Prevalence of Sensory Processing Deficits in Children with Spastic Cerebral Palsy - An Indian Caregiver's Perspective.

This study aims to analyze the prevalence and patterns of sensory processing deficits (SPD) in Indian children with spastic cerebral palsy (CP) using child sensory profile-2 (CSP-2) caregiver questionnaire. The authors surveyed 230 caregivers of children aged 3 to 14 y with spastic CP, using CSP-2. The difference in prevalence and distribution of SPDs among the CP subtypes and Gross Motor Function Classification System (GMFCS) levels was done. Overall prevalence of "Definite" (>2 SD) SPDs was 83%. Forty-seven percent had definite SPDs in more than one sensory subsection. Prevalence of definite SPDs was similar among the spastic CP subtypes. "Conduct" domain had more affection among hemiplegics and quadriplegics. "Avoiding" pattern was observed more in quadriplegics and "Seeking" pattern was observed less in diplegics. Severe GMFCS levels had more definite sensory processing deficits. SPDs are highly prevalent in children with spastic CP with unique patterns of affection among the spastic CP subtypes.

Plant-based Natural Products as inhibitors for Efflux Pumps to Reverse Multidrug Resistance in Staphylococcus aureus: A Mini Review.

Wounds provide a favourable site for microbial infection. Wound infection makes the healing more complex and does not proceed in an orchestrated manner leading to the chronic wound. Clinically infected wounds require proper antimicrobial therapy. Broad-spectrum antibiotics are usually prescribed first before going to targeted therapy. The current conventional mode of therapy mainly depends on the use of antibiotics topically or systemically. Repeated and prolonged use of antibiotics, however, leads to multidrug resistance. Staphylococcus aureus is the most common multidrugresistant microorganism found in wounds. It effectively colonizes the wound and produces many toxins, thereby reducing the host immune response and causing recurrent infection, thus making the wound more complex. The overexpression of efflux pumps is one of the major reasons for the emergence of multidrug resistance. Inhibition of efflux pumps is, therefore, a potential strategy to reverse this resistance. The effective therapy to overcome this antibiotic resistance is to use combination therapy, namely the combination of an inhibitor, and a non-antibiotic compound with an antibiotic for their dual function. Many synthetic efflux pump inhibitors to treat wound infections are still under clinical trials. In this connection, several investigations have been carried out on plant-based natural products as multidrug resistance-modifying agents as they are believed to be safe, inexpensive and suitable for chronic wound infections.

Quality-by-design based fabrication of febuxostat-loaded nanoemulsion: Statistical optimization, characterizations, permeability, and bioavailability studies.

The present work deals with QbD-based development of FEB-loaded nanoemulsion (FEB-NE) in order to enhance bioavailability and permeability. In the beginning, the risk assessment was performed on different experimental variables using the Ishikawa diagram followed by FMEA study in order to find critical process parameter (CPP) and critical material attributes (CMAs). To build quality in nanoemulsion, the quality target product profiles (QTPP) and critical quality attributes (CQAs) were determined. The different batches of FEB-NE were produced by the microemulsification-probe sonication method. Effect of varying levels of independent variables such as oil concentration (X1), Smix concentration (X3), and amplitude (X3) on responses such as globule size (Y1), zeta potential (Y2), and entrapment efficiency (Y3) were studied using Box-Behnken design (BDD). FEB-NE formulation was optimized using a graphical and numerical method. The optimized formulation concentrations and their responses (CQAs) were located as design space in an overlay plot. The spherical shapes of globules were visualized by surface morphology using AFM and TEM. In vitro dissolution study showed 93.32% drug release from the optimized FEB-NE formulation. The drug release mechanism followed by the formulation was the Higuchi-matrix kinetics with a regression coefficient of 0.9236 (R2). FEB-NE showed enhanced permeability using PAMPA (artificial non-cell membrane) and everted gut sac model method. The developed optimized FEB-NE exhibited the enhancement of bioavailability by 2.48 fold as compared to FEB-suspension using Wistar rats suggesting improvement of solubility of a lipophilic drug. The optimized batch remained stable for 90 days at 4 °C and 25 °C. Thus, QbD-based development of FEB-NE can be useful for a better perspective on a commercial scale.

Effectiveness of motor control exercise, aerobic walking, and muscle strengthening programs in improving outcomes in a subgroup of population with chronic low back pain positive for central sensitization: a study protocol for a randomized controlled trial.

BACKGROUND: The role of pain sensitivity in the development and maintenance of chronic pain states, impaired executive functioning, and patient recovery is being investigated. Conditioned pain modulation (CPM) is widely used to measure musculoskeletal pain associated with central sensitization (CS). Despite the recommendations of many reviews and clinical practice guidelines that exercise programs reduce pain and disability, the overall confidence in these results is considered "critically low." The "active ingredient" of exercise programs and the dominant factor influencing CPM remain largely unknown. The objectives of this trial are to determine: • If different exercises cause different results on the CPM in a subgroup of people with chronic low back pain (CLBP) who are labeled as having CS pain, • If a program of exercise interventions for 12 weeks would alter executive functioning, quality of life (QoL), disability, and pain in persons with CLBP. • The relationship between patient characteristics, executive functions, CPM, and QoL METHODS: The trial is a randomized, controlled, multi-center study with four experimental groups and one healthy control group. Both the researchers and the people in the study will be blinded to the results. This paper describes the protocol for a trial examining the effects of 12-week individualized, twice-weekly exercise sessions lasting 30 to 60 min in persons with CLBP, who are positive for CS. Participants will be randomized to receive either patient education with motor control exercises (MCE), superficial strengthening (SS), aerobic exercises (AE), or patient education alone. Another group comprised of healthy volunteers will serve as controls. The primary outcomes are changes in CPM outcomes as measured by the cold pressor test (CPT). The secondary objectives are to evaluate executive functioning, pain, disability, quality of life, and spine muscle strength. The outcomes will be measured at 3 months and at a 6-month follow-up. DISCUSSION: The outcomes of the study will help in gaining more information and evidence about exercise-induced analgesia from the perspective of CPM. Measuring exercise outcomes will aid in scientifically prescribing exercise prescriptions in people with CLBP. The study outcomes will also assist in identifying the characteristics of individuals who will respond or respond indifferently to exercises. Investigating the relationship between the study's various outcomes could provide information for future trials. TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI) identifier: CTRI/2022/03/041143. Registered on 16 March 2022.

Design, Synthesis, Molecular Docking, and Preliminary Pharmacological Screening of some New Benzo[d]thiazol-2-ylamino Containing Chromen-2- one Derivatives with Atypical Antipsychotic Profile.

INTRODUCTION: Mental disorders are very serious complicated disorders. Schizophrenia is one of the most baffling mental disorders. The new series 7-(2-(benzo[d]thiazol-2- ylamino)ethoxy)-4-methyl-2H-chromen-2- synthesized in search of newer compounds for Schizophrenia. METHODS: Synthesis is done by refluxing in dry pyridine with various substituted 2-amino benzothiazoles derivatives (3a-3k) and 7-(2-Chloroethoxy)-4-methyl-2H-chromen-2-one (2). The molecular docking approach was used to screen these generated derivatives. Chem Bio Draw Ultra 12 was used to draw the compounds, which were then exposed to all potential conformations of compounds interacting with receptors. The Glide 7.6, Schrodinger 2017 Maestro 11.3 was used to achieve molecular docking. The Dopamine receptor 6CM4 serotonin 5TUD PDBs were acquired from the database of Brookhaven Protein. Using the OPLS 2005 force field, the ligand-protein hydrogen-bond network was acquired, along with the overall energy reduced. A glide score was used to rate the docking poses. RESULTS: The produced compounds have been identified with the use of analytical and spectral data. All of the produced substances were tested and analyzed for serotonin 5HT2 antagonistic and dopamine D2 activity, which can be considered as a measure of typical antipsychotic properties. CONCLUSION: Compounds 4b, 4c, 4e, 4g & 4i have demonstrated promising pharmacological action in preliminary studies. According to the preceding findings, compounds with electronwithdrawing substitutions, such as 4e & 4b, have a good atypical profile of antipsychotics.

A survey of Indian physiotherapists' clinical practice patterns and adherence to clinical guidelines in the management of patients with acute low back pain.

INTRODUCTION: Clinical practice guidelines (CPG) exist for the management of non-specific low back pain (LBP). The objective of this study is to evaluate if Indian physiotherapists' follow CPGs when treating patients with acute LBP. METHODS: A cross-sectional survey using an online questionnaire was used to collect demographic information, views, and opinion about acute LBP and CPGs, and management strategies of a clinical vignette presenting a patient with acute LBP. RESULTS: Responses from 328 physiotherapists were included in this study. Eighty-one percent of respondents indicated familiarity with CPGs for LBP and 75.3% (n = 328) respondents indicated that their intervention choices aligned with guidelines to at least some extent. Participants with post-graduate and doctoral degrees were more accustomed to CPGs than those with bachelor's degrees (p < 0.01). There were significant differences in clinical practice (p < 0.01) between therapists who expressed familiarity with guidelines and those who were not, as well as those with and without post-graduate and doctoral degrees. CONCLUSION: In general, the study showed adherence to guidelines; however, there were areas that did not align with established evidence, especially referral for radiology and use of electrical modalities.

Multi-sensory feedback improves spatially compatible sensori-motor responses.

To interact with machines, from computers to cars, we need to monitor multiple sensory stimuli, and respond to them with specific motor actions. It has been shown that our ability to react to a sensory stimulus is dependent on both the stimulus modality, as well as the spatial compatibility of the stimulus and the required response. However, the compatibility effects have been examined for sensory modalities individually, and rarely for scenarios requiring individuals to choose from multiple actions. Here, we compared response time of participants when they had to choose one of several spatially distinct, but compatible, responses to visual, tactile or simultaneous visual and tactile stimuli. We observed that the presence of both tactile and visual stimuli consistently improved the response time relative to when either stimulus was presented alone. While we did not observe a difference in response times of visual and tactile stimuli, the spatial stimulus localization was observed to be faster for visual stimuli compared to tactile stimuli.

Potential Epha2 Receptor Blockers Involved in Cerebral Malaria from Taraxacum officinale, Tinospora cordifolia, Rosmarinus officinalis and Ocimum basilicum: A Computational Approach.

Cerebral malaria (CM) is a severe manifestation of parasite infection caused by Plasmodium species. In 2018, there were approximately 228 million malaria cases worldwide, resulting in about 405,000 deaths. Survivors of CM may live with lifelong post-CM consequences apart from an increased risk of childhood neurodisability. EphA2 receptors have been linked to several neurological disorders and have a vital role in the CM-associated breakdown of the blood-brain barrier. Molecular docking (MD) studies of phytochemicals from Taraxacum officinale, Tinospora cordifolia, Rosmarinus officinalis, Ocimum basilicum, and the native ligand ephrin-A were conducted to identify the potential blockers of the EphA2 receptor. The software program Autodock Vina 1.1.2 in PyRx-Virtual Screening Tool and BIOVIA Discovery Studio visualizer was used for this MD study. The present work showed that blocking the EphA2 receptor by these phytochemicals prevents endothelial cell apoptosis by averting ephrin-A ligand-expressing CD8+ T cell bioadhesion. These phytochemicals showed excellent docking scores and binding affinity, demonstrating hydrogen bond, electrostatic, Pi-sigma, and pi alkyl hydrophobic binding interactions when compared with native ligands at the EphA2 receptor. The comparative MD study using two PDB IDs showed that isocolumbin, carnosol, luteolin, and taraxasterol have better binding affinities (viz. -9.3, -9.0, -9.5, and -9.2 kcal/mol, respectively). Ocimum basilicum phytochemicals showed a lower docking score but more binding interactions than native ligands at the EphA2 receptor for both PDB IDs. This suggests that these phytochemicals may serve as potential drug candidates in the management of CM. We consider that the present MD study provides leads in drug development by targeting the EphA2 receptor in managing CM. The approach is innovative because a role for EphA2 receptors in CM has never been highlighted.

Interacting humans use forces in specific frequencies to exchange information by touch.

Object-mediated joint action is believed to be enabled by implicit information exchange between interacting individuals using subtle haptic signals within their interaction forces. The characteristics of these haptic signals have, however, remained unclear. Here we analyzed the interaction forces during an empirical dyadic interaction task using Granger-Geweke causality analysis, which allowed us to quantify the causal influence of each individual's forces on their partner's. We observed that the inter-partner influence was not the same at every frequency. Specifically, in the frequency band of [2.15-7] Hz, we observed inter-partner differences of causal influence that were invariant of the movement frequencies in the task and present only when information exchange was indispensable for task performance. Moreover, the inter-partner difference in this frequency band was observed to be correlated with the task performance by the dyad. Our results suggest that forces in the [2.15-7] Hz band constitute task related information exchange between individuals during physical interactions.

Prevalence, Patterns, and Predictors of Physical Inactivity in an Urban Population of India.

Physical inactivity (PI) is a risk factor for mortality and morbidity. PI and its predictors among the urban population in Bhubaneswar, India, were unknown. Finding out the contribution of PI as a cause of existing noncommunicable diseases (NCD) is difficult without following up with a cohort. The study was hence done to find out the prevalence, patterns, and predictors of physical inactivity in an urban population, and simultaneously investigate its causal relationship with NCD from this cross-sectional study. Cluster random sampling was used with a sample size of 1203 with a design effect of three. Socio-demographic, health profile, physical activity levels, and stage of change for physical activity behavior were collected. Logistic regression and marginal structural model analysis (by inverse probability of treatment weighting {IPTW} using a generalized estimating equation {GEE} to investigate the relationship between physical activity and prevalence of NCDs) were done using IBM SPSS v20 software (Armonk, NY: IBM Corp.). Statistical significance was tested at p=0.05. A total of 1221 subjects participated. The mean age was 35.25 years and 71.9% were physically inactive. General caste, presence of NCD, and being in a static stage of change influenced physical activity positively. PI was found to be a risk factor for NCD with 1.54 times higher odds in this population. The study concluded that the prevalence of physical activity was low and PI was a causative factor for NCD.

Numerical estimation of calibration matrices for 241Am measurements using HPGe based in-vivo monitoring system.

In-vivo measurements of 241Am using HPGe detectors become complicated when the active adjacent source organs interfere with the target organ measurements. It is important to calculate the contribution of confounding organs to estimate the activity of the target organ accurately. In the current study, numerical simulations were performed using FLUKA Monte Carlo code and International Commission on Radiological Protection (ICRP) computational reference phantoms to determine the calibration matrices consisting of the calibration and cross-talk coefficients for three interfering organs namely, lungs, liver and skeleton. It was found that the interference from adjacent organs contaminated with 241Am was found to be significant in the case of lungs and liver. Knee monitoring was least influenced by the activity possessed by other source organs due to their anatomical distance from the knee. A comparison between lung and liver coefficients obtained from the Lawrence Livermore National Laboratory (LLNL) torso phantom and thorax phantom derived from ICRP adult male voxel phantom was performed. It was found that variations in coefficients obtained from simulations and experiments range between 2% and 48%. The differences were attributed to the uncertainties arising from the composition of the phantoms and detectors, size and shape of organs, positional errors, and source distribution. A comparison of calibration matrices of adult male and adult female thorax voxel phantoms revealed that all the coefficients except knee as the target organ were larger for the female thorax phantom owing to the lesser bulk of attenuating tissues on its chest. The coefficients obtained from simulations for different phantoms also showed that the organ activity estimation can be significantly affected by the subject morphology.

STUDY OF EFFECTIVENESS OF SHELTERING FROM RADIATION EXPOSURE DUE TO ACCIDENTAL RELEASE OF RADIOACTIVITY.

Sheltering is one of the important protective actions as a part of emergency response during the early phases of an accident-mostly precautionary in nature. Sheltering via structural shielding reduces the direct exposure from plume/cloud shine and ground shine doses as well as the airborne radioactivity concentration and hence inhalation dose. The present study was aimed at estimating the shielding factor in the case of Indian houses for external exposure pathways using the FLUKA Monte Carlo based radiation transport code. Furthermore, the dose reduction factor due to exposure from the inhalation pathway was estimated using an indoor aerosol model. These factors were assessed for the three major types of dwellings, and they provided important inputs for decision-making for sheltering or evacuation in case of any sudden release of radionuclides into the environment.