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Tuberculosis (TB) is a prominent infective disease and a major reason of mortality/ morbidity globally. Mycobacterium tuberculosis causes a long-lasting latent infection in a significant proportion of human population. The increasing burden of tuberculosis is mainly caused due to multi drug-resistance. The failure of conventional treatment has been observed in large number of cases. Drugs that are used to treat extensively drug-resistant tuberculosis are expensive, have limited efficacy, and have more side effects for a longer duration of time and are often associated with poor prognosis. To regulate the emergence of multidrug resistant tuberculosis, extensively drug-resistant tuberculosis and totally drug resistant tuberculosis, efforts are being made to understand the genetic/molecular basis of target drug delivery and mechanisms of drug resistance. Understanding the molecular approaches and pathology of Mycobacterium tuberculosis through whole genome sequencing may further help in the improvement of new therapeutics to meet the current challenge of global health. Understanding cellular mechanisms that trigger resistance to Mycobacterium tuberculosis infection may expose immune associates of protection, which could be an important way for vaccine development, diagnostics, and novel host-directed therapeutic strategies. The recent development of new drugs and combinational therapies for drug-resistant tuberculosis through major collaboration between industry, donors, and academia gives an improved hope to overcome the challenges in tuberculosis treatment. In this review article, an attempt was made to highlight the new developments of drug resistance to the conventional drugs and the recent progress in the development of new therapeutics for the treatment of drugresistant and non-resistant cases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Infectious diseases constantly represent the source of sickness as well as mortality in human beings. Herbal applications in human life through using plants for antibacterial and anticancer activity have shown the potential medicinal outcome., Objectives: To evaluate the antibacterial and anticancer activities of the crude extract of Matricaria aurea., Materials and Methods: The antibacterial activity of the crude flowers of M. aurea extract was examined against reference and clinical bacterial strains by agar well diffusion method. Minimum inhibitory concentrations and minimum bactericidal concentrations were determined by micro broth dilution assays using MH broth. Herbal extract was employed over human breast adenocarcinoma cell line (MCF-7), hepatocellular carcinoma cell line (HepG-2) and colorectal adenocarcinoma cell line (HCT-116) to optimize cancer cells proliferation by SRB assay., Results: The data has shown that the extract from M. aurea had significant antimicrobial activity against the tested microorganisms. The plant extract showed higher antibacterial activity against the reference strain of Streptococcus pyogenes. The MIC and MBC varied between 0.38-12.5 mg/ml and 3.1-200 mg/ml respectively. Synergy study elucidated the significant bacteriostatic effect of M. aurea extract on S. aureus and S. saprophyticus. The data of SRB assay deliver the potential anticancer activity through cell death., Conclusion: This study delivers innovative information that M. aurea possessed excellent bio-activities against pathogenic microbes and cancer cells, which drive attention for further research to explore the active components responsible for biological efficacies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Apple ( Malus domestica Borkh) is rich in phenolic compounds, which may enhance resistance to scab disease caused by Venturia inaequalis . In present study, apple cv. Golden Delicious was used for estimation of total phenols, flavonoids and quantification of six individual phenolic compounds. between control vs inoculated samples at different inoculation stages. The relative gene expression of phenylalanine ammonia lyase, chalcone synthase and flavanone 3 hydroxylase increased and polyphenolic compounds were constitutively upregulated at different post-inoculation stages. Data suggest that synthesis and accumulation of polyphenols is closely related with disease resistance against Venturia inaequalis. This study may play a vital role in understanding and finding out the governing mechanisms of scab resistance., Competing Interests: No conflict of interest exists neither in the conduct of this research nor in preparation of this manuscript., (© 2020 The Author(s).)

Background: Reports of injuries caused by bear attacks are scarce in the Himalayan region of India, such as Uttarakhand, which is surrounded by hills and thick forests. We retrospectively studied 18 patients attacked by Himalayan black and sloth bears to understand the pattern of the attacks and their management., Materials and Methods: Patients attacked by bears between January 2018 to December 2019 were retrospectively studied., Results: Most of the patients were of low socioeconomic status. The incidence was highest between June and December. The attacks mostly caused soft tissue injuries. There were also fractures of facial bones noted in some cases, but there was no mortality. The best outcomes were found in those cases that were managed with generous tissue preservation, rather than aggressive debridement. We could also follow the bear attack pattern. Himalayan black bears and sloth bears were found to be involved in the attacks., Conclusion: Injuries due to bear attacks mainly affect the face and neck. Although there were no cases of mortality in this study, facial disfigurement had a long-lasting impact on survivors. Tissue preservation and early reconstruction had the best outcomes., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest. We hereby declare that we have no conflicts of interest in the study. No financial support was obtained . The study was not influenced by an interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: None

Background: Apoptosis, a major form of programmed cell death, plays a vital role in regulating tissue development and maintenance of homeostasis in eukaryotes. Apoptosis can occur via a death receptor-dependent extrinsic or a mitochondrial-dependent intrinsic pathway and can be induced by various chemotherapeutic agents. In this study, the anticancer activity of Saussurea costus and its mode of intervention in human cancer cells of breast, colon, and liver were investigated., Results: In this study, the bioactives of S. costus leaves were extensively extracted in five solvents of different polarity. The cytotoxicity and anticancer effect of the extracted secondary metabolites were investigated against breast (MCF-7), liver (HepG2), and colon (HCT116) cancer cell lines using a Sulphorhodamine B (SRB) assay. Secondary metabolites extracted using hexane, methanol, ethyl acetate, and chloroform had the highest cytotoxicity and thus the greatest anticancer effect on all the cancer cell lines tested (IC 50 ; ranging from 0.25 to 2.5  μ g/ml), while butanol was comparatively less active (IC 50 ; ranging from 23.2 to 25.5  μ g/ml). Further investigation using DNA flow cytometry and fluorescent microscopy revealed that the extract arrested the cells in the G 1 phase of cell cycle and induced apoptosis. Furthermore, the elevated expression level of proapoptotic proteins and decreased expression level of antiapoptotic proteins confirmed that the intrinsic (mitochondrial) pathway was involved in mediating the apoptosis of cancer cells upon treatment with S. costus extract. These results altogether suggest that S. costus could be a potential anticancer agent., Conclusion: These results suggest that the S. costus extract is the potential source of the secondary metabolites that could be used as anticancer agent to treat diverse cancers of breast, colon, and liver., Competing Interests: The authors declare that there is no conflict of interest of this study., (Copyright © 2020 Ali A. Shati et al.)

Acquired digital fibrokeratoma is an uncommon, benign fibrous tumor that usually occurs in adults as a solitary lesion with a typical size of less than 1 cm. We present a case with periungual growth and nail plate deformity. The growth was completely excised after raising the epinychial flap and the fold was reconstructed. The histological results confirmed the digital fibrokeratoma. The rarity of digital fibrokeratoma and its unique morphological appearance of the tumor makes it interesting. Acquired periungual fibrokeratoma, an uncommon benign fibrous tumor of an unknown etiology, typically found at the distal end of the digits, may present with nail plate deformation due to chronic pressure, and in order not to damage the matrix, the tumor should be excised carefully, which can cause permanent nail dystrophy. In addition, we emphasize the importance of ruling out other causes of abnormal growths and of considering fibrokeratoma during differential diagnoses., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Cutaneous and Aesthetic Surgery.)

Background: Myrtus communis is a typical plant of Mediterranean area. The different parts of this plant such as berries, branches, and leaves have been used worldwide as a traditional/folk medicine for the treatment of various ailments and diseases., Methods: Ethanolic leaf extract of the plant was prepared by Soxhlet extraction method. Zone of inhibition, minimum inhibitory concentration and minimal bactericidal concentration were determined by well diffusion method and microplate alamar blue assay. GC-MS analysis was carried out to identify the compounds present in the extract. Microscopy and ImageJ software were used respectively for morphology and cell-length measurements. GraphPad Prism was used for statistical analysis., Results: The ethanolic extract showed strong inhibitory effect against Gram-positive and acid-fast bacteria with significant inhibition-zone size (9-25 mm), MIC (4.87-78 μg/ml), as well as MBC (0.3-20 mg/ml). However, no effect was observed on the growth of Gram-negative bacteria. The growth inhibition was found to be associated with the damage of cell wall as the extract-treated cells were sensitive to cell wall-targeting antibiotics and displayed the cell wall damage-depicting morphological defects. GC-MS analysis confirmed the presence of novel compounds in addition to the most representative compounds of the essential oils/extracts of M. communis of other country origins., Conclusion: These results demonstrate that M. communis leaf extract could be the source of compounds to be used for the treatment of Gram-positive bacterial infections. This is the first report, which provides insights into the mechanism of action of the extract in inhibiting the growth of Gram-positive bacteria.

Saffron plant ( Crocus sativus L.) is being used as a source of saffron spice and medicine to cure or prevent different types of diseases including cancers. We report the isolation, characterization of bioactive small molecule ([crocetin (β-d-glucosyl) ester] from the leaf biowastes of saffron plant of Kashmir, India. MTTC assay and Bio-autography aided approach were used to assess anti-oxidant activity and anti-cancer properties of crocin (s) against DPPH free radical and breast cancer cell line respectively. Crocetin beta-d-glucosyl ester restrained proliferation of human breast adeno-carcinoma cell model (MCF-7) without significantly affecting normal cell line (L-6). Further studies involving molecular mechanics generalized born surface area and molecular docking showed that crocetin beta-d-glucosyl ester exhibits strong affinity for estrogen receptor alpha and histone deacetylase 2 (crucial receptors involved in breast cancer signalling) as evidenced by the negative docking score and binding free energy (BFE) values. Therefore, crocetin beta-d-glucosyl ester from Crocus sativus biowastes showed antiproliferative effect possibly by inhibiting estrogen receptor alpha and HDAC2 mediated signalling cascade., (© 2020 The Author(s).)

Antibodies represent a well-established class of clinical diagnostics for medical applications as well as essential research and biotechnological tools. Although both polyclonal and monoclonal antibodies are indispensable reagents in basic research and diagnostics but both of them have their limitations. Hence, there is urgent need to develop strategies aimed at production of alternative scaffolds and recombinant antibodies of smaller dimensions that could be easily produced, selected and manipulated. Unlike conventional antibodies, members of Camelidae and sharks produce antibodies composed only of heavy chains with small size, high solubility, thermal stability, refolding capacity and good tissue penetration in vivo. The discovery of these naturally occurring antibodies having only heavy-chain in Camelidae family and their further development into small recombinant nanobodies represents an attractive alternative in drug delivery, diagnostics and imaging. Nanobody derivatives are soluble, stable, versatile, have unique refolding capacities, reduced aggregation tendencies and high-target binding capabilities. They can be genetically customized to target enzymes, transmembrane proteins or molecular interactions. Their ability to recognize recessed antigenic sites has been attributed to their smaller size and the ability of the extended CDR3 loop to quickly penetrate into such epitopes. With the advent of molecular engineering and phage display technology, they can be of potential use in molecular imaging, drug delivery and therapeutics for several major diseases. In this review we present the recent advances in nanobodies for modulating immune functions, for targeting cancers, viruses, toxins and microbes as well as their utility as diagnostic and biosensor tools.

Triple negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer accounting for 15-20% of cases and is defined by the lack of hormonal receptors viz., estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth receptor 2 (HER2). Treatment of TNBC is more challenging than other subtypes of breast cancer due to the lack of markers for the molecularly targeted therapies (ER, PR, and HER-2/ Neu), the conventional chemotherapeutic agents are still the mainstay of the therapeutic protocols of its patients. Despite, TNBC being more chemo-responsive than other subtypes, unfortunately, the initial good response to the chemotherapy eventually turns into a refractory drug-resistance. Using a monotherapy for the treatment of cancer, especially high-grade tumors like TNBC, is mostly worthless due to the inherent genetic instability of tumor cells to develop intrinsic and acquired resistance. Thus, a cocktail of two or more drugs with different mechanisms of action is more effective and could successfully control the disease. Furthermore, combination therapy reveals more, or at least the same, effectiveness with lower doses of every single agent and decreases the likelihood of chemoresistance. Herein, we shed light on the novel combinatorial approaches targeting PARP, EGFR, PI3K pathway, AR, and wnt signaling, HDAC, MEK pathway for efficient treatment of high-grade tumors like TNBC and decreasing the onset of resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Apple scab caused by Venturia inaequalis Cooke (Wint.) is one the important diseases of trade and industrial significance in apple. In present study variability studies in pathogen isolates were studied, which is one of the most important factors for devising management studies of scab disease in apple. Genetic diversity of 30 Venturia inaequalis isolates from 12 districts of two geographical distinct regions of Jammu and Kashmir was calculated based on the allele frequencies of 28 SSR markers and the internal transcribed spacer (ITS) region of the ribosomal DNA. The ITS based characterized sequences were submitted to NCBI GenBank and accession numbers were sanctioned. Dendrogram showed that all the accessions formed 2 main clusters with various degree of sub clustering within the clusters. Analysis based on SSR study reveals that the heterozygosity ranged from 0.0 and 0.5, with an average value of 0.39. The expected heterozygosis or gene diversity (He) ranged from 0.0 to 0.50 with an average of 0.40. The Fst value ranges from 0 to 0.6 with an average of 0.194. Diversity within each population (HS) values ranging from 0.26 to 0.33. Average differentiation among populations (GST) was 0.11 and populations were isolated by significant distance (r 2 = 0.50, P < 0.01). From the AMOVA analysis, 25% of variation was observed among population, 9% among individuals and 66% within individuals observed in the population. Structure analysis grouped isolates into two populations. Principle coordinate analysis explained variation of 36.6% in population 1, 14.30% in population 2 and 13.10% in population 3(Admixture) with 64.07% as overall cumulative percentage of variation. This indicates that extensive short-distance gene flow occurs in Kashmir region that dispersal over longer distances also appears to occur frequently enough to prevent differentiation due to genetic drift. Also it is evident that Jammu and Kashmir most likely has V. inaequalis subpopulations linked to diverse climatic conditions of the Jammu region compared to the mountainous inland Kashmir region. The results of present study would help to understand the genetic diversity of V. inaequalis from Jammu and Kashmir that would lead in the development of more effective management strategies and development of new resistant cultivars through marker-assisted selection., Competing Interests: The authors have declared that no competing interests exist.

Background: Bacterial cytokinesis is orchestrated by a complex of dozen of proteins called 'divisome' at the mid-cell site. FtsZ, the eukaryotic tubulin homolog, localizes to the mid-cell site where it polymerizes and forms a cytokinetic Z-ring. The Z-ring acts as a docking platform for other proteins to localize. In model organisms, Escherichia coli and Bacillus subtilis, FtsZ is known to interact with several proteins. The role of few of these interactions is known, while of others is yet to be studied. In Mycobacterium tuberculosis, the cell division and its regulation are poorly studied. Although, most of the divisome proteins are conserved in M. tuberculosis, surprisingly the homologues of the protein factors required for membrane association of Z-ring and its stabilization are absent. In E. coli FtsE and FtsX, the constituent ATPase and membrane domains of the ABC transporter complex, localize to the Z-ring immediately after Z-ring stabilizing proteins, ZipA and FtsA. Therefore, investigation of the interaction between MtFtsX and MtFtsZ is demanding., Methods: Bacterial two-hybrid system was used to identify the interaction between MtFtsE and MtFtsZ. This interaction was further confirmed by biochemical methods of Ni2+-NTA agarose pull-down and coimmunoprecipitation., Results and Conclusion: Here, we demonstrated that MtFtsX interacts with MtFtsZ in vivo and ex-vivo. Further, we showed that self-interacting MtFtsX interacts with MtFtsE. However, we did not find any interaction between MtFtsE and MtFtsZ. These results suggest that the membrane domain MtFtsX of the ABC transporter complex 'MtFtsEX' might be the membrane-tethering and stabilizing factor for Z-ring in M. tuberculosis., Competing Interests: None

Background: FLAG (fludarabine, cytarabine, granulocyte colony-stimulating factor) and FLAG-IDA (idarubicin added to standard FLAG) are salvage chemotherapy regimens used for relapsed and refractory acute leukemias. The toxicity of the FLAG-IDA courses is generally more severe than for the FLAG courses, with marked neutropenia and thrombocytopenia. This study aims to compare the outcomes of both regimens in terms of morbidity, mortality and remission/transplant. No comparison has been reported so far in Pakistan or the rest of third world countries., Methodology: This retrospective study was conducted in Hematology and Bone Marrow Transplant unit after approval from Institutional Review Board and Ethics Committee. 76 leukemic patients treated with salvage chemotherapy were included. Our endpoints for patient outcome analysis included disease remission/relapse, HSCT following remission, morbidity, mortality, progression free survival and overall survival. Kaplan Meier curves were made in SPSS for survival analysis., Results: A total of 76 patients were included from 2015 to July 2018. 49 patients were given FLAG, and 27 were given FLAG-IDA. 31.6% in FLAG-IDA achieved complete remission (CR)/complete remission with incomplete counts (CRi). 21% in FLAG-IDA made it to Bone marrow transplant (BMT) (67% of those in CR/CRi). 41.7% in FLAG achieved CR/CRi, and 27.8% in FLAG made it to BMT (67% of those in CR/CRi). Common complications in both regimens were infection, bleeding and other complications e.g., rash, diarrhea, mucositis, etc. A statistically significant difference was found between overall survival of the two regimens, p value 0.033., Conclusions: FLAG regimen was found superior to FLAG-IDA with better survival and subsequent transplant rate.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus that causes severe hemorrhagic fever with a mortality rate of up to 30% in certain outbreaks worldwide. The virus has wide endemic distribution. There is no effective antiviral therapeutic or FDA approved vaccine for this zoonotic viral illness. The multifunctional CCHFV nucleocapsid protein (N protein) plays a crucial role in the establishment of viral infection and is an important structural component of the virion. Here we show that CCHFV N protein has a distant RNA-binding site in the stalk domain that specifically recognizes the vRNA panhandle, formed by the base pairing of complementary nucleotides at the 5' and 3' termini of the vRNA genome. Using multiple approaches, including filter-bonding analysis, GFP reporter assay, and biolayer interferometry we observed an N protein-panhandle interaction both in vitro and in vivo The purified WT CCHFV N protein and the stalk domain also recognize the vRNA panhandle of hazara virus, another Nairovirus in the family Bunyaviridae , demonstrating the genus-specific nature of N protein-panhandle interaction. Another RNA-binding site was identified at the head domain of CCHFV N protein that nonspecifically recognizes the single strand RNA (ssRNA) of viral or nonviral origin. Expression of CCHFV N protein stalk domain active in panhandle binding, dramatically inhibited the hazara virus replication in cell culture, illustrating the role of N protein-panhandle interaction in Nairovirus replication. Our findings reveal the stalk domain of N protein as a potential target in therapeutic interventions to manage CCHFV disease., (© 2019 Jeeva et al.)

Background: Nail disorders comprise approximately 10% of all dermatological conditions. Because diagnosis is not always possible by clinical means alone, additional diagnostic procedures may be required at times. Dermoscopy of nails (onychoscopy) has shown promising results in diagnosing various nail disorders and also avoids time-consuming investigations such as culture and biopsy., Objective: To study the dermoscopic features of various nail disorders to determine the correlation between KOH examination and onychoscopic patterns in patients with the clinical suspicion of onychomycosis, and to differentiate benign pigmented lesions from malignant ones., Methods: An open, observational and cross-sectional study of 237 patients was conducted. All patients underwent clinical examination and the affected nails were examined with a dermatoscope. The onychoscopic patterns were identified and recorded., Results: The study included 237 patients with the following diagnoses: 81 onychomycosis, 63 psoriasis, 27 lichen planus, 30 longitudinal melanonychia, 24 connective tissue disorders, 5 onychophagia and nail tics, 3 subungual verrucae, 2 glomus tumor, 1 Darier disease, and 1 enchondroma. The most common onychoscopic findings were spiked pattern in cases of onychomycosis, dilated and tortuous capillaries in cases of psoriasis, longitudinal streaks and nail fragmentation in cases of lichen planus, and enlarged capillaries in cases of connective tissue diseases., Limitations: The study was only observational and did not compare the results to biopsy and culture., Conclusions: Onychoscopy may be used as an important diagnostic tool when evaluating nail disorders. It should be used to aid in the diagnosis of various nail disorders and to avoid unnecessary and time-consuming investigations., Competing Interests: Competing interests: The authors have no conflicts of interest to disclose.

Objective: The aim of this study was to determine the clinical outcome, microbiological outcome and safety profile of CSE-1034, a novel combination of Ceftriaxone, Sulbactam and EDTA in patients with complicated urinary tract infections (cUTI)., Materials and Methods: This was a randomized, controlled, open-labeled Phase-3 trial with the primary objective of assessing the efficacy and safety of CSE-1034 versus Ceftriaxone for the empirical treatment of cUTI. Adult cUTI patients were randomized to receive either intravenous dose of CSE-1034 or Ceftriaxone. The primary end point was composite cure rate (clinical response and bacterial eradication) in mMITT population at test of cure (TOC) visit. Secondary measures included verification of primary endpoint across other visits in different population sets, safety of patients and treatment duration., Results: Overall, 204 patients were enrolled in the study and received one of the two treatments. At primary endpoint (TOC visit), the composite cure rate was much higher in CSE-1034 treatment arm compared to Ceftriaxone arm i.e. 97% (68/70) vs 83% (58/71) (treatment difference 12.6%; 95% CI: 5.9% to 26.4%). The adverse events (AEs) rates reported in two treatment arms were 21% in CSE-1034 and 36% in Ceftriaxone groups. Additionally, the treatment duration in CSE-1034 arm was significantly less ( P < 0.05)., Conclusions: CSE-1034 3 g every 24 h showed a high favorable clinical and bacteriological response, and 95% CI around the treatment difference prove the superiority of CSE-1034 vs. Ceftriaxone for the treatment of cUTI. Therefore, CSE-1034 provides an effective alternative in the treatment of patients with cUTI., Competing Interests: Manu Chaudhary, Shiekh Gazalla Ayub and Mohd Amin Mir are the employees of Venus Remedies, Panchkula. All other authors declare that they have no conflict of interest.

Objective: CSE-1034 is a novel antibiotic adjuvant entity (AAE) with proven activity against broad range of multi-drug resistant (MDR) pathogens causing various bacterial infections. This phase 3 clinical trial was designed to evaluate the efficacy and safety of CSE-1034 therapy for the treatment of community-acquired pneumonia (CAP) patients of Pneumonia Outcomes Research Team (PORT) risk III-IV., Methods: In this multi-centric, controlled, open-labeled phase 3 trial, adult patients with PORT risk III-IV CAP were randomized to receive either intravenous CSE-1034 (3g every 12h) or Ceftriaxone (2g every 12h) for 3-10 days. The primary endpoint was clinical response in clinically-evaluable (CE) population and microbiological eradication in microbiologically-evaluable (ME) population at test of cure (TOC) visits. Secondary endpoints included verification of the primary endpoints across all other visits, treatment duration and safety of patients., Results: 156 patients were screened at 5 study centers of which 93 subjects were enrolled in the study and randomized in CSE-1034 and Ceftriaxone treatment arms. In CE population (n=90), the clinical cure rates at TOC visit were 96% and 64% in CSE-1034 (n=46) and Ceftriaxone (n=44) treatment arms respectively (treatment difference: 32.0%; 95% CI, 15.8%-47.1%). The bacterial eradication in ME population of two treatment arms were 94% (n=36) and 56% (n=27) at TOC visit (treatment difference: 38.9%; 95% CI, 17.8%-57.6%). Overall, the total number of adverse events (AEs) reported in both groups were 21 (22.5%). The AEs rates reported in two treatment arms were 15.2% in CSE-1034 and 29.8% in Ceftriaxone group., Conclusion: Overall assessment of clinical cure rate, microbiological eradication rate and safety assessment in this study has shown that CSE-1034 is an effective and safe option for the treatment of CAP patients of PORT risk III-IV. Moreover, the superiority of CSE-1034 over Ceftriaxone is also proven., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hantavirus cardiopulmonary syndrome is characterized by pulmonary capillary leakage and alveolar flooding, resulting in 50% mortality due to fulminant hypoxic respiratory failure. In addition, depression of cardiac function ensues, which complicates the picture with cardiogenic shock. Early diagnosis and appropriate use of extracorporeal membrane oxygenation (ECMO) are amongst the lifesaving interventions in this fatal illness. However, a recent case report demonstrates that implementation of high volume continuous hemofilteration along with protective ventilation reverses the cardiogenic shock within few hours in hantavirus infected patients. This review article is focused on the recent advances in clinical features, diagnosis, management, epidemiology, and pathogenesis of hantavirus induced cardiopulmonary syndrome. It provides information for clinicians to help in correct diagnosis during the early stages of viral infection that could improve the prognosis of this viral illness., (© 2018 Wiley Periodicals, Inc.)

Background: The thermal burn is accidental and also is the hidden and worst complication of medical plaster application. This study evaluated clinical and aetiological profile and severity of plaster burns., Methods: In Department of Burns, Plastic and Reconstructive Surgery from 1 st August 2014 to 31 st December 2015, six patients with plaster burn were assessed for total body surface area and depth of burn. The wounds were cultured and dressed with moist dressings daily till the surgical procedure and satisfactory healing., Results: The youngest patient was 10 and oldest 65 years (mean age: 40.20±6.67 years, 4 males and two females with ratio of 2:1). Three patients sustained plaster burn injury accidentally at home and 3 developed burn after medical application of plaster. The hands burns were observed commonly in accidental plaster burns, while ankle was often involved in iatrogenic plaster burns. The iatrogenic burns were mostly deep in thickness varying 2 nd to 4 th degree, while accidental burns were often 2 nd degree. Superficial 2 nd degree burns were managed conservatively, and deep 2 nd degree burns were skin grafted. Fourth degree burn was managed with reverse sural flap alone and another with vacuum-assisted closure followed by reverse sural flap and skin grafting., Conclusion: Plaster burn is still a challenge to plastic surgeon and it is advised for applying casts to utilize all available means to limit the amount of casting material provided. It can be accomplished without compromising the cast strength to minimize the risk of thermal injury when applying plaster or composite casts.

Environmental pollution by alkaline salts, such as Na 2 CO 3 , is a permanent problem in agriculture. Here, we examined the putative role of jasmonic acid (JA) in improving Na 2 CO 3 -stress tolerance in maize seedlings. Pretreatment of maize seedlings with JA was found to significantly mitigate the toxic effects of excessive Na 2 CO 3 on photosynthesis- and plant growth-related parameters. The JA-induced improved tolerance could be attributed to decreased Na uptake and Na 2 CO 3 -induced oxidative damage by lowering the accumulation of reactive oxygen species and malondialdehyde. JA counteracted the salt-induced increase in proline and glutathione content, and significantly improved ascorbic acid content and redox status. The major antioxidant enzyme activities were largely stimulated by JA pretreatment in maize plants exposed to excessive alkaline salts. Additionally, increased activities of glyoxalases I and II were correlated with reduced levels of methylglyoxal in JA-pretreated alkaline-stressed maize plants. These results indicated that modifying the endogenous Na + and K + contents by JA pretreatment improved alkaline tolerance in maize plants by inhibiting Na uptake and regulating the antioxidant and glyoxalase systems, thereby demonstrating the important role of JA in mitigating heavy metal toxicity. Our findings may be useful in the development of alkali stress tolerant crops by genetic engineering of JA biosynthesis.

Background: We investigated outcomes for nondelayed conventional deltopectoral (CDP) flaps and lateral extension deltopectoral (LEDP) flaps., Material and Methods: Fifteen CDP flaps and 17 LEDP flaps were raised in 32 patients. All flaps were nondelayed. The flaps were folded only in the LEDP flap group. Six of 17 LEDP flaps were folded to become bilayered flaps to repair full thickness defects. Flap success rates and complication rates were compared between the CDP flap and LEDP flap groups., Results: Success rates were 93.33% in the CDP flap group and 94.12% in the LEDP flap group. Overall complication rates of the transferred flaps were 6.67% and 11.76% for CDP and LEDP flaps, respectively. Flap failure rates were 6.67% and 5.88% with CDP flaps and LEDP flaps, respectively., Conclusions: Although the CDP flap is the "aged workhorse" in contemporary head and neck reconstructions, it was shown to be a beneficial regional flap with a dependable pedicle and easy technique. The LEDP flap is of value particularly when used to treat full thickness defects of the head and neck or in cases when higher reach is required.

Background: Hemangiomas are the most common benign tumors of infancy. This study evaluated the efficacy of oral propranolol comparing to oral steroids in management of pediatric hemangiomas., Methods: In North India from January 2012 to January 2015, sixty children <6 years old with superficial hemangiomas were divided into 2 groups; oral propranolol vs. oral prednisolone. All participants were assessed for electrocardiogram, heart rate, blood pressure and sugar and initial therapy was started using 1 mg/kg and in absence of adverse effects, 2 mg/kg was administered after 2 weeks. The hemangioma Activity Score (HAS) was used for scoring and patients were followed up for 6 months., Results: The propranolol group mostly showed early response to the drug and needed the drug for less time compared to corticosteroid group. In propranolol group, 16.5%, 23% and 59% needed the drug to be continued for 8-12, 4-8 and 4 months. In corticosteroid group, the therapy was continued for 8-12, and 4-8 months in 76.8% and 16.5% and in 6.6% was stopped within 4 months. In propranolol group, the response was 70% compared to 40% in other group. The mean HAS decreased significantly in propranolol group when compared to steroid group. Three patients on prednisolone developed Cushingoid features, while 1 patient in propranolol group had mild flue like symptoms., Conclusion: Two mg/kg of oral propranolol significantly decreased HAS, when compared to oral prednisolone, with good parent satisfaction, minimal adverse effects and no recurrence/relapse of hemangiomas after a follow up period of 6 months., Competing Interests: The authors declare no conflict of interest.

Background: In this study, we investigated sensory and motor outcomes for different bridging techniques for short nerve gaps., Material and Methods: This study was conducted in the Postdoctoral Department of Burns, Plastic, and Reconstructive Surgery of our institution from August 2014 to May 2017. All patients with posttraumatic short nerve gaps of 3 cm or less of median, ulnar, and/or both in forearm and wrists were included in the study. Patients with known causes of neuropathies were excluded. Groups 1, 2, 3, and 4 included 9 patients each, and the nerve gap was managed with reverse sural nerve autograft, inside-out vein conduit autograft, reverse sural nerve with covering inside-out vein autograft, and inside-out great saphenous vein autograft filled with denervated gastrocnemius skeletal muscle autograft, respectively. All the patients were followed-up and examined for sensory and motor recovery with a 2-point discrimination test (2PD) at finger tips in the distribution of reconstructed nerves and medical research council scale (MRCS) for muscle power innervated by the reconstructed nerves. The 2PD and MRCS muscles were compared between the groups using SPSS version 23 through 1-way analysis of variance., Results: All the patients in each group recovered either completely or partially. The 2PD and MRCS muscle power means were compared between the groups. On comparing the mean 2PD and mean MRCS muscle power were compared between the groups using 1-way analysis of variance test. All the groups have been found statistically comparable in spite of the apparent clinical difference., Conclusions: Although the nerve autograft is the criterion standard for managing the nerve gaps, the vein conduit is a viable alternative to nerve autograft for bridging the nerve gaps 3 cm or less, whereas filled conduit needs more study. However, more patients need to be studied to complete a relevant statistical study.

Crimean Congo hemorrhagic fever, a zoonotic viral disease, has high mortality rate in humans. There is currently no vaccine for Crimean Congo hemorrhagic fever virus (CCHFV) and chemical interventions are limited. The three negative sense genomic RNA segments of CCHFV are specifically encapsidated by the nucleocapsid protein into three ribonucleocapsids, which serve as templates for the viral RNA dependent RNA polymerase. Here we demonstrate that CCHFV nucleocapsid protein has two distinct binding modes for double and single strand RNA. In the double strand RNA binding mode, the nucleocapsid protein preferentially binds to the vRNA panhandle formed by the base pairing of complementary nucleotides at the 5' and 3' termini of viral genome. The CCHFV nucleocapsid protein does not have RNA helix unwinding activity and hence does not melt the duplex vRNA panhandle after binding. In the single strand RNA binding mode, the nucleocapsid protein does not discriminate between viral and non-viral RNA molecules. Binding of both vRNA panhandle and single strand RNA induce a conformational change in the nucleocapsid protein. Nucleocapsid protein remains in a unique conformational state due to simultaneously binding of structurally distinct vRNA panhandle and single strand RNA substrates. Although the role of dual RNA binding modes in the virus replication cycle is unknown, their involvement in the packaging of viral genome and regulation of CCHFV replication in conjunction with RdRp and host derived RNA regulators is highly likely.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus. IMPORTANCE Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5' UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease., (Copyright © 2017 American Society for Microbiology.)

Humans acquire hantavirus infection by the inhalation of aerosolized excreta of infected rodent hosts. There is no treatment for hantavirus diseases at present. Therapeutic intervention during early stages of viral infection can improve the outcome of this zoonotic viral illness. The interaction between an evolutionary conserved sequence at the 5' terminus of hantaviral genomic RNA and hantavirus nucleocapsid protein plays a critical role in the hantavirus replication cycle. This unique interaction is a novel target for therapeutic intervention of hantavirus disease. We developed a very sensitive, tractable, and cost-effective fluorescence-based assay to monitor the interaction between the nucleocapsid protein and the target RNA sequence. The assay was optimized for high-throughput screening of chemical libraries to identify molecules that interrupt this RNA-protein interaction. The assay was validated using a library of 6880 chemical compounds. This validation screen demonstrated the reproducibility and validity of required statistical criteria for high-throughput screening. The assay is ready to use for high-throughput screening of large chemical libraries to identify antihantaviral therapeutic molecules and can be amenable to similar targets in other viruses.

Objective: In India, Elores (CSE-1034: ceftriaxone+sulbactam+disodium edetate) was approved as a broad spectrum antibiotic in year 2011 and is used for management of Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections in tertiary care centers. The objective of this study was to investigate the efficacy of this drug in patients with Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections and identify the incidence of adverse events in real clinical settings., Methods: This Post Marketing Surveillance study was conducted at 17 centers across India and included 2500 patients of all age groups suffering from various bacterial infections and treated with Elores (CSE1034). Information regarding demographic, clinical and microbiological parameters, dosage and treatment duration, efficacy and adverse events (AEs) associated with the treatment were recorded., Results: A total of 2500 patients were included in the study and efficacy was evaluated in 2487 patients. In total, 409 AEs were reported in 211 (8.4%) patients. The major AEs reported were vomiting (3.0%), pain at injection site (2.5%), nausea (2.3%), redness at site (1.96%), thrombophlebitis (1.4%). Of total reported AEs, 40 (5.3%) AEs were reported in pediatric, 310 (20.6%) in adult, and 59 (23.6%) in geriatric group. No AE belonging to grade IV or V was reported in any patient. In terms of efficacy, 1977 (79.4%) patients were cured, 501 (20.1%) patients showed clinical improvement and 5 (0.2%) patients were complete failure. The treatment duration varied from 5 to 7 days in different patients depending on the infection type., Conclusion: In this post-marketing surveillance study, CSE-1034 was found to be an effective and safe option against Pip tazo and meropenem in management of patients with multi-drug resistant (MDR) bacterial infections under routine ward settings., (Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

This is a prospective study with the aim to determine specific patterns of burn wound bacterial colonisation and antimicrobial resistance profiles. There is a high incidence of infections and septicaemia in post-burn patients, which, in turn, are associated with high morbidity and mortality, a fact that compelled us to undertake this study. The study was conducted over a period 11 months, from 1 August 2014 to 30 June 2015, in 50 burn patients admitted in our burn unit. Wound cultures were taken after 72 hours of admission from all the patients, and then, empirical systemic antibiotics were administered. For wound cultures; 1 cubic cm tissue was taken and placed in aerobic and anaerobic culture vials and transported to the microbiology lab under all aseptic precautions as soon as possible. At the time of fever any time after 72 hours of admission, 16 ml of blood was drawn under all aseptic precautions. Both aerobic and anaerobic blood culture vials were filled with 8 ml of blood each and transported to the microbiology lab. The results of culture and sensitivity reports of 50 patients were recorded. The data obtained was analysed using appropriate statistical analytical tests. The most common organism responsible for bacteraemia is Pseudomonas (43%). Most of the strains of organisms isolated were resistant to commonly used antibiotics in the hospital; Pseudomonas was found 100% resistant to a combination of ampicillin + sulbactum, ceftriaxone and was most often sensitive to imipenem, amikacin and vancomycin. Methicillin-resistant Staphylococcus aureus (MRSA) was also found resistant to commonly used antibiotics like ceftriaxone, ampicillin + sulbactum and ceftazidime + calvulanic acid. Linzolid and vancomycin were effective in 83% and 100% cases, respectively. We conclude that similar institution-specific studies should be conducted, and such studies will be helpful in providing useful guidelines for choosing effective empirical therapy that will have a great impact on the prevention of infection and its complications in burn patients because of bacteraemia., (© 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Introduction: Nosocomial infections have been considered as a major health problem causing incremental morbidity, mortality and costs of therapy., Aim: This retrospective study was initiated with aim to analyse the comparative efficacy of a novel Antibiotic Adjuvant Entity (AAE), a combination of ceftriaxone + sulbactam + disodium edetate and meropenem in combination with colistin, for the management of Multi Drug Resistant (MDR) nosocomial Gram-negative bacterial infections., Materials and Methods: Case history sheets of patients with documented MDR nosocomial Gram-negative infections who received either AAE or meropenem in combination with colistin for management of infections over a period of 3 years (November 2012 - October 2015) were included in the study. Data related to clinical management, demographics, vital signs and laboratory parameters along with prior antibiotic therapy, dose and clinical outcomes were evaluated thoroughly to analyse the clinical benefits of this new AAE+ colistin therapy for management of MDR nosocomial infections., Results: Out of 115 patients short listed for the study, 52 patients had received AAE + colistin therapy and 63 patients have received meropenem + colistin. AAE + colistin therapy resulted in significantly higher efficacy (86.53%) as compared to meropenem + colistin (63.49%). A rising trend in clinical cure rates was observed in AAE based combination therapy in contrast to the decreasing trend in meropenem based combination therapy. A progressive decline in clinical cure rates was observed in meropenem treated group over a period of 3 years due to rising carbapenemases and multiple resistance by pathogens, where as AAE maintained the same efficacy., Conclusion: The AAE + colistin therapy has shown better bacteriological and clinical efficacy as compared to meropenem + colistin in the management of various nosocomial MDR Gram-negative infections. A significant number of meropenem failure patients responded to the AAE therapy highlighting the new hope to spare carbapenems.

An evolutionarily conserved sequence at the 5' terminus of hantaviral genomic RNA plays an important role in viral transcription initiation and packaging of the viral genome into viral nucleocapsids. Interaction of viral nucleocapsid protein (N) with this conserved sequence facilitates mRNA translation by a unique N-mediated translation strategy. Whereas this evolutionarily conserved sequence facilitates virus replication with the assistance of N in eukaryotic hosts having multifaceted antiviral defense, we demonstrate its interaction with N presents a novel target for therapeutic intervention of hantavirus disease. Using a high throughput screening approach, we identified three lead inhibitors that bind and induce structural perturbations in N. The inhibitors interrupt N-RNA interaction and abrogate both viral genomic RNA synthesis and N-mediated translation strategy without affecting the canonical translation machinery of the host cell. The inhibitors are well tolerated by cells and inhibit hantavirus replication with the same potency as ribavarin, a commercially available antiviral. We report the identification of a unique chemical scaffold that disrupts a critical RNA-protein interaction in hantaviruses and holds promise for the development of the first anti-hantaviral therapeutic with broad spectrum antiviral activity., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Carboxymethyl cellulose (CMC) coatings alone and in combination with gamma irradiation was tested for maintaining the storage quality, inhibiting fungal incidence and extending shelf-life of cherry fruit. Two commercial cherry varieties viz. Misri and Double after harvest at commercial maturity were coated with CMC at levels 0.5-1.0 % w/v and gamma irradiated at 1.2 kGy. The treated fruit including control was stored under ambient (temperature 25 ± 2 °C, RH 70 %) and refrigerated (temperature 3 ± 1 °C, RH 80 %) conditions for evaluation of various physico-chemical parameters. Fruits were evaluated after every 3 and 7 days under ambient and refrigerated conditions. CMC coating alone at levels 0.5 and 0.75 % w/v was not found effective with respect to mold growth inhibition under either of the two conditions. Individual treatment of CMC coating at 1.0 % w/v and 1.2 kGy irradiation proved helpful in delaying the onset of mold growth up to 5 and 8 days of ambient storage. During post-refrigerated storage at 25 ± 2 °C, RH 70 %, irradiation alone at 1.2 kGy gave further 4 days extension in shelf-life of cherry varieties following 28 days of refrigeration. All combinatory treatments of CMC coating and irradiation proved beneficial in maintaining the storage quality as well as delaying the decaying of cherry fruit during post-refrigerated storage at 25 ± 2 °C, RH 70 % but, combination of CMC at 1.0 % w/v and 1.2 kGy irradiation was found significantly ( p  ≤ 0.05) superior to all other treatments in maintaining the storage quality and delaying the decaying of cherry fruit. The above combinatory treatment besides maintaining storage quality resulted in extension of 6 days in shelf life of cherry varieties during post-refrigerated storage at 25 ± 2 °C, RH 80 % following 28 days of refrigeration. Above Combination treatment gave a maximum of 2.3 and 1.5 log reduction in yeast and mold count of cherry fruits after 9 and 28 days of ambient and refrigerated storage, thereby ensuring consumer safety.

In present study, we evaluated the effects of Jasmonic acid (JA) on physio-biochemical attributes, antioxidant enzyme activity, and gene expression in soybean (Glycine max L.) plants subjected to nickel (Ni) stress. Ni stress decreases the shoot and root length and chlorophyll content by 37.23, 38.31, and 39.21%, respectively, over the control. However, application of JA was found to improve the chlorophyll content and length of shoot and root of Ni-fed seedlings. Plants supplemented with JA restores the chlorophyll fluorescence, which was disturbed by Ni stress. The present study demonstrated increase in proline, glycinebetaine, total protein, and total soluble sugar (TSS) by 33.09, 51.26, 22.58, and 49.15%, respectively, under Ni toxicity over the control. Addition of JA to Ni stressed plants further enhanced the above parameters. Ni stress increases hydrogen peroxide (H2O2) by 68.49%, lipid peroxidation (MDA) by 50.57% and NADPH oxidase by 50.92% over the control. Supplementation of JA minimizes the accumulation of H2O2, MDA, and NADPH oxidase, which helps in stabilization of biomolecules. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) increases by 40.04, 28.22, 48.53, and 56.79%, respectively, over the control in Ni treated seedlings and further enhancement in the antioxidant activity was observed by the application of JA. Ni treated soybean seedlings showed increase in expression of Fe-SOD by 77.62, CAT by 15.25, POD by 58.33, and APX by 80.58% over the control. Nevertheless, application of JA further enhanced the expression of the above genes in the present study. Our results signified that Ni stress caused negative impacts on soybean seedlings, but, co-application of JA facilitate the seedlings to combat the detrimental effects of Ni through enhanced osmolytes, activity of antioxidant enzymes and gene expression.

Acute pancreatitis is a rare complication of chemotherapy agents. We describe the case of a patient with multiple myeloma who developed acute pancreatitis after treatment with bortezomib, a proteasome inhibitor commonly used in the treatment of this disease. We reviewed the available medical literature on this topic, and found other seven similar cases, all after intravenous bortezomib. Our case is the first one occurring with the subcutaneous route of administration., (© The Author(s) 2014.)

This study has been undertaken to explore the therapeutic effects of deguelin and specific siRNAs in HeLa cells. The data provided clearly show the silencing of ERK 1/2 with siRNAs and inhibition of ERK1/2 with deguelin treatment in HeLa cells. Additionally, we are providing information that deguelin binds directly to anti-apoptotic Bcl-2, Bcl-xl and Mcl-1 in the hydrophobic grooves, thereby releasing BAD and BAX from dimerization with these proteins. This results in increased apoptotic activity through the intrinsic pathway involved in rupture of mitochondrial membrane and release of cytochrome C. Evidence for inhibition of ERK1/2 by deguelin and escape of BAD phosphorylation at serine 112 through ERK/RSK pathway has been further fortified by obtaining similar results by silencing ERK 1/2 each with specific siRNAs. Increase in BAD after treatment with deguelin or siRNAs has been interpreted to mean that deguelin acts through several alternative pathways and therefore can be used as effective therapeutic agent.

Background: This study has been conducted with the aim of evaluating modified T-plate interpositional arthroplasty., Methods: A prospective comparative study in patients admitted with temporomandibular joint ankylosis. Ankylotic temporomandibular joint arthroplasty included condylectomy gap arthroplasty in 7, temporalis muscle flap interpositional arthroplasty in 8, and modified T-plate interpositional arthroplasty in 13 cases. The patients were followed for three years. Collected data were tabulated and subjected to Fisher's exact test, chi-square test and probability estimation., Results: A significant increase in interincisal distance of 32 mm was seen in 12 (92.31%) patients in the T-plate interposition group, in 2 (25%) cases of the temporalis muscle flap interposition group, and in 1 case (14.28%) of the condylectomy group at 12, 24, and 36 months. Re-ankylosis was observed in 1 case (9.69%) of the T-plate interposition group, while as it was observed in 4 (50%) cases in the temporalis muscle flap interposition group and 4 (57.14%) cases in the condylectomy group, and these differences were statistically significant., Conclusions: Our clinical experience with the use of the T-plate over the past 5 years has been encouraging, and our physiotherapy technique is quite simple. Even illiterate parents can assess it easily. Hence, we recommend this easy technique that does not damage the temporalis muscle for the management of temporomandibular joint ankylosis.

Aim: This study was carried out to investigate the effect of incorporation of different level of walnut cake in concentrate mixture on in vitro dry matter degradation in order to determine its level of supplementation in ruminant ration., Materials and Methods: Walnut cake was used @ 0, 10, 15, 20, 25 and 30% level to formulate an iso-nitrogenous concentrate mixtures and designated as T1, T2, T3, T4, T5 and T6 respectively. The different formulae of concentrate mixtures were used for in vitro gas production studies using goat rumen liquor with wheat straw in 40:60 ratio. Proximate composition, fiber fractionation and calcium and phosphrous content of walnut cake were estimated., Result: The per cent IVDMD value of T1 and T2 diets was 68.42 ± 1.20 and 67.25 ± 1.37 respectively which was found highest (P<0.05) T3, T4, T5 and T6. Similar trend was also found for TDOM and MBP. Inclusion of walnut cake at 10% level in the concentrate mixture does not affect in vitro dry matter digestibility (IVDMD), truly degradable organic matter (TDOM, mg/200 mg DM), total gas production, microbial biomass production (MBP) and efficiency of microbial biomass production (EMP)., Conclusion: It is concluded that walnut cake incorporation up to 10% level in the iso -nitrogenous concentrate mixture has no any negative effect on in vitro digestibility of dry matter (DM), TDOM, MBP, EMP and total gas production in goat.

Jasmonic acid (JA) is a very young candidate of plant growth regulators which is being explored for various antistress properties. Present study deals with the hypothesis that JA can modulate antioxidant mechanism of higher plants with tight regulation of biomembrane peroxidation, making plants tolerant to toxic Ni(2+). 2 mM NiCl2 as a source of Ni(2+) appeared as sub lethal dose for the growth of 15 days old Glycine max seedlings. Exogenous application of 1 μM and 1 nM JA prior to NiCl2 exposure, made seedlings of Glycine max more tolerant to Ni(2+)stress as compared to control untreated seedlings. Regulatory inhibition of MDA and H2O2 production by JA with or without Ni(2+) treatment made plants more resistant to Ni(2+) stress which may be associated with ameliorative activity of antioxidant enzymes system composed of SOD, POD, CAT and APOX. Ascorbate, a secondary metabolite synthesized from D-glucose act as an antioxidant in plant cells. Many fold enhancements in AsA content of Ni(2+) treated seedlings supplemented with different concentrations of JA was observed. Significant improvement in AsA levels by JA with or without Ni(2+) stress may involve two aspects, either denovo synthesis level regulation of AsA or recycling of AsA from an oxidized form. Improvement in total protein content showed the uplift modulation of transcriptional machinery by JA which was also maintained under Ni(2+) stress. Photosynthetic pigments as total chl, chl a and b showed inhibition in presence of Ni(2+) stress which was not found much effective under JA supplementation as compared to control. Present findings revealed that although JA was not helpful for protection of photosynthetic pigments but it modulates the other machinery of plants significantly including various antioxidants positively, while tightly inhibiting stress related processes responsible for lipid peroxidation to make plants tolerant to Ni(2+) stress.

Aim: The objective of the study was to evaluate the effects of non-genetic factors on reproduction traits viz. age at first semen freezing and age at first semen use of breeding bulls in Sahiwal bulls by fitting least-squares analysis., Materials and Methods: The information on reproduction traits of 43 Sahiwal breeding bulls belonging to 8 sets of Sahiwal breeding program at Indian Council of Agricultural Research-National Dairy Research Institute (ICAR-NDRI), Karnal (Haryana), India during 27 years (1987-2013) were analyzed using fixed linear model. The information was collected from AI records, reproduction sheets, and bull AI register maintained at different sections of Institute viz. record room of Dairy Cattle Breeding Division (DCB), Cattle Yard, Artificial Breeding Research Centre, ICAR-NDRI, Karnal., Results: The average age at first semen freezing and age at first semen use of Sahiwal breeding bulls was estimated as 3.17±0.01 years and 5.35±0.01 years, with the coefficient of variation 18.93% and 20%, respectively. The overall least-squares mean for age at first semen freezing and age at first semen use was estimated as 3.14±0.09 years and 5.25±0.02 years, respectively, in Sahiwal breeding bulls. Period of freezing/use had significant effects on reproductive traits (p<0.01). Season had no significant effect on any of the traits considered in this study., Conclusion: It can be concluded that management inputs such as nutrition, breeding, and optimum environment should be taken care of to optimize age at first semen freezing and age at first semen use for better utilization of superior germplasm.

Anti-MAG neuropathy is a very rare form of acquired polyneuropathy associated with IgM monoclonal gammopathy of undetermined significance (MGUS). We conducted a retrospective review of 194 consecutive MGUS patients seen at the Penn State Hershey Cancer Institute. We identified six patients among 37 (16 %) with IgM MGUS with anti-MAG neuropathy. Interestingly, an additional patient had anti-MAG neuropathy without MGUS. Common clinical manifestations were numbness and paresthesias of the extremities and gait imbalance. All four patients treated with rituximab and none of the three untreated ones had a subjective improvement of their symptoms. We conclude that all patients with IgM MGUS and neuropathy should be screened for anti-MAG antibodies and, if positive, they should be offered treatment with rituximab.

Background: Allogeneic transplant in myeloma remains controversial., Patients and Methods: We performed a retrospective review of 76 patients in the Mayo Clinic database from 1993 to 2013 who underwent allogeneic hematopoietic stem cell transplant (HSCT) for myeloma., Results: After excluding ineligible patients, among the remaining 66 patients, median age at transplant was 42 years and 87% had residual disease at the time of transplant. Myeloablative (71%) versus reduced intensity conditioning (29%), matched sibling donors (70%) versus unrelated donors showed no outcome difference. Median overall survival from the time of diagnosis and transplant were 75 and 24 months, respectively. Median time to disease progression (TTP) was 15 months and treatment-related mortality was 20% at day 100. Acute and chronic graft versus host disease (cGVHD) developed in 61% and 48% patients, respectively. In univariate analysis of overall survival (OS), factors predicting adverse outcome were pretransplant 24-hour total urinary protein (P = .035), peripheral blood versus bone marrow (OS 18 vs. 41 months; P = .02), number of previous therapies (P = .014), time from autologous to allogeneic HSCT (P = .019), and cGVHD (P = .01). TTP was adversely affected by number of previous regimens (P = .036) and PB as graft source (P = .016). In multivariate analysis for progression-free survival, number of previous regimens (P = .04), and for OS, time between autologous and allogeneic HSCT was significant (P = .009)., Conclusion: In 162 matched control subjects who were human leukocytoe antigen-typed, there were no survivors at 12 years compared with 20% in the group who received a transplant. In a second control group with 197 second autologous transplants, 10-year OS was 8%., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: The aim of the present investigation was to optimize the age at first use (AAFU) of semen of Murrah breeding bulls, which will help in early selection of bulls under progeny testing program for improving the reproductive performance in the herd., Materials and Methods: The data on AAFU, conception rate based on first A.I. (CRFAI), overall conception rate (OCR), and birth weight (B.WT) of 57 Murrah bulls during 1993-2014 at NDRI center pertaining to 14 sets of Network Project on Buffalo Improvement at ICAR-National Dairy Research Institute, Karnal, Haryana, India were adjusted for significant environmental influences and subsequently analyzed. Simple and multiple regression models were used for prediction of CRFAI and OCR of Murrah breeding bulls. Comparative evaluation of three developed models (I-III) showed that Model III, having AAFU and B.WT, fulfill the accuracy of model as revealed by high coefficient of determination, low mean sum of squares due to error, low conceptual predictive value, and low Bayesian information criterion., Results: The results revealed that the average predicted CRFAI was highest (39.95%) at <3.5 years and lowest (34.87%) at >4.5 years of age at first A.I/use. Similarly, average predicted OCR was highest (41.05%) at <3.5 years and lowest (39.42%) at >4.5 years of age at first A.I/use of Murrah bulls., Conclusion: In organized herd under progeny testing program, Murrah bulls should be used at young age, i.e. prior to 3.5 years, which is expected to result in 5.08% better CRFAI and 1.63% better OCR in comparison to Murrah bulls used after 4.5 years of age.