment outcomes.

Clinical practice guidelines (CPGs) relating to laboratory diagnostic testing are increasingly produced with the aim of standardizing practice and improving patient care based on the best available evidence. However, the production of a CPG is merely the first step in the process of getting evidence into practice, to be undertaken by laboratories and other stakeholders. This process should evaluate the information provided in the guidelines on laboratory tests, devise a strategy for implementing the CPG or the laboratory aspects of the CPG and finally, once implemented, assess the impact of the CPG on clinical practice, patient outcomes and costs of care. The purpose of CPG evaluation by the laboratory is to determine whether sufficient information is provided on the particular test recommended. CPGs may not always be written with the involvement of a laboratory specialist and this underlies the paucity of relevant information in some national guidelines. When laboratory specialists are involved, CPGs can provide practical information which supports local laboratories as well as clinicians in the implementation and appropriate use of recommendations. Implementation of CPGs is an often neglected area that needs attention and thought. There are many barriers to successful implementation, which may vary at local level. These need to be identified early if CPGs are to be successfully adhered to. The effectiveness of CPGs also needs to be audited using process and health outcome indicators. Clinical audit is an effective tool for assessing adherence to recommendations and for measuring the impact and success of the CPG.

Background: Several studies reported prognostic value of biomarker in intracerebral hemorrhagic (ICH) but they are either preliminary observation or inadequately powered to analyse independent contribution of biomarkers over and above clinical and neuroimaging data., Objective: To examine whether the biomarker can significantly add to the predictive accuracy of prognosis of ICH., Method/design: In a multi-centric prospective cohort study, 1020 patients with ICH within 72 hours of onset are being recruited. After obtaining written informed consent from patients/proxy, venous blood sample (10 ml) is being collected and analysed for C-reactive protein (CRP) level, S100B, Glial fibrillary acidic protein (GFAP), Troponin, change in leukocyte count and Copeptin levels. The patients are telephonically followed using stroke scales (Barthel Index and modified Rankin Scale) at 3, 6, 12 months and 2 years after the recruitment., Discussion: This protocol will aim at predicting the short term or long term prognosis with the use of clinical, neuroimaging and biomarkers in order to help clinician to stratify patients for early referral or intervention.

We show that a scanning capacitance microscope (SCM) can image buried delta-doped donor nanostructures fabricated in Si via a recently developed atomic-precision scanning tunneling microscopy (STM) lithography technique. A critical challenge in completing atomic-precision nanoelectronic devices is to accurately align mesoscopic metal contacts to the STM defined nanostructures. Utilizing the SCMs ability to image buried dopant nanostructures, we have developed a technique by which we are able to position metal electrodes on the surface to form contacts to underlying STM fabricated donor nanostructures with a measured accuracy of 300 nm. Low temperature (T = 4 K) transport measurements confirm successful placement of the contacts to the donor nanostructures.

Ketone measurement is advocated for the diagnosis of diabetic ketoacidosis and assessment of its severity. Assessing the evidence base for ketone measurement in clinical practice is challenging because multiple methods are available but there is a lack of consensus about which is preferable. Evaluating the utility of ketone measurement is additionally problematic because of variability in the biochemical definition of ketoacidosis internationally and in the proposed thresholds for ketone measures. This has led to conflicting guidance from expert bodies on how ketone measurement should be used in the management of ketoacidosis. The development of point-of-care devices that can reliably measure the capillary blood ketone β-hydroxybutyrate (BOHB) has widened the spectrum of applications of ketone measurement, but whether the evidence base supporting these applications is robust enough to warrant their incorporation into routine clinical practice remains unclear. The imprecision of capillary blood ketone measures at higher values, the lack of availability of routine laboratory-based assays for BOHB and the continued cost-effectiveness of urine ketone assessment prompt further discussion on the role of capillary blood ketone assessment in ketoacidosis. In the present article, we review the various existing methods of ketone measurement, the precision of capillary blood ketone as compared with other measures, its diagnostic accuracy in predicting ketoacidosis and other clinical applications including prevention, assessment of severity and resolution of ketoacidosis., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

The aim of this review was to provide current scenario linking obesity and male fertility. Obesity has been linked to male fertility because of lifestyle changes, internal hormonal environment alterations, and sperm genetic factors. A few studies assessing the impact of obesity on sperm genetic factor have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm genetic factor and obesity. There are emerging facts that obesity negatively affects male reproductive potential not only by reducing sperm quality, but in particular it alters the physical and molecular structure of germ cells in the testes and ultimately affects the maturity and function of sperm cells. Inhibition of microRNA in the male pronucleus of fertilized zygotes produces offspring of phenotypes of variable severity depending on miRNAs ratios. Hence, these RNAs have a role in the oocyte development during fertilization and in embryo development, fetal survival, and offspring phenotype. It has been reported that the miRNA profile is altered in spermatozoa of obese males, however, the impact of these changes in fertilization and embryo health remains as yet not known., (© 2014 American Society of Andrology and European Academy of Andrology.)

The aim of this study was to evaluate the clinical outcome of the surgical repair of oral mucosal defects using cryopreserved human amniotic membrane (HAM) as a graft material. Thirty-four patients with precancerous lesions such as leukoplakia, erythroplakia, and verrucous hyperplasia were included. Fresh amniotic membrane was obtained from women undergoing elective caesarean section; the membrane was cleaned, prepared in antibiotic solutions, and preserved at -80°C. Results suggested that HAM promotes healing and epithelialization without specific complications. Thus we conclude that the use of HAM gives promising results in the repair of post-surgical oral mucosal defects., (Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Tumor-associated macrophages (TAMs), represent a major subpopulation of tumor infiltrating immune cells. These alternatively activated M2-polarized macrophages are well known for their pro-tumor functions. Owing to their established role in potentiating tumor-neovasculogenesis and metastasis, TAMs have emerged as promising target for anti-cancer immunotherapy. One of the key TAMs related phenomenon that is amenable to therapeutic intervention is their phenotype switching into alternatively activated M2-polarized macrophages. Hindering macrophage polarization towards a pro-tumor M2 phenotype, or better still reprogramming the M2 like TAMs towards M1 subtype is being considered a beneficial anti-cancer strategy. Hypoxic tumor milieu has been proposed as one of the most plausible factor governing M2-polarization of macrophages. We recently demonstrated that hypoxic tumor cells imparted a pro—angiogenic M2 skewed phenotype to macrophages. Furthermore, sizeable body of data indicates for participation of cyclooxygenase-2 (COX-2) in macrophage polarization. Concordantly, inhibition of COX-2 is associated with impaired macrophage polarization. Prompted by this in the current study we decided to explore if inhibition of COX-2 activity via chemical inhibitors may prevent hypoxic cancer cell induced M2-polarization of macrophages. We observed that treatment with Flunixin meglumine, an established preferential inhibitor of COX-2 activity markedly inhibited hypoxic cancer cell induced of M2-polarization of macrophages thereby indicating for usage of COX-2 inhibition as possible anti-cancer treatment modality.

The immunoprophylactic and therapeutic potentials of root extracts of Withania somnifera chemotypes (NMITLI-118, NMITLI-101) and pure withanolide-withaferin A was investigated against Leishmania donovani infection in hamsters. The naive animals, fed orally with immunostimulatory doses of chemotypes 101R, 118R (10 and 3 mg/kg) and withaferin A (9 and 3 mg/kg) for five consecutive days and challenged with Leishmania parasites on day 6, were euthanized on days 30 and 45 p.c. for the assessment of parasite clearance, real-time analysis of mRNAs of Th1/Th2 cytokines (IFN-γ, IL-12, TNF-α, iNOS/IL-4, IL-10 and TGF-β), NO production, reactive oxygen species (ROS) generation, lymphocyte transformation test and antibody responses. By day 45 p.c., there was a significant increase in the mRNA expression of iNOS, IFN-γ, IL-12 and TNF-α but decrease in IL-4, IL-10 and TGF-β, an enhanced Leishmania-specific LTT response as well as ROS, NO and antileishmanial IgG2 levels in 101R-treated hamsters followed by 118R- and withaferin A-treated ones, respectively. When these chemotypes were given to L. donovani-infected hamsters at different doses, there was moderate therapeutic efficacy of chemotype 101R (~50%) at 30 mg/kg × 5 followed by the other two. The results established that the 101R is the most potential chemotype and can be evaluated for combination therapy along with available antileishmanials., (© 2014 John Wiley & Sons Ltd.)