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Setting: Tuberculosis Research Laboratory, Division of Clinical Microbiology and Molecular Medicine, Department of Laboratory Medicine, All India Institute of Medical Sciences, and the National Institute of Tuberculosis and Respiratory Diseases (NITRD), both situated in New Delhi. Objectives: We aimed to identify the distribution of various genotypes of M. tuberculosis among HIV-positive and HIV-negative patients suspected of having Tuberculosis, seen at the National Institute of Tuberculosis and Respiratory Diseases, New Delhi, which is a tertiary care dedicated TB hospital. Patients and methods: Genotyping by Spoligotyping and 24 loci MIRU-VNTR was performed and analyzed using SITVITWEB and MIRU-VNTRplus. Drug susceptibility patterns were also analyzed. Results: A total of 503 subjects who were PTB/EPTB suspected were recruited and 287 were culture positive. Among them, 276 had growth of Mycobacterium tuberculosis (MTB) and in 11 patients non-tuberculous mycobacteria (NTM) were grown. The isolation rate of NTM was predominantly from HIV positive [10 of 130 (7.6%)] patients. Of the total isolates of MTB, 156 (56.5%) were from HIV negative patients and 120 (43.5%) were from HIV positive patients. All 276 M. tuberculosis isolates were genotyped and tested for drug susceptibility patterns. The CAS genotype was most predominant [153 (55.4%)], followed by Beijing lineage [44 (15.9%)], East African India [25 (9.1%)] and others [54 (19.6%)]. Beijing genotype was significantly more common in HIV positive patients (22.5%) than in HIV negative patients (10.9%). In MIRU-VNTR analysis, clustering was found to be more frequent in CAS strains irrespective of HIV status. In the HIV positive group, spoligotyping could differentiate various genotypes in 90% of isolates and MIRU-VNTR analysis in 84.2% of isolates. The clustering of various MTB strains was more associated with drug resistance. Conclusion: The Beijing lineage was predominant in HIV-TB coinfected cases, even though the Central Asian Strain (CAS) was overall more predominant in the region. [ABSTRACT FROM AUTHOR]

Drawing on institutional theory and resource dependence theory, this study examines whether mandating gender quotas for corporate boards is associated with a greater presence of women on boards, better accounting-based and market-based performance, more innovativeness, and more external female directors. Based on a cross-country comparative sample of companies from 18 countries, our results suggest that organizations in countries where gender quotas are implemented show better market-based performance and better board vigilance through a higher number of external directors than organizations in countries where quotas are not implemented. The direct impact of gender quotas on innovativeness and accounting performance is not observed. Our findings add to the institutional theory literature by suggesting that companies respond strategically and show acquiescence in their strategic response when institutional pressure addresses ethical concerns (gender diversity). The results support institutional theory's contentions that companies from countries mandating gender quotas are valued more highly by the market. Nevertheless, the impacts on accounting performance and innovativeness are not apparent. Additionally, adopting a resource dependence approach, we find that the presence of women on boards is associated with more efficient corporate governance practices. The results of this study demonstrate the positive implications of gender quotas for company boards. The upper echelons of companies and country policymakers may better understand the importance of diversity and the presence of female directors on company boards. [ABSTRACT FROM AUTHOR]

Objectives. The aim of this study is to assess the effect of open apex on working length (WL) determination with aid of cone-beam computed tomography (CBCT) and electronic apex locators (EALs). Methods. Thirty-two extracted human mandibular premolars were selected, and apical 5 mm was removed. Root canals were prepared from the apical to the coronal direction of the canal using peeso reamers up to size 5 (retrograde) to simulate open apex. The samples were analyzed by CBCT, and WL was established (CWL) by a radiologist. An endodontist prepared the access cavities, and visual working length (VWL) was recorded. The samples were embedded in a freshly mixed alginate mould up to cementoenamel junction. Each root canal length was measured with two different EALs—Root ZX mini and i Root. The measurements were repeated 3 times by using a digital caliper, and the mean was recorded by the endodontist who was blinded to the results of the CWL. The recorded data was statistically analyzed using the SPSS software. Results. The results of this study showed statistically significant difference between VWL and i Root, CWL and i Root, and Root ZX mini and i Root (p < 0.05). Amongst EALs, a superior accuracy was noted for Root ZX mini than as compared to i Root. However, no statistically significant difference was seen between Root ZX mini and CWL (p > 0.05). Conclusion. The present study showed that CWL is as accurate and reliable as VWL which is the gold standard. Amongst EALs, Root ZX mini performed more accurately than i Root. Preexisting CBCT scans should be used as an advantage in determining WL. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to evaluate the maximum tolerated dose of hypofractionated proton beam radiation therapy with concurrent weekly carboplatin/paclitaxel in patients with stage II-III non-small cell lung cancer.Methods and Materials: A phase I trial was designed using the time-to-event continuous reassessment method. Maximum tolerated dose was defined as the dose associated with a 20% probability of Common Terminology Criteria for Adverse Events protocol-specified serious adverse events (SAEs). Starting dose was 3.5 Gy/fx for 15 fractions with 2 potential escalation and de-escalation levels in 0.25 Gy/fx increments. Chemotherapy was weekly concurrent carboplatin/paclitaxel with 2 cycles of optional consolidation carboplatin/paclitaxel.Results: From May 2015 to September 2016, 23 patients enrolled at a single institution. Of 20 evaluable, median age was 66.5 years (range, 54-89) and 12 were male (60%). Fourteen (70%) had squamous cell and 15 (75%) were stage IIIA. Nineteen (95%) completed all 3 cycles of concurrent chemotherapy, and 16 (80%) received at least 1 cycle of consolidation chemotherapy. Within the 6-month time-to-event continuous reassessment method assessment window, no SAEs were reported, and most patients were treated at the highest dose level. Dose level assignment was 52.5 Gy (n = 2), 56.25 Gy (n = 4), and 60 Gy (n = 14). The posterior probability of dose-limiting toxicity for 60 Gy was 5.3% (95% confidence interval, 1%-18.1%). Acute, nonserious AEs included grade 2 esophagitis in 7 patients (35%) and grade 2 pneumonitis in 1 patient (5%). At a median follow-up of 20.3 months for all and 44.9 months for living patients, there were no grade 4 or 5 AEs, though there were 3 (21% at 24 months) SAEs outside of the dose-escalation window. The 2-year overall survival, local, regional, and distant control rates were 48%, 84%, 77%, and 79%, respectively.Conclusions: Hypofractionated proton beam radiation therapy and chemotherapy up to 60 Gy in 15 fractions is acutely well tolerated, with high rates of locoregional control and overall survival, though late SAEs were noted. [ABSTRACT FROM AUTHOR]

This article examined the association among polyvictimization, sex work, and depressive symptomology among transgender women and men who have sex with men (MSM) in India. Data comes from a cross-sectional epidemiological study with 1,366 transgender women (from three states) and 2,182 MSM participants from five states of India. Multivariate regressions were used to examine how polyvictimization and sex work are associated with depressive symptoms. In total, 70% of transgender women and 44% of MSM participants in the sample reported being in sex work; 30% of transgender women and 17% of MSM reported at least one experience of abuse in last 6 months. In bivariate analysis, transgender women in sex work were more likely to report sexual abuse, and MSM in sex work more likely to report all types of abuse (physical, sexual, verbal, and property), compared to their peers. In multivariate models (with transgender women and MSM), increase in endorsement on types of abuses (polyvictimization) and being in sex work were associated with higher odds of reporting depressive symptoms. Both models controlled for age and marital status, while the model with transgender women also controlled for gender transitioning, and the model with MSM controlled for identity typology. National intervention program on HIV risk reduction must prioritize victimization screening and crisis management as part of their work. In addition, the interventions must be responsive to the diversity of the population, including those who engage in sex work, and address issues of access and support to gender transitioning services, and focus on psychosocial interventions to reduce stress due to gender-based stigma and discrimination among transgender women and MSM. [ABSTRACT FROM AUTHOR]

Objective: The objective was to evaluate the clinical experience and treatment patterns of generic dapagliflozin usage in different patient profiles in Indian settings. Materials and Methods: A retrospective, multicentric, real-world study included patients with type 2 diabetes mellitus (T2DM) (aged >18 years), inadequately controlled by existing antidiabetic therapy and receiving generic dapagliflozin as an add-on to existing oral antidiabetic drug(s) with or without insulin or switch therapy. Baseline characteristics and treatment-related outcomes were retrieved from the medical records and analyzed. Results: A total of 1935 patients were included, of which 1279 (66.1%) were males. The mean age was 57.4 years, and around half of the patients (51.4%) were aged from 45 to 60 years. Hypertension (55.9%) and dyslipidemia (19.8%) were the common comorbidities. The majority (n = 1122; 60%) of patients received dapagliflozin in combination with one or two antihyperglycemic drugs. More than half of the patients received metformin (56.8%) or sulfonylurea (52.3%) in combination with dapagliflozin. A dose of 10 mg (93.4%) was the most commonly used dose of dapagliflozin. The mean levels of glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose were significantly reduced to 1.1% (1.0-1.1), 30.5 mg/dL (29.2-31.9), and 57.5 mg/dL (55.1-59.9), respectively, after the initiation of dapagliflozin. A total of 1935 patients experienced weight changes during the treatment, of which 90.5% of patients showed weight loss. Hypoglycemic events were reported in 12.5% of patients. Physician global evaluation of efficacy and tolerability showed a majority of patients on a good-to-excellent scale (97.3% and 97.1%). Conclusion: Generic dapagliflozin showed a significant improvement in glycemic parameters and reduced body weight with low hypoglycemic events. The administration of dapagliflozin provided a good-to-excellent efficacy and tolerability profile in patients with T2DM. To the best of our knowledge, this is the first study confirming the efficacy, safety, and usefulness of generic dapagliflozin in patients with T2DM. [ABSTRACT FROM AUTHOR]

On 11 March 2020, the World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a global pandemic. Knowledge about COVID-19 is an important determinant towards successful disease control. This study was designed to elucidate the knowledge, attitudes and practices (KAP) and mental health status regarding COVID-19 amongst trainees of two institutes in the state of Uttar Pradesh, India. The cross-sectional study was conducted from January to March 2021. A bilingual survey recorded the responses of 400 participants from the institutes. Variables, such as sex, age, marital status, occupation, level of education, number of family members and living place, were collected in a structured proforma. Unstandardised regression coefficients (95%) were used for evaluating the association among variables with KAP and mental health during COVID-19. The statistical significance level was determined at p<0.05.The mean correct answer score regarding knowledge about COVID-19 was 23.5 (SD=2.1), indicating an overall 87% correct rate. The mean correct answer score regarding attitude towards COVID-19was 18.4 (SD=2.3), indicating an overall 87.2% correct rate. The mean correct answer score regarding practice towards COVID-19 was 35 (SD=3.4), indicating an overall 89.7% correct rate. The mean correct answer score regarding mental health status during COVID-19 was 24 (SD=4.7), indicating an overall 80% correct rate. Thus, the results showed that being female; belonging to a higher age group; having a healthcare related occupation; being married; and having a higher level of education were significantly associated with higher KAP test scores. Furthermore, belonging to a higher age group; having a healthcare related occupation; being married; and having a higher level of education were significantly associated with poor mental health. [ABSTRACT FROM AUTHOR]

Background: Spinocerebellar ataxia is a neurodegenerative disease. Information on comparative assessment of quality of life (QoL) among SCAs, particularly SCA 12, is scarce. We aimed to compare health-related QoL in SCA 1, 2 and 12. Methods: We conducted a cross-sectional study among individuals with genetically-confirmed SCAs. Ataxia severity was assessed using Brief Ataxia Rating Scale (BARS), independence in activities of daily living (ADL) using Katz index (Katz ADL) and depression using Beck's Depression Inventory-II (BDI-II). QoL was assessed via Short Form Health Survey version 2.0 (SF-36). Results: We enrolled 89 individuals (SCA1 = 17, SCA2 = 43, SCA12 = 29; 56% males). Mean age at onset (41.0 ± 11.6 for SCA12 versus 24.9 + 7.0 for SCA1 and 28.8 ± 9.8 years for SCA2) was significantly higher among SCA12. SCA12 had lower BARS (mean score 4.1 ± 4.5 versus 10.6 ± 4.6 for SCA1 and 12.5 ± 4.5 for SCA2). SCA12 scored better on all SF-36 subdomains including Physical (PCS) and Mental Component Summary (MCS) scores. PCS score amongst SCA12 was 44.4 ± 9.0 versus 30.4 ± 9.1 for SCA1 and 33.3 ± 8.9 for SCA2. MCS score for SCA12 was 51.4 ± 11.4 versus 41.8 ± 11.5 for SCA1 and 41.8 ± 11.2 for SCA2. SCA12 had lower mean BDI scores (5.0 ± 6.0) versus SCA1 (9.5 ± 11.6) and SCA2 (10.9 ± 10.3). BARS and BDI emerged as significant predictors of most SF-36 subdomains. Conclusions: Our study suggests that despite older age and comparable disease duration, SCA12 patients experience better QoL, less severe depression and ataxia versus SCA1 and SCA2. Severity of ataxia and depression are significant predictors of QoL among the three SCA types. [ABSTRACT FROM AUTHOR]

Background: Passive immunization using egg yolk-based antibodies has been tested against oral microorganisms. Our study assessed the effect of immunoglobulin Y (IgY) formulations on Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans in human subjects.Highlights: VS and UT independently searched articles using keyword combinations in four search engines; studies in English were selected. Either parallel-arm or split-mouth randomized controlled trials on healthy human subjects were considered. Ten studies remained in the selection; six studies compared the effect of IgY formulations on S. mutans, three on P. gingivalis, and one on C. albicans. Five studies (422 subjects) compared the effect of IgY formulations on S. mutans. When fixed-effect model (FEM) was applied, the risk ratio (RR) (confidence interval [CI]) was found to be 7.81 (6.00, 10.18). Three studies (167 subjects) compared the effect of IgY formulations on P. gingivalis. When FEM was applied, the RR (CI) was found to be 0.06 (-0.03, 0.15) in relation to reduction in probing depth. When FEM was applied, for percentage reduction in bleeding on probing (BOP), the RR (CI) was 1.99 (1.64, 2.41). Only one study (26 subjects) was available of IgY formulation and C. albicans; hence meta-analysis was not performed.The search was extended using Google Scholar, Semantic Scholar, cross-references and by contacting authors and researchers in the field which further yielded five articles. .Conclusions: IgY formulations were effective in the reduction of S. mutans. They were not effective on P. gingivalis in relation to probing depth but were effective in relation to reduction in BOP. No harms were reported. Evidence is of low quality due to high heterogeneity. The ROB was moderate and publication bias was low. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to perform an objective and subjective evaluation of the efficacy of positioning stents in radiation-induced xerostomia in patients with tongue carcinoma.Materials and Methods: A total of 30 patients with tongue carcinoma and undergoing conventional radiotherapy were randomly assigned to control (n = 15) and study (n = 15) groups, without and with a positioning stent, respectively. Assessment of salivary output reduction was done before and after radiotherapy, at 3- and 6-month intervals, by measurement of unstimulated and stimulated salivary flow rates (objective evaluation). Xerostomia (subjective evaluation) was noted using six items from the Quality of Life Head and Neck Module (QLQ-H&N35) as proposed by the European Organization for Research and Treatment of Cancer. The significance level was set at .05.Results: Mean unstimulated and stimulated salivary flow rates at 3- and 6-month intervals revealed significantly (P < .05) higher scores for the study group as compared with the control group. The mean quality of life scores in the study group were significantly (P < .05) lower compared with the control group.Conclusion: The use of a positioning stent minimized radiation-induced xerostomia and its symptoms. [ABSTRACT FROM AUTHOR]

Purpose: To compare the short-term outcome of botulinum neurotoxin A (BoNT-A) with or without sodium hyaluronate in the treatment of infantile esotropia (IE).Methods: In this tertiary care hospital-based prospective, interventional, non-randomized study on infants with IE below one year of age, 25 cases were enrolled in the sodium hyaluronate (SH) group to receive 2.5 U BoNT-A injection combined with SH in each medial rectus muscle (MR). Thirty patients were enrolled in the control group to receive 2.5 U BoNT-A injection with normal saline in each MR. The change in mean primary ocular deviation (POD) and complications were assessed at 2 weeks, 1 month, 3 months, and 6 months post injection. Mann-Whitney U test was used for non-parametric unpaired data. Chi-square test and Fisher's exact test were used to test for the strength of the association between the two categorical variables.Results: Satisfactory ocular alignment was achieved in 76% in SH group and 73% in the control group (P value = 0.80). While the change in mean POD was comparable (29.2 prism diopters [PD] vs 29.3 PD; P value = 0.65), the complication rates were significantly lesser in SH (16% vs 33.3%; P value = 0.14).Conclusion: BoNT-A combined with SH is equally effective with lesser complications as compared to botulinum toxin alone in the treatment of IE. [ABSTRACT FROM AUTHOR]

Recognition of β-cell antigens by autoreactive T cells is a critical step in the initiation of autoimmune type1 diabetes. A complete protection from diabetes development in NOD mice harboring a point mutation in the insulin B-chain 9-23 epitope points to a dominant role of insulin in diabetogenesis. Generation of NOD mice lacking the chromogranin A protein (NOD.ChgA-/-) completely nullified the autoreactivity of the BDC2.5 T cell and conferred protection from diabetes onset. These results raised the issue concerning the dominant antigen that drives the autoimmune process. Here we revisited the NOD.ChgA-/- mice and found that their lack of diabetes development may not be solely explained by the absence of chromogranin A reactivity. NOD.ChgA-/- mice displayed reduced presentation of insulin peptides in the islets and periphery, which corresponded to impaired T-cell priming. Diabetes development in these mice was restored by antibody treatment targeting regulatory T cells or inhibiting transforming growth factor-β and programmed death-1 pathways. Therefore, the global deficiency of chromogranin A impairs recognition of the major diabetogenic antigen insulin, leading to broadly impaired autoimmune responses controlled by multiple regulatory mechanisms. [ABSTRACT FROM AUTHOR]

Graves' ophthalmopathy (GO) is an autoimmune disease of the retroocular tissue occurring in patients with Grave's disease leading to exophthalmos. Exophthalmos is usually detected by inspection using Nafziger's method and objectively measured with Hertel's exophthalmometry. Here we have described a novel technique "Pen touch test" to clinically diagnose exophthalmos. This cross-sectional study was conducted on patients with suspicious hyperthyroid ophthalmopathy/Grave's ophthalmopathy (GO) who underwent eye examination by Nafziger's method and our proposed new method "Pen Touch Test (PTT)". In this test, a clean ruler or pen is held straight over the middle of orbital ridge touching the superior orbital margin and ipsilateral malar eminence. In normal persons, the ruler or pen touches both the superior orbital margin and ipsilateral malar eminence with or without touching eyelids. In patients with GO, there is true bulging forward of the eyeball. Hence, the ruler or pen cannot be made to touch both upper orbital margin and malar eminence simultanously. The presence and degree of exophthalmos was measured objectively on Hertel's exophthalmometry, which was considered the "gold standard". Pen touch test was found to have 100% sensitivity, 100% specificity and 100% Positive Predictive value. Whereas Nafziger's method had a sensitivity of only 75% compared to Hertel's exophthalmometry as gold standard test. "Pen touch test" is simple and sensitive method that can be used to screen for exophthalmos in suspected cases of Grave's ophthalmopathy. [ABSTRACT FROM AUTHOR]

Background: This randomized clinical trial (RCT) aimed to compare the 3-year survival rates of high viscosity glass ionomer restorations (HVGIC) using conventional cavity preparation and atraumatic restorative technique (ART) in primary molars. Materials and Methods: In this RCT, 139 schoolchildren aged 6-9 years with dentinal caries in primary molars were randomly allocated to groups, i.e. the ART group and the conventional group, utilizing a random number generator. Adequate allocation concealment was done. Intervention was delivered using standard procedure and GC Fuji IX ART HVGIC was used as restorations in both the groups. Analysis was carried in 92 participants, and survival rates in both the groups were compared at 12, 24, and 36-month intervals. IBM SPSS software was utilized to analyze the time taken for the procedure and the Kaplan-Meier estimate was used to assess the survival rates. P value of 0.05 was considered statistically significant. Results: The ART took longer to complete (16.48 ± 2.02 min) versus conventional rotary instrumentation (13.15 ± 1.32 min). The conventional method was slightly superior as compared to ART; excellent survival rates (i.e. >90%) were achieved in both groups at the end of 12-month follow-up with no significant differences at the end of 24 and 36 months as evident from Kaplan-Meier estimate (P = 0.255). Conclusion: Three-year follow-up showed that GIC restorations with ART and conventional method carried out using GC Fuji IX ART HVGIC were acceptably successful, substantiating the use of ART for the primary dentition in areas with high caries prevalence and limited access to dental care. [ABSTRACT FROM AUTHOR]

Background: The need to study prognosis after incidence of acute ischemic stroke (AIS) has fueled researchers to identify predictors apart from neurological, functional, or disability measures. The purpose of this study was to test and validate a newly developed clinico-biomarker assessment module in AIS and also to investigate the role of serum vascular endothelial growth factor (VEGF) after AIS.Materials and Methods: A randomized controlled study with sample size of 250 patients suffering from AIS within 2 weeks of the index event were conducted and followed up for a period of three months. Age, gender, stroke subtype, previous stroke history, dysarthria, stroke localization, wakeup strokes, and Glasgow Coma Scale (GCS) were dichotomized as present or absent using the National Institute of Health Stroke Scale (NIHSS) which consists of four subcategories. The additional serum VEGF was scored between 1 and 4 (0-200 = 1, 200-300 = 2, 300-400 = 3, and 400-500 = 4). All these were summed under a clinical biomarker (CB) module with highest score of 30.Results: The mean VEGF in 125 patients was 378.4 + 98.9 pg/ml, indicating a moderately high increase with a score of 3 on CB module. Multiple regression analysis revealed that the CB model was fit to predict prognosis and severity [R2 = 0.86, F (23.4, 6);P = 0.001], with NIHSS subscore, prestroke status, and VEGF being very strong predictors. When only the clinical module was tested on all 250 patients, it was found that the NIHSS subscore, time to stroke onset and prestroke functional status were the most common [R2 = 0.79; F (45,9);P = 0.005].Conclusion: This study demonstrates that VEGF is highly upregulated in AIS with severe disability as compared to healthy controls. This biomarker is a strong predictor of severity and functionality when combined with clinical variables three months post the ishemic event. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study. Aim: To retrospectively evaluate and compare the long-term outcome of anterior vertebral body reconstruction in tuberculosis (TB) of the dorsal spine by direct anterior-versus-posterior approach. Materials and Methods: A total of 127 patients operated by posterior approach, 118 by anterior for TB-thoracic spine with at least 1-year follow-up were included and retrospectively analyzed. Patients were assessed clinically, radiologically and data regarding age, sex, levels involved, surgical approach, operative time, blood loss, neurological recovery using Frankel grade, pre- and post-operative kyphosis, % correction of kyphosis, time for fusion, fusion grading using Bridwell criteria, % loss of correction, mobilization time and complications if any were collected, analyzed, compared in anterior-v/s-posterior approaches. Results: The mean age in anterior-approach was 36.03 and 39.83 years in posterior. Mean operative time in anterior-approach was 6.11 and 5 h in posterior. Mean blood loss of 1.6 L in anterior approach and 1.11 L in posterior. Mean preoperative kyphosis angle in posterior-approach was 34.803°and 11.286° (P < 0.001) at 3 months postopandtotal correction of 67.216%. Mean preoperative kyphosis angle in anterior-approach was 41.154° and 9.498° at 3 months postopandtotal correction of 77.467% (P < 0.001). Mean loss of correction at 1 year was 4.186°in posterior-approach and 6.184°in anterior. The mean time for fusion was 4.69 months in anterior-approach while 6.34 months in posterior as per Bridwell criteria. Meantime for mobilization in posterior-approach was 1.18 and 2.51 weeks in anterior. Significant improvement in neurology was seen in patients operated by either approach, slightly better in anterior. Complications were more in posterior-approach. Conclusions: Anterior-approach allows for thorough debridement, neural decompression, better anterior column reconstruction, and deformity correction under direct vision than posterior. Direct cord visualization while correcting kyphosis reduces the chances of neurological complications significantly. Both approaches have unique advantages and limitations. Though the posterior approach is easy to master, results shown by the anterior cannot be overseen. To conclude, better functional outcome and significantly better kyphosis correction are seen with anterior-approach, which are strong pointers favoring it. [ABSTRACT FROM AUTHOR]

Background: Choledochal cyst is a common congenital anomaly requiring surgical treatment. Nowadays, laparoscopic excision is the preferred approach. We studied a modification in the classical laparoscopic approach to facilitate the dissection of a cyst. Materials and Methods: A prospective comparative study was done on 42 Type I choledochal cyst children. One group was operated by classical laparoscopic technique, while the other group was operated by modification of classical technique by deliberately opening the cyst wall and dividing the cyst into two hemi-cups, followed by dissection and excision. The intraoperative and postoperative parameters were assessed in both the groups. Results: The age, gender ratio, clinical presentation, and cyst diameter were comparable in both the groups. There was a significantly higher success rate (95.7% vs. 73.7%, P = 0.042) and lesser time for cyst excision (96.43 ± 12.15 vs. 120.91 ± 17.38 min P < 0.001) in the modified technique when compared to the classical technique. Further in three patients, it was possible to convert the classical procedure to a modified technique and complete the cyst excision. The postoperative outcomes were similar in both the groups. Conclusion: The modified laparoscopic excision shortens the operative time with higher success rate and comparable short-term morbidity vis-a-vis classical laparoscopic technique. [ABSTRACT FROM AUTHOR]

Purpose: Medical assistants (MAs) have seen their roles expand as a result of team-based primary care models. Unlike their physician counterparts, MAs rarely receive financial incentives as a part of their compensation. This exploratory study aims to understand MA acceptability of financial incentives and perceived MA control over common population health measures.Methods: We conducted semistructured focus groups between August and December of 2019 across 10 clinics affiliated with 3 institutions in California and Utah. MAs' perceptions of experienced and hypothetical financial incentives, their potential influence on workflow processes, and perceived levels of control over population health measures were discussed, recorded, and qualitatively analyzed for emerging themes. Perceived levels of control were further quantified using a Likert survey; measures were grouped into factors representing vaccinations, and workflow completed in the same day or multiple days (multiday). Mean scores for each factor were compared using repeated 1-way ANOVA with Tukey-Kramer adjustment.Results: MAs reported little direct experience with financial incentives. They indicated that a hypothetical bonus representing 2% to 3% of their average annual base pay would be acceptable and influential in improving consistent performance during patient rooming workflow. MAs reported having greater perceived control over vaccinations (P <.001) and same-day measures (P <.001) as compared with multiday measures.Conclusions: MAs perceived that relatively small financial incentives would increase their motivation and quality of care. Our findings suggests target measures should focus on MA work processes that are completed in the same day as the patient encounter, particularly vaccinations. Future investigation is needed to understand the effectiveness of MA financial incentives in practice. [ABSTRACT FROM AUTHOR]

Objectives The aetiology of primary chronic pain syndromes (CPS) is highly disputed. We performed a systematic review and meta-analysis aiming to assess differences in circulating cytokine levels in patients with diffuse CPS (fibromyalgia) vs healthy controls (HC). Methods Human studies published in English from the PubMed, MEDLINE/Scopus and Cochrane databases were systematically searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with baseline cytokine measurements, reporting differences in circulating cytokine levels between fibromyalgia patients and HC. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. This study is registered with PROSPERO (CRD42020193774). Results Our initial search yielded 324 papers and identified 29 studies (2458 participants) eligible for systematic review and 22 studies (1772 participants) suitable for meta-analysis. The systematic analysis revealed reproducible findings supporting different trends of cytokine levels when fibromyalgia patients were compared with HC, while the chemokine eotaxin, was consistently raised in fibromyalgia. Meta-analysis showed significantly increased TNF-α [standardized mean difference (SMD) = 0.36, 95% CI: 0.12, 0.60, P  = 0.0034; I 2 = 71%, Q 2 P  = 0.0002], IL-6 (SMD = 0.15, 95% CI: 0.003, 0.29, P  = 0.045; I 2 = 39%, Q 2 P  = 0.059), IL-8 (SMD = 0.26, 95% CI: 0.05, 0.47, P  = 0.01; I 2 = 61%, Q 2 P  = 0.005) and IL-10 (SMD = 0.61, 95% CI: 0.34, 0.89, P  < 0.001; I 2 = 10%, Q 2 P  = 0.34) in fibromyalgia patients compared with HC. Conclusion We found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared with HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia. [ABSTRACT FROM AUTHOR]

A computer views all kinds of visual media as an array of numerical values. As a consequence of this approach, they require image processing algorithms to inspect contents of images. This project compares 3 major image processing algorithms: Single Shot Detection (SSD), Faster Region based Convolutional Neural Networks (Faster R-CNN), and You Only Look Once (YOLO) to find the fastest and most efficient of three. In this comparative analysis, using the Microsoft COCO (Common Object in Context) dataset, the performance of these three algorithms is evaluated and their strengths and limitations are analysed based on parameters such as accuracy, precision and F1 score. From the results of the analysis, it can be concluded that the suitability of any of the algorithms over the other two is dictated to a great extent by the use cases they are applied in. In an identical testing environment, YOLO-v3 outperforms SSD and Faster R-CNN, making it the best of the three algorithms. [ABSTRACT FROM AUTHOR]

Purpose: In the present study, we aimed at assessing the effect of femoral and tibial coronal bowing on varus malalignment and Oxford knee score (OKS) at different grades of knee osteoarthritis (OA). Materials and Methods: This prospective observational study was conducted at a tertiary referral centre in New Delhi, India. Consecutive patients presenting to the "knee OA" outpatient clinics were invited to take part in the study conducted over a 12-month period. All consented patients underwent long-leg standing alignment radiographs using standardised technique and patient reported knee pain and function were recorded using Oxford knee score. The following radiological parameters were measured from weight-bearing long-leg radiographs of 824 varus aligned limbs via a morphometric software (Matlab R2009a) (1) hip–knee–ankle angle (HKAA), (2) femoral bowing, (3) tibial bowing. The knees were graded according to Kellegren and Lawrence grade (K&L) and OKS was recorded. 3 groups of HKAA were made based on the angle, A (0° to − 3°), B (− 3° to − 10°) and C (< − 10°). Both the femoral and tibial bow were also categorized into three groups depending upon the angle; in-range (− 2° to + 2°), varus (< − 2°), valgus (> + 2°). Results: The mean (± SD) of HKAA, femoral bow and tibial bow of the whole cohort was − 6.97° ± 5.64°, − 1.54° ± 4.31° and − 1.96° ± 3.5°, respectively. An increase in the lateral bow of both femur and tibia was seen with an increase in the severity of OA. A consequent increase in the varus malalignment was observed with an increase in the lateral bow of both femur as well as the tibia at all grades of OA, with significant correlation observed between HKAA with Femoral bowing and HKAA with tibial bowing. The mean OKS for femoral bow, in-range, varus and valgus was 30.6 ± 11.5, 21.3 ± 11.5 and 35.3 ± 11.4, respectively, and for tibial bow, in-range, varus and valgus was 27.6 ± 11.5, 26. ± 11.5 and 28 ± 11.4, respectively. The difference in the mean OKS was observed to be significant when the varus bow group was compared to in range as well as valgus group (p < 0.01) for both femur and tibia for all the grades of OA. Conclusion: The present study shows a significant correlation between varus malalignment and the bowing of extremities. Varus coronal bowing of both femur and tibia were seen to have significantly lower mean OKS as compared to valgus bowing or in-range bowing at all grades of knee OA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human-Robot Interaction (HRI) has become a prominent solution to improve the robustness of real-time service provisioning through assisted functions for day-to-day activities. The application of the robotic system in security services helps to improve the precision of event detection and environmental monitoring with ease. OBJECTIVES: This paper discusses activity detection and analysis (ADA) using security robots in workplaces. The application scenario of this method relies on processing image and sensor data for event and activity detection. The events that are detected are classified for its abnormality based on the analysis performed using the sensor and image data operated using a convolution neural network. This method aims to improve the accuracy of detection by mitigating the deviations that are classified in different levels of the convolution process. RESULTS: The differences are identified based on independent data correlation and information processing. The performance of the proposed method is verified for the three human activities, such as standing, walking, and running, as detected using the images and sensor dataset. CONCLUSION: The results are compared with the existing method for metrics accuracy, classification time, and recall. [ABSTRACT FROM AUTHOR]

Introduction: Ethanol is a traditional cytofixative which is widely used for oral exfoliative cytology. Due to its limitations, a search of better, eco-friendly, and cost-effective fixative was explored. The present study was conducted to evaluate the efficacy and reliability of 10%, 20%, and 30% processed honey as a cytofixatives, and was compared with that of 95% ethanol. Materials and Methods: Four oral smears were obtained from each individual (n = 80) by gently scraping the buccal mucosa. One slide was fixed in ethanol (95%) and the other in various grades of processed honey (10%, 20%, and 30%), and stained with Papanicolaou stain. Two separate pathologists who were kept in blind for the fixative used evaluated the slides based on the five parameters (cell morphology, nuclear and cytoplasmic staining, clarity, and uniformity of staining). Results: In the present study, it was observed that 20% of processed honey showed overall good results, followed by (95% alcohol) and (10% honey). However, poor results were observed in (30% honey). When compared, no statistically significant difference was observed between the groups. Conclusion: The present study offers an innovative application using honey as a cytofixative. Honey in lower concentration is an excellent alternative to ethanol as a cytofixative. [ABSTRACT FROM AUTHOR]

Polymer capping matrix plays an important role in the synthesis of quantum dots via chemical methods. In this article, polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) polymers are used as capping matrix for the synthesis of quantum dots. Quantum dots of zinc oxide are directly synthesized from ZnO powder by thermal quenching methods on PVA and PVP capping matrix, and standard characterization techniques are utilized to characterize the samples. Thereafter, comparative analysis for the properties of ZnO quantum dots for PVA and PVP is presented. [ABSTRACT FROM AUTHOR]

Alcohol consumption can lead to a wide range of systemic disorders brought about by transcriptional changes. Recent studies have documented altered behavior and physiology in zebrafish exposed to alcohol. In this work, we have identified the changes in the zebrafish transcriptome in response to chronic alcohol exposure. We have further followed the extent of transcriptional recovery upon withdrawal from alcohol and found evidence of tissue-specific responses. Our results indicate a greater extent of recovery of the brain transcriptome compared to the liver. We identify two distinct classes of genes in response to withdrawal from alcohol exposure - those that recover their pre-alcohol expression profile versus those that retain altered expression even after the fish are removed from the alcohol environment. Finally, we have examined gender-specific responses to alcohol exposure in zebrafish and find evidence for distinct alcohol tolerance levels. Upon chronic alcohol exposure, a higher percentage of genes show perturbation in expression profile in males compared to females. Female fish also recover better with more genes regaining the control expression level upon withdrawal from alcohol. Overall, our work identifies genes and pathways perturbed by exposure to alcohol, and demonstrates the extent of gender- and tissue-specific transcriptional changes associated with chronic alcoholism and withdrawal. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of presurgical infant orthopedics using 2 different methods, that is, the Dynacleft with Nasal elevator system versus the modified Grayson's technique in patients with complete unilateral cleft lip and palate. Design: Prospective comparative cohort study. Materials and Methods: Twenty-eight patients were divided into 2 groups, that is, Group A consisting of 14 patients who underwent correction with DynaCleft with Nasal elevator system and Group B consisting of 14 patients undergoing correction using the modified Grayson technique. Maxillary cast measurements were taken at 2-time intervals (pre- and posttreatment) to assess various parameters using a laser scanning machine (C500 Solutionix) and 3D software (GOM Inspect). Similarly, standardized anterior–posterior and worm's-eye view photographs using a custom box were taken and imported to Adobe Photoshop CS6 for measurements. Paired t test and independent t test were used to compare intra- and intergroup changes, respectively. Results: The analysis of cast (primary outcome) and photographic (secondary outcome) measurements showed improved nasal asymmetry and alveolar correction in both groups which showed no significant intergroup difference when assessed using the independent t test (P >.05). Group A showed higher chances (42.8%) of causing a T-shaped defect (due to excessive mesial-inward rotation of the minor segment) when compared to the Group B possibly due to a more controlled molding vector (P <.05). Conclusion: Both methods proved effective in improving the nasal asymmetry, reducing the alveolar cleft gap, and approximating the lips together; but care must be taken when applying the alveolar molding vector in the Dynacleft system. [ABSTRACT FROM AUTHOR]

To achieve breakthrough innovation, firms often need to acquire complementary knowledge from cross-industry actors in the innovation ecosystem, where unique and supermodular complementarities make knowledge exchange essential for value co-creation. This study examines the impact of the acquisition of knowledge transfer on breakthrough innovation by considering the complementors of unique and supermodular complementarity. We draw on data from 51 firms in the Chinese information and communication technology sector and apply the fuzzy set qualitative comparative analysis (fsQCA), in which we adopt factors on the complementor, relationship, and knowledge characteristics to determine the configurations that lead to firms' breakthrough innovation in the innovation ecosystem. The results show that several combinations of conditions drive firms' breakthrough innovation. Unique complementarities require conditions of explicit knowledge and cultural similarity within the realm of knowledge and complementors' characteristics. Conversely, supermodular complementarity underscores the importance of tacit knowledge, along with trust and tie strength within the characteristics of knowledge and relationships. Our study has practical and theoretical implications for complementors seeking breakthrough innovation in non-generic complementarities. • Unique and supermodular complementarities in the innovation ecosystem are heterogeneous. • We examine the acquisition of knowledge transfer's impact on breakthrough innovation to unpack these differences. • The results show that several combinations of knowledge transfer conditions drive focal firms' breakthrough innovation. • Unique complementarities emphasize knowledge specificity and require explicit knowledge and cultural similarity. • Supermodular complementarity underscores an extensive connection, considering trust and tie strength as the core. [ABSTRACT FROM AUTHOR]

Background: Plateletpheresis is generally safe but may have adverse reactions. Adverse reactions can negatively influence donor recruitment and retention. Valsalva is a proven method of attenuating pain caused by venipuncture. Aims: The aim was to evaluate the efficacy of the Valsalva maneuver on the attenuation of needle pain and donor anxiety. Settings and Design: This prospective randomized controlled trial was conducted between November 2015 and April 2016 at the Department of Transfusion Medicine. Subjects and Methods: One-hundred and sixty consecutive donors were grouped into control group (C) and Valsalva group (V) each of sample size 80. The Valsalva group performed a Valsalva maneuver and control did nothing before the venipuncture. Anxiety and pain were scored using a 10 cm visual analog scale (VAS). Severity was graded as VAS = 0 defines no pain and anxiety, VAS = 1–3 as mild pain and anxiety, VAS = 4–6 as moderate pain and anxiety, VAS = 7–9 as severe pain and anxiety, whereas VAS = 10 denotes extreme pain and anxiety. Statistical Analysis: Statistical Package for Social Sciences, version 23 was used for analysis. Independent samples t-test/Mann–Whitney U-test was used to compare between treatment and control group, whereas the Wilcoxon signed-rank test was used to test the difference between pre- and postobservations. Results: In the Valsalva group, post-Valsalva anxiety levels were significantly reduced to (1 [0–2]) from their pre-Valsalva values of (2 [0–3]); (P < 0.001). Pain was significantly lower (2[1-2]) in Valsalva group compared to control (4[2–5]); (P < 0.001). Conclusions: Valsalva reduced both severity of venipuncture pain and anxiety. Valsalva can be performed by donors as it is an easy, painless, and nonpharmacological method of pain and anxiety attenuation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Accurate staging of disease severity and its serial monitoring thus is central to the effective management protocols of interstitial lung disease (ILD). PURPOSE: The aim is to evaluate the effectiveness of semi-quantitative parameters of lung ultrasound (LUS) in patients of ILD as a means of staging disease severity. MATERIALS AND METHODS: LUS of 47 patients of ILD and 20 age-matched controls was performed, and findings such as B-line distance, pleural thickening, subpleural changes, decreased lung sliding, and fragmented pleural lining were charted, and an LUS score was done using these parameters. Findings were compared with the Modified Medical Research Council (MMRC) dyspnea grade and spirometry parameters. RESULTS: The presence of B-lines and fragmented pleural lining were the most common findings observed in patients of ILD. Predicted forced vital capacity (FVC) and predicted forced expiratory volume in 1 s (FEV1) showed a good correlation with all the LUS parameters. B-line distance was the most significant LUS parameter to predict the variability in predicted FEVI, FVC, and MMRC dyspnea score. LUS severity score also showed good negative correlation with predicted FEV1 (r = −0.674, P < 0.001) and predicted FVC (r = −0.65, P < 0.001). LUS severity score of 4 or more predicted MMRC dyspnea score of > 3 with 82% sensitivity and 70% specificity. CONCLUSION: Semi-quantitative LUS score and B-line distance can provide a simple but effective estimate of disease severity in ILD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Access control system (ACS) plays a major role in data security. It becomes more challenging for the system to provide accurate ACS, if data is huge and data requesters are not fixed. This is very predominant in the era of big data where new data are adding to the system very frequently. The main issue here is to justify adaptability in ACS. OBJECTIVE: The objective of this research is to have a comparative analysis of machine learning based access control methods with Rule based access control methods. Propose the most suitable method in detail. METHODS: Role based access control methods are highly robust and works effectively under known scenarios. We need additional methods to handle unknown scenarios. A decision-making method is used to identify the certainty of the rules and Mamdani fuzzy model is used to evaluate the situation based on current environmental factors. For machine learning based access control method Random Forest is used. RESULTS: Limitations of machine learning methods are discussed with respect to imbalanced data and bias in the algorithm. The proof of concept for rule-based access control method is tested for all the three modules involved in the framework. Certainty of the rules were accessed with the help of domain experts and accuracy of fuzzy rules were evaluated. Under critical conditions our framework was found to be accurate. CONCLUSIONS: Machine learning systems are not suitable for access control if they suffer with imbalance data problem. Rule based system are consistent and highly adaptable to unknown situations. Rule based systems have evaluated the genuineness of the requester based on sensitivity of information, time, location, previous history and emergency parameters. [ABSTRACT FROM AUTHOR]

Context: Aphasia is a major disabling condition after a stroke that profoundly affects the quality of life of stroke survivors (SS) and their caregivers. Comprehensive neuropsychological rehabilitation has emerged as a complementary intervention that helps in improving the associated cognitive and psychological deficits and quality of life following a brain injury. A standardized, simple, and easy to administer intervention that can be delivered as a home-based intervention can assist in faster recovery. Aims: To describe the development, validation, and feasibility of a home-based, caregiver-delivered comprehensive neuropsychological and language rehabilitation for SS. Methods and Material: A culture-specific picture and task-based 8-week training workbook and manual were developed based on extensive review and focused group discussions. This intervention targeted areas of language (comprehension, fluency, and naming) and cognition (working memory, attention and concentration, executive functioning, and response inhibition). It was standardized on 40 healthy controls (HC) and 15 SS. Before recruitment, written informed consent was obtained from each patient, their primary caregiver, and the HCs. Results: All tasks were found to be effective in discriminating the performance of SS from the HC. The performance of the HC with respect to the errors and the time taken for each task was used for the hierarchical arrangement of the tasks. The developed intervention was later validated on 15 SS where they significantly improved in the pre-post assessment of language functioning (P < 0.001), quality of life (P < 0.001), and depression (P < 0.001). Conclusions: This intervention can be feasible to administer as a home-based intervention and may help to alleviate language and neuropsychological complaints after stroke in low-literate or mixed-cultural populations. Further, large sample size studies are recommended. [ABSTRACT FROM AUTHOR]

The synchondrosis in the cranial base is an important growth center for the craniofacial region. Abnormalities in the synchondroses affect the development of adjacent regions, including the craniofacial skeleton. Here, we report that the transcription factor TBX1, the candidate gene for DiGeorge syndrome, is expressed in mesoderm-derived chondrocytes and plays an essential and specific role in spheno-occipital synchondrosis development by inhibiting the expression of genes involved in chondrocyte hypertrophy and osteogenesis. In Tbx1-deficient mice, the spheno-occipital synchondrosis was completely mineralized at birth. TBX1 interacts with RUNX2, a master molecule of osteoblastogenesis and a regulator of chondrocyte maturation, and suppresses its transcriptional activity. Indeed, deleting Tbx1 triggers accelerated mineralization due to accelerated chondrocyte differentiation, which is associated with ectopic expression of downstream targets of RUNX2 in the spheno-occipital synchondrosis. These findings reveal that TBX1 acts as a regulator of chondrocyte maturation and osteogenesis during the spheno-occipital synchondrosis development. Thus, the tight regulation of endochondral ossification by TBX1 is crucial for the normal progression of chondrocyte differentiation in the spheno-occipital synchondrosis. [ABSTRACT FROM AUTHOR]

Background: Variation in the shape of the femur and tibia has been shown to influence hip–kneeankle-axis angle (HKAA) and bears a role in reconstructive surgeries such as total knee arthroplasty (TKA). However, data on the axial alignment of the lower extremity specific to sex largely remains unavailable. Thus, we conducted a study with an aim to measure alignment and calculate differences in both the sexes in Indian population. Materials and Methods: The following radiological parameters were measured from weight-bearing long leg radiographs of 966 limbs of Indian subjects via a morphometric software (Matlab R2009a) (1) Hip–Knee–Ankle angle (HKAA), (2) femoral bowing, (3) tibial bowing, (4) condylar plateau angle (CPA). The knees were classified according to the Kellegren and Lawrence grading and the differences between both the sexes were calculated with appropriate statistical tests. Results: 56.04% of the subjects were female. An increase in the mean age was observed for both the genders with an increase in the severity of OA. Height did not show any significant association with the alignment of the limb. The mean HKAA observed was − 5.88° ± 0.35° in females and − 4.99° ± 0.41° in males. The overall mean femoral bow and tibial bow was − 1.26° ± 0.24°, − 1.60° ± 0.18° in females and − 1.09 ± 0.28, − 1.47° ± 0.21° in males. The mean condylar plateau angle was higher in females − 2.67 ± 0.34 as compared to males − 2.35° ± 0.39°. A greater lateral bow was seen in males at higher grades of OA for femur and at lower grades of OA for tibia. Conclusion: This study provides gender-based differences in the various axial radio-graphic parameters in a long leg radio-graphs in Indian population which might help in a better understanding of the etiopathogenesis of osteoarthritis and also help planning and execution of reconstructive surgeries such as TKA. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to characterize the prevalence and risk of pain, pain interference, and recurrent pain in adult survivors of childhood cancer in comparison with siblings.Methods: This study analyzed longitudinal data from survivors (n = 10,012; 48.7% female; median age, 31 years [range, 17-57 years]; median time since diagnosis, 23 years) and siblings (n = 3173) from the Childhood Cancer Survivor Study. Survivors were diagnosed between 1970 and 1986 at 1 of 26 participating sites. Associations between risk factors (demographics, cancer-related factors, and psychological symptoms) and pain, pain interference, and recurrent pain (5 years apart) were assessed with multinomial logistic regression. Path analyses examined cross-sectional associations between risk factors and pain outcomes.Results: Twenty-nine percent of survivors reported moderate to severe pain, 20% reported moderate to extreme pain interference, and 9% reported moderate to severe recurrent pain. Female sex, a sarcoma/bone tumor diagnosis, and severe/life-threatening chronic medical conditions were associated with recurrent pain. Depression and anxiety were associated with increased risk for all pain outcomes. Poor vitality mediated the effects of anxiety on high pain and pain interference (root mean square error of approximation, 0.002).Conclusions: A large proportion of adult survivors report moderate to severe pain and pain interference more than 20 years after their diagnosis. Increased screening and early intervention for pain interference and recurrent pain are warranted. [ABSTRACT FROM AUTHOR]

Rationale: Neuroendocrine cell hyperplasia of infancy (NEHI) is an important form of children's interstitial and diffuse lung disease for which the diagnostic strategy has evolved. The prevalence of comorbidities in NEHI that may influence treatment has not been previously assessed.Objectives: To evaluate a previously unpublished NEHI clinical score for assistance in diagnosis of NEHI and to assess comorbidities in NEHI.Methods: We performed a retrospective chart review of 199 deidentified patients with NEHI from 11 centers. Data were collected in a centralized Research Electronic Data Capture registry and we performed descriptive statistics.Results: The majority of patients with NEHI were male (66%). The sensitivity of the NEHI Clinical Score was 87% (95% confidence interval [CI], 0.82-0.91) for all patients from included centers and 93% (95% CI, 0.86-0.97) for those with complete scores (e.g., no missing data). Findings were similar when we limited the population to the 75 patients diagnosed by lung biopsy (87%; 95% CI, 0.77-0.93). Of those patients evaluated for comorbidities, 51% had gastroesophageal reflux, 35% had aspiration or were at risk for aspiration, and 17% had evidence of immune system abnormalities.Conclusions: The NEHI Clinical Score is a sensitive tool for clinically evaluating NEHI; however, its specificity has not yet been addressed. Clinicians should consider evaluating patients with NEHI for comorbidities, including gastroesophageal reflux, aspiration, and immune system abnormalities, because these can contribute to the child's clinical picture and may influence clinical course and treatment. [ABSTRACT FROM AUTHOR]

Background: The current treatment regimens recommended for Mycobacterium abscessus subspecies abscessus (Mab) pulmonary disease are not effective. We identified 16 drugs with potential to build new regimens, translating to 560 possible three-drug combination regimens.Objectives: To determine MICs and efficacy of drugs from different antibiotic classes for treatment against Mab, in order to winnow down the potential drugs for combination therapy to tractable numbers, for future use in hollow-fibre studies.Methods: The MICs of levofloxacin, minocycline, meropenem, imipenem, tedizolid, bedaquiline, azithromycin, clarithromycin, amikacin, vancomycin, delafloxacin, tebipenem/avibactam and omadacycline were determined for 20 Mab isolates. In addition, concentration-response studies with tedizolid, bedaquiline, clarithromycin, amikacin, tebipenem/avibactam, cefdinir, faropenem, omadacycline and daunorubicin were performed and data were fitted to the inhibitory sigmoid Emax model. Efficacy was defined as maximal kill, expressed as cfu/mL kill below day 0 burden.Results: The lowest MICs among the 13 antibiotics were of bedaquiline, tebipenem/avibactam and omadacycline. The antibiotics that killed Mab below the day 0 burden were the anticancer agent daunorubicin (3.36 log10 cfu/mL), cefdinir (1.85 log10 cfu/mL), faropenem (2.48 log10 cfu/mL) and tebipenem/avibactam (1.71 log10 cfu/mL kill). The EC50 values of these drugs were 11.67, 9.52, 48.2 and 0.33 mg/L, respectively, below peak concentrations of these drugs.Conclusions: The low MICs and efficacy at clinically achievable concentrations mean that tebipenem/avibactam, daunorubicin, omadacycline and bedaquiline give a view of components of a three-drug regimen likely to effectively kill Mab. We propose pharmacokinetic/pharmacodynamic studies to identify such a regimen and the doses to be combined. [ABSTRACT FROM AUTHOR]

Background: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target.Methods: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity.Results: Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment.Conclusions: The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy.Lay Summary: Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs. [ABSTRACT FROM AUTHOR]

In this paper, we have solved one of the widely popular problems in the domain of control systems – distance optimization using two separate swarm intelligence algorithms – particle swarm and ant colony optimization. The problem is successfully solved with both algorithms and subsequently quantitative comparison between their performances is done. Simulated results show the more recently developed ant colony optimization algorithm to be better and more robust of the two. The requisite simulations are carried out and results are obtained in the MATLAB environment. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to evaluate the effectiveness of airway sonographic parameters as the predictors of difficult laryngoscopy and to evaluate the validity of combined sonographic and clinical tests. Materials and Methods: This prospective and observational study analyzed a sample of 200 patients who were categorized as having easy (Grades 1 and 2) or difficult (Grades 3 and 4) laryngoscopy based on the laryngoscopic criteria of Cormack-Lahane (CL). Sonographic parameters, including the anterior neck soft-tissue thickness at the level of vocal cord (ANS-VC), ANS tissue thickness at the level of hyoid, and ratio of depth of pre-epiglottic space to distance from epiglottis to midpoint of the distance between vocal cords and clinical parameters, including modified Mallampati class, thyromental distance, and hyomental distance ratio (HMDR), were analyzed. Univariate and multivariate regression analysis was used for the statistical analysis. Results: Twenty patients (10%) were categorized as having difficult laryngoscopy. Statistically significant differences between patients with difficult and easy laryngoscopy were noted for 5 of 6 parameters. The diagnostic validity profiles showed variable sensitivity (26.5%–87.5%) and good specificity (58.9%–94.2%) and negative predictive value (88.8%–97.03%). ANS-VC has the highest sensitivity (87.50%) and area under curve value (0.887), whereas HMDR showed highest specificity (94.2%) and highest accuracy (89.60%) which means it has low false-positive prediction rate. The combination of tests improved the diagnostic validity profile (highest area under the curve, 0.897). Conclusion: Sonographic predictors can help in identifying difficult laryngoscopy. Combined clinical and ultrasonographic parameters showed better validity profiles in comparison to the individual tests. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, few studies to date have examined long-term neurocognitive outcomes in survivors of childhood soft-tissue sarcoma.Methods: A total of 150 survivors (41% of whom were female with a mean current age of 33 years [SD, 8.9 years] and a time since diagnosis of 24 years [SD, 8.7 years]) and 349 community controls (56% of whom were female with a mean current age of 35 years [SD, 10.2 years]) completed comprehensive neuropsychological testing, echocardiography, electrocardiography, pulmonary function tests, endocrine evaluation, and physical examination. Patient-reported outcomes of health-related quality of life (HRQOL) and social attainment were collected. Survivors were compared with norms and controls on neurocognitive outcomes using general linear models, and on HRQOL and social attainment using modified Poisson models. The impacts of treatment and chronic health conditions on outcomes were examined using multivariable general linear models (effect size was expressed as unstandardized β estimates that reflected the unit of change from a mean of 0 and an SD of 1) and modified Poisson models (effect size expressed as relative risks).Results: Compared with controls and population norms, survivors demonstrated lower performance on measures of verbal reasoning (mean z score, -0.45 [SD, 1.15]; P < .001) mathematics (mean z score, -0.63 [SD, 1.07]; P < .001), and long-term memory (mean z score, -0.37 [SD, 1.14]; P < .001). Cumulative anthracycline exposure (per 100 mg/m2 ) was found to be associated with poorer verbal reasoning (β = -0.14 z scores; P = .04), reading (β = -0.09 z score; P = .04), and patient-reported vitality (relative risk, 1.32; 95% CI, 1.09-1.59). Neurologic and neurosensory chronic conditions were associated with poorer mathematics (neurologic conditions: β = -0.63 z score [P = 0.02]; and hearing impairment: β = -0.75 z scores [P < 0.01]). Better cognitive performance was associated with higher social attainment.Conclusions: Long-term survivors of soft-tissue sarcoma are at risk of neurocognitive problems and poor HRQOL associated with anthracycline treatment and chronic health conditions. [ABSTRACT FROM AUTHOR]

Objectives: Animal models have suggested that the combination of pretomanid with pyrazinamide and moxifloxacin (PaMZ) may shorten TB therapy duration to 3-4 months. Here, we tested that in the hollow-fibre system model of TB (HFS-TB).Methods: A series of HFS-TB experiments were performed to compare the kill rates of the PaMZ regimen with the standard three-drug combination therapy. HFS-TB experiments were performed with bacilli in log-phase growth treated for 28 days, intracellular bacilli treated daily for 28 days and semi-dormant Mycobacterium tuberculosis treated with daily therapy for 56 days for sterilizing effect. Next, time-to-extinction equations were employed, followed by morphism transformation and Latin hypercube sampling, to determine the proportion of patients who achieved a time to extinction of 3, 4 or 6 months with each regimen.Results: Using linear regression, the HFS-TB sterilizing effect rates of the PaMZ regimen versus the standard-therapy regimen during the 56 days were 0.18 (95% credible interval=0.13-0.23) versus 0.15 (95% credible interval=0.08-0.21) log10 cfu/mL/day, compared with 0.16 (95% credible interval=0.13-0.18) versus 0.11 (95% credible interval=0.09-0.13) log10 cfu/mL/day in the Phase II clinical trial, respectively. Using time-to-extinction and Latin hypercube sampling modelling, the expected percentages of patients in which the PaMZ regimen would achieve sterilization were 40.37% (95% credible interval=39.1-41.34) and 72.30% (95% credible interval=71.41-73.17) at 3 and 4 months duration of therapy, respectively, versus 93.67% (95% credible interval=93.18-94.13) at 6 months for standard therapy.Conclusions: The kill rates of the PaMZ regimen were predicted to be insufficient to achieve cure in less than 6 months in most patients. [ABSTRACT FROM AUTHOR]

Objectives: The emergence of MDR Gram-negative pathogens and increasing prevalence of chronic infections presents an unmet need for the discovery of novel antibacterial agents. The aim of this study was to evaluate the biological properties of a small molecule, IITR06144, identified in a phenotypic screen against the Gram-negative model organism Escherichia coli.Methods: A small-molecule library of 10956 compounds was screened for growth inhibition against E. coli ATCC 25922 at concentration 50 μM. MICs of lead compounds were determined by the broth microdilution method. Time-kill kinetics, anti-persister activity, spontaneous frequency of resistance, biofilm inhibition and disruption were assessed by standard protocols. Resistant mutants were generated by serial passaging followed by WGS. In vitro toxicity studies were carried out via the MTT assay. In vivo toxicity and efficacy in a mouse model were also evaluated.Results: IITR06144 was identified as the most promising candidate amongst 29 other potential antibacterial leads, exhibiting the lowest MIC, 0.5 mg/L. IITR06144 belongs to the nitrofuran class and exhibited broad-spectrum bactericidal activity against most MDR bacteria, including the 'priority pathogen', carbapenem-resistant Acinetobacter baumannii. IITR06144 retained its potency against nitrofurantoin-resistant clinical isolates. It displayed anti-persister, anti-biofilm activity and lack of spontaneous resistance development. IITR06144 demonstrated a large therapeutic index with no associated in vitro and in vivo toxicity.Conclusions: In the light of excellent in vitro properties displayed by IITR06144 coupled with its considerable in vivo efficacy, further evaluation of IITR06144 as a therapeutic lead against antibiotic-resistant infections is warranted. [ABSTRACT FROM AUTHOR]

In this paper, a simplified yet efficient architecture of a deep convolutional neural network is presented for lung image classification. The images used for classification are computed tomography (CT) scan images obtained from two scientifically used databases available publicly. Six external shape-based features, viz. solidity, circularity, discrete Fourier transform of radial length (RL) function, histogram of oriented gradient (HOG), moment, and histogram of active contour image, have also been identified and embedded into the proposed convolutional neural network. The performance is measured in terms of average recall and average precision values and compared with six similar methods for biomedical image classification. The average precision obtained for the proposed system is found to be 95.26% and the average recall value is found to be 69.56% in average for the two databases. [ABSTRACT FROM AUTHOR]

Measurement of nitrate nitrogen is relatively less easy and reliable, given the complexity of analytical procedures already marred by interferences. Interfering constituents like organics are frequently integral to the nature of the samples. As a result, in practice nitrate nitrogen () concentrations often go under-/over-reported. Objective of this study was to compare three analytical procedures extensively used for determination of , namely Ultraviolet Spectrophotometric Screening (UV) Method, Nitrate Electrode Method (Ion-Electrode method) and Phenol Disulphonic Acid (PDA) Method. Usually, these methods of nitrate measurement are commonly employed based on availability of analytical facilities rather than the characteristics of the samples that carry many constituents other than nitrates also, which can limit their application in certain cases. The paper can help serve as a guide to method selection. Comparative investigation on the basis of Passing–Bablok and Bland–Altman analyses showed that when samples had no organics, the accuracy of the three methods was in the order: UV > PDA > Ion-Electrode. Ion-Electrode method was found to be affected by a positive bias of 0.799 for a confidence interval of (0.161, 1.436). For samples containing organics, all three methods were affected by proportional bias. UV method was most affected by interference, exhibiting a bias, regression intercept and slope coefficient of −1.733, −1.359 and 0.922, respectively. Interference due to organics was further analysed experimentally and accuracy with respect to rising organic concentration was found to be in the order: UV < Ion-Electrode < PDA, i.e. PDA method gave least percentage error for high organic concentrations. Multiple linear regression (MLR) models were developed for predicting more accurate readings. MLR models based on two and four explanatory variables for PDA (R2 = 92.86%, predicted R2 = 91.33%) and UV method (R2 = 99.87%, predicted R2 = 99.83%) respectively are reported. [ABSTRACT FROM AUTHOR]

Risk and uncertainty are inherently associated with every novel developmental effort. Project Management integrates a variety of activities undertaken to successfully achieve project objectives. Various organizations across the globe have developed frameworks for guidance in these activities focused on different facet and elements in projects. In this paper based on open source literature review information about various project management frameworks is obtained, and a brief description of various frameworks for project management, their evolution, global utilization, their comparative analysis and tradeoff is presented. The mandate of Defence Research and Development Organization to indigenously develop defense technology and systems and become self-reliant is dependent on technological innovations and development which is managed using Procedures for Project Formulation and Management in DRDO (PPFM) guidelines. To attain the project objectives within time, budget and scope (QRs) constraints, over the years a systematic framework is devised. The intent of this research is to obtain best project management practices from available frameworks, assess their applicability and to enrich DRDO PPFM 2016 framework by augmenting it with the available best practices. [ABSTRACT FROM AUTHOR]

Rationale: There is poor understanding about protective immunity and the pathogenesis of cavitation in patients with tuberculosis.Objectives: To map pathophysiological pathways at anatomically distinct positions within the human tuberculosis cavity.Methods: Biopsies were obtained from eight predetermined locations within lung cavities of patients with multidrug-resistant tuberculosis undergoing therapeutic surgical resection (n = 14) and healthy lung tissue from control subjects without tuberculosis (n = 10). RNA sequencing, immunohistochemistry, and bacterial load determination were performed at each cavity position. Differentially expressed genes were normalized to control subjects without tuberculosis, and ontologically mapped to identify a spatially compartmentalized pathophysiological map of the cavity. In silico perturbation using a novel distance-dependent dynamical sink model was used to investigate interactions between immune networks and bacterial burden, and to integrate these identified pathways.Measurements and Main Results: The median (range) lung cavity volume on positron emission tomography/computed tomography scans was 50 cm3 (15-389 cm3). RNA sequence reads (31% splice variants) mapped to 19,049 annotated human genes. Multiple proinflammatory pathways were upregulated in the cavity wall, whereas a downregulation "sink" in the central caseum-fluid interface characterized 53% of pathways including neuroendocrine signaling, calcium signaling, triggering receptor expressed on myeloid cells-1, reactive oxygen and nitrogen species production, retinoic acid-mediated apoptosis, and RIG-I-like receptor signaling. The mathematical model demonstrated that neuroendocrine, protein kinase C-θ, and triggering receptor expressed on myeloid cells-1 pathways, and macrophage and neutrophil numbers, had the highest correlation with bacterial burden (r > 0.6), whereas T-helper effector systems did not.Conclusions: These data provide novel insights into host immunity to Mycobacterium tuberculosis-related cavitation. The pathways defined may serve as useful targets for the design of host-directed therapies, and transmission prevention interventions. [ABSTRACT FROM AUTHOR]

This randomized double-blind placebo-controlled trial evaluated the effects of early postnatal oral vitamin A supplementation (VAS) in 196 inborn very-low birth weight (VLBW) infants requiring respiratory support at 24 h of age. Eligible infants were randomized to receive aqueous syrup of vitamin A (10,000 IU of retinol/dose; n = 98) or placebo (n = 98) on alternate days for 28 days. Primary outcome variable was composite incidence of all-cause mortality and/or oxygen requirement for 28 days. Secondary outcome variables were safety/tolerability of VAS, serum retinol concentration at recruitment and day 28, duration of oxygen requirement and respiratory support and incidences of complications. On intention-to-treat analysis, composite incidence of all-cause mortality and oxygen requirement for 28 days was significantly lower in vitamin A group (relative risk (95% confidence interval), 0.440 (0.229-0.844); p < 0.05, number needed to benefit, 7). Requirement and duration of oxygen supplementation and non-invasive respiratory support, incidences of late-onset sepsis, patent ductus arteriosus, and duration of hospital stay were also significantly lower in vitamin A group. Serum retinol concentration improved significantly after VAS. No major adverse effect was observed.Conclusions: Early postnatal oral VAS was associated with better composite outcome of all-cause mortality and oxygen requirement without any major adverse effects.Clinical Trial Registration: Clinical Trials Registry of India (CTRI/2017/03/008131). What is Known: • Postnatal intramuscular vitamin A supplementation improves the survival, respiratory outcome and other morbidities in very low birth weight neonates without major adverse effects. • Limited studies on oral vitamin A supplementation did not document substantial benefits. What is New: • Early postnatal alternate-day oral vitamin A supplementation at the dose of 10,000 IU/dose for 28 days improves the composite outcome of death and oxygen requirement in very low birth weight neonates with respiratory distress • No major adverse effects were documented. [ABSTRACT FROM AUTHOR]

Purpose: This study describes the prevalence and predisposing factors for potentially modifiable unmet emotional, care/support, and information needs among adult survivors of childhood malignancies.Methods: A randomly selected/stratified sample of participants in the Childhood Cancer Survivor Study (CCSS) responded to the CCSS-Needs Assessment Questionnaire (CCSS-NAQ) (n = 1189; mean [SD] current age, 39.7 [7.7], range = 26-61 years; 60.9 % women; mean [SD] years since diagnosis, 31.6 [4.7]). Survivors self-reported demographic information, health concerns, and needs; diagnosis/treatment data were obtained from medical records. Adjusted proportional risk ratios (prevalence ratios, PRs) were used to evaluate 77 separate needs.Results: Fifty-four percent of survivors reported unmet psycho-emotional, 41 % coping, and 35 % care/support needs; 51, 35, and 33 %, respectively, reported unmet information needs related to cancer/treatment, the health care system, and surveillance. Female sex and annual income <$60K were associated with multiple needs; fewer needs were linked to diagnosis/years since/or age at diagnosis. Having moderate/extreme cancer-related anxiety/fear was associated with all needs, including a >6-fold increased prevalence for help dealing with "worry" (PR = 6.06; 95 % confidence interval [CI], 3.79-9.69) and anxiety (PR = 6.10; 95 % CI, 3.82-9.72) and a >5-fold increased prevalence for "needing to move on with life" (PR = 5.56; 95 % CI, 3.34-9.25) and dealing with "uncertainty about the future" (PR = 5.50; 95 % CI, 3.44-8.77). Radiation exposure and perceived health status were related to 42 and 29 needs, respectively.Conclusions: Demographic factors, disease/treatment characteristics, and intrapersonal factors can be used to profile survivors' unmet emotional, care/support, and information needs.Implications For Cancer Survivors: These data can be used to enhance provider-survivor communication, identify at-risk subsamples, and appraise core intervention content. [ABSTRACT FROM AUTHOR]

Introduction: and objective: Tremor is a disabling symptom of PD that usually responds poorly to available standard pharmacological agents. This study aimed to assess the effect of Zonisamide 25 mg on tremor in tremor-dominant PD patients as compared to placebo.Methods: This was a randomized, placebo-controlled, double-blind study. Parkinson's disease patients were allocated either to the intervention group (standard treatment along with Zonisamide 25 mg add-on) or the placebo group (standard treatment along with placebo). Baseline Unified Parkinson's Disease Rating Scale (UPDRS) and Tremor Research Group Essential Tremor Rating Scale (TETRAS) scores, as well as accelerometric tremor analysis were done and follow-up assessments of the same were done after 12 weeks of intervention. Percentage change from baseline in the UPDRS tremor score was the primary outcome whereas percentage change from baseline of total UPDRS score, UPDRS rigidity and bradykinesia scores, TETRAS score, and accelerometric tremor analysis values were the secondary outcomes.Results: There was no significant difference in the percentage change from baseline UPDRS tremor scores between the two groups (placebo: 8.33 [-19.89-23.86] vs drug: 26.14 [-35.58 to -16.07], p-value: 0.164, CI: 0.157-0.171). Best-case analysis for missing values showed a significant improvement in the drug group, compared to the placebo group (p-value: < 0.001, CI: <0.001 - <0.001).Conclusion: Zonisamide at a dose of 25 mg per day did not improve tremor in tremor-dominant PD patients, however, a positive trend was seen as compared to Placebo in the UPDRS tremor score. Larger studies are required to confirm this finding. [ABSTRACT FROM AUTHOR]