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Cardiorespiratory complications are among the most common causes of postoperative morbidity and mortality and impose a significant financial burden on the NHS. Patients with premorbid cardiorespiratory diseases can be identified preoperatively with a thorough history taking along with targeted investigations. Preoperative evaluation, risk assessment and stratification allows for clear identification of higher risk patients who would benefit from preoperative medical optimization, appropriate planning of perioperative care including anaesthetic management, modification of surgical procedure and the level of postoperative care required as a part of risk reduction strategies.

This case report demostrates an unusual occurence of orbital metastasis along with liver metastasis 5 years following enucleation for ciliochoroidal melanoma with no extraocular extension. It exemplifies that metastasis of the tumour can occur in the ipsilateral orbit after enucleation. Importance of close clinical follow-up after enucleation for choroidal melanoma, careful socket examination, and regular systemic metastatic workup is demonstrated. To the best of our knowledge, this is the first case report of uveal melanoma with ipsilateral orbital metastasis.

An 8-year-old girl presented with painless decreased vision and leukocoria in the right eye since 6 days. There was no antecedent history of trauma. Visual acuity in the right eye was counting fingers 1 m. Ocular examination revealed right exotropia, conjunctival congestion, anterior chamber cells

Alkaptonuria is a rare genetic disorder resulting in abnormality of tyrosine metabolism. It is one of the Garrod’s tetrad of ‘inborn errors of metabolism’ proposed to have Mendelian recessive inheritance. The disorder is characterised by deposition of homogentisic acid leading to ochronosis and ochronotic osteoarthropathy; however, blackish discoloration of urine is the only childhood manifestation. Other manifestations present only after third decade. A 13-year-old boy presented to paediatric nephrology clinic with blackish discolouration of urine since infancy. Examination revealed bluish black discolouration of bilateral sclera and ear cartilage; however, he had no symptoms of ochronotic osteoarthropathy. Genetic test pointed towards alkaptonuria. Currently, he is on regular follow-up and is being treated with vitamin C to delay the progression of the disease. Early diagnosis with appropriate intervention delays the onset of complications and preserves the quality of life of the patient.

The aim of this study is to recognize human emotions from electroencephalographic (EEG) signals using deep neural networks. Large training data is an important prerequisite for successful implementation of deep neural networks. In this view, we propose an independent component analysis (ICA) - evolution based data augmentation method. This method performs ICA to extract and accumulate clean independent components (ICs) of each class. The new ICs are generated by selection which uses a fitness function such as mutual information (MI) and crossover in component space. Data augmentation is done by performing mutation, and crossover on generated data in sensor space. Since EEG signals are non-stationary, with time-varying frequency contents, emotional patterns associated with EEG are detected in the time-frequency (TF) domain using a spectrogram. To extract emotion related features from a spectrogram, we train an ensemble convolutional neural networks (CNNs) with convolutional kernels in the time and frequency axes. The information integrated over both the axes is concatenated and fed to long short-term memory (LSTM). We used the benchmark DEAP dataset for emotion classification to evaluate our approach. The results highlight the potential of proposed ICA-evolution based data augmentation and an ensemble CNNs with LSTM model for emotion recognition.

Summary Aim Orbital subperiosteal hematoma (OSPH) is a rare entity following blunt trauma that can significantly affect the vision of a growing child. The purpose of this study was to describe the spectrum of the clinical presentations along with the imaging findings and treatment outcome of traumatic OSPH. Case Series This is a retrospective case series of six patients below 16 years of age, diagnosed with OSPH following trauma. Electronic medical records were reviewed for details of clinical features, imaging findings, management details and outcomes. Discussion The median duration of the presentation was 7 days (range 6–50 days). Proptosis and dystopia remained the most common presenting features. Significant vision loss was noted in four patients at presentation. A computed tomography (CT) scan revealed the superior quadrant of the orbit to be involved most frequently. Five patients were treated surgically and one conservatively. Significant vision loss was noted in one patient despite of initial surgical management. Conclusion Although rare, OSPH should be considered as a differential in children presenting with proptosis and dystopia following blunt trauma. Younger children are particularly at higher risk for developing permanent visual loss and should be treated promptly by draining the OSPH.

BACKGROUND & AIMS: A non-endoscopic approach to Barrett’s esophagus (BE) surveillance after radiofrequency ablation (RFA) would offer a less invasive method for monitoring. We assessed the test characteristics and cost-effectiveness of the Cytosponge® in post-RFA patients. METHODS: We performed a multicenter study of dysplastic BE patients after at least one round of RFA. A positive Cytosponge® before endoscopy was defined as intestinal metaplasia (IM) on cytological assessment and/or TFF3 immunohistochemistry. Sensitivity, specificity, and receiver operator characteristic (ROC) curves were calculated. Multivariable regression was used to estimate the odds of a positive Cytosponge® in BE. A microsimulation cost-effectiveness model was performed to assess outcomes of various surveillance strategies: endoscopy-only, Cytosponge®-only, and alternating endoscopy/Cytosponge®. RESULTS: Of 234 patients, Cytosponge® adequately sampled the distal esophagus in 175 (75%). Of the 142 with both endoscopic and histologic data, 19 (13%) had residual/recurrent BE. For detecting any residual Barrett’s, Cytosponge® had a sensitivity of 74%, specificity of 85%, accuracy of 84%, and ROC curve showed an area under the curve of 0.74. The adjusted odds of a positive Cytosponge® in BE were 17.1 (95% CI: 5.2–55.9). Cytosponge®-only surveillance dominated all the surveillance strategies, being both less costly and more effective. Cytosponge®-only surveillance required

Background The case-fatality ratio (CFR) for enteric fever is essential for estimating disease burden and calibrating measures that balance the likely health gains from interventions against social and economic costs. Methods We aimed to estimate the CFR for enteric fever using multiple data sources within the National Surveillance System for Enteric Fever in India. This surveillance (2017–2020) was established as a multitiered surveillance system including community cohorts (tier 1), facility-based (tier 2), and tertiary care surveillance (tier 3) for estimating the burden of enteric fever in India. The CFR was calculated after accounting for healthcare-seeking behavior for enteric fever and deaths occurring outside the hospital. Results A total of 1236 hospitalized patients with blood culture–confirmed enteric fever were enrolled, of which 9 fatal cases were identified, for an estimated hospitalized CFR of 0.73% (95% confidence interval [CI], .33%–1.38%). After adjusting for severity, healthcare-seeking behavior, and deaths occurring out-of-hospital, the CFR was estimated to be 0.16% (95% CI, .07%–.29%) for all enteric fevers. Conclusions Our estimates of the CFR are relatively lower than previously estimated, accounting for care-seeking behavior and deaths outside the hospital.

Background Sentinel events are negative health-related events that trigger change in risky health behaviors. Despite its presumed major role in behavior change, the sentinel event effect has received little empirical attention. Through analysis of qualitative interviews, we explored how sentinel events trigger behavior change. Methods Thematic analysis and concept mapping were used to develop a preliminary model of the sentinel event effect among a sample of 24 adult heavy drinking Mexican-origin men previously admitted to a hospital due to injury. The model was checked against cases that did versus did not report change in alcohol use following an alcohol-related negative event. Results Findings suggest that sentinel events may arouse negative emotional reactions, encourage reflection on the negative consequences of drinking, and cause reevaluation of the severity and significance of drinking. These processes may increase motivation to change. Conclusions Findings support the concept of the sentinel event as a natural intervention, and identifies potential social-cognitive and motivational mechanisms through which it influences change. Findings stand to inform research on mechanisms underlying brief intervention effects, and research that seeks to identify treatment targets.

Females have been understudied in pre-clinical and clinical traumatic brain injury (TBI), despite distinct biology and worse clinical outcomes versus males. Sulfonylurea receptor 1 (SUR1) inhibition has shown promising results in predominantly male TBI. A phase II trial is ongoing. We investigated whether SUR1 inhibition effects on contusional TBI differ by sex given that this may inform clinical trial design and/or interpretation. We studied the moderating effects of sex on post-injury brain tissue loss in 142 male and female ATP-binding cassette transporter subfamily C member 8 (Abcc8) wild-type, heterozygote, and knockout mice (12–15 weeks). Monkey fibroblast-like cells and mouse brain endothelium-derived cells were used for in vitro studies. Mice were injured with controlled cortical impact and euthanized 21 days post-injury to assess contusion, brain, and hemisphere volumes (vs. genotype- and sex-matched naïves). Abcc8 knockout mice had smaller contusion volumes (p = 0.012) and larger normalized contralateral (right) hemisphere volumes (nRHV; p = 0.03) after injury versus wild type. This was moderated by sex: Contusions were smaller (p = 0.020), nRHV was higher (p = 0.001), and there was less global atrophy (p = 0.003) in male, but not female, knockout versus wild-type mice after TBI. Less atrophy occurred in males for each copy of Abcc8 lost (p = 0.023–0.002, all outcomes). In vitro, sex-determining region Y (SRY) stimulated Abcc8 promoter activity and increased Abcc8 expression. Loss of Abcc8 strongly protected against post-traumatic cerebral atrophy in male, but not female, mice. This may partly be mediated by SRY on the Y-chromosome. Sex differences may have important implications for ongoing and future trials of SUR1 blockade.

Objective To investigate in a large global sample of patients with retinoblastoma whether sex predilection exists for this childhood eye cancer. Methods A cross-sectional analysis including 4351 treatment-naive retinoblastoma patients from 153 countries who presented to 278 treatment centers across the world in 2017. The sex ratio (male/female) in the sample was compared to the sex ratio at birth by means of a two-sided proportions test at global level, country economic grouping, continent, and for selected countries. Results For the entire sample, the mean retinoblastoma sex ratio, 1.20, was higher than the weighted global sex ratio at birth, 1.07 (p n = 1940), 1.23 vs. 1.07 (p = 0.019); Asia (n = 2276), 1.28 vs. 1.06 (p n = 558), 1.52 vs. 1.11 (p = 0.008). Sensitivity analysis, excluding data from India, showed that differences remained significant for the remaining sample (χ2 = 6.925, corrected p = 0.025) and for Asia (χ2 = 5.084, corrected p = 0.036). Excluding data from Asia, differences for the remaining sample were nonsignificant (χ2 = 2.205, p = 0.14). Conclusions No proof of sex predilection in retinoblastoma was found in the present study, which is estimated to include over half of new retinoblastoma patients worldwide in 2017. A high male to female ratio in Asian countries, India in specific, which may have had an impact on global-level analysis, is likely due to gender discrimination in access to care in these countries, rather than a biological difference between sexes.

Neocortical projection neurons are generated by neural progenitor cells (NPCs) within the ventricular and subventricular zone. While early NPCs can give rise to both deep and upper layer neurons, late progenitors are restricted to upper layer neurogenesis. The molecular mechanisms controlling the differentiation potential of early versus late NPCs are unknown. Here, we report a novel function for TrkC-T1, the non-catalytic isoform of the neurotrophin receptor TrkC, that is distinct from TrkC-TK+, the full-length isoform. We provide direct evidence that TrkC-T1 regulates the switch in NPC fate from deep to upper layer neuron production. Elevated levels of TrkC-T1 in early NPCs promote the generation of deep layer neurons. Conversely, downregulation of TrkC-T1 in these cells promotes upper layer neuron fate. Furthermore, we show that TrkC-T1 exerts this control by interaction with the signaling adaptor protein ShcA. TrkC-T1 prevents the phosphorylation of Shc and the downstream activation of the MAP kinase (Erk1/2) pathway. In vivo manipulation of the activity of ShcA or Erk1/2, directly affects cortical neuron cell fate. We thus show that the generation of upper layer neurons by late progenitors is dependent on the downregulation of TrkC-T1 in late progenitor cells and the resulting activation of the ShcA/Erk1/2 pathway.

BACKGROUND The purpose of present study was to compare and evaluate both topical lignocaine and intravenous lignocaine for laryngeal mask airway (LMA) insertion prior to propofol. Main objective was to study the conditions for LMA insertion with respect to gagging, coughing, Laryngospasm and No. of attempts for LMA insertion and also study the hemodynamic parameters in both the groups (Heart rate, SBP,DBP, MAP, SpO2) METHODS This study included 60 patients of 30 in each group, ASA I & II day care surgeries were performed in our hospital between 2019 and 2021. Patients were randomized into two groups. Group I received intravenous lignocaine 1.5 mg / kg over 30 seconds and group II received topical lignocaine 40 mg. Conditions of LMA insertion, gagging, laryngospasm, coughing were noted at the time of insertion, ECG, NIBP, SPO2 and ETCO2 were recorded according to scheduled times. RESULTS In conditions of LMA insertion, difference between both the groups was found to be significant, P < 0.05 in groups with first minute rise in heart rate, fall in Systolic blood pressure, diastolic blood pressure, mean arterial pressure was significant. At two minutes and three minutes after the LMA insertion, HR, SBP, DBP, MAP all these parameters changed slightly but these changes were statistically not significant. CONCLUSIONS Prior to Propofol induction, compared to intravenous lignocaine, topical lignocaine 10 % aerosol provided excellent conditions for the insertion of LMA without the use of neuromuscular blockers. KEY WORDS IV Lignocaine, Topical Lignocaine, LMA

A pandemic leads to disruption and stretching of an existing health care system and its resources. Coronavirus disease 2019 (COVID-19) data show distinct and severe manifestations in children necessitating critical care. Children need prioritization as they are susceptible to COVID-19 as part of the family cluster, varied presentations, and mortality. The purpose of this report is to discuss the optimization of the health care system for pediatric care. The key initiatives were to identify our objectives, bring out changes to the organizational processes, and integrate the same into the existing system. A systems approach to health care delivery by optimizing infrastructure, human resources, materials, funding, leadership, and governance was undertaken. This resulted in creation of distinct COVID-19 and non-COVID-19 service areas, management protocols, and trained health care workers. Partnership was forged with the public health system. This preparedness and continued responses to the demands of the health care system helped us manage children ranging from neonates to adolescents efficiently. Though the health care system is mostly open, acting upon the modifiable factors gave better preparedness in a short time.

Objective To understand the utilisation of drug information services provided in India. Key findings The quantitative aspects of drug information queries were assessed. Majority of the queries were raised from the General Medicine Department (43.64%) and by clinicians (41.77%), most of them were regarding adverse drug reactions (18.17%) and the prime purpose of the enquirer was to update knowledge (46.73%). The three steps for qualitative assessment and evaluation of drug information services were assessed and the overall response from the receiver’s perspective was found to be very good/satisfactory and the provider’s perspective was rendered excellent. Summary There is an increased need to expand the scope of drug information services and promote awareness regarding the services and it is recommended that every hospital have a Drug Information Centre.

Background: laminectomy surgeries are usually performed in cases of spinal canal stenosis, disc prolapse etc. It has been reported that the use of regional anesthesia techniques in combination to general anaesthesia has shown better heamodynamic stability intraoperatively, better pain scores and reduced intraoperative blood loss. The present study was conducted to evaluate the efficacy of fusion technique of combining epidural and general anaesthesia in patients undergoing lumbar laminectomies. Aim: To evaluate the efficacy of combined epidural general anesthesia for lumbar laminectomy surgeries with epidural ropivacaine. Materials and Methods: A prospective randomised study was conducted in 100 patients who are scheduled for lumbar laminectomy surgeries belonging to ASA Class I and II age between 40-60 years were randomly allocated into two groups (Group E and Group F) of 50 each. Group E: 12ml of 0.5% Ropivacaine and 50µg fentanyl epidurally. Group F:12ml of Normal Saline and 50µg fentanyl epidurally. The parameters recorded were intraoperative analgesia by heart rate and blood pressure, Rescue analgesia, Blood loss. Results: Intraoperatively requirement of general anesthetics, Heart rate, MBP, Blood loss, is lesser in Group E when compared with Group F. It was observed that longer time to rescue analgesia in group E than in group F. Conclusion: combined epidural general anesthesia with local anesthetic (ropivacaine) with narcotic (fentanyl) is a better technique for anesthetic management of patients posted for lumbar laminectomy. Thus from our study we conclude that combined epidural general anesthesia technique with epidural ropivacaine is a better alternative to general anesthesia providing stable hemodynamics, reducing dose of general anesthetics, less blood loss.

Tizanidine is an α 2 receptor agonist derived from clonidine with primary central myotonolytic action along with antinociceptive and anticonvulsant action. Unlike clonidine, there are few studies evaluating the role of tizanidine as an effective anaesthetic premedication. Hence this study was undertaken to evaluate oral tizanidine [2 mg and 4 mg] administered preoperatively in decreasing the intraoperative consumption of isoflurane. This prospective, randomised, double blind control trial was undertaken in 75 adult patients scheduled for elective laparoscopic surgeries. The subjects were randomly allocated into 3 groups with Group A (2 mg tizanidine), Group B (4 mg tizanidine), Group C (sugar pellet). The study drug was administered orally 90 minutes preoperatively. Intraoperative isoflurane consumption and end tidal isoflurane was recorded. Demographic data was comparable between the 3 groups. We observed a significant fall in isoflurane consumption in the tizanidine groups [Total: group A = 10.24 (2.07) ml, group B = 8.09 (2.17) ml, group C = 15.43 (4.77), p < 0.001; at 30 min: group A = 6.86 (0.91), group B = 5.22 (0.67), group C = 8.10 (1.15), p < 0.001; at 60 min: group A = 9.29 (0.73), group B = 7.92 (1.31), group C = 12.88 (2.45), p < 0.001; at 90 min: group A = 11.13 (0.83), group B = 10.25 (2.63), group C = 17.25 (2.5), p Oral tizanidine [2mg and 4 mg] is as effective and safe anaesthetic premedication in decreasing isoflurane consumption.

OBJECTIVE To assess the effectiveness in preventing cesarean section for failed induction by using Foley catheter for cervical ripening in comparison to Foley catheter with a weight attached to it. METHODS A randomized control trial conducted between November 2018 and July 2020, which looked at induction of labor with 30-ml Foley catheter in one arm and the Foley placed with a 500 ml weight attached to it in the other arm. Primary outcome was the cesarean section rate. RESULTS We randomized 399 women. Modes of delivery were similar in both groups. Numbers undergoing cesarean section for failed induction were higher in the group that underwent induction with Foley with weight but this was not statistically significant (45.7% vs 26.5%, P = 0.1). There was a shorter time to expulsion of the Foley with weight attached (mean ± standard deviation: 2.6 ± 3.3 h vs 10.9 ± 3.2 h, P

Background Patients with COVID-19 acute respiratory distress syndrome (ARDS) have been shown to have high sedation requirements. Objective The purpose of this study was to compare sedative use between patients with COVID-19 ARDS and non-COVID-19 ARDS. Methods This was a retrospective study of patients with COVID-19 ARDS compared with historical controls of non-COVID-19 ARDS who were admitted to 2 hospitals from March 1, 2020, to April 30, 2020, and April 1, 2018, to December 31, 2019, respectively. The primary outcome was median cumulative dose of propofol (µg/kg) at 24 hours after intubation. Results There were 92 patients with COVID-19 ARDS and 37 patients with non-COVID-19 ARDS included. Within the first 24 hours of intubation, patients with COVID-19 ARDS required higher total median doses of propofol: 51 045 µg/kg (interquartile range, 26 150-62 365 µg/kg) versus 33 350 µg/kg (9632-51 455 µg/kg; P = 0.004). COVID-19 patients were more likely receive intravenous lorazepam (37% vs 14%; P = 0.02) and higher cumulative median doses of midazolam by days 5 (14 vs 4 mg; P = 0.04) and 7 of intubation (89 vs 4 mg; P = 0.03) to achieve the same median Richmond Analgesia-Sedation Scale scores. COVID-19 ARDS patients required more ventilator days (10 vs 6 days; P = 0.02). There was no difference in 30-day mortality. Conclusion and Relevance Patients with COVID-19 ARDS required higher doses of propofol and benzodiazepines than patients with non-COVID-19 ARDS to achieve the same median levels of sedation.

Gender disparities remain in the field of gastroenterology (GI) despite the decreasing gender gap in the medical field overall. We sought to examine primary and last female authorship as a marker of academic opportunity and advancement to assess the proportion of women publishing in GI over 20 years (1997–2017). In this observational study, we assessed the gender and nationality of primary and last authors of original research manuscripts in three GI journals (Gastroenterology, Gut, and American Journal of Gastroenterology) across a 20-year period in 5-year intervals (in 1997, 2002, 2007, and 2012). We used a validated gender-determining algorithm, genderize.io, to classify gender. Our primary outcome was the proportion of female primary and last authors, with secondary measures assessing trends in gender and nationality. Through the Genderize.io gender database, we were able to identify the gender for 3,673 (95.9%) of primary author names and 3,504 (95.4%) of last author names in the 3,615 manuscripts evaluated. Overall, there was a significant increase in female primary authors over time, from 18.1% in 1997 to 42.6% in 2017, a 6.0% increase per 5-year period (95% CI 4.8–7.2%). A similar trend was found for female last authors, however, at a slower rate, from 8.3% in 1997 to 24.7% in 2017, a 3.5% increase per 5 years (95% CI 2.5–4.4%). These trends were noted cumulatively, and in each journal individually. Manuscripts with a female last author were more likely to demonstrate a female primary author. Female authorship in high-impact gastroenterology journals has increased over time. Last authorship has lagged primary authorship in female representation and has increased more slowly over time. Interventions to reduce gender disparity in GI research should focus on the transition from first to last authorship.

Background: Calculous cholecystitis is the most common lesion of the gallbladder. Pain abdomen is the common clinical presentation.Calculous and acalculous cholecystitis are the most common indications for cholecystectomy. Gross and microscopic examination of the gall bladder indicates the outcome of the lesions. The various histological findings will reveal the type of the disease entity and prognosis. Materials and Methods: Retrospective study was done, total 120 cases of cholecystectomy specimens were received in pathology department. Formalin fixed specimens were analysed. After processing, H&E stained sections were studied. Results: Chronic calculous cholecystitis is the most common non-neoplastic lesion. calculous cholecystitis(92 cases), acalculous cholecystitis (21 cases), follicular cholecystitis (4 cases), empyema gallbladder (1 case), xanthogranulomatous cholecystitis (1 case), eosinophilic cholecystitis (1 case). Among premalignant lesions, cholecystitis with metaplasia was seen in 40 (33.3%) cases. Pyloric metaplasia (25 cases), Intestinalmetaplasia (15 cases). Conclusion: Chronic calculous cholecystitis was the most common lesion. Histopathological evaluation plays an important role in identifying the metaplastic, dysplastic and incidental carcinoma of the gallbladder. Keywords: Chronic Calculous Cholecystitis, Cholecystectomy, Metaplasia.

The bacterial leaf blight in rice caused by Xanthomonas oryzae pv. oryzae (Xoo) affects crop losses worldwide. In spite of developing resistant varieties by introgressing different Xa genes, the occurrence of diseases is evident. Here we report identification of several genes that are associated with improved plant immunity against Xoo in a resistant genotype BPT-5204 in comparison with susceptible genotype TN-1. The RNA sequencing information was developed to identify the genes that could provide durable resistance in rice. Xoo-resistant rice genotype BPT-5204 with Xa 5, 13 and 21 genes is compared with sensitive Taichung Native 1 (TN-1) to identify the genetic pathways and gene networks involved in resistance mechanisms. The higher levels of salicylic acid resulted in upregulation of many pathogenesis-related (PR) and redox protein encoding transcripts which resulted in higher hypersensitive response in BPT-5204. Many Serine/threonine protein kinase, leucine-rich repeat (LRR) transmembrane protein kinase, protein kinase family genes, Wall-associated kinase (WAK) were upregulated that resulted in activation of bZIP, WRKY, MYB, DOF and HSFs transcription factors that are associated with improved plant immunity. The study provided roles of many genes and their associated plant immunity pathways that can be used for developing resistant rice cultivars.

Aim: Carcinoma of the breast is one of the most common malignancy in women. Considering the tumour size, histological grade and number of lymph nodes involved, Nottingham Prognostic index (NPI) is calculated. This study has been designed to acquire information about various parameters in breast carcinomas and to calculate NPI score in each case and determine the relationship of NPI with various prognostic markers in breast carcinomas. Materials and Methods: The present study was undertaken in the Department of Pathology, Father Muller Medical College, Mangalore for a period of two years. Breast cancers, diagnosed as Invasive carcinoma breast of no special type on lumpectomy and mastectomy was studied and cases were assessed with regard to age, laterality, quadrant involved, size of the tumour, lymph node status, modified SBR grade, hormonal receptor status (ER, PR), HER-2/Neu, Ki-67 and NPI status of the tumour. Statistics: Cross tabulation was done to check for correlation and Kappa statistics was done to check the level of agreement between NPI and modified SBR grade, ER, PR, HER-2/Neu and Ki-67. Results and Conclusion: This study included a total of 100 infiltrating ductal carcinomas of the breast. The mean age of presentation was 52.05 years. On cross tabulation of NPI with pathological parameters only modified SBR grade showed statistically significant association with NPI at 5% level of significance(‘p’ Keywords: Breast neoplasms, Carcinoma, Ductal, NPI.

Introduction Basal angle, Boogaard’s angle, and clival angle are frequently used in diagnosing the craniometric angle malformations either on radiography or now more on MRI. But anatomic and clinical studies have used varied terms for these parameters. We aimed to look for these parameters among a normal south Indian adult population to standardize the measurements and their terminology. Materials and Methods One hundred MRI images (50 males and 50 female) were studied retrospectively. MRI images that were reported as normal by neuroradiologist were taken up for the study. Mean and the standard deviation of males and females were calculated for basal angle, Boogaard’s angle, and clival angle, separately. Unpaired t-test was used to analyze the significant difference (p < 0.05) between the genders. The intraclass coefficient correlation was used to analyze the interobserver variability. Results The mean value of basal angle in males and females are 113°and 114°, respectively. The mean value of Boogaard’s angle in males and females are 120°and 121°, respectively. The mean value of clival angle in males and females are 157°and 155°, respectively. There was no statistically significant difference (p > 0.05) between males and females in all three angles. Conclusion Knowledge about the normal angles will be an important tool in understanding the normal and abnormal skull base. Since the type of skull varies in accordance with race, the normal craniometric angle also varies in accordance with race. The present study tried to standardize the parameters of normal skull base angles for appropriate correction of the anomalies and uniform usage of terminology.

Measles (Me) and rubella (Ru) viral diseases are targeted for elimination by ensuring a high level of vaccination coverage worldwide. Less costly, more convenient MeRu vaccine delivery systems should improve global vaccine coverage, especially in low - and middle - income countries (LMICs). In this work, we examine formulating a live, attenuated Me and Ru combination viral vaccine with Nanopatch™, a solid polymer micro-projection array for intradermal delivery. First, high throughput, qPCR-based viral infectivity and genome assays were established to enable formulation development to stabilize Me and Ru in a scaled-down, custom-built evaporative drying system to mimic the Nanopatch™ vaccine coating process. Second, excipient screening and optimization studies identified virus stabilizers for use during the drying process and upon storage in the dried state. Finally, a series of real-time and accelerated stability studies identified eight candidate formulations that met a target thermal stability criterion for live vaccines (

Predicting language therapy outcomes in bilinguals with aphasia (BWA) remains challenging due to the multiple pre- and poststroke factors that determine the deficits and recovery of their two languages. Computational models that simulate language impairment and treatment outcomes in BWA can help predict therapy response and identify the optimal language for treatment. Here we used the BiLex computational model to simulate the behavioral profile of language deficits and treatment response of a retrospective sample of 13 Spanish-English BWA who received therapy in one of their languages. Specifically, we simulated their prestroke naming ability and poststroke naming impairment in each language, and their treatment response in the treated and the untreated language. BiLex predicted treatment effects accurately and robustly in the treated language and captured different degrees of cross-language generalization in the untreated language in BWA. Our cross-validation approach further demonstrated that BiLex generalizes to predict treatment response for patients whose data were not used in model training. These findings support the potential of BiLex to predict therapy outcomes for BWA and suggest that computational modeling may be helpful to guide individually tailored rehabilitation plans for this population.

Background We have previously demonstrated that a pooled population of bone marrow-derived, allogeneic mesenchymal stromal cells (BMMSC), Stempeucel®-1, produced under good manufacturing practices (GMP) conditions, showed clinical efficacy and safety in patients suffering from critical limb ischemia (CLI) due to Buerger’s disease. While Stempeucel®-1 is currently used for CLI and other clinical indications, we wanted to ensure that the product’s continuity is addressed by developing and characterizing a second generation of pooled product (Stempeucel®-1A), manufactured identically from second BM aspirates of the same three donors after a 2-year interval. Methods The two versions of Stempeucel® were manufactured and subjected to gene and protein expression analysis. The nature of various growth factors/cytokines secreted and immunomodulatory activity of these two cell populations were compared directly by various in vitro assays. The preclinical efficacy of these two cell types was compared in an experimental model of hind limb ischemia (HLI) in BALB/c nude mice. The reversal of ischemia, blood flow, and muscle regeneration were determined by functional scoring, laser Doppler imaging, and immunohistochemical analyses. Results Qualitative and quantitative analyses of genes and proteins involved in promoting angiogenic activity and immune regulatory functions revealed high levels of correlation between Stempeucel®-1 and Stempeucel®-1A cell populations. Moreover, intramuscular (i.m) administration of these two cell products in the ischemic limbs of BALB/c nude mice showed significant repair (≥ 70%) of toe and foot necrosis, leading to improved ambulatory function and limb salvage. Furthermore, a biodistribution kinetics study showed that Stempeucel®-1 was mostly localized in the ischemic muscles of mice for a significantly longer time compared to normal muscles, thus playing an essential role in modulating and reversing HLI damage. Conclusions This study shows that with a reproducible manufacturing procedure, it is possible to generate large numbers of pooled mesenchymal stromal cells from human bone marrow samples to establish product equivalence. We conclude from these results that, for the first time, two pooled, allogeneic BMMSC products can be repeatedly manufactured at different time intervals using a two-tier cell banking process with robust and comparable angiogenic properties to treat ischemic diseases.

Objectives Cardiovascular diseases (CVDs) are highly prevalent in various countries, and heart failure accounts for the majority of deaths. The present study focuses on determining the protective effect of ethanol extract of leaves of Tamarindus indica (TIEE) by in vitro and in vivo methods. Methods In vitro cardiotonic activity was determined using Langendorff’s heart perfusion assembly. In vivo studies were performed using Doxorubicin (1.5 mg/kg, i.p for seven days) induced cardiotoxicity in rats. These animals were simultaneously treated with the TIEE at a low dose (200 mg/kg, p.o), high dose (400 mg/kg, p.o) and standard drug Digoxin (100 μg/kg, p.o) for seven days. At the end of the study, various parameters like electrocardiogram (ECG) recording, serum levels of serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), and presence of cardiac troponin (cTnI) were determined. Isolated hearts were subjected to histopathological studies. Results The TIEE at a concentration of 60 μg/mL showed a significant cardiotonic effect in vitro that was evident by increased force of contraction, heart rate, and cardiac output. In vivo studies revealed that the TIEE decreased the prolongation of QT and RR interval of ECG, lowered the serum enzyme levels like LDH, CPK indicating cardiac protection, and the same was established by the absence of cTnI in blood. Histopathological examinations of heart tissue sections showed improved architecture in the treatment groups when compared with diseased groups. Conclusions The study revealed the cardioprotective activity of T. indica leaf extract by both in vitro and in vivo methods.

Background Little is known about esophageal dilation as a long-term treatment approach for eosinophilic esophagitis (EoE). We examined the impact of a “dilate and wait” strategy on symptom management and safety of patients with EoE. Methods This retrospective cohort study included two patient groups: those who underwent a dilation-predominant approach (≥ 3 dilations as sole therapy or for histologically refractory disease [> 15 eos/hpf]); and those who had routine care ( Results 53/205 patients (26 %) received the dilation-predominant strategy (total 408 dilations), predominantly for histologic treatment nonresponse (75 %). These patients were younger (33 vs. 41 years; P = 0.003), had a narrower baseline esophageal diameter (9.8 vs. 11.5 mm; P = 0.005), underwent more dilations (7.7 vs. 3.4; P Conclusions A dilation-predominant long-term treatment strategy allowed for symptom control or bridge to clinical trials for patients with difficult-to-treat EoE. Close follow-up and monitoring for complications are required.

Selective serotonin reuptake inhibitors (SSRI's) are the most commonly prescribed antidepressants. They are mainly prescribed to treat depression. SSRI's are considered to be safer and generally cost effective when compared to some newer antidepressant classes. SSRI's acts by inhibiting the serotonin transporter (SERT) at the presynaptic axon terminal. A number of factors must be considered when evaluating SSRI's. An SSRI drug utilization study is performed for further evaluation. The study was a prospective obs Methodology: ervational study on “Utilization and Evaluation of SSRI's in Psychiatry Patients”, which was carried out in the 'Department of Psychiatry' in a Secondary care teaching hospital of South India. Study the maximum number of patients was 786 and the age groups of 981 out of which m Results: aximum were of age group 46-54 and minimum were above 60, the female were more suffered in that maximum were married and the educational levels of the patients were mostly secondary, the hygienic conditions, surroundings and cleanliness were good. Discussion: Recent studies also found that mostly used SSRIs are Fluoxetine, Paroxetine, Citalopram and Sertraline. We found that in our hospitals the data reveals the status for some mostly used Fluoxetine as 386 (49.10%) and Paroxetine 288 (36.64%). Conclusion: Our study concluded that most of the patients suffered with psychological conditions and symptoms are considered. After using SSRI their overall effect in the patient health and outcome was observed with better outcome.

Objective Clitoria ternatea is a well-known bioactive plant used to treat several inflammatory ailments in Ayurvedic system of medicine in India. The present investigation aimed to determine the anti-inflammatory and anti-arthritic activity of ethanolic extract of Clitoria ternatea roots (EECT) in animal models. Methods The anti-inflammatory activity of the EECT was evaluated by carrageenan and histamine-induced paw edema. Results EECT showed a significant reduction in mean paw edema volume in both carrageenan and histamine-induced inflammation. The efficacy of EECT in rheumatoid arthritis was tested against Freund’s complete adjuvant (CFA) induced arthritic model in Wistar rats. The anti-arthritic effect of EECT was determined by systematic scoring of arthritis symptoms and measuring paw edema. A considerable decrease in paw diameter was observed in the EECT (200 and 400 mg/kg) and diclofenac (10 mg/kg) treated groups after day 7. Diclofenac (10 mg/kg) and EECT (400 mg/kg) showed a significant reduction in paw diameter from day 14 compared with CFA control (P Conclusion This study provides a pharmacological rationale for the traditional use of C. ternatea against inflammation and rheumatoid arthritis in India.

The COVID-19 pandemic has impacted neurosurgery in unforeseeable ways. Neurosurgical patient care, research, and education have undergone extraordinary modifications as medicine and mankind have adapted to overcome the challenges posed by this pandemic. Some changes will disappear as the situation slowly recovers to a prepandemic status quo. Others will remain: This pandemic has sparked some long-overdue systemic transformations across all levels of medicine, including in neurosurgery, that will be beneficial in the future. In this paper, we present some of the challenges faced across different levels of neurosurgical clinical care, research, and education, the changes that followed, and how some of these modifications have transformed into opportunities for improvement and growth in the future.

Deciphering sperm transcriptome is the key to understanding the molecular mechanisms governing peri-fertilization, embryonic development, and pregnancy establishment. This study aimed to profile sperm transcriptome to identify signature transcripts regulating male fertility. Semen samples were collected from 47 bulls with varied fertility rates. The sperm total RNA was isolated (n = 8) and subjected to transcriptome sequencing. Based on the expression pattern obtained from RNA profiling, the bulls were grouped (p = 0.03) into high-fertile and sub-fertile, and signature transcripts controlling sperm functions and fertility were identified. The results were validated using the OMIM database, qPCR, and sperm function tests. The sperm contains 1100 to 1700 intact transcripts, of which BCL2L11 and CAPZA3 were abundant and associated (p

We sought to establish norms and correlates for the Musical Ear Test (MET), an objective test of musical ability. A large sample of undergraduates at a Canadian university (N > 500) took the 20-min test, which provided a Total score as well as separate scores for its Melody and Rhythm subtests. On each trial, listeners judged whether standard and comparison auditory sequences were the same or different. Norms were derived as percentiles, Z-scores, and T-scores. The distribution of scores was approximately normal without floor or ceiling effects. There were no gender differences on either subtest or the total score. As expected, scores on both subtests were correlated with performance on a test of immediate recall for nonmusical auditory stimuli (Digit Span Forward). Moreover, as duration of music training increased, so did performance on both subtests, but starting lessons at a younger age was not predictive of better musical abilities. Listeners who spoke a tone language exhibited enhanced performance on the Melody subtest but not on the Rhythm subtest. The MET appears to have adequate psychometric characteristics that make it suitable for researchers who seek to measure musical abilities objectively.

PURPOSE The aim of this study was to review the literature on various screening programs, devices, and applications described for the early detection of retinoblastoma. DESIGN Systematic review article. METHODS A PubMed® search was performed to identify articles published with specific reference to screening of neonates, infants and children for retinoblastoma. RESULTS Various devices and mobile phone-based applications based on altered red reflex are finding their way into community screening. Diagnosis of retinoblastoma by newborn eye screening is emphasized in several countries, and red reflex is the most widely employed technique. CONCLUSIONS Several screening programs for early detection of retinoblastoma are evolving in the developing countries, but the practices are not uniform. Universal newborn screening should be the norm. Newer tools and software can be utilized to screen infants on a community scale. Focussed research on revolutionizing digital imaging for a versatile screening tool holds promise for early diagnosis of retinoblastoma.

BackgroundThe occurrence of retained ear mould impression material is rare and can lead to complications. The current case report describes one such complication, where the silicone impression material used to take the impression of the ear canal flowed into the middle ear through the pre-existing tympanic membrane perforation. Five days later, the patient presented with worsened hearing and blood-tinged discharge from the ear. Ear microscopy revealed a greenish foreign body in the middle ear.Case reportThe foreign body was removed by tympanotomy and the perforation repaired using a temporalis fascia graft. A hearing aid was prescribed after ensuring that the perforation had healed.ConclusionIt is essential that the audiologist perform a basic otological examination before prescribing a hearing aid and preparing an ear mould. A clinical approach algorithm for audiologists, for prior to taking an impression, is suggested.

To analyze the risk factors and estimate the risk period for tumor recurrence in intraocular retinoblastoma (RB). Retrospective study of 60 RB patients. The mean age at presentation with RB was 16 months (median 11 months; range 1–84 months). Tumor was unilateral in 13 (22%) and bilateral in 47 (78%) patients. Of 83 eyes with intraocular RB, group B (n = 27; 33%) tumors were more common based on International Classification of Intraocular Retinoblastoma. All cases received intravenous chemotherapy as a primary treatment. Over a mean follow-up period of 57 months (median 38 months; range 12–185 months) post-primary treatment, 44 (73%) patients developed tumor recurrence. The mean interval between the completion of primary treatment and first tumor recurrence was 5 months (median 3 months; range 1–24 months). The total duration of treatment for complete tumor control including treatment of tumor recurrences was 20 months (median 19 months; 2–58 months). By multivariate analysis, the factors predictive of tumor recurrence were multiple tumors (p = 0.008) and retinal detachment (p = 0.003) at presentation. Kaplan–Meier estimate of tumor recurrence at 6 months, 1 year, 3 years, and 5 years was 20%, 31%, 68%, and 73%, respectively. There was no tumor recurrence beyond 5 years since primary treatment. Multiple tumors and retinal detachment at presentation are risk factors for tumor recurrence in RB. Close follow-up is mandatory for at least 5 years since the initiation of treatment for RB.

Phototherapy-induced hypocalcemia has been postulated to result from a decline in serum melatonin levels. The present observational study evaluated the effects of phototherapy on serum calcium and melatonin levels, and assessed their correlation, if any. Eighty-nine neonates with a total serum bilirubin levels of 14.1 ± 2.8 mg/dL were recruited at the mean age of 51.9 ± 21.7 h. After a median interquartile range (IQR) duration of phototherapy for 24.0 (24-25.5) h, serum calcium levels decreased significantly, from 9.6 ± 0.8 to 9.4 ± 0.6 mg/dL; p = 0.02, leading to asymptomatic hypocalcemia in 2.2% of the neonates. Median (IQR) serum melatonin levels also decreased from 187.8 (133.5-227.6) to 176.3 (145.6-202.5) pg/mL after phototherapy, the difference being statistically insignificant. No significant correlation was documented between the duration of phototherapy with calcium and melatonin levels. The authors conclude that phototherapy resulted in a small but significant reduction of serum calcium levels without any significant correlation with serum melatonin.

Introduction Student assessment by multiple-choice questions (MCQs) is an integral part of student evaluation in medicine. The medical teacher should be trained to construct an item with proper stem and valid options. Periodic item analyses will make the process of assessment more meaningful. Hence, we conducted the study to analyze MCQs (item analysis) tested on a batch of MBBS students in pharmacology in their three internal assessment examinations.Methods The study was conducted in the Department of Pharmacology of a medical college in Mangaluru on 150 students. The MCQs of the three internal assessment examinations (20 each) respectively were analyzed. We analyzed each question for difficulty index (DI), discrimination index (DsI), and distracter efficacy or functionality and expressed the percentage results.Results The DI was in an acceptable range of 60, 75, and 90%, respectively, in the three internal assessments. The percentage of “too difficult” questions was 10, 20, and 10% and the average DsI was 0.32 ± 0.04, 0.28 ± 0.02, and 0.26 ± 0.02, respectively. In the second and third internal assessments, 95% of questions had functional distracters, while in the first internal assessment, only 60% of questions had functional distracters.Conclusion We conclude from our study that even though the items (MCQs) framed for the internal assessments were in the acceptable range of quality in terms of the parameters assessed, we must improve MCQ’s construction in selecting distracters in some topics.

The enzyme Tpt1 is an essential agent of fungal tRNA splicing that removes an internal RNA 2′-PO4 generated by fungal tRNA ligase. Tpt1 performs a two-step reaction in which: (i) the 2′-PO4 attacks NAD+ to form an RNA-2′-phospho-(ADP-ribose) intermediate; and (ii) transesterification of the ADP-ribose O2″ to the RNA 2′-phosphodiester yields 2′-OH RNA and ADP-ribose-1″,2″-cyclic phosphate. Because Tpt1 does not participate in metazoan tRNA splicing, and Tpt1 knockout has no apparent impact on mammalian physiology, Tpt1 is considered a potential antifungal drug target. Here we characterize Tpt1 enzymes from four human fungal pathogens: Coccidioides immitis, the agent of Valley Fever; Aspergillus fumigatus and Candida albicans, which cause invasive, often fatal, infections in immunocompromised hosts; and Candida auris, an emerging pathogen that is resistant to current therapies. All four pathogen Tpt1s were active in vivo in complementing a lethal Saccharomyces cerevisiae tpt1Δ mutation and in vitro in NAD+-dependent conversion of a 2′-PO4 to a 2′-OH. The fungal Tpt1s utilized nicotinamide hypoxanthine dinucleotide as a substrate in lieu of NAD+, albeit with much lower affinity, whereas nicotinic acid adenine dinucleotide was ineffective. Fungal Tpt1s efficiently removed an internal ribonucleotide 2′-phosphate from an otherwise all-DNA substrate. Replacement of an RNA ribose-2′-PO4 nucleotide with arabinose-2′-PO4 diminished enzyme specific activity by ≥2000-fold and selectively slowed step 2 of the reaction pathway, resulting in transient accumulation of an ara-2′-phospho-ADP-ribosylated intermediate. Our results implicate the 2′-PO4 ribonucleotide as the principal determinant of fungal Tpt1 nucleic acid substrate specificity.

AIM: To summarize the experience of response to COVID-19 outbreak at a tertiary eye care institute and its network of health facilities in India. METHODS: Our responses are based on the principles of social distancing, hand hygiene, respiratory etiquettes, surface disinfection protocol, and rational use of appropriate personal protective equipment (PPE). We describe our response in terms of administrative controls, clinical protocols, staff protection, environmental controls, and social distancing measures. We also discuss our communication strategies and monitoring systems, to ensure compliance to protocols. RESULTS: Administrative control is mainly related to formation of task force and its functions. Clinical protocols are related to patient triaging methods and clinical examination guidelines in Outpatient, Inpatient and Operating Room. Staff protection is focused on training staff on the protocols to be followed in hospital as well as at home, and use of PPE. Environmental protocol is focused on cleaning and disinfectant methods to be used in the hospital. In addition, there are systems for communication as well as monitoring compliance to protocols. CONCLUSION: We hope that these protocols and our experience would help the ophthalmic community globally and serve as a guide to protect ophthalmologists and ophthalmic care personnel, and their patients across the world.

Bacterial cell cycle is divided into well-coordinated phases; chromosome duplication and segregation, cell elongation, septum formation, and cytokinesis. The temporal separation of these phases depends upon the growth rates and doubling time in different bacteria. The entire process of cell division starts with the assembly of divisome complex at mid-cell position followed by constriction of the cell wall and septum formation. In the mapping of mid-cell position for septum formation, the gradient of oscillating Min proteins across the poles plays a pivotal role in several bacteria genus. The cues in the cell that defines the poles and plane of cell division are not fully characterized in cocci. Recent studies have shed some lights on molecular interactions at the poles and the underlying mechanisms involved in pole determination in non-cocci. In this review, we have brought forth recent findings on these aspects together, which would suggest a model to explain the mechanisms of pole determination in rod shaped bacteria and could be extrapolated as a working model in cocci.

To identify morphological parameters aiding clinical differentiation of conjunctival intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (iSCC) and to demonstrate the utility of image processing software to objectively assess ocular surface squamous neoplasia (OSSN). This retrospective case series included all biopsy-proven cases of OSSN presenting as an ocular surface nodule. Based on histopathology, lesions were classified as CIN and iSCC. Clinical image analysis utilized ‘Contour’ and ‘ImageJ’ software. The effect of predictors demography, seropositivity, lesion dimensions, keratin, pigmentation, corneal involvement, vascularity and feeder vessels on the final histopathologic grade were assessed. A total of 108 OSSN lesions (74 CIN and 33 iSCC) were included. Mean age was 46.1 ± 17.2 years in CIN and 47.2 ± 13.9 years in iSCC. By univariate logistic regression analysis, significant predictors of iSCC were HIV seropositivity (p

Benign Paroxysmal Positional Vertigo (BPPV), the most common vestibular disorder characterized by recurrent, brief episodes of vertigo, is attributed to the presence of otoconia in the semicircular canals. Two mechanisms contribute to its cause-canalolithiasis (otoconia freely mobile in the semicircular canal) and cupulolithiasis (otoconia adherent to the cupula). Posterior semicircular canal is the most common canal involved. Although the occurrence of BPPV in lateral and superior semicircular canal is rare, with the advancement in diagnostic techniques, their incidence is being reported in the past few years. Various diagnostic tests and therapeutic maneuvers have been described in the management of BPPV. The present report is a comprehensive review of the tests and maneuvers for BPPV written as a guide intended to help the clinicians in the accurate diagnosis and application of a canal-specific treatment maneuver for BPPV. A simplified algorithmic approach ("The Bangalore BPPV Algorithm") for the management of BPPV is described.

Background Increasingly, public health interventions are delivered via telephone and/or text messages. Recent systematic reviews of early childhood obesity prevention interventions have not adequately reported on the way interventions are delivered and the experiences/perceptions of stakeholders. We aimed to summarise the literature in early childhood obesity prevention interventions delivered via telephone or text messages for evidence of application of process evaluation primarily to evaluate stakeholders’ acceptability of interventions. Methods A systematic search of major electronic databases was carried out using the Population, Intervention, Comparison, Outcomes framework. Studies were included if interventions were delivered via telephone/text messages; aimed at changing caregivers’ behaviours to prevent early childhood obesity; with one or more outcomes related to early obesity risk factors such as breastfeeding, solid feeding, tummy time, sleep and settling, physical activity and screen time; published from inception to May 2020. All eligible studies were independently assessed by two reviewers using the Cochrane Collaboration tool for assessing risk of bias. Qualitative studies were assessed using the Consolidated Criteria for Reporting Qualitative Research and Standards for Reporting Qualitative Research tools. Results Twenty-four studies were eligible, and the overall risk of bias was low. Eight studies (33%) had evidence of process evaluation that examined participants’ perceptions of interventions. Participants appreciated the convenience of receiving interventions via telephone or text messages. 63% of all studies in this review showed improvement in one or more behaviours related to childhood obesity prevention. Participants were likely to modify behaviours if they received information from a credible source such as from health professionals. Conclusion There is limited reporting of stakeholders’ experiences in early obesity prevention studies delivered by telephone or text messages. Only one-third of studies examined participants’ acceptability and the potential for delivery of childhood obesity prevention interventions conveniently using this mode of delivery. Interventions delivered remotely via telephone or text messages have the potential to reach equal or a greater number of participants than those delivered via face-to-face methods. Future research should build in process evaluation alongside effectiveness measurements to provide important insight into intervention reach, acceptability and to inform scale up. Trial registration PROSPERO registration: CRD42019108658

Background & Aims Despite recent advances in antiviral therapy for hepatitis C virus (HCV), a proportion of patients with genotype 3 (G3) HCV infection do not respond to current all oral treatment regimens. Genomic analyses have identified key polymorphisms correlating with increased resistance to direct-acting antivirals. We previously reported that amino acid polymorphisms (A150V and K206E) in the polymerase (NS5B) of G3 HCV reduce response to sofosbuvir. We now demonstrate that these polymorphisms alter the response to interferon alpha. Methods Quantitative polymerase chain reaction, immunofluorescence, luciferase activity assay, immunoblotting, and flow cytometry were used to study the antiviral effect of interferon (IFN) on DBN G3 HCV-infected cells and G3 HCV replicons. Results We show the presence of the A150V polymorphism markedly reduces the response to IFN alpha (IC50 of S52_WT = 1.162 IU/mL and IC50 of S52_A150V = 14.45 IU/mL, 12.4-fold difference). The induction of IFN-stimulated genes in A150V replicon cells is unaffected, but nuclear localization of active protein kinase R (PKR) is reduced. Blockade of PKR activity reduced the antiviral effect of IFN on wild-type replicons, whereas augmented PKR activation promoted the antiviral effect of IFN on A150V replicons. Furthermore, we show that impaired activation of PKR in A150V replicon cells diminishes cellular apoptosis. Conclusions These results demonstrate that polymorphisms reducing response rates to direct-acting antivirals may function beyond conferring drug resistance by modulating the intrinsic cellular antiviral response.

Summary Inter-areal coherence between field potentials is a widespread phenomenon in cortex. Coherence has been hypothesized to reflect phase-synchronization between oscillators and flexibly gate communication according to behavioral and cognitive demands. We reveal an alternative mechanism where coherence is not the cause but the consequence of communication and naturally emerges because spiking activity in a sending area causes post-synaptic potentials both in the same and in other areas. Consequently, coherence depends in a lawful manner on power and phase-locking in the sender and connectivity. Changes in oscillatory power explained prominent changes in fronto-parietal and LGN-V1 coherence across behavioral conditions. Optogenetic experiments and excitatory-inhibitory network simulations identified afferent synaptic inputs rather than spiking entrainment as the principal determinant of coherence. These findings suggest that unique spectral profiles of different brain areas automatically give rise to large-scale coherence patterns that follow anatomical connectivity and continuously reconfigure as a function of behavior and cognition., Highlights • Synaptic projections from a sending to a receiving area explain long-range coherence • Inter-areal coherence can be predicted by power and connectivity • Power explains major changes in long-range coherence across behavioral states • Coherence emerges without spiking entrainment due to afferent synaptic inputs, Schneider et al. establish a mechanism for inter-areal coherence between field potentials, where it is the result and not the cause of communication. Consequently, coherence depends in a lawful manner on connectivity and power and does not require spiking entrainment. This mechanism explains behavior-related changes in fronto-parietal and LGN-V1 coherence.

The objective of this study was to assess the influence of spermatozoa surface antigenic proteins on the functional competence of bovine neat and frozen-thawed semen. The breeding bulls (n = 38) were screened for seminal antigenic levels in neat semen based on the agglutination titrations with anti-sperm antibody (ASA). Bulls having high (n = 8) and low (n = 7) antigenic levels were selected and spermatozoa functional parameters were analyzed in neat and frozen-thawed semen samples. In neat semen, kinematics such as straightness (73.6 ± 1.0 and 66.9 ± 1.5%), linearity (48.6 ± 1.2 and 40.1 ± 3.9%), curvilinear velocity (103.3 ± 2.6 and 93.4 ± 3.8 μm/s), straight-line velocity (65.7 ± 2.6 and 53.7 ± 2.2 μm/s) and average path velocity (53.8 ± 2.5 and 39.8 ± 2.3 μm/s) were significantly high (p 0.05) in samples with lower antigenicity. The percentage of spermatozoa that can penetrate mucus (49.9 ± 2.3 and 37.1 ± 3.2) was significantly higher in semen samples with low ASAs. The total motile (84.0 ± 2.5 and 86.0 ± 1.5) and progressive motile (68.4 ± 3.7 and 69.2 ± 1.6) spermatozoa were higher in neat semen samples with higher antigenicity. A significantly (p 0.05) higher mitochondrial membrane potential was observed in neat (82.5 ± 2.8 and 69.0 ± 2.0%) and post-thaw (28 ± 5. 6 and 16 ± 3.7%) samples of the lower antigenic group. The percentage of acrosome-reacted spermatozoa was significantly (p 0.05) higher in neat (58.7 ± 2.9 and 52.6 ± 1.8), but reduced significantly (p 0.05) in post-thaw (32.0 ± 2.0 and 48.0 ± 2.6) semen of higher antigenic groups. The study reveals that higher seminal antigenicity reduces mitochondrial membrane potential and acrosome reaction ability in post-thaw spermatozoa.

Highlights • A low-cost manufacturing process for a neonatal rotavirus vaccine was developed. • The formulation process developed resulted in a stable liquid vaccine at 2–8 °C. • No pretreatment of vaccinees with antacid needed before oral administration. • Tech. transfer package includes manufacturing, formulation, assays and COGs model., Despite solid evidence of the success of rotavirus vaccines in saving children from fatal gastroenteritis, more than 82 million infants worldwide still lack access to a rotavirus vaccine. The main barriers to global rotavirus vaccine coverage include cost, manufacturing capacity and suboptimal efficacy in low- and lower-middle income countries. One vaccine candidate with the potential to address the latter is based on the novel, naturally attenuated RV3 strain of rotavirus, RV3-BB vaccine administered in a birth dose strategy had a vaccine efficacy against severe rotavirus gastroenteritis of 94% at 12 months of age in infants in Indonesia. To further develop this vaccine candidate, a well-documented and low-cost manufacturing process is required. A target fully loaded cost of goods (COGs) of ≤$3.50 per course of three doses was set based on predicted market requirements. COGs modelling was leveraged to develop a process using Vero cells in cell factories reaching high titers, reducing or replacing expensive reagents and shortening process time to maximise output. Stable candidate liquid formulations were developed allowing two-year storage at 2–8 °C. In addition, the formulation potentially renders needless the pretreatment of vaccinees with antacid to ensure adequate gastric acid neutralization for routine oral vaccination. As a result, the formulation allows small volume dosing and reduction of supply chain costs. A dose ranging study is currently underway in Malawi that will inform the final clinical dose required. At a clinical dose of ≤6.3 log10 FFU, the COGs target of ≤$3.50 per three dose course was met. At a clinical dose of 6.5 log10 FFU, the final manufacturing process resulted in a COGs that is substantially lower than the current average market price, 2.44 USD per dose. The manufacturing and formulation processes were transferred to BioFarma in Indonesia to enable future RV3-BB vaccine production.

Background: The placement of a wet cotton pellet against Mineral Trioxide Aggregate (MTA) is often recommended to ensure the completion of its setting reaction. Objective: This study aimed to evaluate the setting behaviour of MTA Angelus and NeoMTA by comparing their hardness after placing them in dry and moist conditions. Methodology: A simulated open apex was created on 40 polyvinyl tubes. The apical 4 mm of the tubes was filled with the two materials, NeoMTA Plus (Avalon Biomed Inc. Bradenton, FL, USA) and MTA Angelus (Angelus, Londrina, PR, Brazil) (n=20 per group). Both groups were subdivided into two subgroups based on the dry and wet conditions (n=10 per group). A wet cotton pellet was placed above the two materials in the wet group, and the coronal segment was sealed using Type II Glass ionomer cement (GC corporation Tokyo, Japan). Gutta-percha was placed against the test materials in the dry group with the coronal segment sealed with amalgam. Samples were placed in an oasis soaked in phosphate-buffered saline for seven days in 100% humidity and at 37°C. Microhardness was measured independently at 4 and 2 mm from the apex. Hardness was compared between materials and conditions, applying analysis of variance (a = .05). Results: The presence of dry or wet conditions had no significant effect on material hardness. MTA Angelus showed significantly higher hardness values compared with NeoMTA Plus. Conclusion: The moisture of the periapical environment can compensate for the absence of a wet cotton pellet and is adequate for the setting of the materials.