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Entrepreneurship catalyzes economic growth; it generates jobs, advances the economy and solves global challenges. Hence, it is crucial to understand the factors contributing to entrepreneurship and entrepreneurs' development. While many studies have investigated intrapersonal factors for entrepreneurial tendencies, the present study focuses on a critical yet often overlooked interpersonal aspect: attachment orientations. Specifically, this article examines the relationship between adult attachment orientations and entrepreneurial tendencies. Three studies across three countries (Israel, the UK, and Singapore) indicated that an anxious attachment orientation in close relationships is negatively associated with enterprising tendencies. In Israel (Study 1) and Singapore (Study 2), avoidant attachment in close relationships was also negatively correlated to such tendencies. Overall, the more people feel secure in close relationships (lower scores on attachment anxiety or avoidance), the higher their enterprising tendencies. Limitations and future research suggestions are discussed.

Retinitis pigmentosa is a group of progressive inherited retinal dystrophies that may present clinically as part of a syndromic entity or as an isolated (nonsyndromic) manifestation. In an Indian family suffering from retinitis pigmentosa, we identified a missense variation in CNGA1 affecting the cyclic nucleotide binding domain (CNBD) and characterized a mouse model developed with mutated CNBD. A gene panel analysis comprising 105 known RP genes was used to analyze a family with autosomal-recessive retinitis pigmentosa (arRP) and revealed that CNGA1 was affected. From sperm samples of ENU mutagenesis derived F 1 mice, we re-derived a mutant with a Cnga1 mutation. Homozygous mutant mice, developing retinal degeneration, were examined for morphological and functional consequences of the mutation. In the family, we identified a rare CNGA1 variant (NM_001379270.1) c.1525 G > A; (p.Gly509Arg), which co-segregated among the affected family members. Homozygous Cnga1 mice harboring a (ENSMUST00000087213.12) c.1526 A > G (p.Tyr509Cys) mutation showed progressive degeneration in the retinal photoreceptors from 8 weeks on. This study supports a role for CNGA1 as a disease gene for arRP and provides new insights on the pathobiology of cGMP-binding domain mutations in CNGA1-RP., (© 2022. The Author(s).)

Introduction: The aim of this audit was to compare the data from the Wellington Blood and Cancer Centre (WBCC) with international reported experience by quantifying the dosimetric impact of interstitial needles on target coverage and organ at risk (OAR) doses., Methods: All patients identified as having had interstitial needles as part of their treatment out of a cohort of 120 radically treated cervical cancer patients between 2013 and 2019 were included. Each patient acted as their own control with two treatment plans optimised for each fraction; the clinically treated plan and a re-optimisation without the use of interstitial needles. Plan optimisation was completed according to the departmental protocol and cumulative equivalent doses for 2 Gy fractions (EQD2) were calculated., Results: Eighteen patients were suitable for evaluation. A total of 52 insertions with interstitial needles were performed, of the 148 needles inserted, 119 (80.4%) were loaded. HRCTV D90% coverage mean was EQD2 5.4 Gy (0.5-10.6 Gy) higher for the course containing loaded interstitial needles, while no significant change was observed with regards to OAR doses. This improved coverage is in line with international standards which report 4.4-9.0 Gy., Conclusion: WBCC's early experience of interstitial cervix brachytherapy has shown our target coverage improvements meet previously published international standards and confirms the value of this technique. This audit supports ongoing use of interstitial needles at the WBCC., (© 2021 The Royal Australian and New Zealand College of Radiologists.)

Background: Laparoscopic port entry is crucial and vital step in any laparoscopic surgery. As laparoscopy is widely used, complications related to it are also increasing which are not seen in conventional laparotomy., Aim: The present study was undertaken to compare the ease of primary trocar entry after pneumoperitoneum at 20 mmHg pressure and direct trocar entry without pneumoperitoneum., Methods: Total 100 nulliparous patients who presented for elective gynaecologic laparoscopic surgery were enrolled for the study. In operating theatre, randomization of patients was done using a sealed envelope technique which divides patients into two equal groups and assigned as either low-pressure group or high-pressure group. Verres needle insertion and trocar entry was done by fellowship trainee in laparoscopy assisted by senior laparoscopy surgeon., Result: In high-pressure group we had trocar entry in first attempt in 80% of patient, second attempt in 20% where as in direct trocar entry group required first attempt in 88%, second attempt in 10% and third attempt in 2%. Time taken for trocar entry between two groups was significantly different requiring 4.42 ± 0.55 min for high pressure and 1.2 ± 0.28 min for direct trocar entry., Conclusion: The study concluded that high-pressure trocar entry requires more time; require less attempts, easier and surgeon will be more comfortable in repeating the same technique than direct trocar entry., Competing Interests: Conflict of interestThe authors have no conflicts of interest., (© Federation of Obstetric & Gynecological Societies of India 2021.)

Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the transformation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticulate agent (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of anti-tumor cytokines (IL-12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). In the MGF-AuNPs treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about 50-fold, while IL-10 and IL-6 were reduced by two-fold. Ability of MGF-AuNPs to target splenic macrophages is invoked via targeting of NF-kB signaling pathway. Finally, therapeutic efficacy of MGF-AuNPs, in treating prostate cancer in vivo in tumor bearing mice, is described taking into consideration various immunomodulatory interventions triggered by this green nanotechnology-based nanomedicine agent., (© 2021. The Author(s).)

Safety of sanitation workers remains an often-ignored aspect in Fecal Sludge Management. While shifting workers from manual to mechanical means of de-sludging remains a priority, this paper highlights that there are a number of safety issues, including exposure to sludge, faced by sanitation workers, even in a mechanised context, where de-sludging trucks are utilised to provide de-sludging services. Based on a detailed analysis of observation of stakeholders and extensive process documentation (of de-sludging process), and expert interviews, the study identified three key safety concerns: inhalation of harmful gases, contact with sludge, and physical injury, and determined the underlying cause for the same, using a systems thinking approach. These causes are varied including behaviours and practices by households such as non-compliance of septic tank construction to design standards, irregular cleaning, improper disposal of inappropriate items in toilets; inappropriate or inadequate design of decanting stations, tools and equipment, and inadequate awareness and knowledge among all stakeholders. Using the hierarchy of controls framework, a set of measures are described to increase the safety of workers. These proposed interventions go beyond the provision of Personal Protective Equipment (PPE), and range from behaviour change campaigns, improvements in decanting stations, better access to appropriately designed tools. The study highlights the need to place emphasis on eliminating, substituting and controlling the hazards as necessary steps for PPE to be relevant. Finally, the paper places the issue of occupational safety within the larger context of the informal nature of de-sludging occupation and the overall vulnerability of workers. It posits that this makes safety more complicated to address as several factors need to be taken into account, and actions are required by multiple sets of actors., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: The study aimed to compare the efficacy of methylprednisolone and dexamethasone injected into masseter muscle preoperatively in surgical extraction of lower third molars., Materials and Methods: This study was carried out on 20 patients who reported to the department of Oral and Maxillofacial surgery, Sri Rajiv Gandhi College of Dental Sciences and Hospital Bangalore, requiring surgical removal of bilateral mandibular third molars. The efficacy of corticosteroid was evaluated based on its ability to reduce pain, swelling and trismus following the surgical extraction of impacted lower third molars., Results: There was no statistical difference between the two steroids with both of them achieving equal level of pain control. There was a statistically significant difference on the second postoperative day with dexamethasone showing clinically superior result. The difference in oral aperture was found to be statistically significant with dexamethasone showing a decreased reduction in postoperative mouth opening on both second and seventh day., Conclusion: This study conclusively proves that patient comfort levels are far better with the use of dexamethasone., Competing Interests: Conflict of interestNil., (© The Association of Oral and Maxillofacial Surgeons of India 2020.)

Fecal Sludge Treatment or Septage Management is increasingly being recognised as an effective and appropriate method to scale urban sanitation systems to achieve safe sanitation, particularly in small towns and cities. As implementation progresses, data-based evidence is emerging, highlighting the challenges faced on the ground, and the requisite planning necessary to address them. This paper presents the findings, challenges and possible ways ahead from a study conducted to provide data for Fecal Sludge Management (FSM) planning for a small town in a state in southern India. With the objective of understanding the nature of containment structures and on-ground desludging practices, 8,001 households and 1,667 establishments were studied in Periyanaicken-Palayam (PNP), a non-sewered Town Panchayat in Coimbatore District, Tamil Nadu, to provide evidence for effective decision-making. The study showed wide variations in the sizing and design of the containment systems, which, when combined with the irregular frequency of desludging, has implications for FSM planning by municipal bodies. This study also highlights the methodological difficulties in studying containment systems, exposes a significant response bias given the limited understanding of containment systems within households, and spotlights the difficulty in physically verifying the reported data given the underground nature of these systems., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, is a cell surface glycoprotein that belongs to the immunoglobulin superfamily and plays a significant role in intercellular recognition in immunology, cellular differentiation and development. Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. Since one of the routes of entry for the virus is the oral cavity, it becomes imperative to percept oral comorbidities such oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) in terms of EMMPRIN as a target for SARS-CoV-2. In the present paper, it is proposed that OSCC, by the virtue of upregulation of EMMPRIN expression, increases the susceptibility to coronavirus disease (COVID-19). In turn, COVID-19 in OSCC patients causes exhaustion of EMMPRIN receptor due to binding with 'S' receptor leading to a downregulation of related carcinogenesis events. We proposed that in the ACE-2 depleted situation in OSCC, EMMPRIN receptor might get high jacked by the COVID-19 virus for the entry into the host cells. Apart from the anti-monoclonal antibody, it is recommended to explore the use of grape seed and skin containing mouthwash as an adjunct, which could also have anti EMMPRIN effects in patients with OSCC and OPMDs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

There has been steady progress in developing reliable and cost-effective strategies for the clean production of zinc oxide (ZnO) nanoparticles (NPs) owing to their unique structural and wide functional characteristics. While the green synthesis of such NPs from plant extracts has emerged as a sustainable and eco-friendly protocol, it is greatly restricted owing to the scarcity of potential natural precursors necessitating comprehensive investigations in this direction. Herein, we report a facile, low-cost green synthesis and characterization of ZnO NPs along with the demonstration of their usage as an active media in organic field-effect transistor (OFET) devices for sensing carbon monoxide (CO) gas. The ZnO NPs obtained from Nelumbo nucifera (lotus) leaf extract-mediated solution combustion synthesis at a much lower initiation temperature, the first of its kind, were characterized by various techniques such as UV-vis spectroscopy, XRD, EDX analysis, TEM and FESEM. The data derived from these experiments clearly evidence the formation of very pure and crystalline ZnO NPs possessing nearly spherical-shape with a size of 3-4 nm. The p-type organic field-effect transistor (OFET) device, fabricated using poly(3-hexylthiophene-2,5-diyl) (P3HT) and ZnO NPs, showed a field-effect mobility of 10 -2 cm 2 V -1 sec -1 with a slightly enhanced response of detecting CO gas at room temperature (RT). The phenomenon was further confirmed by the variation in electrical parameters of the OFET such as field-effect mobility ( μ ), on-current ( I on ), and off-current ( I off ). The selectivity and sensitivity of the fabricated device in CO gas detection was found to be more prominent than the other reducing gases (hydrogen sulphide, H 2 S and ammonia, NH 3 ) and methanol vapours tested., Competing Interests: There is no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: This is an updated version of the Cochrane Review previously published in 2016. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. For nearly 30% of these people, their epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is one of the newer antiepileptic drugs. Lamotrigine, in combination with other antiepileptic drugs (add-on), can reduce seizures, but with some adverse effects., Objectives: To determine the effects of lamotrigine on (1) seizures, (2) adverse-effect profile, and (3) cognition and quality of life, compared to placebo, when used as an add-on treatment for people with drug-resistant focal epilepsy., Search Methods: For the latest update of the review, we searched the following databases on 9 March 2020: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to March 06, 2020). CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. No language restrictions were imposed., Selection Criteria: Randomised placebo-controlled trials of people with drug-resistant focal epilepsy of any age, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded, placebo-controlled. For cross-over studies, the first treatment period was treated as a parallel trial. Eligible participants were adults or children with drug-resistant focal epilepsy., Data Collection and Analysis: For this update, two review authors independently assessed the trials for inclusion, and extracted data. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition and quality of life. Primary analyses were by intention-to-treat. Sensitivity best- and worse-case analyses were undertaken to account for missing outcome data. Pooled risk ratios (RRs) with 95% confidence intervals (95% Cls) were estimated for the primary outcomes of seizure frequency and treatment withdrawal. For adverse effects, we calculated pooled RRs and 99% Cls., Main Results: We did not identify any new studies for this update, therefore, the results and conclusions are unchanged. In previous updates of this review, the authors found five parallel add-on studies, eight cross-over studies in adults or children with drug-resistant focal epilepsy, and one parallel add-on study with a responder-enriched design in infants. In total, these 14 studies included 1806 eligible participants (38 infants, 199 children, 1569 adults). Baseline phases ranged from four to 12 weeks; treatment phases from eight to 36 weeks. Overall, 11 studies (1243 participants) were rated as having low risk of bias, and three (697 participants) had unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in four studies (563 participants). The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate-certainty evidence) indicating that lamotrigine was significantly more effective than placebo in reducing seizure frequency. The overall RR for treatment withdrawal (for any reason) was 1.11 (95% CI 0.91 to 1.37; 14 trials; 1806 participants; moderate-certainty evidence). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, diplopia (double vision), and nausea. The RR of these adverse effects were as follows: ataxia 3.34 (99% Cl 2.01 to 5.55; 12 trials; 1525 participants; high-certainty evidence); dizziness 2.00 (99% Cl 1.52 to 2.64;13 trials; 1768 participants; moderate-certainty evidence); diplopia 3.79 (99% Cl 2.15 to 6.68; 3 trials, 944 participants; high-certainty evidence); nausea 1.81 (99% Cl 1.22 to 2.68; 12 studies,1486 participants; moderate-certainty evidence). The limited data available precluded any conclusions about effects on cognition and quality of life. No important heterogeneity between studies was found for any of the outcomes. Overall, we assessed the evidence as high to moderate certainty, due to incomplete data for some outcomes., Authors' Conclusions: Lamotrigine as an add-on treatment for drug-resistant focal seizures appears to be effective in reducing seizure frequency, and seems to be fairly well-tolerated. However, the trials were of relatively short duration and provided no evidence for the long term. Further trials are needed to assess the long-term effects of lamotrigine, and to compare lamotrigine with other add-on drugs., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Although hydroxyzine is widely used for symptom relief in pruritus, its clinical safety and efficacy data in the Indian setting are scarce. We conducted a study to assess the effectiveness and tolerability of hydroxyzine in the management of Indian patients with chronic pruritus in a real-world setting., Methods: This was a prospective, observational, patient-reported outcomes (PRO) study in patients with chronic pruritus due to dermatological causes treated with hydroxyzine as per the clinician's discretion for a period of up to 12 weeks. The primary outcome was improvement in quality of life from baseline, assessed using the 10-point Dermatology Quality of Life Index (DLQI) at week 12 of the study period. Secondary outcomes were improvement in the pruritus scores (5-D itch scale) at 12 weeks, improvements in the DLQI and 5-D itch scores at 2, 4 and 8 weeks and safety., Results: The study included 400 patients (179 males, 221 females) from 7 dermatology centres across India. Of the 400 patients recruited, 391 patients completed at least 2 weeks of treatment. There was significant (p < 0.0001) improvement from baseline in the DLQI scores and 5-D itch scores at 2, 4, 8 and 12 weeks; 189/391 (48.34%) patients had symptom relief leading to early termination. Overall, the treatment was well tolerated with a total of 11 mild-to-moderate adverse events reported during the study, which included dizziness, constipation, drowsiness, dry mouth and sedation. All events resolved without any intervention. There were no serious adverse events., Conclusion: This real-world, observational, PRO study demonstrates that hydroxyzine significantly improves symptoms of pruritus and quality of life in patients with chronic pruritus due to dermatological causes over 12 weeks. Despite the sedating potential of the drug, hydroxyzine is well tolerated in real-world settings., Trial Registration: CTRI/2017/06/008847., Funding: Dr. Reddy's Laboratories.

Using Zebrafish (Danio rerio) as a model organism, we evaluated the radioprotective and antioxidant effects of the Indian traditional medicine Shilajit exposed to X-Ray. The Zebrafish were divided into three experimental groups and control group, each group containing ten fish. The three experimental fish groups, group I, group II and group III were fed with 3, 5 and 7ppm shilajit encapsulated Chironomous larvae and group IV served as a control fed with non- encapsulated larvae. After 60 days of feeding trial, fish were irradiated with X-Ray at a single acute dose of 1Gy. 72h of post-irradiation, each experimental fish were observed for its morphological, behavioral, clinical symptoms, antioxidant levels and DNA damage were evaluated. Among the experimental groups 5ppm shilajit encapsulated Chironomous larvae fed fish group shows the most significant radioprotective effects compared with control and other experimental fish groups. The present study indicates that shilajit have significant radioprotective and antioxidant enhancing capability. The humus substance of shilajit may be the factor responsible to react with radiation-derived or radiation related reactive species on zebrafish., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.jaapos.2017.03.007. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: This is an updated version of the Cochrane review published in The Cochrane Library 2010, Issue 1.Epilepsy is a common neurological disorder, affecting almost 0.5% to 1% of the population. For nearly 30% of these people, their epilepsy is refractory to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. Lamotrigine in combination with other antiepileptic drugs (add-on) can reduce seizures, but with some adverse effects. The aim of this systematic review was to overview the current evidence for the efficacy and tolerability of lamotrigine when used as an adjunctive treatment for people with refractory partial epilepsy., Objectives: To determine the effects of lamotrigine on (1) seizures, (2) adverse effect profile, and (3) cognition and quality of life, compared to placebo controls, when used as an add-on treatment for people with refractory partial epilepsy., Search Methods: For the previous version of the review, the authors searched the Cochrane Epilepsy Group Specialized Register (January 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 1), MEDLINE (1950 to January 2010), and reference lists of articles.For this update, we searched the Cochrane Epilepsy Group Specialized Register (28 May 2015), CENTRAL (The Cochrane Library 2015, Issue 4), MEDLINE (Ovid, 1946 to May 2015), and reference lists of articles. We also contacted the manufacturers of lamotrigine (GlaxoSmithKline). No language restrictions were imposed., Selection Criteria: Randomised placebo-controlled trials of people with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. For cross-over studies, the first treatment period was treated as a parallel trial. Eligible participants were adults or children with drug-resistant partial epilepsy., Data Collection and Analysis: For this update, two review authors independently assessed the trials for inclusion, and extracted data. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition and quality of life. Primary analyses were by intention-to-treat. Sensitivity best and worse case analyses were undertaken to account for missing outcome data. Pooled Risk Ratios (RR) with 95% confidence intervals (95% Cl) were estimated for the primary outcomes of seizure frequency and treatment withdrawal. For adverse effects, pooled RRs and 99% Cls were calculated., Main Results: We did not identify any new studies for this update, therefore, the results are unchanged.For the previous version of the review, the authors found five parallel add-on studies and eight cross-over studies in adults or children with refractory focal epilepsy, and one parallel add-on study with a responder-enriched design in infants. In total, these 14 studies included 1958 participants (38 infants, 199 children, and 1721 adults). Baseline phases ranged from 4 to 12 weeks; treatment phases from 8 to 36 weeks. Overall, eleven studies (n = 1243 participants) were rated as having a low risk of bias, and three (n = 715 participants) had un unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in three studies (n = 504 participants). The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 RCTs) for twelve studies (n = 1322 participants, adults and children) indicating that lamotrigine was significantly more effective than placebo in reducing seizure frequency. The overall RR for treatment withdrawal (for any reason) was 1.11 (95% CI 0.90 to 1.36; 14 RCTs) for fourteen studies (n = 1958 participants). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, diplopia, and nausea. The RR of these adverse effects were as follows: ataxia 3.34 (99% Cl 2.01 to 5.55; 12 RCTs; n = 1524); dizziness 2.00 (99% Cl 1.51 to 2.64;13 RCTs; n = 1767); diplopia 3.79 (99% Cl 2.15 to 6.68; 3 RCTs; n = 943); nausea 1.81 (99% Cl 1.22 to 2.68; 12 RCTs; n = 1486). The limited data available precluded any conclusions about effects on cognition and quality of life. No important heterogeneity between studies was found for any of the outcomes. Overall, we assessed the evidence as high to moderate quality, due to incomplete data for some outcomes., Authors' Conclusions: Lamotrigine as an add-on treatment for partial seizures appears to be effective in reducing seizure frequency, and seems to be fairly well tolerated. However, the trials were of relatively short duration and provided no evidence for the long-term. Further trials are needed to assess the long-term effects of lamotrigine, and to compare it with other add-on drugs.Since we did not find any new studies, our conclusions remain unchanged.

This rare case report presents the 2 nostrils 4 hands expanded endoscopic excision of the suprasellar dermoid through planum sphenoidale approach. This minimally invasive technique through the natural passage offers panaromic view of vital structures, complete excision of the lesion with reconstruction of the skull base defect at the same procedure.

Background and Objective: Male infertility has been associated with aneuploidies and structural chromosomal abnormalities, Yq microdeletions and specific gene mutations and/or polymorphisms. Besides genetic factors, any block in sperm delivery, endocrine disorders, testicular tumours, infectious diseases, medications, lifestyle factors and environmental toxins can also play a causative role. This study aimed to determine the constitutional karyotype in infertile males having normal female partners in a south Indian population., Materials and Methods: A total of 180 men with a complaint of primary infertility ranging from 1 to 25 years were screened for chromosomal abnormalities through conventional analysis of GTG-banded metaphases from cultured lymphocytes., Results: Four individuals were diagnosed to have Klinefelter syndrome. Two cases exhibited reciprocal translocations and one showed a maternally inherited insertion. Polymorphisms were seen in sixty-seven patients (37.2%)., Conclusion: The occurrence of chromosomal abnormalities in 4.6% and variants involving the heterochromatic regions of Y, chromosome 9 and the acrocentric chromosomes in 38.2% of the infertile men with an abnormal seminogram strongly reiterates the inclusion of routine cytogenetic testing and counselling in the diagnostic work-up prior to the use of assisted reproduction technologies.

Aim: To study the role of Doppler imaging in prediction of high-risk pregnancies and their outcomes., Methods and Material: This prospective study in a setup of tertiary-level care center includes 500 high-risk pregnant women from rural and urban sectors and evaluates the predictive values of various Doppler indices., Results: Out of 500 patients, 110 patients had abnormal Doppler among them, 70 patients had abnormal uterine artery Doppler, and 50 patients had abnormal umbilical artery Doppler flow indices. In all, 10 patients had both umbilical artery and uterine artery abnormal Doppler indices. When uterine artery was abnormal (70 patients), 20 patients had preeclampsia, 10 patients had pregnancy-induced hypertension (PIH), and 25 patients had intrauterine growth restriction (IUGR). Systolic/diastolic (S/D) ratio and notch had sensitivity of 60% and positive predictive value of 33.3% and 37.5%, respectively. When umbilical artery was abnormal (50 patients), 10 had preeclampsia, 15 had PIH, and 15 had IUGR. S/D ratio had the highest positive predictive value of 40%; sensitivity is same for all. In uterine artery, combination of parameters had the best sensitivity of 80%, followed by notch and S/D ratio. In umbilical artery, combination of parameters, S/D ratio, and RI (resistance index) had sensitivity of 40%; specificity of all the indices was 91-96%. In all, 20 patients had bilateral notch, and among them 15 developed preeclampsia and 15 developed IUGR. When both uterine and umbilical artery Doppler were abnormal (10 patients), all patients had preeclampsia and IUGR., Conclusion: Therefore, Doppler study may be used for the prediction of preeclampsia and IUGR to reduce the maternal and perinatal morbidity and mortality.

Innate immune system forms the first line of defense against microbial infections, as it exerts an immediate response. Innate immunity works through Toll-like receptors (TLRs) which functions as primary sensors of pathogens. TLR activates multiple signaling cascades leading to the induction of genes responsible for the release of inflammatory cytokines and type I interferon. Thus, they induce antimicrobial responses and also have an instructive role in adaptive immunity. However, TLR-mediated inflammation is said to be responsible for many of the destructive host responses in inflammatory diseases like periodontitis. Hence, therapeutics targeting TLRs are being used to treat disease such as HIV, Hepatitis B, asthma etc. Recently, synthetic TLR agonists are tried as novel vaccine adjuvant in treating periodontal diseases. This paper reviews the scope of TLR-based therapeutics in treating periodontitis.

This first report describes the purification and identification of an orange-red pigment produced by Achromobacter denitrificans strain SP1 (isolated from sewage sludge heavily contaminated with plastics) during its growth in a simple basal salt medium supplemented with the hazardous di(2-ethylhexyl)phthalate (DEHP) blended in PVC blood bag (in situ) or free DEHP (ex situ) as carbon source. The cell-bound pigment was elucidated, characterized at molecular level, and described as an unusual 25C prodigiosin analog for the first time. At laboratory conditions (in flasks), the dry cell mass was 75.2mg/g blood bag, which upon extraction yielded 7.1mg prodigiosin; at this stage the pH of the medium was dropped from 7.2 to 3.5. Considering its pharmaceutical importance, taking 10 known prodigiosins as controls, this 25C prodigiosin was subjected to molecular docking studies, showed comparable and promising binding efficiencies with the crucial molecular human targets like cycloxygenase-2, ZAP-70 kinase and Jak-3 kinase., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

There are about 28,500 people who inject drugs (PWID) in Nepal and HIV prevalence among this group is high. Nepal introduced harm reduction services for PWID much earlier than other countries in South Asia. Methadone maintenance treatment (MMT) was first introduced in Nepal in 1994. This initial small scale MMT programme was closed in 2002 but reopened in 2007 as an emergency HIV prevention response. It has since been scaled up to include three MMT clinics and continuation of MMT is supported by the Ministry of Home Affairs (MOHA; the nodal ministry for drug supply reduction activities) and has been endorsed in the recent National Narcotics policy. Pressure from drug user groups has also helped its reintroduction. Interestingly, these developments have taken place during a period of political instability in Nepal, with the help of strong advocacy from multiple stakeholders. The MMT programme has also had to face resistance from those who were running drug treatment centres. Despite overcoming such troubles, the MMT programme faces a number of challenges. Coverage of MMT is low and high-risk injecting and sexual behaviour among PWID continues. The finance for MMT is largely from external donors and these donations have become scarce with the current global economic problems. With a multitude of developmental challenges for Nepal, the position of MMT in the national priority list is uncertain. Ownership of the programme by government, a cost-effective national MMT scale up plan and rigorous monitoring of its implementation is needed., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Knowledge of the structural basis of protein-protein interactions (PPI) is of fundamental importance for understanding the organization and functioning of biological networks and advancing the design of therapeutics which target PPI. Allosteric modulators play an important role in regulating such interactions by binding at site(s) orthogonal to the complex interface and altering the protein's propensity for complex formation. In this work, we apply an approach recently developed by us for analyzing protein surfaces based on steered molecular dynamics simulation (SMD) to the study of the dynamic properties of functionally distinct conformations of a model protein, calmodulin (CaM), whose ability to interact with target proteins is regulated by the presence of the allosteric modulator Ca(2+). Calmodulin is a regulatory protein that acts as an intracellular Ca(2+) sensor to control a wide variety of cellular processes. We demonstrate that SMD analysis is capable of pinpointing CaM surfaces implicated in the recognition of both the allosteric modulator Ca(2+) and target proteins. Our analysis of changes in the dynamic properties of the CaM backbone elicited by Ca(2+) binding yielded new insights into the molecular mechanism of allosteric regulation of CaM-target interactions.

Background: Patients with diabetes frequently use complimentary and alternative medications including Ayurvedic medications and hence it is important to determine their efficacy and safety., Objectives: To assess the effects of Ayurvedic treatments for diabetes mellitus., Search Methods: We searched The Cochrane Library (issue 10, 2011), MEDLINE (until 31 August 2011), EMBASE (until 31 August 2011), AMED (until 14 October 2011), the database of randomised trials from South Asia (until 14 October 2011), the database of the grey literature (OpenSigle, until 14 October 2011) and databases of ongoing trials (until 14 October 2011). In addition we performed hand searches of several journals and reference lists of potentially relevant trials., Selection Criteria: We included randomized trials of at least two months duration of Ayurvedic interventions for diabetes mellitus. Participants of both genders, all ages and any type of diabetes were included irrespective of duration of diabetes, antidiabetic treatment, comorbidity or diabetes related complications., Data Collection and Analysis: Two authors independently extracted data. Risk of bias of trials was evaluated as indicated in the Cochrane Handbook for Systematic Reviews of Intervention., Main Results: Results of only a limited number of studies could be combined, in view of different types of interventions and variable quality of data. We found six trials of proprietary herbal mixtures and one of whole system Ayurvedic treatment. These studies enrolled 354 participants ( 172 on treatment, 158 on controls, 24 allocation unknown). The treatment duration ranged from 3 to 6 months. All these studies included adults with type 2 diabetes mellitus.With regard to our primary outcomes, significant reductions in glycosylated haemoglobin A1c (HbA1c), fasting blood sugar (FBS) or both were observed with Diabecon, Inolter and Cogent DB compared to placebo or no additional treatment, while no significant hypoglycaemic response was found with Pancreas tonic and Hyponidd treatment. The study of whole system Ayurvedic treatment did not provide data on HbA1c and FBS values. One study of Pancreas tonic treatment did not detect a significant change in health-related quality of life. The main adverse effects reported were drug hypersensitivity (one study, one patient in the treatment arm); hypoglycaemic episodes (one study, one participant in the treatment arm; none had severe hypoglycaemia) and gastrointestinal side effects in one study (1 of 20 in the intervention group and 0 of 20 participants in the control group). None of the included studies reported any deaths, renal, hematological or liver toxicity.With regard to our secondary outcomes, post prandial blood sugar (PPBS) was lower among participants treated with Diabecon, was unchanged with Hyponidd and was higher in patients treated with Cogent DB. Treatment with Pancreas tonic and Hyponidd did not affect lipid profile significantly, while patients treated with Inolter had significantly higher HDL- and lower LDL-cholesterol as well as lower triglycerides. Cogent DB treated participants also had lower total cholesterol and triglycerides.Studies of treatment with Diabecon reported increased fasting insulin levels; one study of treatment with Diabecon reported higher stimulated insulin levels and fasting C-peptide levels in the treatment group. There was no significant difference in fasting and stimulated C-peptide and insulin levels with Hyponidd, Cogent DB and Pancreas tonic treatment. The study of Inolter did not assess these outcomes.No study reported on or was designed to investigate diabetic complications, death from any cause and economic data., Authors' Conclusions: Although there were significant glucose-lowering effects with the use of some herbal mixtures, due to methodological deficiencies and small sample sizes we are unable to draw any definite conclusions regarding their efficacy. Though no significant adverse events were reported, there is insufficient evidence at present to recommend the use of these interventions in routine clinical practice and further studies are needed.

The use of Next-Generation Sequencing of mitochondrial DNA is becoming widespread in biological and clinical research. This, in turn, creates a need for a convenient tool that detects and analyzes heteroplasmy. Here we present MitoBamAnnotator, a user friendly web-based tool that allows maximum flexibility and control in heteroplasmy research. MitoBamAnnotator provides the user with a comprehensively annotated overview of mitochondrial genetic variation, allowing for an in-depth analysis with no prior knowledge in programming., (Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.)

Genetic disorders of excessive salt loss from sweat glands have been observed in pseudohypoaldosteronism type I (PHA) and cystic fibrosis that result from mutations in genes encoding epithelial Na+ channel (ENaC) subunits and the transmembrane conductance regulator (CFTR), respectively. We identified a novel autosomal recessive form of isolated salt wasting in sweat, which leads to severe infantile hyponatremic dehydration. Three affected individuals from a small Bedouin clan presented with failure to thrive, hyponatremic dehydration and hyperkalemia with isolated sweat salt wasting. Using positional cloning, we identified the association of a Glu143Lys mutation in carbonic anhydrase 12 (CA12) with the disease. Carbonic anhydrase is a zinc metalloenzyme that catalyzes the reversible hydration of carbon dioxide to form a bicarbonate anion and a proton. Glu143 in CA12 is essential for zinc coordination in this metalloenzyme and lowering of the protein-metal affinity reduces its catalytic activity. This is the first presentation of an isolated loss of salt from sweat gland mimicking PHA, associated with a mutation in the CA12 gene not previously implicated in human disorders. Our data demonstrate the importance of bicarbonate anion and proton production on salt concentration in sweat and its significance for sodium homeostasis.

Plant response to various stress conditions often results in expression of common genes, known as stress-responsive/inducible genes. Accumulating data point to a common, yet elusive process underlying the response of plant cells to stress. Evidence derived from transcriptome profiling of shoot apical meristem stem cells, dedifferentiating protoplast cells as well as from senescing cells lends support to a model in which a common response of cells to certain biotic and abiotic stresses converges on cellular dedifferentiation whereby cells first acquire a stem cell-like state before assuming a new fate.

Consanguineous families affected with a recessive genetic disease caused by homozygotisation of a mutation offer a unique advantage for positional cloning of rare diseases. Homozygosity mapping of patient genotypes is a powerful technique for the identification of the genomic locus harbouring the causing mutation. This strategy relies on the observation that in these patients a large region spanning the disease locus is also homozygous with high probability. The high marker density in single nucleotide polymorphism (SNP) arrays is extremely advantageous for homozygosity mapping. We present KinSNP, a user-friendly software tool for homozygosity mapping using SNP arrays. The software searches for stretches of SNPs which are homozygous to the same allele in all ascertained sick individuals. User-specified parameters control the number of allowed genotyping 'errors' within homozygous blocks. Candidate disease regions are then reported in a detailed, coloured Excel file, along with genotypes of family members and healthy controls. An interactive genome browser has been included which shows homozygous blocks, individual genotypes, genes and further annotations along the chromosomes, with zooming and scrolling capabilities. The software has been used to identify the location of a mutated gene causing insensitivity to pain in a large Bedouin family. KinSNP is freely available from.

Cognitive rehabilitation (CR) is a specialized treatment procedure to develop the cognition affected by internal or external injury to the brain. The process of cognitive rehabilitation involves assessment of cognitive functions, goal setting, and applying appropriate cognitive exercises to improve the cognitive function. There are two types of CR: Restorative rehabilitation and Compensatory rehabilitation. The CR therapist will make a comprehensive assessment of the impairment and design appropriate cognitive exercises. Studies on the efficacy of CR for brain damage have shown two extremes; one opinion was CR has a positive effect on the patients cognitive functioning and the other opinion was that CR has no effect on the cognitive functioning. This case study examines the dynamics and relevance of CR in reversible and progressive brain injury. It was observed that in reversible condition CR improves cognition and thereby functional ability. In progressive conditions like Alzheimer's disease (AD), CR improves the cognition marginally and thereby improves functional ability and also reduces Behavioral and Psychological Symptoms in Dementia (BPSD).

We report an adolescent with recurrent bilateral parotitis with pneumoparotitis and subcutaneous emphysema due to self pneumoinsufflation by a Valsalva like maneuver. Investigations for recurrent parotitis did not yield any clue. His la belle indifference, prolonged school absence and the presence of sibling rivalry helped us identify the psychological cause.

We report a case of an 18-month-old child with regression of attained developmental milestones as a manifestation of HIV encephalopathy. This is the first such report in Indian literature. Commencing antiretroviral therapy in this child resulted in arrest of further regression of milestones. This alerts pediatricians to be aware that early developmental delay and regression may be a presenting manifestation of HIV infection in a child.

HIV infection among injecting drug users (IDUs) is preventable, and in order to develop appropriate interventions, an assessment was carried out at Madras, South India using the Rapid Assessment and Response Guide on Injecting Drug Use developed by WHO. Data were collected with multiple methods from multiple sources using the principles of triangulation and induction. A total of 100 IDUs were interviewed. These interviews were complemented by focus groups and observations. A community advisory board ensured community ownership and participation. Findings showed that heroin, buprenorphine, diazepam and avil were the drugs most commonly injected. The use of pharmaceutical preparations as a 'cocktail' was also prevalent. Drug injectors interviewed were males, and most (81%) were from low-income groups living in slums. Direct (69%) as well as indirect sharing (94%) was common. Such unhygienic injecting practices, and the lack of access to sterile water, contribute to the high incidence of adverse health consequences. Compared with the buprenorphine injectors, heroin injectors were more likely to share injecting equipment (P=0.0022), inject more frequently (P=0.0013), have more drug using network members (P=0.0104), frequent 'shooting' locations (P=0.002), use the dealer's place to inject (P=0.0317), and face threats of arrest (P=0.0023). Many buprenorphine injectors managed their life without serious crises, and seemed to adopt a 'natural' harm reduction response. Sexual risk behaviour was prevalent among opioid users, and a history of commercial sex was associated with daily alcohol use (P=0.0221). The assessment led to an action plan which was presented and endorsed in an advocacy meeting by key stake-holders and decision-makers. The critical importance of implementing quality, accessible, community-oriented, and effective HIV interventions with the capacity to reach the majority of IDUs is discussed. Public health responses to injecting drug use must target changes among individuals at-risk, as well as in the community and risk environment.