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Anxiety is a psychiatric non-motor symptom of Parkinson’s that can appear in the prodromal period, prior to significant loss of midbrain dopamine neurons and motor symptoms. Parkinson’s-related anxiety affects females more than males, despite the greater prevalence of Parkinson’s in males. How stress, anxiety and Parkinson’s are related and the basis for a sex-specific impact of stress in Parkinson’s are not clear. We addressed this using young adult male and female mice carrying a G2019S knockin mutation of leucine-rich repeat kinase 2 (Lrrk2G2019S) and Lrrk2WT control mice. In humans, LRRK2G2019S significantly elevates the risk of late-onset Parkinson’s. To assess within-sex differences between Lrrk2G2019S and control mice in stress-induced anxiety-like behaviors in young adulthood, we used a within-subject design whereby Lrrk2G2019S and Lrrk2WT control mice underwent tests of anxiety-like behaviors before (baseline) and following a 28 day (d) variable stress paradigm. There were no differences in behavioral measures between genotypes in males or females at baseline, indicating that the mutation alone does not produce anxiety-like responses. Following chronic stress, male Lrrk2G2019S mice were affected similarly to male wildtypes except for novelty-suppressed feeding, where stress had no impact on Lrrk2G2019S mice while significantly increasing latency to feed in Lrrk2WT control mice. Female Lrrk2G2019S mice were impacted by chronic stress similarly to wildtype females across all behavioral measures. Subsequent post-stress analyses compared cFos immunolabeling-based cellular activity patterns across several stress-relevant brain regions. The density of cFos-activated neurons across brain regions in both male and female Lrrk2G2019S mice was generally lower compared to stressed Lrrk2WT mice, except for the nucleus accumbens of male Lrrk2G2019S mice, where cFos-labeled cell density was significantly higher than all other groups. Together, these data suggest that the Lrrk2G2019S mutation differentially impacts anxiety-like behavioral responses to chronic stress in males and females that may reflect sex-specific adaptations observed in circuit activation patterns in some, but not all stress-related brain regions.

Predictive algorithms, also known as mathematical models, utilize historical data to accurately predict future outcomes. These algorithms identify patterns and relationships within the data, resulting in precise predictions. The growing importance of predictive algorithms in various domains, such as finance, healthcare, marketing, weather forecasting, E-commerce, etc., has led to an increasing need for robust and accurate models. Machine learning (ML) and deep learning (DL) algorithms, including supervised, unsupervised, & reinforcement learning, play a crucial role in prediction. Supervised algorithms include classification and regression, while unsupervised algorithms primarily focus on clustering. In this study, a detailed comparative analysis of eight classification algorithms, six regression algorithms, and five clustering algorithms is performed using diverse datasets and performance metrics. ROBERTA, ResNet, Random Forest Regression, and K-means clustering algorithms outperformed traditional algorithms in textual classification, image classification, regression, and clustering. This study enables data scientists and practitioners to make informed decisions when selecting appropriate models for their specific applications.

ABSTRACT: Objectives: Artemisinin (ART) resistance in Plasmodium is threatening the artemisinin combination therapies—the first line of defence against malaria. ART resistance has been established to be mediated by the Plasmodium Kelch13 (PfK13) protein. For the crucial role of PfK13 in multiple pathways of the Plasmodium life cycle and ART resistance, it is imperative that we investigate its interacting partners. Methods: We recombinantly expressed PfK13-p (Bric a brac/Poxvirus and zinc finger and propeller domains), generating anti-PfK13-p antibodies to perform co-immunoprecipitation assays and probed PfK13 interacting partners. Surface plasmon resonance and pull-down assays were performed to establish physical interactions of representative proteins with PfK13-p. Results: The co-immunoprecipitation assays identified 17 proteins with distinct functions in the parasite life cycle– protein folding, cellular metabolism, and protein binding and invasion. In addition to the overlap with previously identified proteins, our study identified 10 unique proteins. Fructose-biphosphate aldolase and heat shock protein 70 demonstrated strong biophysical interaction with PfK13-p, with KD values of 6.6 µM and 7.6 µM, respectively. Additionally, Plasmodium merozoite surface protein 1 formed a complex with PfK13-p, which is evident from the pull-down assay. Conclusion: This study adds to our knowledge of the PfK13 protein in mediating ART resistance by identifying new PfK13 interacting partners. Three representative proteins—fructose-biphosphate aldolase, heat shock protein 70, and merozoite surface protein 1—demonstrated clear evidence of biophysical interactions with PfK13-p. However, elucidation of the functional relevance of these physical interactions are crucial in context of PfK13 role in ART resistance.

IntroductionIndia launched the COVID-19 vaccination drive on 16th January 2021 by vaccinating the adult population above 18 years of age. This was followed by the introduction of an additional precaution dose. As on 18th October 2022, 1,02,66,96,808 (1.02 Billion) first dose and 94, 95, 39,516 (949 Million) second doses of COVID-19 vaccine were administered. However, when compared to the uptake of the primary doses, the precaution dose uptake lagged behind with only 21,75, 12,721 (217 million) doses administered. Even though, the uptake of the primary doses remained optimal, irrespective of different interventions by the Government of India, the uptake of the precaution dose remained poor. In this context, the Ministry of Health & Family Welfare wanted to understand the facilitators and Barriers for precaution dose uptake among adults so that future immunization campaigns could address these issues.MethodsAn exploratory qualitative study was conducted to assess the facilitators and barriers for COVID-19 precaution dose uptake at community level across 6 different states in India. From each of the states, two districts with the highest and lowest rates of COVID-19 vaccine precaution dose uptake were selected. In each of these districts, 2 block Primary Healthcare Centres (PHCs), one with high and one with low uptake were identified. Within these block PHCs, a PHC field area with high and low precaution dose uptakes was identified. From the identified sites a minimum of four IDIs, four FGDs were conducted among the community members. KIIs of the State Immunization Officers, District Immunisation Officers, PHC Medical Officers, healthcare workers like Accredited Social Health Activist/Auxiliary Nurse Midwife were also conducted. The data was audio recorded and it was transcribed, translated and analysed using framework approach.ResultsIt was observed that rise in COVID-19 cases prompted the community to take the precaution dose, this along with the cost of hospitalization and the number of productive days being lost as a result of being infected resulted in vaccine uptake. The fear of non-availability of COVID-19 vaccines latter on also prompted people for vaccine uptake. While the barriers were, poor accessibility to vaccination centers, long hours of travel, poor road connectivity and lack of transportation facilities. However, the most prominent barriers observed across all study sites was that a sense of pandemic fatigue and complacency had developed both among the providers as well as the beneficiaries. Other barriers include differences in vaccination schedules and longer duration between the primary doses of some vaccines. Media was identified to be both a barrier and facilitator for Covid-19 Precaution dose uptake. Even though media played an important role in disseminating information in the beginning of the campaign, it was soon followed by the circulation of both misinformation and disinformation.DiscussionThe study identified that dissemination of accurate information and community involvement at each stage of planning and implementation are crucial for the success of any campaign. Efforts should be constantly made to address and re-invent strategies that will be most suitable for the needs of the community. Therefore, in order to ensure successful vaccination campaigns, it is crucial that along with political will it is also important to have a decentralized approach with inter-sectoral coordination with different stakeholders such as healthcare workers, community members and the different departments such as the local self-governments, education department, law & order department etc. These lessons learnt from COVID-19 vaccination campaigns must not be forgotten and must be applied in future vaccination campaigns and while framing public health policies.

Abstract The eye, which is under constant exposure to environmental pathogens, has evolved various anatomic and immunological barriers critical to the protection of tissues lacking regenerative capacity, and the maintenance of a clear optic pathway essential to vision. By bypassing the ocular barriers, intravitreal (IVT) injection has become the mainstay for the delivery of drugs to treat conditions that affect the back of the eye. Both small molecules and biotherapeutics have been successfully administered intravitreally, and several drugs have been approved for the treatment of (wet) age‐related macular degeneration and diabetic macular edema. However, IVT injection is an invasive procedure, which requires sufficient technical expertise from the healthcare professional administering the drug. Potential side effects include bleeding, retinal tear, cataracts, infection, uveitis, loss of vision, and increased ocular pressure. Pharmaceutical companies often differ in their drug development plan, including drug administration techniques, collection of ocular tissues and fluids, ophthalmology monitoring, and overall conduct of nonclinical and clinical studies. The present effort, under the aegis of the Innovation & Quality Ophthalmic Working Group, aims at understanding these differences, identifying pros and cons of the various approaches, determining the gaps in knowledge, and suggesting feasible good practices for nonclinical and early clinical IVT drug development.

Abstract This study devised a dual-species biofilm model to investigate bacteria, lipoteichoic acid (LTA), and lipopolysaccharide (LPS) simultaneously, and compared the efficacy of conventional and contemporary disinfection protocols. Seventy single-rooted mandibular premolars were included. Fourteen teeth were negative control, and 56 teeth were infected with 3-week-old E. faecalis and E. coli GFP biofilm. Fourteen/56 teeth were positive control, with seven teeth processed for CLSM analysis and seven teeth sampled with paper points (PPs) and cryogenically ground for bacterial, LTA, and LPS analyses. Forty-two teeth were randomly divided into three groups: GWS (GentleWave system) + MIT (minimally invasive technique), PUI (passive ultrasonic irrigation) + CIT (conventional instrumentation technique), and XP-EF (XP-endo Finisher) + CIT (All, n = 14). Samples were collected before (s1) and after disinfection (s2) with PPs and after cryogenically ground (s3). CFUs were counted, and LTA and LPS were quantified with LTA-ELISA and LAL assay, respectively. XP-EF was as effective as PUI (p > 0.05). GWS + MIT was the most effective disinfection protocol against bacteria, LTA, and LPS (p

Abstract Background Since inception of the COVID-19 pandemic, early detection and isolation of positive cases is one of the key strategies to restrict disease transmission. Real time reverse transcription polymerase chain reaction (qRTPCR) has been the mainstay of diagnosis. Most of the qRTPCR kits were designed against the target genes of original strain of SARS-CoV-2. However, with the emergence of variant strains of SARS-CoV-2, sensitivity of the qRTPCR assays has reportedly reduced. In view of this, it is critical to continuously monitor the performance of the qRTPCR kits in the backdrop of variant strains of SARS-CoV-2. Real world monitoring of assay performance is challenging. Therefore, we developed a two-step in-silico screening process for evaluating the performance of various qRTPCR kits used in India. Results We analysed 73 qRT-PCR kits marketed in India, against the two SARS-CoV-2 VoCs. Sequences of both Delta (B.1.617.2) and Omicron (B.1.1.529) VoCs submitted to GISAID within a specific timeframe were downloaded, clustered to identify unique sequences and aligned with primer and probe sequences. Results were analysed following a two-step screening process. Out of 73 kits analysed, seven were unsatisfactory for detection of both Delta and Omicron VoCs, 10 were unsatisfactory for Delta VoC whereas 2 were unsatisfactory for only Omicron VoC. Conclusion Overall, we have developed a useful screening process for evaluating the performance of qRTPCR assays against Delta and Omicron VoCs of SARS-CoV-2 which can be used for detecting SARS-CoV-2 VoCs that may emerge in future and can also be redeployed for other evolving pathogens of public health importance.

Therapeutic Area: Heart Failure Background: Heart failure (HF) exacerbations lead to an estimated 1 million congestive heart failure (CHF)-related admissions annually, costing between $11-15,667 with a hospital stay of 7-21 days. The etiology is multifactorial, but regular monitoring is essential for preventing readmissions. We propose an at-home machine learning (ML) monitoring model, incorporating multiple variables and including bioimpedance technology to measure Extracellular fluid/total body water (ECF/TBW), to develop a predictive CHF exacerbation model that improves CHF care and reduces its burden on health systems. Methods: Trials investigating remote CHF monitoring have shown varying results. The TIM-HF2 trial showed a significant reduction in hospitalization and mortality when monitoring vitals, reporting symptoms, and conducting monthly telehealth visits. Another trial utilized ML models incorporating vitals, medication adherence, symptoms, demographics, diagnoses, and risk factors to triage patients better than physicians.No ML trials have incorporated ECF/TBW, despite its established correlation with inferior vena cava size on ultrasound, a surrogate marker of fluid overload status (Pearson coefficient=-0.73, p

Introduction Tobacco smoking is associated with a substantially increased risk of perioperative complications. The perioperative period is an opportunity to introduce tobacco-cessation strategies. A previous systematic review provided evidence that perioperative interventions increase short-term abstinence and may reduce postoperative complications. The evidence base has since expanded, with the subsequent publication of numerous randomised studies. This protocol outlines a systematic review examining the impact of perioperative tobacco-cessation interventions on successful abstinence from tobacco smoking, and on the incidence of perioperative complications.Methods and analysis A systematic search of the literature will be run across EMBASE (Ovid), MEDLINE (Ovid), CINAHL (Ebsco) and PsycInfo (ProQuest), from inception to present, using text words and subject headings. Randomised controlled trials published in English, examining adults in the perioperative period and reporting the outcomes from tobacco-cessation interventions will be included.Abstract screening and data extraction will be performed by five reviewers. Each abstract will be screened by two blinded reviewers, with discrepancies resolved by group consensus. The primary outcome will be point prevalence abstinence from tobacco-use at the time of surgery. Secondary outcomes are prolonged abstinence from tobacco use at 6 months and 12 months, and postoperative complications. Any other reported outcomes will be documented in the descriptive analysis. The review will also describe details of the investigated perioperative tobacco-cessation interventions. If sufficient studies report relevant data, meta-analysis of the primary and secondary outcomes will be undertaken. Results will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement.Ethics and dissemination No ethical approval is required. Results will be disseminated by open-access, peer-reviewed journal publication and conference presentations. Results will underpin future work to modify perioperative tobacco-cessation interventions to enhance engagement and accessibility, and to develop trials aiming to facilitate abstinence from tobacco-use in patients presenting for surgery.

The severe acute respiratory syndrome coronavirus 2 pandemic started in the December of 2019 at China. The second wave of the pandemic in India peaked between April-May 2021. In order to reduce the transmission and infectivity of the virus several vaccines were approved for emergent use. Studies have shown the effectiveness of vaccination in reducing the clinical severity of infection by the corona virus. In this study we aim to assess the effect of vaccination on the computed tomography severity score (CTSS). The study included 140 patients who tested positive for COVID 19 on RT PCR or rapid antigen test. Seventy of these patients had received at least one dose of vaccination and 70 patients were unvaccinated. CT scan of the chest was done for all patients and a CTSS ranging from 0 to 25 was assigned depending on the extent of lobar involvement. We found that a higher percentage (72.86%) of unvaccinated patients had severe disease compared to the vaccinated group (38.57%), 5.71% of unvaccinated patients had mild disease compared to 30% of vaccinated patients. The difference between the two groups was found to be statistically significant. On comparing the CTSS of patients with and without vaccination in our study, we found a significant reduction in the severity scores in the vaccinated group. Through this study the vaccine’s efficacy could be validated objectively. This article aims to emphasize the role of vaccination in our fight against the pandemic caused by the corona virus.

Immunogenicity has imposed a challenge to efficacy and safety evaluation of adeno-associated virus (AAV) vector-based gene therapies. Mild to severe adverse events observed in clinical development have been implicated with host immune responses against AAV gene therapies, resulting in comprehensive evaluation of immunogenicity during nonclinical and clinical studies mandated by health authorities. Immunogenicity of AAV gene therapies is complex due to the number of risk factors associated with product components and pre-existing immunity in human subjects. Different clinical mitigation strategies have been employed to alleviate treatment-induced or -boosted immunogenicity in order to achieve desired efficacy, reduce toxicity, or treat more patients who are seropositive to AAV vectors. In this review, the immunogenicity risk assessment, manifestation of immunogenicity and its impact in nonclinical and clinical studies, and various clinical mitigation strategies are summarized. Last, we present bioanalytical strategies, methodologies, and assay validation applied to appropriately monitor immunogenicity in AAV gene therapy-treated subjects.

Current situation: The global influenza surveillance and response system (GISRS), coordinated by the World Health Organization (WHO), is a global framework for surveillance of influenza and other respiratory viruses, data collection, laboratory capacity building, genomic data submission and archival, standardization, and calibration of reagents and vaccine strains, production of seasonal influenza vaccines and creating a facilitatory regulatory environment for the same. Gaps: WHO-designated national influenza centers (NICs) are entrusted with establishing surveillance in their respective countries. National and subnational surveillance remains weak in most parts of the world because of varying capacities of the NICs, lack of funds, poor human and veterinary surveillance mechanisms, lack of intersectoral coordination, and varying commitments of the local government. Way forward: As influenza viruses have a wide variety of nonhuman hosts, it is critical to strengthen surveillance at local levels for timely detection of untypable or novel strains with potential to cause epidemics or pandemics. In this article, we have proposed possible strategies to strengthen and expand local capacities for respiratory virus surveillance through the designated NICs of the WHO.

Germ cell tumour (GCT) is the most common testicular tumour that commonly presents as a painless mass. Bone marrow metastasis in cases of testicular GCT is rare; only few case reports are available till date in the literature. Here an adult male presented with an intra-abdominal mass in right iliac fossa with inguinal lymphadenopathy with a deranged kidney function test. Bone marrow (BM) aspirate smear revealed metastatic tumour cells, but BM-biopsy was unremarkable. High serum Beta - HCG (38286 mIU/L) pointed towards germ cell lesion. Lymph node biopsy along with immunomarkers confirmed metastatic foci from germ cell tumor and managed as per standard protocol. Rarely BM aspirate is seen positive for malignancy, while biopsy turns out to be negative. Secondly, BM metastasis of GCT should be considered while dealing with cases like this. Informed consent: This is certified that the informed consent has been obtained from the patient.

Abstract Background As the rate of crime is constantly increasing, the workload on the forensic analyst also piles up. The availability of a limited number of seized samples makes it crucial to directly analyze the sample, thereby preventing wastage in the prior steps of sample preparation. Due to such needs, the forensic community is consistently working on broadening the usage of direct analysis in real-time mass spectrometry (DART-MS). DART-MS is a relatively new technique for rapid mass spectral analysis. Its use for chemical analysis credits its ability to analyze the sample at atmospheric pressure. Main body This article gives insight into the ionization mechanisms, data analysis tools, and the use of hyphenated techniques like thermal-desorption-DART-MS, infrared-thermal-desorption-DART-MS, Joule-heating thermal-desorption-DART-MS, etc. This review summarizes the applications of DART-MS in the field of Forensic Science reported from 2005 to 2021. The applications include analysis of drugs, warfare agents, gun-shot residues, ink differentiation, and other forensically relevant samples. The paper also presents the relation between the type of DART-MS technique and the ionization mode used for a particular class of compounds. Conclusion The review follows that the high-resolution mass-spectrometers or low-resolution mass-spectrometers systems in the positive or negative mode were highly dependent on the type of analyte under investigation. Drugs, inks, dyes, and paints were mainly analyzed using the positive ionization mode in the HRMS technique. The examinations of fire accelerants predominantly used the positive ionization mode in the LRMS technique. Moreover, the limit of detection values obtained from the qualitative screening of street drugs were of ppb level, indicating high sensitivity of DART-MS. Considering the work done in the past years, there are potential future research needs of this technology, especially in forensic science. Graphical Abstract

A 13-year-old girl child with B-cell precursor acute lymphoblastic leukemia presented with complaints of fever, fatigue and left-sided iliac mass of 20 days duration. Preliminary blood culture from the peripherally inserted central catheter (PICC) demonstrated the presence of budding yeast cells. This is a rare form of “Disseminated cryptococcosis”. Budding yeast cells emphasizes the significance of various differentials of yeast in positive blood cultures bottles, as identifying Cryptococcus from gram stain can be complicated. This manuscript also highlights the presence of crystalloid geometric appearance like “Buckminsterfullerene”, which is derived from the mucopolysaccharide capsule in Cryptococcus. These structures are rarely observed, and in this case, are exceptionally remarkable.

Introduction: Testicular torsion is a urological emergency, and long-term outcomes of testicular torsion on infertility, hormonal function, and salvaged testicular size are unclear. Materials and Methods: We conducted an ambispective, observational study from January 2014 to December 2019. Baseline demographics, time of presentation, clinical features, and management details of all the patients of testicular torsion were recorded from the database. All the patients were followed up in the outpatient clinic for testicular size, hormone levels, semen analysis, and erectile function. Results: Of 85 patients, only 67 could be contacted and included in the final analysis. Group 1(orchiectomy) comprised 44 patients, and Group 2(salvage) had 23 patients. Follow-up duration ranged from 2 to 6 years and mean follow-up was 42 ± 12 months. The median time to presentation was significantly higher in Group 1 (48 hours) as compared to Group 2 (12 hours). The rate of testicular salvage did not vary with age of the patients. Doppler ultrasonography of the scrotum detected 92.5% of all cases of torsion. Antisperm antibody levels were within normal range in all patients. Approximately 47% of patients in the salvage group developed testicular atrophy on follow-up. Serum testosterone level was significantly lower in Group 1 and the subset of patients with testicular atrophy. Rest of the hormonal parameters, semen analysis, and erectile function were comparable between two groups. Conclusion: The time between onset and presentation is an important contributing factor in guiding testicular salvage. Even after salvage, many testes may atrophy on follow-up. Orchiectomy and testicular atrophy in the long term have negative impact on serum testosterone. The patients should be counseled for a long-term follow-up for the risk of testicular atrophy and low testosterone levels.

Background: Biological effects of radiation include deterministic and stochastic effects. Dental colleges still follow radiation protection principles due to guidelines laid by the Dental Council of India and the Atomic Energy Regulatory Board, but private practitioners sometimes are negligent about the significance of radiation protection. The study focuses on the awareness of radiation protection among dental practitioners based on their knowledge, attitude, and application. Aim and Objectives: The aim and objectives of this study were to evaluate the level of awareness and attitude about radiation protection among dental practitioners in Uttar Pradesh and the NCR region, India. Materials and Methods: The survey was performed on dental practitioners from UP and NCR region, India. The survey comprised two sections: one section on basic information of the dentists and their working place, consisting of two questions. The second section consisted of 21 questions regarding patient and personnel protection methods and knowledge about radiation exposure. The questionnaire was disseminated through Google Forms. Results: Among 200 dentists, 84% use Radio visual graph (RVG) in their clinics. Ninety percent of the specialists attended the basic lecture on radiation exposure, nearly 50% of the dentists use digital receptors in pediatric patients, 86% of the specialists use their hands when adjusting the X-ray tube, 98.4% of the dentists know the related complications of radiation, 46.8% of the specialists explain the radiation measures to the patients, 76.2% of the dentists use lead barriers in their clinics, and 76.2% of the clinicians often get their X-ray machines serviced yearly. Conclusion: The current study shows the utmost need for further implementation of radiation protection. The majority of dentists are negligent in practicing radiation protection procedures properly. Emphasis on radiation safety and mandatory professional education is needed.

Introduction: The Dynamic Neuromuscular Stabilisation (DNS) technique uses feed forward feedback to involuntarily activate the diaphragm and deep abdominal muscles prior to purposeful movement in humans. It is an efficient approach for facilitating deep core muscle activation of the underactive muscle chain consisting of the Internal Oblique (IO), transverse abdominals and diaphragm, thereby enhancing age appropriate jumping, walking and standing, in participants with Spastic Diplegic Cerebral Palsy (SDCP), whereas the primary goal of Neurodevelopmental Therapy (NDT) is to facilitate more normal movement patterns for performing performance skills and rectifying abnormal postural tone Need of the study: Even though studies have been done in the past, utilising DNS and NDT in children with diplegic CP, for improving core stability, balance, posture and diaphragmatic movement; however, Gross Motor Function (GMF) and trunk control are the aspects that have not been aimed with DNS. There is scarcity in the literature related to impact of DNS on GMF and trunk control in children with diplegic CP. As DNS has specific role on core strength it can be a valuable in the management of trunk control. Because no study comparing the impact of DNS and NDT on trunk control and functions of gross motor in diplegic children has been found; there is a strong need to perform a study to evaluate the same. Aim: To compare the impact of DNS to NDT on gross motor performance and trunk control in children with SDCP. Materials and Methods: It will be a Randomised Clinical Trial (RCT) with the assessor blinded, conducted in the Outpatient Department of Physiotherapy, AVBRH Sawangi, Meghe, Wardha, Maharashtra, India, from July 2022 to April 2023. Following the baseline assessments, children with SDCP (n=36) will be enlisted and randomly assigned into two groups, groups A and group B. Group A will be treated using conventional therapy along with NDT; group B will be given conventional therapy as well as DNS. Treatment will be given for four weeks, five days a week. On the first and the last day of the intervention, primary outcome measures Gross Motor Function Measure-88 (GMFM-88), Trunk Impairment Scale (TIS) and secondary outcome measure Modified Ashworth Scale (MAS) will be employed (on the first day and after the completion of four weeks). Mini-mental Scale Examination (MMSE) will be used as inclusion criteria for the children. Statistical analysis will be carried out using Statistical Package for the Social Sciences (SPSS) software version 27.0. Conclusion: The present study is expected to prove that DNS approach to be successful in enhancing the control of the trunk and gross motor abilities in children with SDCP.

Introduction: Uterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. Method: Whole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. Result: Serum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P

We generalize the Quantum Approximate Optimization Algorithm (QAOA) of Farhi et al. (2014) to allow for arbitrary separable initial states with corresponding mixers such that the starting state is the most excited state of the mixing Hamiltonian. We demonstrate this version of QAOA, which we call $QAOA-warmest$, by simulating Max-Cut on weighted graphs. We initialize the starting state as a $warm-start$ using $2$ and $3$-dimensional approximations obtained using randomized projections of solutions to Max-Cut's semi-definite program, and define a warm-start dependent $custom mixer$. We show that these warm-starts initialize the QAOA circuit with constant-factor approximations of $0.658$ for $2$-dimensional and $0.585$ for $3$-dimensional warm-starts for graphs with non-negative edge weights, improving upon previously known trivial (i.e., $0.5$ for standard initialization) worst-case bounds at $p=0$. These factors in fact lower bound the approximation achieved for Max-Cut at higher circuit depths, since we also show that QAOA-warmest with any separable initial state converges to Max-Cut under the adiabatic limit as $p\rightarrow \infty$. However, the choice of warm-starts significantly impacts the rate of convergence to Max-Cut, and we show empirically that our warm-starts achieve a faster convergence compared to existing approaches. Additionally, our numerical simulations show higher quality cuts compared to standard QAOA, the classical Goemans-Williamson algorithm, and a warm-started QAOA without custom mixers for an instance library of $1148$ graphs (upto $11$ nodes) and depth $p=8$. We further show that QAOA-warmest outperforms the standard QAOA of Farhi et al. in experiments on current IBM-Q and Quantinuum hardware.

Abstract Intrinsic transcription termination (ITT) sites are currently identified by locating single and double-adjacent RNA hairpins downstream of the stop codon. ITTs for a limited number of genes/operons in only a few bacterial genomes are currently known. This lack of coverage is a lacuna in the existing ITT inference methods. We have studied the inter-operon regions of 13 genomes covering all major phyla in bacteria, for which good quality public RNA-seq data exist. We identify ITT sites in 87% of cases by predicting hairpin(s) and validate against 81% of cases for which the RNA-seq derived sites could be calculated. We identify 72% of these sites correctly, with 98% of them located ≤ 80 bases downstream of the stop codon. The predicted hairpins form a cluster (when present

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate of NAb formation using an expanded dataset composed of 33 prospective placebo-controlled and open-label clinical trials with nearly 30,000 longitudinal subject records prior to and following onabotulinumtoxinA treatment in 10 therapeutic and aesthetic indications. Total onabotulinumtoxinA doses per treatment ranged from 10 U to 600 U administered in ≤15 treatment cycles. The NAb formation at baseline and post-treatment was tested and examined for impact on clinical safety and efficacy. Overall, 27 of the 5876 evaluable subjects (0.5%) developed NAbs after onabotulinumtoxinA treatment. At study exit, 16 of the 5876 subjects (0.3%) remained NAb positive. Due to the low incidence of NAb formation, no clear relationship was discernable between positive NAb results and gender, indication, dose level, dosing interval, treatment cycles, or the site of injection. Only five subjects who developed NAbs post-treatment were considered secondary nonresponders. Subjects who developed NAbs revealed no other evidence of immunological reactions or clinical disorders. This comprehensive meta-analysis confirms the low NAb formation rate following onabotulinumtoxinA treatment across multiple indications, and its limited clinical impact on treatment safety and efficacy.

Background: Ebola virus (EBOV); a public health emergency of international concern,is known to pose threat of global outbreaks. EBOV has spread in African continent and due to unchecked international travel, importation of cases has been reported in different countries. In this alarming scenario, developing countries need to evaluate and upgrade their preparedness plan to contain the spread of EBOV. The present review lays down the updated preparedness plan for developing countries to contain future EBOV outbreaks. Methods: The literature on EBOV outbreaks and preparedness strategies reported were searched on Pubmed and Google Scholar using the MeSH terms such as ''Ebola virus disease, Epidemic, Outbreak, Imported case, Preparedness, Public health interventions'' combined with Boolean operator (OR) for the period of 2011–2020. Additionally, World Health organization (WHO) and Centers for Disease Control & Prevention (CDC) websites were searched for the guidelines, reports, containment strategies, containment plan of countries, actions taken by countries and international partners, etc. Results: The present review analyzed the EBOV outbreaks between 2011–2020 and containment strategies used by the affected countries. Based on the lessons learned from EBOV outbreaks and personal experience in infectious disease management, we have recommended a preparedness and response plan for EBOV containment in developing countries. Conclusion: Developing countries are particularly vulnerable to major outbreaks of EBOV due to increased international travel and unchecked transmission. The recommended preparedness plan will help developing counties to contain EBOV outbreaks in future.

Cholera is a diarrheal disease causing major health issue in developing countries where it is endemic and causes outbreaks. India ranks first with an estimated 675,188 number of cases and 20,256 number of deaths annually with one-third of its population at risk. The two broad approaches for cholera control are improving sanitation and vaccination. Now both live and killed oral vaccines are available. Live vaccines are advantageous in respect of intestinal colonization and rapid immune response and also lead to in vivo exposure of bacterial products leading to good immunological response against wild Vibrio cholerae infection. The three major delivery strategies which can be considered for the implementation of oral cholera vaccine are preemptive vaccination, reactive vaccinations, and National Immunization Program. We propose the use of cholera live oral vaccines for achieving control of this disease by repeated vaccination of the susceptible population in a series of pulses to control it from the entire population.

BackgroundStructural and cultural barriers limit Indian women’s access to adequate postnatal care and support despite their importance for maternal and neonatal health. Targeted postnatal education and support through a mobile health intervention may improve postnatal recovery, neonatal care practices, nutritional status, knowledge and care seeking, and mental health. ObjectiveWe sought to understand the feasibility and acceptability of our first pilot phase, a flexible 6-week postnatal mobile health intervention delivered to 3 groups of women in Punjab, India, and adapt our intervention for our next pilot phase, which will formally assess intervention feasibility, acceptability, and preliminary efficacy. MethodsOur intervention prototype was designed to deliver culturally tailored educational programming via a provider-moderated, voice- and text-based group approach to connect new mothers with a social support group of other new mothers, increase their health-related communication with providers, and refer them to care needed. We targeted deployment using feature phones to include participants from diverse socioeconomic groups. We held moderated group calls weekly, disseminated educational audios, and created SMS text messaging groups. We varied content delivery, group discussion participation, and chat moderation. Three groups of postpartum women from Punjab were recruited for the pilot through community health workers. Sociodemographic data were collected at baseline. Intervention feasibility and acceptability were assessed through weekly participant check-ins (N=29), weekly moderator reports, structured end-line in-depth interviews among a subgroup of participants (15/29, 52%), and back-end technology data. ResultsThe participants were aged 24 to 28 years and 1 to 3 months postpartum. Of the 29 participants, 17 (59%) had their own phones. Half of the participants (14/29, 48%) attended ≥3 of the 6 calls; the main barriers were childcare and household responsibilities and network or phone issues. Most participants were very satisfied with the intervention (16/19, 84%) and found the educational content (20/20, 100%) and group discussions (17/20, 85%) very useful. The participants used the SMS text messaging chat, particularly when facilitator-moderated. Sustaining participation and fostering group interactions was limited by technological and sociocultural challenges. ConclusionsThe intervention was considered generally feasible and acceptable, and protocol adjustments were identified to improve intervention delivery and engagement. To address technological issues, we engaged a cloud-based service provider for group calls and an interactive voice response service provider for educational recordings and developed a smartphone app for the participants. We seek to overcome sociocultural challenges through new strategies for increasing group engagement, including targeting midlevel female community health care providers as moderators. Our second pilot will assess intervention feasibility, acceptability, and preliminary effectiveness at 6 months. Ultimately, we seek to support the health and well-being of postpartum women and their infants in South Asia and beyond through the development of efficient, acceptable, and effective intervention strategies.

Summary: Astrocytic GLT-1 is the main glutamate transporter involved in glutamate buffering in the brain, pivotal for glutamate removal at excitatory synapses to terminate neurotransmission and for preventing excitotoxicity. We show here that the surface expression and function of GLT-1 can be rapidly modulated through the interaction of its N-terminus with the nonadrenergic imidazoline-1 receptor protein, Nischarin. The phox domain of Nischarin is critical for interaction and internalization of surface GLT-1. Using live super-resolution imaging, we found that glutamate accelerated Nischarin-GLT-1 internalization into endosomal structures. The surface GLT-1 level increased in Nischarin knockout astrocytes, and this correlated with a significant increase in transporter uptake current. In addition, Nischarin knockout in astrocytes is neuroprotective against glutamate excitotoxicity. These data provide new molecular insights into regulation of GLT-1 surface level and function and suggest new drug targets for the treatment of neurological disorders.

Phakomatoses or Neurocutaneous syndromes are a heterogeneous group of disorders and have variable inheritance pattern. Currently, more than 30 entities are included in this group. These disorders primarily affect the central nervous system; however, skin, viscera, and other connective tissues can also be involved with variable clinical presentation. We will describe and illustrate the various radiological findings of the common entities through the iconography of the cases presented to our department.

Abstract Background and Objectives The emergence of resistant strains of Cutibacterium acnes can limit the efficacy of currently approved antibiotics for acne. VB-1953 is a next-generation antibiotic that exerts a bactericidal effect on resistant C. acnes. In this study, we investigated the safety, tolerability, and efficacy of VB-1953 topical gel in patients with moderate to severe acne having clindamycin-resistant C. acnes. Methods An investigator-initiated, open label, single-arm clinical study was conducted in patients with moderate to severe facial acne vulgaris showing poor or no response to previous clindamycin treatment. Nineteen subjects were enrolled in the study based on laboratory screening for the presence of clindamycin-resistant C. acnes in acne swab samples collected from patients. VB-1953 2% gel was applied on the entire face twice daily over 12 weeks. The primary efficacy endpoints were absolute changes in inflammatory and noninflammatory lesion counts from baseline at week 12, while the secondary efficacy endpoint was the proportion of subjects achieving Investigator Global Assessment success (score of 0 or 1) or a grade 2 or higher improvement from baseline at week 12. The presence and severity of local skin reactions (erythema, edema, scaling/dryness, burning/stinging, pruritus) were evaluated for safety. Additionally, the detection and quantification of drug-resistant C. acnes strains were performed in the laboratory using acne swab samples collected from patients. Results The occurrence of treatment-emergent adverse events or changes in vital signs, physical examinations, and urinalysis for any of the patients during the course of the entire study were clinically insignificant. Topical application of 2% VB-1953 topical gel resulted in a significant reduction of mean absolute inflammatory and noninflammatory lesion counts by 53.1% and 52.2%, respectively (p

Sudden emergence and rapid spread of COVID-19 created an inevitable need for expansion of the COVID-19 laboratory testing network across the world. The strategy to test-track-treat was advocated for quick detection and containment of the disease. Being the second most populous country in the world, India was challenged to make COVID-19 testing available and accessible in all parts of the country. The molecular laboratory testing network was augmented expeditiously, and number of laboratories was increased from one in January 2020 to 2951 till mid-September, 2021. This rapid expansion warranted the need to have inbuilt systems of quality control/ quality assurance. In addition to the ongoing inter-laboratory quality control (ILQC), India implemented an External Quality Assurance Program (EQAP) with assistance from World Health Organization (WHO) and Royal College of Pathologists, Australasia. Out of the 953 open system rRTPCR laboratories in both public and private sector who participated in the first round of EQAP, 891(93.4%) laboratories obtained a passing score of > = 80%. The satisfactory performance of Indian COVID-19 testing laboratories has boosted the confidence of the public and policy makers in the quality of testing. ILQC and EQAP need to continue to ensure adherence of the testing laboratories to the desired quality standards.

Stevia rebaudiana (Bert.) Bertoni, commonly called “sweet leaf” is a medicinally and industrially important plant known to be rich in zero-calorie natural sweetening compound(s) known as “steviol glycosides”. However, due to its poor seed germination and slow vegetative propagation, it has become rather difficult to meet the increasing global demand for Stevia-based products. Different biotechnological approaches have been developed over the past few decades to overcome these limitations and allow for mass propagation of the plant. Several protocols for in vitro organogenesis, callogenesis, and cell suspension cultures have been developed during the past few years. Apart from this, attempts have also been made to improve the production of steviol glycosides through nutrient manipulation, the use of elicitors, hairy root cultures, genetic transformation, and metabolic pathway engineering. Therefore, this review provides an up-to-date report on the applications of various biotechnological tools for mass propagation and enhanced steviol glycoside production, along with a detailed bibliometrics analysis. This review also highlights research gaps and future considerations that could be fruitful for the scientific community to delve deeper into the various unexplored aspects of the architecture and functionality of this natural sweetening plant.

In the original article [...]

Moringa oleifera Lam. (MO) is a fast-growing drought-resistant tree belonging to the family Moringaceae and native to the Indian subcontinent and cultivated and/or naturalized worldwide with a semi-arid climate. MO is also popularly known as a miracle tree for its repertoire of nutraceutical, pharmacological, and phytochemical properties. The MO germplasm is collected, conserved, and maintained by various institutions across the globe. Various morphological, biochemical, and molecular markers are used for determining the genetic diversity in MO accessions. A higher yield of leaves and pods is often desirable for making various products with commercial viability and amenable for trade in the international market. Therefore, breeding elite varieties adapted to local agroclimatic conditions and in vitro propagation are viable and sustainable approaches. Here, we provide a comprehensive overview of MO germplasm conservation and various markers that are employed for assessing the genetic diversity among them. Further, breeding and in vitro propagation of MO for various desirable agronomic traits are discussed. Finally, trade and commerce of various functional and biofortified foods and non-food products are enumerated albeit with a need for a rigorous and stringent toxicity evaluation.

We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article:Swati Gupta, Yashwant Pathak, Manish K. Gupta & Suresh P. Vyas (2019) Nanoscale drug delivery strategies for therapy of ovarian cancer: conventional vs targeted, Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 4066–4088, DOI: 10.1080/21691401.2019.1677680Due to high levels of overlap with published content, the Editor had rejected the article for publication in the Journal, but unfortunately due to a technical error, the article was published. The Publisher apologizes for the technical error.We have informed the authors and they do not agree with the retraction.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Histology data exists for many cancer samples and the ability to automatically image this data may provide prognostic information. Here, the authors generated an algorithm to measure tumour infiltrating lymphocytes in melanoma histology specimens and show that the ratio of these immune cells to tumour cells has prognostic value.

Abstract Chronically discharging ear is a common cause of morbidity in developing countries, and it is also associated with intratemporal and intracranial complications. The surgeon is often able to detect the disease. However, cholesteatoma in the “hidden areas” like anterior epitympanic recess and sinus tympani can be missed. Facial nerve involvement and cholesteatomatous erosion of the bony labyrinth are dreaded complications, the extent of which cannot be assessed completely on clinical examination. Adding to the complexity are the various variations in anatomy like high riding jugular bulb and aberrant internal carotid artery which could lead to catastrophic complications during surgery if left undetected preoperatively. HRCT temporal bone is useful to detect the extent of the disease, various complications, and guide the surgeon for pre-operative planning. In this review, we go through the various HRCT imaging features of acquired cholesteatoma, a reporting template, and a few words about imaging of the post-operative ear.

Abstract Background In melanoma, there is no companion diagnostic test to predict response to programmed cell death 1 (PD-1) axis immune checkpoint inhibitor (ICI) therapy. In the adjuvant setting, only one in five patients may benefit from ICI, so a biomarker is needed to select those that may or may not benefit. Here, we test a new 4-gene multiplex immunotherapy panel with research use only (RUO) prototype mRNA expression profile on the GeneXpert closed system using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) for association with clinical benefit after treatment with ICI therapy in metastatic melanoma patients. Methods Pretreatment formalin-fixed paraffin-embedded (FFPE) tissue sections from melanoma patients treated with anti-PD-1 therapy (pembrolizumab, nivolumab, or ipilimumab plus nivolumab) between 2011 and 17 were selected from the Yale Pathology archives. FFPE sections were macrodissected to enrich for tumor for quantitative assessment of CD274 (PD-L1), PDCD1LG2 (PD-L2), CD8A, and IRF1 by RT-qPCR multiplex mRNA panel. Multiplex panel transcript levels were correlated with clinical benefit (complete response [CR], partial response [PR], stable disease [SD]); disease outcomes (progression-free survival [PFS] and overall survival [OS]); and protein levels assessed by quantitative immunofluorescence (QIF). Results Transcript levels were significantly higher in responders (CR/PR/SD) than in nonresponders (PD) for CD8A (p = 0.0001) and IRF1 (p = 0.0019). PFS was strongly associated with high CD274 (p = 0.0046), PDCD1LG2 (p = 0.0039), CD8A (p = 0.0002), and IRF1 (p = 0.0030) mRNA expression. Similar associations were observed for OS with high CD274 (p = 0.0004), CD8A (p = 0.0030), and IRF1 (p = 0.0096) mRNA expression. Multivariate analyses revealed significant PFS and OS associations with immunotherapy panel markers independent of baseline variables. Exploratory analyses revealed a novel significant association of high combined CD274 & PDCD1LG2 (L1/L2) transcript expression with PFS (p

Abstract Background The cancer-associated fibroblast (CAF) population is implicated in immune dysregulation. Here, we test the hypothesis that CAF profiles in pretreatment tumor specimens are associated with response to immune checkpoint blockade of programmed cell death 1 (PD-1). Methods Pretreatment whole tissue sections from 117 melanoma patients treated with anti-PD-1 therapy were assessed by multiplex immunofluorescence to detect CAFs defined by Thy1, smooth muscle actin (SMA), and fibroblast activation protein (FAP). Two independent image analysis technologies were used: inForm software (PerkinElmer) to quantify cell counts, and AQUA™ to measure protein by quantitative immunofluorescence (QIF). CAF parameters by both methodologies were assessed for association with previously measured immune markers (CD3, CD4, CD8, CD20, CD68, PD-L1), best overall response, progression-free survival (PFS), and overall survival (OS). Results CAF parameters, by cell counts or QIF, did not correlate with immune markers nor with best overall response. However, both Thy1 and FAP cell counts had significant positive associations with PFS (all P

Abstract The review aimed at assessing the osteopromotive potential as well as soft tissue and temporomandibular joint (TMJ) cartilage healing properties of simvastatin by summarizing its efficacy on the current dental treatment of periodontal bone and soft tissue defects, and temporomandibular joint (TMJ) arthritis from the available animals and human studies. An electronic search was performed on MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) using a combination of keywords. A hand search was undertaken on seven oral surgery journals. No limitation of publication year in the English language was placed. Controlled randomized animal and human clinical trials, as well as prospective comparative studies, were included. Data on the comparison of topical/systemic simvastatin on bone healing in intrabony and furcation defects, extraction sockets, distraction osteogenesis, as well as soft tissue healing in mucogingival grafting procedures and cartilage protection in TMJ arthritis were extracted from all the eligible studies. Studies with a minimum of ten participants and follow up at least 6 months were included. Ten animal studies and six clinical studies were included in this study. All the animal studies included a minimum of eight sites per group assessed clinically, histologically, and radiographically. All human studies included clinical and radiological evaluation. The results of the review show that simvastatin administration displays positive treatment outcomes in the full range of therapies investigated in the oral regions such as periodontal infection control, periodontal and alveolar bone regeneration, soft tissue grafting, TMJ inflammation reduction, and cartilage repair. Its mechanism includes stimulating bone formation, promoting soft tissue healing, increasing articular and condylar cartilage thickness, as well as reducing inflammation at surgical sites in TMJ disorders. Simvastatin administration is beneficial to the healing of oral bone and cartilage. More studies are desired to determine its potential in soft tissue healing.

Mycetoma, a chronic granulomatous disease more common in tropical countries such as India, has been conventionally diagnosed by invasive and time-consuming modalities like biopsy and microbiological culture. This case series aims to stress on the benefits of leveraging magnetic resonance imaging and ultrasonography in the early diagnosis of mycetoma, avoiding the invasive techniques and preventing debilitating complications that may develop from delay in diagnosis.

Abstract Background Dyslipidemia is one of the most frequently implicated risk factors for development of atherosclerosis. This study evaluated the efficacy of amla (Emblica officinalis) extract (composed of polyphenols, triterpenoids, oils etc. as found in the fresh wild amla fruit) in patients with dyslipidemia. Methods A total of 98 dyslipidemic patients were enrolled and divided into amla and placebo groups. Amla extract (500 mg) or a matching placebo capsule was administered twice daily for 12 weeks to the respective group of patients. The patients were followed up for 12 weeks and efficacy of study medication was assessed by analyzing lipid profile. Other parameters evaluated were apolipoprotein B (Apo B), apolipoprotein A1 (Apo A1), Coenzyme Q10 (CoQ10), high-sensitive C-reactive protein (hsCRP), fasting blood sugar (FBS), homocysteine and thyroid stimulating hormone (TSH). Results In 12 weeks, the major lipids such as total cholesterol (TC) (p = 0.0003), triglyceride (TG) (p = 0.0003), low density lipoprotein cholesterol (LDL-C) (p = 0.0064) and very low density lipoprotein cholesterol (VLDL-C) (p = 0.0001) were significantly lower in amla group as compared to placebo group. Additionally, a 39% reduction in atherogenic index of the plasma (AIP) (p = 0.0177) was also noted in amla group. The ratio of Apo B to Apo A1 was reduced more (p = 0.0866) in the amla group as compared to the placebo. There was no significant change in CoQ10 level of amla (p = 0.2942) or placebo groups (p = 0.6744). Although there was a general trend of FBS reduction, the numbers of participants who may be classified as pre-diabetes and diabetes groups (FBS > 100 mg/dl) in the amla group were only 8. These results show that the amla extract used in the study is potentially a hypoglycaemic as well. However, this needs reconfirmation in a larger study. Conclusions The Amla extract has shown significant potential in reducing TC and TG levels as well as lipid ratios, AIP and apoB/apo A-I in dyslipidemic persons and thus has scope to treat general as well as diabetic dyslipidemia. A single agent to reduce cholesterol as well as TG is rare. Cholesterol reduction is achieved without concomitant reduction of Co Q10, in contrast to what is observed with statins. Trial registration Registered with Clinical Trials Registry- India at www.ctri.nic.in (Registration number: CTRI/2015/04/005682) on 8 April 2015 (retrospectively registered).

Background: Orofacial pain disorders and their management forms an important and integral part of our oral medicine specialty. Only oral physicians are well-trained to provide non-surgical treatment of these complex disorders. Today, the escalating costs of drugs and several adverse effects associated with modern medicines have led to the search of alternative systems all over the world. Hence, this study is an effort to assess the efficacy of holistic approaches (naturopathy and yoga) alone as well as in combination with pharmacological therapy in the treatment of chronic orofacial pain of non-odontogenic origin. Materials and Methods: The present study was conducted on 60 patients who were randomized into three groups A, B and C, each group consisting of 20 patients (10 of myofascial pain and 10 of trigeminal neuralgia). In group A it was prescribed conventional medicines for their respective treatment. Holistic approaches (naturopathy and yoga) were added with conventional pharmacological therapy in group B and only holistic approaches were performed in group C. The duration of treatment was of 3 months a and the patients were analysed using pain scale, quality of life scale (QOL) and stress scale after every ten days follow-up. Results: The patients of trigeminal neuralgia showed best result when treated with pharmacological treatment. The holistic approaches showed significant results only when combined with pharmacological therapy for the treatment of trigeminal neuralgia. On the other hand, holistic approaches works best in myofascial pain both alone and in combination with pharmacological therapy. Acupuncture and facial massage along with yoga have a great impact on quality of life by reducing stress and anxiety of the patient. Conclusion: Holistic approaches are useful means in treating patients with chronic orofacial pain as it eliminates the risk of adverse effects associated with long term use of muscle relaxants and anti-convulsants.

Zinner syndrome is a rare cystic malformation of seminal vesicle which consists a triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst, and ejaculatory duct obstruction. The usual presentation is between the third and fourth decades of life, with infertility being the most common complaint. Ultrasound, cystoscopy, and magnetic resonance tomography (MRI) can easily detect this condition. Treatment option varies according to the presenting symptoms of the patient. We present a case of a 19-year-old male with recurrent episodes of urinary tract infection (UTI) and poor urinary stream. On ultrasound examination, the patient was found to have absent right kidney with a cystic swelling noted to be arising from prostate or seminal vesicle region which was further confirmed on MRI examination. Cystoscopy reveals a bulge on the right side of the verumontanum abutting the neck of the bladder. An ultrasound-guided aspiration of the cyst was performed which relieved the symptoms of the patient. Cystic abnormalities of the seminal vesicle are very uncommon. Symptomatic cases may present as recurrent UTI, infertility, bladder outlet obstruction, and painful ejaculation. Surveillance may be the option in the absence of clinical manifestations. Interventions such as image-guided aspiration or surgical procedures are appropriate when conservative measures prove ineffective.

Background: Plantation of road-side avenue trees has become a major part of urbanization programme for megacity beautification and environmental management. Due to evergreen habit and vibrant flower colour, Delonix regia (Gulmohor/Flamboyant) is frequently selected as ornamental tree for plantation programme. However, D. regia pollen is related to IgE mediated allergic reactions and no allergen has been reported so far. Objective: Measuring the prevalence of D. regia pollen sensitivity among the local atopic individuals and identifying the allergens using immunoproteomic tools. Methods: Aerobiological study was conducted for a period of two years to record the D. regia pollen concentration in the outdoor ambient air. Clinico-immunological tests were performed on atopic individuals to check the prevalence of sensitivity against D. regia pollen. Allergens were detected in the pollen proteome, fractionated in 1D and 2D gel by IgE serology and finally identified by mass spectrometry. Result: In the study area D. regia pollen grains were present in ample amount in the air during May to July. About 38% of atopic individuals displayed positive Skin Prick Test (SPT) against D. regia pollen along with elevated level of specific IgE and histamine in the sera. Immunoproteomic analyses revealed the presence of 14 IgE reactive proteins in the 2D pollen proteome, of which 8 IgE reactive proteins were identified by MALDI TOF/TOF using homology driven proteomic approach. Conclusion: This study demonstrated pollen related allergy symptoms by D. regia and gave significant message regarding the plantation programme to avoid the unnecessary load of allergic pollen. Also, a panel of 8 allergens were identified for the first time from D. regia pollen. Detailed study of these allergens would help to design immunotherapeutic strategies for pollinosis management.

Epstein-Barr virus (EBV) and Kaposi sarcoma herpesvirus (KSHV) are cancer-causing viruses that establish lifelong infections in humans. Gene editing using the Cas9-guideRNA (gRNA) CRISPR system has been applied to decrease the latent load of EBV in human Burkitt lymphoma cells. Validating the efficacy of Cas9-gRNA system in eradicating infection in vivo without off-target effects to the host genome will require animal model systems. To this end, we evaluated a series of gRNAs against individual genes and functional genomic elements of murine gammaherpesvirus 68 (MHV68) that are both conserved with KSHV and important for the establishment of latency or reactivation from latency in the host. gRNA sequences against ORF50, ORF72 and ORF73 led to insertion, deletion and substitution mutations in these target regions of the genome in cell culture. Murine NIH3T3 fibroblast cells that stably express Cas9 and gRNAs to ORF50 were most resistant to replication upon de novo infection. Latent murine A20 B cell lines that stably express Cas9 and gRNAs against MHV68 were reduced in their reactivation by approximately 50%, regardless of the viral gene target. Lastly, co-transfection of HEK293T cells with the vector expressing the Cas9-MHV68 gRNA components along with the viral genome provided a rapid read-out of gene editing and biological impact. Combinatorial, multiplex MHV68 gRNA transfections in HEK293T cells led to near complete ablation of infectious particle production. Our findings indicate that Cas9-gRNA editing of the murine gammaherpesvirus genome has a deleterious impact on productive replication in three independent infection systems.

The development of oligonucleotide conjugates for in vivo targeting is one of the most exciting areas for oligonucleotide therapeutics. A major breakthrough in this field was the development of multifunctional GalNAc-oligonucleotides with high affinity to asialoglycoprotein receptors (ASGPR) that directed therapeutic oligonucleotides to hepatocytes. In the present study, we explore the use of G-rich sequences functionalized with one unit of GalNAc at the 3′-end for the formation of tetrameric GalNAc nanostructures upon formation of a parallel G-quadruplex. These compounds are expected to facilitate the synthetic protocols by providing the multifunctionality needed for the binding to ASGPR. To this end, several G-rich oligonucleotides carrying a TGGGGGGT sequence at the 3′-end functionalized with one molecule of N-acetylgalactosamine (GalNAc) were synthesized together with appropriate control sequences. The formation of a self-assembled parallel G-quadruplex was confirmed through various biophysical techniques such as circular dichroism, nuclear magnetic resonance, polyacrylamide electrophoresis and denaturation curves. Binding experiments to ASGPR show that the size and the relative position of the therapeutic cargo are critical for the binding of these nanostructures. The biological properties of the resulting parallel G-quadruplex were evaluated demonstrating the absence of the toxicity in cell lines. The internalization preferences of GalNAc-quadruplexes to hepatic cells were also demonstrated as well as the enhancement of the luciferase inhibition using the luciferase assay in HepG2 cell lines versus HeLa cells. All together, we demonstrate that tetramerization of G-rich oligonucleotide is a novel and simple route to obtain the beneficial effects of multivalent N-acetylgalactosamine functionalization.

Introduction: Dengue and Chikungunya fever are arboviral diseases which are spread by a common vector. Being clinically indistinguishable, it is necessary to distinguish both either by molecular or serology testing. Aim: To estimate the seroprevalence of Dengue and Chikungunya mono-infection as well as dual infection in patients with acute febrile illness. Materials and Methods: Two hundred patients with acute febrile illness were enrolled from April 2015 to October 2016. Detailed clinical history was documented. Samples were collected and subjected to Polymerase Chain Reaction (PCR) and Enzyme Linked Immuno Sorbent Assay (ELISA) testing. For qualitative data, frequency percentage table was used and association was done using Chi-square test. Results: Out of 200 patients, 8.5% had Chikungunya monoinfection and 41.5% patients had Dengue mono-infection. Dengue and Chikungunya co-infection was found in 4.5% patients. Most affected age group was 18-60 years wherein male preponderance was seen. In Chikungunya fever, 82.4% had morning stiffness and 35.3% had joint swelling; elbow and knee were the most commonly affected joints. In Chikungunya fever, 76.5% patients had restricted joint movements and 52.9% had Visual Analog Score (VAS) of 6-10. In Dengue fever, myalgia (67.5%) and rash (20.5%) were common symptoms. A total of 61.4% patients of Dengue fever had low platelet count. All Chikungunya cases and 88.1% Dengue cases detected by PCR had fever duration of less than five days. 85% of Chikungunya and 69% of Dengue cases detected by IgM ELISA had fever duration of more than five days. Conclusion: Diagnostic algorithms of acute febrile illness cases should include testing by both molecular and serology for both the viruses, which is the absolute need of the hour.

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) pollution is accompanied by other co-contaminants, such as perchlorate and chlorates, which can retard biodegradation. The effects of perchlorate and chlorate on aerobic RDX degradation remain unclear. We hypothesized that they have a negative or no impact on aerobic RDX-degrading bacteria. We used three aerobic RDX-degrading strains—Rhodococcus strains YH1 and T7 and Gordonia YY1—to examine this hypothesis. The strains were exposed to perchlorate, chlorate, and nitrate as single components or in a mixture. Their growth, degradation activity, and gene expression were monitored. Strain-specific responses to the co-contaminants were observed: enhanced growth of strain YH1 and inhibition of strain T7. Vmax and Km of cytochrome P450 (XplA) in the presence of the co-contaminants were not significantly different from the control, suggesting no direct influence on cytochrome P450. Surprisingly, xplA expression increased fourfold in cultures pre-grown on RDX and, after washing, transferred to a medium containing only perchlorate. This culture did not grow, but xplA was translated and active, albeit at lower levels than in the control. We explained this observation as being due to nitrogen limitation in the culture and not due to perchlorate induction. Our results suggest that the aerobic strain YH1 is effective for aerobic remediation of RDX in groundwater.