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Background: WHO reported that the epidemic SARS-CoV-2 spread was a public health emergency of international tension in January 2020 and pandemic in March 2020. In this regard, National Institute of Mental Health and Neuro Sciences (NIMHANS) launched a national helpline with the support of the Ministry of Health and Family Welfare for addressing psychosocial issues and mental health concerns of people during the COVID-19 pandemic. The recorded calls made to the National Psychosocial Support helpline were analysed to elicit the psychosocial issues seen among the elderly during the pandemic., Methods: The data of 70 randomly selected helpline callers were collected by using the sociodemographic data sheet and the semistructured questionnaire. The study employed descriptive research design., Results: In total, 71.1% of callers belonged to the 60-70 years' age group. 57.1% of callers had approached the helpline by themselves. 38.6% of the callers had reported a preexisting mental illness, of which the majority (33%) reported anxiety and/or sleeplessness. 28.6% of callers complained of comorbid medical issues. Interventions provided to the callers were in the form of supportive psychotherapy (84.28%), the COVID-19-related information (72.85%), referral services (62.9%), lifestyle modifications (41.42%), and behavioural activation (35.71%)., Conclusion: Study findings indicate that the older population encountered several mental health issues during COVID-19, and the telephonic interventions were the most feasible, accessible, and helpful method to reach out to them., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Squamous odontogenic tumour-like proliferations (SOTLPs) in the wall of odontogenic cysts are rare occurrences. Due to the histopathological similarity of these proliferations to neoplasms, such as squamous odontogenic tumour, intraosseous well-differentiated squamous cell carcinoma, and acanthomatous ameloblastoma, their correct elucidation is of paramount importance to avoid unnecessary and unwanted treatment. SOTLPs are uncommon in dentigerous cysts and rare in those that occur in the maxilla particularly the anterior region. This paper presents a case of maxillary dentigerous cyst involving 33 and a mesiodens in a 32 year old male which on histopathological examination showed SOTLPs in a dentigerous cyst., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Oral and Maxillofacial Pathology.)

Introduction: Composite Index of Anthropometric Failure (CIAF) and its further modifications have not incorporated all the combinations of malnutrition. We propose a new model incorporating all the forms of malnutrition among children under five years of age. However, the current models might misclassify a growing child as malnourished. Our objective is to develop a comprehensive scoring system using the three anthropometric Z-scores [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) Z-scores] and demonstrate the proposed CIAF model using the National Family Health Survey-5 (NFHS-5) data from India., Methods: A new scoring system was developed using the WAZ, HAZ, and WHZ scores to determine the child's nutritional status. We also proposed a new CIAF model by including all possible categories of malnutrition and practically demonstrated it using the NFHS-5 dataset after applying the new scoring system. Under-five children with heights, weights, and ages available were included in the analysis. The groups of malnutrition are presented as weighted proportions before and after applying the new score to the proposed model., Results: Our final analysis included individual-level data of 198,802 children under five years of age (weighted N = 195,197). After applying the new scoring system to the proposed model, the prevalence of stunting has reduced to 11.8% (95% CI 11.66-11.94) from 13.2% (95% CI 13.09-13.39) and wasting prevalence has reduced to 4.9% (95% CI 4.85-5.04) from 6.4% (95% CI 6.29-6.51). The most common forms of anthropometric failures among Indian children by using the newly developed CIAF model are: "Stunting and underweight" (30,127; 15.4%), Stunting only (23,035; 11.8%), and "wasting and underweight" (14,698; 7.5%). We found a new category called "Stunting, underweight, and overweight" (stunting = HAZ < -2SD, underweight = WAZ < -2SD, overweight = WHZ > +2SD). It constituted 0.1% (220 children) of the total sample., Conclusion: When the new scoring system is applied to the proposed CIAF model, it captures all forms and combinations of malnutrition among under-five children without overlap and prevents misclassifying a growing child as malnourished. The newly identified category shows that stunting (HAZ < -2SD), overweight (WHZ > +2SD) and underweight (WAZ < -2SD) can co-exist in the same child., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nandeep, Jaleel, Reddy, Geddam, Reddy and Hemalatha.)

Background and Objective: Automatic segmentation and annotation of medical image plays a critical role in scientific research and the medical care community. Automatic segmentation and annotation not only increase the efficiency of clinical workflow, but also prevent overburdening of radiologists. The objective of this work is to improve the accuracy and give a probabilistic map for automatic annotation from small data set to reduce the use of tedious and prone to error manual annotations from chest X-rays., Method: In this paper, we have proposed an attention UW-Net, which introduces an intermediate layer acting as a bridge between the encoder and decoder pathways. The intermediate layer is a series of fully connected convolutional layers generated from the upsampling of the final encoder layer connected to the corresponding up sampled and down sampled blocks via skip-connections. The intermediate layer is further connected to the decoder pathway using a downsampling layer., Results: The proposed attention UW-Net is giving a very good performance, achieving an average F1-score of 95.7%, 80.9%, 81.0% and 77.6% for lung (large), heart (medium), trachea (small), and collarbone (small) object segmentations, respectively. The attention UW-Net outperforms not only in comparison to U-Net and its variations but also with respect to other standard recent automatic and semi-automatic segmentation/annotation models. An ablation study was also performed to find the best suited high-performing architecture., Conclusion: The uniformity in prediction accuracy of segmentation masks for all kinds of segmentation masks (large, medium, and small lesions) makes this model best for automatic annotation of organs., Competing Interests: Declaration of competing interest Authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

An experiment was conducted to evaluate the effect of supplementation of zinc in the diet in the form of nano zinc oxide (nano ZnO) on the performance of broilers. A total of 240 day-old commercial broiler chicks were distributed in a completely randomized design into 6 treatments with 8 replicates of 5 chicks each. Treatments comprised of T 1 - basal diet (BD) without ZnO supplementation, T 2 - 2.5 ppm ZnO, T 3 - 5 ppm ZnO, T 4 - 10 ppm ZnO, T 5 - 20 ppm ZnO, and T 6 - 40 ppm inorganic ZnO. The results revealed that supplementation of nano ZnO at 2.5 ppm recorded significantly (P < 0.05) higher body weight gain, feed intake, and better feed conversion ratio (FCR) compared to control and other treatment groups at 42 days of age. All dietary treatments failed to exert any significant (P > 0.05) effect on various carcass parameters (dressing percentage, abdominal fat, giblet yields), serum protein and cholesterol concentrations, and meat quality parameters (water holding capacity and pH) of broiler chicken at 42 days of age. Finally, it could be concluded that supplementation of nano ZnO at 2.5 ppm improved the performance of broilers., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to elicit nAbs and cellular immunity, including CD8 + tissue-resident memory T cells. After ten vaginal challenges with autologous virus, protection was observed in both vaccine groups at 53.3% and 66.7%, respectively. A nAb titer >300 was generally associated with protection but in the heterologous viral vector + nAb group, titers <300 were sufficient. In this group, protection was durable as the animals resisted six more challenges 5 months later. Antigen stimulation of T cells in ex vivo vaginal tissue cultures triggered antiviral responses in myeloid and CD4 + T cells. We propose that cellular immune responses reduce the threshold of nAbs required to confer superior and durable protection.

Isothicyanates present in cruciferous vegetables are known to exhibit chemoprevention by various mechanisms. Presently, there is growing evidence that a phytochemical compound known as sulforaphane in these green leafy vegetables is found to be effective in preventing and treating various cancers such as prostate cancer, breast cancer, colon cancer, skin, urinary bladder and oral cancers. This component is naturally present in the broccoli sprouts, kale, cabbage, cauliflower and garden cress and is available as a commercial supplementary pill called Broccoli extract. Availability of many bioactive substances such as vitamins, polyphenols, sulfides, glucosinolates and antioxidants makes broccoli consumption important in daily diet regularly. Researchers have named it as "Green chemoprevention." It is easily affordable and more cost-effective than the traditional chemopreventive drugs. Results from the epidemiological and experimental studies have emphasized the role of sulforophane as a complementary or alternative chemopreventive agent., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Oral and Maxillofacial Pathology.)

Multiple cytokines play a pivotal role in the pathogenesis of Rheumatoid Arthritis by inducing intracellular signaling and it is known that the members of the Janus kinase (JAK) family are essential for such signal transduction. Janus kinase 3 is a tyrosine kinase that belongs to the Janus family of kinases. Drugs targeting JAK3 in the treatment of Rheumatoid arthritis is relevant. Therefore, it is of interest to design suitable inhibitors for JAK3 dimer using molecular docking with Molegro Virtual Docker. The compound possessing the highest affinity score is subjected to virtual screening to retrieve inhibitors. The compound SCHEMBL19100243 (PubChem CID- 76749591) displays a high affinity with the target protein. The affinity scores of this compound are more than known drugs. ADMET analysis and BOILED Egg plot provide insights into this compound as a potent inhibitor of JAK3.

Background: Orphan nuclear receptors ERRα, ERRβ and ERRγ that belong to NR3B or type IV nuclear receptor family are well studied for their role in breast cancer pathophysiology. Their homology with the canonical estrogen receptor dictates their possible contributing role in mammary gland development and disease. Although function and regulation of ERRα, ERRγ and less about ERRβ is reported, role of histone methylation in their altered expression in cancer cells is not studied. Transcriptional activity of nuclear receptors depends on co-regulatory proteins. The present study for the first time gives an insight into regulation of estrogen-related receptors by histone methylation specifically through methyltransferase EZH2 in breast cancer., Methods: Expression of ERRα, ERRβ, ERRγ and EZH2 was assessed by immunohistochemistry in four identical tissue array slides that were prepared as per the protocol. The array slides were stained with ERRα, ERRβ, ERRγ and EZH2 simultaneously. Array data was correlated with expression in MERAV expression dataset. Pearson correlation coeficient r was calculated from the partial matrix expression values available at MERAV database to study the strength of association between EZH2 and three orphan nuclear receptors under study. By western blot and real time PCR, their correlated expression was studied in breast cancer cell lines MCF-7, MDA-MB-231, T47D and MDA-MB-453 including normal breast epithelial MCF-10A cells at both protein and RNA level. Regulation of ERRα, ERRβ, ERRγ by EZH2 was further investigated upon overexpression and silencing of EZH2. The interaction between ERRs and EZH2 was validated in vivo by CHIP-qPCR., Results: We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, a global repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERRα and ERRβ was observed in-vivo., Conclusion: Our findings identify EZH2 as a relevant coregulator for estrogen-related receptors in breast carcinoma.

Aim: The study was aimed at evaluating the efficacy of cryosurgery in the management of oral mucosal lesions. Time taken for healing, postoperative pain, secondary infection, and recurrence of lesion was evaluated., Materials and Methods: A total of 30 patients with oral mucosal lesions were included in the study. The patients were evaluated for pain and postoperative infection which was documented on the 1 st , 3 rd , 7 th , 21 st day after the procedure. Other parameters such as healing time and scarring were assessed at 21 st day. Recurrence of the lesion was evaluated in the 3 rd and 6 th postoperative month. All these data were statistically evaluated., Results: The pain and swelling which reduced mainly during the 7 th postoperative day which was highly significant. The discomfort of the patient was relatively less. Only three patients showed delayed healing out of all patients. Recurrence of lesion was noted in two cases which conclude to about 6.7%., Conclusion: The cryosurgery is overall a better modality for treatment of oral lesions as it is more reasonable with adequate success. The procedure is relatively more acceptable and has shown to have a faster recovery., Competing Interests: There are no conflicts of interest.

Introduction: This paper reports preliminary data of an ongoing study that evaluates the association of systemic inflammatory response (SIRS) with early severe acute pancreatitis (ESAP) and compensatory anti-inflammatory response syndrome (characterized by HLA-DR down-regulation) with infected pancreatic necrosis (IPN)., Methods: Consecutive patients presenting within 72 h of symptom onset with organ dysfunction and/or local complications were included. Following parameters were recorded: demographics, etiology, SIRS, APACHE II, creatinine, BUN. Circulating IL-8, IL-6, IL-10, TNF-alpha concentrations and expression of HLA-DR and IL-10 by qRT-PCR in PBMCs were measured. Strength of associations of cytokine concentration and HLA-DR/IL-10 expression with outcomes was expressed as Hedges' G and relative risk (95% CI)., Results: Twenty-eight patients (10 MSAP; 18 SAP) fulfilled inclusion criteria. Twelve patients had ESAP and eight presented with organ failure. Admission SIRS worsened in eight (28.6%) patients over 48 h. Sixteen (57.1%) patients developed primary IPN. Twenty-one (75%) patients had HLA-DR down-regulation during the first week, which persisted to the second week in 12 (42.9%) patients. IL-8, IL-6, and TNF-α progressively increased from healthy controls to MAP to MSAP to SAP. IL-6 and TNF-α was higher in the patients who developed ESAP (p = 0.01 and 0.05, respectively). Patients who died within the first week also had a significantly elevated concentration of IL-6 and TNF-α (p = 0.02 and 0.01, respectively). The relative risk (95% CI) of developing primary IPN with persistent HLA-DR down-regulation till the second week of illness was 11.3 (1.6-82.4; p = 0.01)., Conclusions: Our study objectively demonstrates significant association of ESAP and early mortality with primary cytokine response, and development of IPN with persistent HLA-DR down-regulation.

Background and Aims: Accurate prediction of the Cormack-Lehane (CL) grade preoperatively can help in better airway management of the patient during induction of anaesthesia. Our aim was to determine the utility of ultrasonography in predicting CL grade., Methods: We studied 100 patients undergoing general endotracheal anaesthesia. Mallampati (MP) class, thyromental distance (TMD) and sternomental distance (SMD) were noted. Ultrasound measurements of the anterior neck soft tissue thickness at the level of the hyoid (ANS-Hyoid), anterior neck soft tissue thickness at the level of the vocal cords (ANS-VC) and ratio of the depth of the pre-epiglottic space (Pre-E) to the distance from the epiglottis to the mid-point of the distance between the vocal cords (E-VC) were obtained. CL grade was noted during intubation. Chi-square test was employed to determine if there was any statistical difference in the measurements of patients with different CL grades. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for the various parameters., Results: The incidence of difficult intubation was 14%. An ANS-VC >0.23 cm had a sensitivity of 85.7% in predicting a CL Grade of 3 or 4, which was higher than that of MP class, TMD and SMD. However, the specificity, PPV and accuracy were lower than the physical parameters. The NPV was comparable., Conclusion: Ultrasound is a useful tool in airway assessment. ANS-VC >0.23 cm is a potential predictor of difficult intubation. ANS-Hyoid is not indicative of difficult intubation. The ratio Pre-E/E-VC has a low to moderate predictive value., Competing Interests: There are no conflicts of interest.

We tested, in rhesus macaques, the effects of a 500-fold range of an admixed recombinant modified vaccinia Ankara (MVA) expressing rhesus GM-CSF (MVA/GM-CSF) on the immunogenicity and protection elicited by an MVA/SIV macaque 239 vaccine. High doses of MVA/GM-CSF did not affect the levels of systemic envelope (Env)-specific Ab, but it did decrease the expression of the gut-homing receptor α4β7 on plasmacytoid dendritic cells (p < 0.01) and the magnitudes of Env-specific IgA (p = 0.01) and IgG (p < 0.05) in rectal secretions. The protective effect of the vaccine was evaluated using 12 weekly rectal challenges in rhesus macaques subgrouped by tripartite motif-containing protein 5α (TRIM5α) genotypes that are restrictive or permissive for infection by the challenge virus SIVsmE660. Eight of nine TRIM5α-restrictive animals receiving no or the lowest dose (1 × 10 5 PFU) of MVA/GM-CSF resisted all 12 challenges. In the comparable TRIM5α-permissive group, only 1 of 12 animals resisted all 12 challenges. In the TRIM5α-restrictive animals, but not in the TRIM5α-permissive animals, the number of challenges to infection directly correlated with the magnitudes of Env-specific rectal IgG (r = +0.6) and IgA (r = +0.6), the avidity of Env-specific serum IgG (r = +0.5), and Ab dependent cell-mediated virus inhibition (r = +0.6). Titers of neutralizing Ab did not correlate with protection. We conclude that 1) protection elicited by MVA/SIVmac239 is strongly dependent on the presence of TRIM5α restriction, 2) nonneutralizing Ab responses contribute to protection against SIVsmE660 in TRIM5α-restrictive animals, and 3) high doses of codelivered MVA/GM-CSF inhibit mucosal Ab responses and the protection elicited by MVA expressing noninfectious SIV macaque 239 virus-like particles., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Unlabelled: The encouraging results of the RV144 vaccine trial have spurred interest in poxvirus prime-protein boost human immunodeficiency virus (HIV) vaccine modalities as a strategy to induce protective immunity. Because vaccine-induced protective immunity is critically determined by HIV envelope (Env) conformation, significant efforts are directed toward generating soluble trimeric Env immunogens that assume native structures. Using the simian immunodeficiency virus (SIV)-macaque model, we tested the immunogenicity and efficacy of sequential immunizations with DNA (D), modified vaccinia virus Ankara (MVA) (M), and protein immunogens, all expressing virus-like particles (VLPs) displaying membrane-anchored trimeric Env. A single VLP protein boost displaying trimeric gp160 adjuvanted with nanoparticle-encapsulated Toll-like receptor 4/7/8 (TLR4/7/8) agonists, administered 44 weeks after the second MVA immunization, induced up to a 3-fold increase in Env-specific IgG binding titers in serum and mucosa. Importantly, the VLP protein boost increased binding antibody against scaffolded V1V2, antibody-dependent phagocytic activity against VLP-coated beads, and antibody breadth and neutralizing antibody titers against homologous and heterologous tier 1 SIVs. Following 5 weekly intrarectal SIVmac251 challenges, two of seven DNA/MVA and VLP (DM+VLP)-vaccinated animals were completely protected compared to productive infection in all seven DM-vaccinated animals. Vaccinated animals demonstrated stronger acute viral pulldown than controls, but a trend for higher acute viremia was observed in the DM+VLP group, likely due to a slower recall of Gag-specific CD8 T cells. Our findings support immunization with VLPs containing trimeric Env as a strategy to augment protective antibody but underscore the need for optimal engagement of CD8 T cells to achieve robust early viral control., Importance: The development of an effective HIV vaccine remains a global necessity for preventing HIV infection and reducing the burden of AIDS. While this goal represents a formidable challenge, the modest efficacy of the RV144 trial indicates that multicomponent vaccination regimens that elicit both cellular and humoral immune responses can prevent HIV infection in humans. However, whether protein immunizations synergize with DNA prime-viral vector boosts to enhance cellular and humoral immune responses remains poorly understood. We addressed this question in a nonhuman primate model, and our findings show benefit for sequential protein immunization combined with a potent adjuvant in boosting antibody titers induced by a preceding DNA/MVA immunization. This promising strategy can be further developed to enhance neutralizing antibody responses and boost CD8 T cells to provide robust protection and viral control., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

A simple, selective, sensitive and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been developed and validated for the simultaneous quantification of simvastatin (SS), simvastatin acid (SSA, active metabolite of SS) and ezetimibe (EZM) in K2 EDTA containing human plasma, using simvastatin D6, simvastatin acid D3 and ezetimibe D4 as internal standards (ISTDs), respectively. A volume of plasma sample of only 400 µL was processed by the solid phase extraction technique; then 20 µL of processed sample was run on a Phenomenex, Kinetix XB C18, 150 × 4.6 mm, 5 µm column using an isocratic mobile phase consisting of 10 mM ammonium formate buffer (pH 4.0 ± 0.3): acetonitrile (27 : 73, v/v) with a run time of 6.3 min. The precursor and product ions of SSA, EZM and their ISTDs were monitored on a triple quadrupole instrument operated in the negative ionization mode, and SS was monitored in the positive mode. The method was validated over a concentration range of 0.2-80 ng/mL for SS, 0.1-60 ng/mL for SSA and 0.05-15 ng/mL for EZM. The method has been successfully applied in clinical pharmacokinetic study in the Indian population. The Cmax, AUC0-inf and Tmax values obtained in our study were 10.61 ± 5.287, 77.58 ± 29.367 and 1.62 ± 0.436 for EZM; 69.74 ± 45.274, 190.71 ± 107.271 and 1.74 ± 0.480 for SS; and 25.36 ± 23.576, 139.24 ± 131.653 and 3.95 ± 0.671 for SSA, respectively., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: Present experiment was conducted to investigate the effect of selenium (Se) supplementation on performance, carcass characteristics, meat composition, shelflife of meat and biochemical profile in Nellore ram lambs., Materials and Methods: 24 male Nellore ram lambs (15.75±0.47 kg) were randomly divided into four dietary groups with six lambs in each and reared under uniform management conditions for 120 days. Basal diet was not supplemented with Se and consisted of green fodder (Se 0.09 mg/kg dry matter [DM]), dry roughage (Se 0.11 mg/kg DM) and concentrate mixture (Se 0.019 mg/kg DM) and fed individually. Dietary treatments were prepared by adding graded levels Se (0, 0.45, 0.9, and 1.8 ppm) to concentrate mixture (1% body weight [BW]) from sodium selenite. Feed offered and refusal measured daily; and BWs were measured at fortnight interval to find out average daily gain (g), feed conversion ratio (FCR), cost economics and plane of nutrition. Serum biochemical profile (concentration of glucose, total protein, albumin, globulin, cholesterol, and hemoglobin) was assessed on 0, 60(th), and 120(th) day. At the end of experiment, the carcass characteristics (dressing percentage, cut-up parts, meat to bone ratio) and meat chemical composition were evaluated. Meat keeping (thiobarbituric acid reactive substances) quality from different groups was evaluated on day 0, 3, and 6 post-slaughter., Results: Dietary Se supplementation did not show any effect on weight gain, FCR, cost economics, plane of nutrition, and serum biochemical profile in Nellore ram lambs. However, Se supplemented lambs had numerically higher weight gain than the unsupplemented lambs. Similarly, carcass characteristics and keeping quality were comparable among the four treatments. However, numerical increase in post-slaughter keeping quality with increasing Se supplementation was observed., Conclusion: It can be concluded that supplementation of Se in the form of sodium selenite (inorganic source) at different levels did not influence animal performance in growing Nellore ram lambs had no effect on lamb performance, cost economics, carcass characteristics, and serum biochemical profile.

Ocular infection with herpes simplex virus 1 can result in a chronic immunoinflammatory stromal keratitis (SK) lesion that is a significant cause of human blindness. A key to controlling SK lesion severity is to identify cellular and molecular events responsible for tissue damage and to manipulate them therapeutically. Potential targets for therapy are miRNAs, but these are minimally explored especially in responses to infection. Here, we demonstrated that Mir155 expression was up-regulated after ocular herpes simplex virus 1 infection, with the increased Mir155 expression occurring mainly in macrophages and CD4(+) T cells and to a lesser extent in neutrophils. In vivo studies indicated that Mir155 knockout mice were more resistant to herpes SK with marked suppression of T helper cells type 1 and 17 responses both in the ocular lesions and the lymphoid organs. The reduced SK lesion severity was reflected by increased phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 and interferon-γ receptor α-chain levels in activated CD4(+) T cells in the lymph nodes. Finally, in vivo silencing of miR-155 by the provision of antagomir-155 nanoparticles to herpes simplex virus 1-infected mice led to diminished SK lesions and corneal vascularization. In conclusion, our results indicate that miR-155 contributes to the pathogenesis of SK and represents a promising target to control SK severity., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Long-term treatment with the fungal metabolite drug FTY720 (Fingolimod) was shown to be highly effective in controlling viral immunopathological lesions. However, in this report we show that the anti-inflammatory effect of FTY720 in herpes simplex virus-1 (HSV-1) induced ocular inflammation is lost upon the discontinuation of treatment and lesions rapidly recurred. The lesions that developed after FTY720 treatment withdrawal involved mainly Th17 cells rather than Th1 cells explained in part by differential expression of surface CD103, an integrin that permits migration of effector cells to inflammatory sites. The expression of IL-6, a proinflammatory cytokine involved in the generation of Th17 cells, was found to be increased in FTY treated mice as compared to controls and this effect could be abrogated upon administration of neutralizing antibody to IL-6. Furthermore, IL-17RKO mice failed to show the recurrence of stromal keratitis (SK) lesions upon FTY720 withdrawal. These results indicate that approaches such as neutralization of proinflammatory cytokines might be considered along with FTY720 treatment if interruption of drug therapy becomes necessary.

HSV infection of adult humans occasionally results in life-threatening herpes simplex encephalitis (HSE) for reasons that remain to be defined. An animal system that could prove useful to model HSE could be microRNA-155 knockout (miR-155KO) mice. Thus, we observe that mice with a deficiency of miR-155 are highly susceptible to HSE with a majority of animals (75-80%) experiencing development of HSE after ocular infection with HSV-1. The lesions appeared to primarily represent the destructive consequences of viral replication, and animals could be protected from HSE by acyclovir treatment provided 4 d after ocular infection. The miR-155KO animals were also more susceptible to development of zosteriform lesions, a reflection of viral replication and dissemination within the nervous system. One explanation for the heightened susceptibility to HSE and zosteriform lesions could be because miR-155KO animals develop diminished CD8 T cell responses when the numbers, functionality, and homing capacity of effector CD8 T cell responses were compared. Indeed, adoptive transfer of HSV-immune CD8 T cells to infected miR-155KO mice at 24 h postinfection provided protection from HSE. Deficiencies in CD8 T cell numbers and function also explained the observation that miR-155KO animals were less able than control animals to maintain HSV latency. To our knowledge, our observations may be the first to link miR-155 expression with increased susceptibility of the nervous system to virus infection.

Purpose: Neuroprotectin D1 (NPD1) is an anti-inflammatory and proresolving lipid mediator biosynthesized from the omega-3-polyunsaturated fatty acid docosahexaenoic acid (DHA). The purpose of this study is to test the therapeutic potential of NPD1 for the treatment of herpes simplex virus (HSV)-induced stromal keratitis (SK) using a mouse model., Methods: C57BL/6 mice were infected ocularly with HSV-1 strain RE. Infected animals were treated topically with methyl ester prodrug NPD1 (300 ng/eye, 5-μL drop). Development of SK lesions, infiltration of inflammatory cells into the cornea, and production of proinflammatory cytokines, chemokines, and angiogenic factors were compared to untreated animals using slit-lamp biomicroscopy, flow cytometry, ELISA, and quantitative PCR (qPCR)., Results: Topical administration of NPD1 resulted in a significant reduction in the severity and incidence of SK, as well as the extent of corneal neovascularization in the NPD1-treated animals compared to their untreated counterparts. Infiltration of fewer neutrophils and pathogenic CD4⁺ T cells into the cornea, along with a lower number of cells that could be induced ex vivo to produce IFN-γ and IL-17, occurred with NPD1 treatment. Additionally, treatment with NPD1 diminished the production of proinflammatory cytokines, chemokines, and angiogenic factors, such as IL-6, CXCL1, CXCL-10, CCL-20, VEGF-A, MMP-2, and MMP-9 in the corneas of infected animals. Importantly, treatment with NPD1 increased the production of the anti-inflammatory cytokine, IL-10., Conclusions: Our novel findings demonstrate that NPD1 treatment could represent a valuable therapeutic approach to control SK lesions.

This study aims to evaluate incidence, patterns and epidemiology of mandibular condylar fractures (MCF) to propose a treatment strategy for managing MCF and analyze the factors which influence the outcome. One hundred and seventy-five MCF's were evaluated over a four year period and their pattern was recorded in terms of displacement, level of fracture, age of incidence and dental occlusion. Of the 2,718 facial bone fractures, MCF incidence was the third most common at 18.39 %. Of 175 MCF 58.8 % were unilateral and 41.12 % were bilateral. 67 % of bilateral fractures and 43.8 % of unilateral fractures were associated with midline symphysis and contralateral parasymphysis fractures respectively. Most of the MCF was seen in the age group of above 16 years and 50 % of them were at subcondylar level (below the neck of the condyle). Majority of MCF sustained due to inter personal violence were undisplaced (72.7 %) and contrary to this majority of MCF sustained during road traffic accident were displaced. 62.9 % of total fractures required open reduction and rigid fixation and 37.1 % were managed with closed reduction. 80 % of MCF managed with closed reduction were in the age group of below 16 years. From this study it can be concluded that the treatment algorithm proposed for managing MCF is reliable and easy to adopt. We observed that absolute indication for open reduction of MCF is inability to achieve satisfactory occlusion by closed method and absolute contraindication for open reduction is condylar head fracture irrespective of the age of the patient.

The paper describes a new technique for closure of the oro-antral communication, in which both hard (bone) and soft tissue closure was achieved. The technique uses a Guided Tissue Regeeration (GTR) membrane and Freez Dried Mineralized Bone (FDMB) allograft for closure of the defect. Aim of the study was to assess the advantages of the surgical management of oro-antral communications using resorbable GTR membrane and FDMB sandwich technique. A total 10 patients were selected in whom dental extractions were complicated by formation of oro-antral communication (OAC). The resorbable guided tissue regeneration membrane (PERIOCOL-GTR) and freeze dried mineralized bone allograft material was used. Some cancellous granules of freeze dried bone allograft was sandwiched between sheaths of appropriately trimmed collagen membrane which was previously sutured together on three sides using 3/0 resorbable polyglycolic acid suture (vicryl). The fourth side was then adequately closed using the same suture after the bone graft had been inserted, thus creating a closed sandwich. The prepared sandwich was then tucked into the OAC in such a way that it formed a convexity towards the sinus and a concavity towards the alveolar bone. The rough surface of the sandwich is faced to the alveolar bone and additional bone graft is filled into this concavity. Suturing done without tension. Post-operative orthopantomogram was taken to radiologically quantify the amount of bone grafting/augmentation and closure of oro-antral fistula. There was an average of 11.84 mm bone formation after 6 months, the average width preserved and obtained was 6.9 mm. By the end of 4 months there was evidence of bone formation in 7 subjects and in three subjects bony trabeculae formed was almost similar to the adjacent bone. By the end of 6 months follow-up of 7 subjects showed trabeculae indistinguishable from the adjacent bone. The study was done in 10 patients with a follow-up period of 6 months and found to be excellent in the formation of new bone. The technique is simple and excellent for closure of the oro-antral communications especially when subsequent placement of end osseous implant is considered without the need of donor site surgery for bone grafting.

Vertebrates are constantly exposed to pathogens, and the adaptive immunity has most likely evolved to control and clear such infectious agents. CD4(+) T cells are the major players in the adaptive immune response to pathogens. Following recognition of pathogen-derived antigens naïve CD4(+) T cells differentiate into effectors which then control pathogen replication either directly by killing pathogen-infected cells or by assisting with generation of cytotoxic T lymphocytes (CTLs) or pathogen-specific antibodies. Pathogen-specific effector CD4(+) T cells are highly heterogeneous in terms of cytokines they produce. Three major subtypes of effector CD4(+) T cells have been identified: T-helper 1 (Th1) cells producing IFN-γ and TNF-α, Th2 cells producing IL-4 and IL-10, and Th17 cells producing IL-17. How this heterogeneity is maintained and what regulates changes in effector T cell composition during chronic infections remains poorly understood. In this review we discuss recent advances in our understanding of CD4(+) T cell differentiation in response to microbial infections. We propose that a change in the phenotype of pathogen-specific effector CD4(+) T cells during chronic infections, for example, from Th1 to Th2 response as observed in Mycobactrium avium ssp. paratuberculosis (MAP) infection of ruminants, can be achieved by conversion of T cells from one effector subset to another (cellular plasticity) or due to differences in kinetics (differentiation, proliferation, death) of different effector T cell subsets (population plasticity). We also shortly review mathematical models aimed at describing CD4(+) T cell differentiation and outline areas for future experimental and theoretical research.

A selective and high throughput liquid chromatography-mass spectrometry method has been developed and validated for the simultaneous quantification of tenofovir (TFV), lamivudine (3TC) and nevirapine (NVP) in human plasma using emtricitabine (FTC) as internal standard (ISTD). Following solid phase extraction (SPE), the analytes and ISTD were run on Prontosil C18AQ column (100mm×4.6mm, 3μm) using an isocratic mobile phase consisting of 1mM ammonium acetate in water (pH 6.5±0.3):acetonitrile (50:50, v/v). The precursor and product ions of the drugs were monitored on a triple quadrupole instrument operated in the negative ionization mode. The method was validated over a concentration range of 2-500ng/mL for TFV and over a concentration range of 10-4000ng/mL for 3TC and NVP with relative recoveries ranging from 61 to 85%. The intra and inter batch precision (%CV) across four validation runs was less than 12.2%. The accuracy determined at four QC levels (LLOQ, LQC, MQC and HQC) was within ±8.5%, in terms of relative error., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background and Objectives: The purpose of this prospective study was to evaluate the incidence and various risk factors influencing the sensory deficit in case of lingual nerve injury (LNI) in individuals whose impacted mandibular third molars are surgically removed under local anesthesia., Materials and Methods: The study was based on the data collected prospectively from a random group of 100 patients who underwent surgical removal of bony impacted lower third molar in a dental hospital. Details of the patient, reason for extraction, type of impaction, method of surgery and signs and symptoms of nerve injury are recorded. Neurosensory testing was done to evaluate the LNI at 1 week, 1 months, 3 months and 6 months interval. Comparison was carried out using Chi square test. For all tests a P < 0.05 was considered significant., Results: The incidence of LNI was 4 % and of temporary in nature which recovered well within 6 months postoperatively. The age of the patient above 26 years, lingual flap retraction, depth of impaction (red line ≥10 mm) and duration of surgery above 30 min were the significant factors for causing LNI., Conclusions: The age of the patient, depth of impaction, lingual flap retraction and longer duration of surgery are significant risk factors for LNI during mandibular third molar surgery. Greater care should be taken to avoid the morbidity and patients should be informed well ahead about the probable complications.

Background: High mobility group box1 (HMGB1) and poly(ADP-ribose) polymerase1 (PARP1) proteins repair cellular DNA damage. Reduced expression of the corresponding genes can lead to an impaired DNA damage repair mechanism. Intracellular replication of hepatitis B virus (HBV) in such conditions can favor the integration of viral DNA into host genome leading to the development of hepatocellular carcinoma (HCC)., Objective: This study was performed to assess the expression of HMGB1 and PARP1 mRNAs in conjunction with the estimation of HBV replication intermediate pregenomic RNA (PgRNA) in various phases of HBV infection., Materials: Eighty eight patients and 26 voluntary blood donors as controls were included in the study. Patients were grouped in to acute (AHB; n = 15), inactive carriers (IC; n = 36), cirrhosis (Cirr; n = 25) and hepatocellular carcinoma (HCC; n = 12). Serum HBV DNA was quantified by real time polymerase chain reaction (PCR) assay. Expression of HMGB1, PARP1 and PgRNA were evaluated using peripheral blood mononuclear cells (PBMCs) derived RNA by reverse transcription PCR (RT-PCR) and densitometry., Results: Significant reduction of HMGB1 and PARP1 gene expressions (P < 0.05) were observed in patients than controls with more explicit decline of PARP1 (P = 0.0002). Both genes were significantly downregulated (P < 0.001) in ICs than controls. In ICs, HMGB1 was significantly lowered than cirrhosis (P = 0.002) and HCC (P = 0.0006) while PARP1 declined significantly (P = 0.04) than HCC. Level of PgRNA was comparable in all the disease categories., Conclusion: In conclusion, our findings indicate impaired DNA damage repair mechanisms in HBV infected cells of ICs. This, along with low viral load but higher level of PgRNA in this group is suggestive of the diversion of HBV replication pathway that might facilitate viral DNA integration in to host genome. Intrusion of HBV PgRNA reverse transcription in early stage of infection might appear advantageous to thwart the development of HCC.

A growth and digestibility study was conducted using Osmanabadi goat male kids by feeding complete diets in the form of mash or expander extruded pellets containing different levels of red gram (Cajanus cajan) straw (RGS). Two iso-nitrogenous complete diets were prepared by incorporating RGS at 35% and 50% levels. Half the quantity of each complete mash feed was then converted into pellets through expander extruder processing. Thirty two kids of 4 to 5 months age were divided into four groups of eight each and were fed for 150 d with four experimental diets (T1: mash with 35% RGS, T2: mash with 50% RGS, T3: pellets with 35% RGS and T4: pellets with 50% RGS). Pelleting of complete diets significantly (p<0.001) increased the voluntary feed intake (671.45 vs 426.28 g/d) at both levels of RGS in the feeds. Average daily gain (ADG, g/d) also increased significantly (p<0.001) from 48.79 in kids fed mash diet to 71.29 in those fed with pelleted diets. Feed conversion efficiency (dry matter (DM) intake: weight gain) was comparable among all the treatment groups. Digestibility of nutrients was not affected by pelleting of the feeds whereas, increasing the level of inclusion of RGS in feeds from 35% to 50% decreased (p<0.05) the digestibility of DM and crude protein (CP) resulting in lower (p<0.001) metabolizable energy (ME) content (MJ/kg DM) in feeds with 50% RGS (7.93 vs 8.75). Daily intake (MJ/kg BW(-0.75)) of ME decreased (p<0.05) in feeds containing 50% RGS while pelleting of feeds increased (p<0.05) the intake of DM, CP, digestible crude protein (DCP) and ME. It is inferred that expander extruder pelleting can efficiently utilize RGS up to 50% level in complete diets for growing goat kids.

Ocular infection with herpes simplex virus 1 (HSV-1) results in a chronic immunoinflamammtory reaction in the cornea, which is primarily orchestrated by CD4(+) T cells. Hence, targeting proinflammatory CD4(+) T cells or increasing the representation of cells that regulate their function is a relevant therapeutic strategy. In this report, we demonstrate that effective therapeutic control can be achieved using a combination of approaches under circumstances where monotherapy is ineffective. We use a convenient and highly effective monoclonal antibody (MAb) approach with MAbT25 to expand cells that express the tumor necrosis factor receptor superfamily member 25 (TNFRSF25). In naïve animals, these are predominantly cells that are Foxp3-positive regulatory T cells. MAbT25 treatment before or at the time of initial HSV infection was an effective means of reducing the severity of subsequent stromal keratitis lesions. However, MAbT25 treatment was not effective if given 6 days after infection since it expanded proinflammatory effector T cells, which also express TNFRSF25. Therefore, the MAbT25 procedure was combined with galectin-9 (Gal-9), an approach that compromises the activity of T cells involved in tissue damage. The combination therapy provided highly effective lesion control over that achieved by treatment with one of them. The beneficial outcome of the combination therapy was attributed to the expansion of the regulatory T cell population that additionally expressed activation markers such as CD103 needed to access inflammatory sites. Additionally, there was a marked reduction of CD4(+) gamma interferon-producing effector T cells responsible for orchestrating the tissue damage. The approach that we describe has potential application to control a wide range of inflammatory diseases, in addition to stromal keratitis, an important cause of human blindness.

MicroRNAs (miRNAs) are small regulatory molecules that control diverse biological processes that include angiogenesis. Herpes simplex virus (HSV) causes a chronic immuno-inflammatory response in the eye that may result in corneal neovascularization during blinding immunopathological lesion stromal keratitis (SK). miR-132 is a highly conserved miRNA that is induced in endothelial cells in response to growth factors, such as vascular endothelial growth factor (VEGF). In this study, we show that miR-132 expression was up-regulated (10- to 20-fold) after ocular infection with HSV, an event that involved the production of both VEGF-A and IL-17. Consequently, blockade of VEGF-A activity using soluble VEGF receptor 1 resulted in significantly lower levels of corneal miR-132 after HSV infection. In addition, low levels of corneal miR-132 were detected in IL-17 receptor knockout mice after HSV infection. In vivo silencing of miR-132 by the provision of anti-miR-132 (antagomir-132) nanoparticles to HSV-infected mice led to reduced corneal neovascularization and diminished SK lesions. The anti-angiogenic effect of antagomir-132 was reflected by a reduction in angiogenic Ras activity in corneal CD31-enriched cells (presumably blood vessel endothelial cells) during SK. To our knowledge, this is one of the first reports of miRNA involvement in an infectious ocular disease. Manipulating miRNA expression holds promise as a therapeutic approach to control an ocular lesion that is an important cause of human blindness., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Dengue hemorrhagic fever and dengue shock syndrome are the severe manifestations of dengue infection. The quest for reliable dengue diagnostics and a dengue vaccine remained elusive for decades. Domain III of dengue virus envelope contains multiple conformation dependant neutralizing epitopes, thus making it an attractive diagnostic and vaccine candidate. In this report we show the expression of dengue virus type 3 envelope domain III protein (D3EDIII) and demonstrate its potential as a diagnostic and vaccine candidate. Accordingly, D3EDIII was expressed to high levels in Escherichia coli and purified by Ni-NTA affinity chromatography. The purified protein was used to develop an in-house plate ELISA and was further tested with a panel of 40 dengue infected serum samples previously characterized by commercially available serological tests. The in-house results were in excellent agreement with the commercial kits. D3EDIII was refolded by rapid dilution method and the refolded monomer protein was purified by Ion exchange chromatography. Further, the recombinant protein was biologically functional and found to inhibit dengue virus type 3 plaque formation on LLC-MK2 cells demonstrating its function of receptor interaction. Furthermore, D3EDIII in combination with Freund's complete adjuvant induced high antibody titers in BALB/c mice and these antibodies efficiently neutralized dengue 3 virus. Additionally, D3EDIII induced expression of Th1 cytokines that can inhibit the intracellular viral infections. Thus, our results demonstrate that D3EDIII protein has tremendous potential both in diagnosis of dengue infections and in vaccine development.

Stromal keratitis is a chronic immunopathological lesion of the eye caused by HSV-1 infection that can result in blindness. Because the inflammatory lesions are primarily orchestrated by Th1 cells, and to a lesser extent by Th17 cells, inhibiting their activity represents a useful form of therapy. In this study we evaluated the therapeutic potential of galectin-1 (gal-1), an endogenous lectin that in some autoimmune diseases was shown to suppress the functions of Th1 and Th17 cells. Treatment was begun at different times after ocular infection with HSV and the outcome was assessed clinically as well as for effects on various immune parameters. Treatment with recombinant gal-1 significantly diminished stromal keratitis lesion severity and the extent of corneal neovascularization. Treated mice had reduced numbers of IFN-γ- and IL-17-producing CD4(+) T cells, as well as neutrophil infiltration in the cornea. Furthermore, disease severity was greater in gal-1 knockout mice compared with their wild-type counterparts. The many effects of gal-1 treatment include reduction in the production of proinflammatory cytokines and chemokines, increased production of IL-10, and inhibitory effects on molecules involved in neovascularization. To our knowledge, our findings are the first to show that gal-1 treatment represents a useful approach to control lesion severity in a virally induced immunopathological disease.

Ocular infection with HSV causes corneal neovascularization (CV), an essential step in the pathogenesis of the blinding immunoinflammatory lesion stromal keratitis. The infection results in IL-17A production, which contributes to CV in ways that together serve to shift the balance between corneal concentrations of vascular endothelial growth factor A (VEGF-A) and the soluble vascular endothelial growth factor receptor 1 molecule, which binds to VEGF-A and blocks its function (a so-called VEGF trap). Accordingly, animals lacking responses to IL-17A signaling, either because of IL-17 receptor A knockout or wild-type animals that received neutralizing mAb to IL-17A, had diminished CV, compared with controls. The procedures reduced VEGF-A protein levels but had no effect on the levels of soluble vascular endothelial growth factor receptor 1. Hence the VEGF trap was strengthened. IL-17A also caused increased CXCL1/KC synthesis, which attracts neutrophils to the inflammatory site. Neutrophils further influenced the extent of CV by acting as an additional source of VEGF-A, as did metalloproteinase enzymes that degrade the soluble receptor, inhibiting its VEGF-blocking activity. Our results indicate that suppressing the expression of IL-17A, or increasing the activity of the VEGF trap, represents a useful approach to inhibiting CV and the control of an ocular lesion that is an important cause of human blindness.

Rheum emodi is a storehouse of a large number of anthraquinone derivatives which are known for a large number of biological activities of significant potency. In this work, a study on the interactions between anthraquinone derivatives based natural dye isolated from R. emodi and different proteins has been reported for the first time, revealing the use of dye as an extrinsic probe to determine the stability of these proteins alone and in the presence of additives. The stability parameters have been evaluated as a change in the fluorescence intensity of the dye as a function of temperature due to the differential interaction of the dye with various conformations of a protein. Also, the effect of the change in polarity of the solvent on the fluorescence emission spectra of dye was studied where high quantum yield was observed in alcohol as compared to water. The RP-HPLC characterization of the dye revealed the presence of anthraquinones glycosides as main compounds in it. Thus, natural dyes may be used as biosensors to follow the conformational changes in proteins., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The interferon regulatory factors (IRFs) are a family of transcription factors known to be involved in the modulation of cellular responses to interferons (IFNs) and viral infection. While IRF-1 acts as a positive regulator, IRF-2 is known to repress IFN-mediated gene expression. The increase in the IRF-1/IRF-2 ratio is considered as an important event in the transcriptional activation of IFN-α gene toward development of the cellular antiviral response., Objective: This study was performed to assess the expression of IRF mRNAs along with the expression level of IFN-α, its receptor (IFNAR-1), and the signal transduction factor (STAT-1) in treatment naive hepatitis C virus (HCV)-infected subjects., Materials: Thirty-five chronically infected (CHC) patients and 39 voluntary blood donors as controls were included in the study. Quantification of HCV-RNA (ribonucleic acid) and genotyping were done by real-time polymerase chain reaction (PCR) and hybridization assays, respectively, using patient's serum/plasma. In both controls and patients, the serum level of IFN-α and IFN-α was measured by flow cytometry. Target gene expressions were studied by retro-transcription of respective mRNAs extracted from peripheral blood mononuclear cells (PBMCs) followed by PCR amplification and densitometry. Minus-strand HCV-RNA as a marker of viral replication in PBMCs was detected by an inhouse PCR assay., Results: Both IRF-1 and IRF-2 genes were significantly enhanced in CHC than in control subjects (P < 0.001). A significant positive correlation (r (2) = 0.386, P <0.01) was obtained between higher IRF-2 gene expression and increasing level of HCV-RNA. Chronically infected subjects (13%) harboring replicating HCV in PBMCs showed no significant differences in gene expressions than the subjects without HCV in PBMCs., Conclusion: Our findings indicate that HCV modulates host immunity by inducing IRF-2 gene to counteract IRF-1-mediated IFN-α gene expression. Since the IRF-2 gene is known to encode oncogenic protein, the role of IRF-2 in CHC patients developing hepatocellular carcinoma warrants further studies.