Comparative Evaluation of Intraarticular Facet Joint Injection Versus Medial Branch Block in Patients With Low Back Pain: A Randomised Controlled Study.

INTRODUCTION: Lumbar facet joint pain may refer to the back, buttocks, and proximal parts of the lower extremities. Intraarticular facet joint injections, facet joint nerve blocks, or facet joint neurolytic procedures are popular for the management of facet joint pain. MATERIAL AND METHODS: In this prospective, randomised study, 60 patients with a medical evaluation and pain pattern consistent with lumbar facet joint pain were randomly allocated to two groups. Group Ⅰ (n=30) patients were administered fluoroscope-guided lumbar facet joint injection, and group Ⅱ (n=30) patients were administered fluoroscope-guided lumbar facet joint nerve block. The primary objective is to compare the efficacy of both in managing facet joint pain in terms of pain and disability improvement. Secondary objectives were to compare the requirement for repeat injections and parameters related to the block, such as ease of administering the block, and to note the side effects pertaining to either of the blocks. RESULTS: There was a statistically significant improvement in pain score after injection in both groups (p>0.05). The mean pain score in both groups remained less than two at all time intervals throughout the study period (p>0.05) Excellent patient satisfaction was reported by the majority of the patients at different time intervals in both groups. CONCLUSION: Both lumbar facet joint injection and lumbar facet joint nerve block are safe and effective techniques for managing lower back pain patients. Both techniques provide adequate pain relief and disability improvement.

Inhibition of HEV Replication by FDA-Approved RdRp Inhibitors.

Hepatitis E virus (HEV) is primarily a hepatotropic virus that is responsible for acute hepatitis E in the general population and for chronic hepatitis in immunocompromised individuals. In the absence of a globally accessible vaccine, pegylated interferon-α and ribavirin are the only antiviral agents available for the treatment of chronic patients. As viral RNA-dependent RNA polymerases (RdRps) are indispensable for RNA replication, they are considered potential drug targets. In this study, we screened some well-known RdRp inhibitor molecules, notably, favipiravir, sofosbuvir, remdesivir, filibuvir, and tegobuvir. Of these, monotherapy with favipiravir and sofosbuvir inhibited the RdRp activity with an IC50 value of 10.2 ± 4.9 and 5.2 ± 2.9 µM, respectively, compared to the reference drug ribavirin (3.5 ± 1.6 µM). Further investigation of the combination therapy showed a reduction in viral RNA copy numbers by approximately 90%. Therefore, favipiravir has an additive effect when used with sofosbuvir. Therefore, we propose that favipiravir is a promising anti-HEV drug that can be used in combination with sofosbuvir.

Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replication.

Hepatitis E Virus (HEV) is a positively oriented RNA virus having a 7.2 kb genome. HEV consists of three open reading frames (ORF1-3). Of these, ORF1 codes for the enzymes Methyltransferase (Mtase), Papain-like cysteine protease (PCP), RNA helicase, and RNA-dependent RNA polymerase (RdRp). Unavailability of a vaccine or effective drug against HEV and considering the side effects associated with the off-label use of ribavirin (RBV) and pegylated interferons, an alternative approach is required by the modulation of specific enzymes to prevent the infection. HEV helicase is involved in unwinding the double-stranded RNA, RNA processing, transcriptional regulation, and pre-mRNA processing. Therefore, we screened FDA-approved compounds from the ZINC15 database against the modelled 3D structure of HEV helicase and found that methotrexate and compound A (Pubchem ID BTB07890) inhibit the NTPase and dsRNA unwinding activity leading to inhibition of HEV RNA replication. This may be further authenticated by in vivo study.

Digital lifestyle treatment improves long-term metabolic control in type 2 diabetes with different effects in pathophysiological and genetic subgroups.

To address the unmet need for scalable solutions for lifestyle treatment, we developed a new digital method to promote behavioral change. Here we report that patients with type-2 diabetes in Sweden (n = 331) exposed to the intervention have significantly improved HbA1c during a median follow-up of 1038 days (4 mmol/mol compared with matched controls; P = 0.009). This is paralleled by reduced body weight, ameliorated insulin secretion, increased physical activity, and cognitive eating restraints. Participants with high BMI and insulin resistance have an even larger response, as have non-risk allele carriers for the FTO gene. The findings open a new avenue for scalable lifestyle management with sustained efficacy and highlight a previously unrecognized opportunity for digital precision treatment based on genetics and individual pathophysiology. ClinicalTrials.gov NCT04624321.

Obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer's disease risk allele.

Introduction: Excess body weight and Alzheimer's disease (AD) disproportionately affect older African Americans. While mid-life obesity increases risk for AD, few data exist on the relationship between late-life obesity and AD, or how obesity-based and genetic risk for AD interact. Although the APOE-ε4 allele confers a strong genetic risk for AD, it is unclear if late-life obesity poses a greater risk for APOE-ε4 carriers compared to non-carriers. Here we assessed: (1) the influence of body mass index (BMI) (normal; overweight; class 1 obese; ≥ class 2 obese) on cognitive and structural MRI measures of AD risk; and (2) the interaction between BMI and APOE-ε4 in older African Americans. Methods: Seventy cognitively normal older African American participants (Mage = 69.50 years; MBMI = 31.01 kg/m2; 39% APOE-ε4 allele carriers; 86% female) completed anthropometric measurements, physical assessments, saliva collection for APOE-ε4 genotyping, cognitive testing, health and lifestyle questionnaires, and structural neuroimaging [volume/surface area (SA) for medial temporal lobe subregions and hippocampal subfields]. Covariates included age, sex, education, literacy, depressive symptomology, and estimated aerobic fitness. Results: Using ANCOVAs, we observed that individuals who were overweight demonstrated better hippocampal cognitive function (generalization of learning: a sensitive marker of preclinical AD) than individuals with normal BMI, p = 0.016, ηp2 = 0.18. However, individuals in the obese categories who were APOE-ε4 non-carriers had larger hippocampal subfield cornu Ammonis region 1 (CA1) volumes, while those who were APOE-ε4 carriers had smaller CA1 volumes, p = 0.003, ηp2 = 0.23. Discussion: Thus, being overweight by BMI standards may preserve hippocampal function, but obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer's disease risk allele.

Multicenter retrospective database evaluation of Takotsubo syndrome in subjects undergoing catheter ablation for atrial fibrillation.

Background: Intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation may result in Takotsubo syndrome (TS), but the frequency, predisposing factors (age, sex, mental health disorders), and outcomes are currently unknown. This study sought to assess the frequency, predisposing factors, and outcomes of subjects who underwent intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation and were diagnosed with TS. Methods: This was a retrospective observational cohort study utilizing TriNetX® electronic health record (EHR) data. We included subjects aged older than 18 years who underwent intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation. The study population was divided into two groups (no TS diagnostic code presence and TS diagnostic code presence). We analyzed the distributions of age, sex, race, diagnostic codes, common terminology procedures (CPT), and vasoactive medication codes and examined mortality rate within 30 days. Results: We included 69,116 subjects. Of these, 27 (0.04%) had a TS diagnostic code, the cohort was comprised mostly of females [17 (63.0%)], and 1 (3.7%) death within 30 days was reported. There were no significant differences in age and frequency of mental health disorders between those patients in TS and non-TS cohorts. Adjusting for age, sex, race, ethnicity, patient regionality, and mental health disorder diagnostic code, those patients who developed TS had a significantly higher odds of dying in 30 days after catheter ablation compared to those without TS (OR = 15.97, 95% CI: 2.10-121.55, p = .007). Conclusions: Approximately 0.04% of subjects who underwent intracardiac catheter ablation of atrial fibrillation by pulmonary vein isolation had a subsequent diagnostic code of TS. Further study is needed to determine whether there are predisposing factors associated with the development of TS in subjects who undergo catheter ablation of atrial fibrillation by pulmonary vein isolation.

High-Quality Sleep Mitigates ABCA7-Related Generalization Deficits in Healthy Older African Americans.

BACKGROUND: Both sleep deficiencies and Alzheimer's disease (AD) disproportionately affect older African Americans. Genetic susceptibility to AD further compounds risk for cognitive decline in this population. Aside from APOE ɛ4, ABCA7 rs115550680 is the strongest genetic locus associated with late-onset AD in African Americans. While sleep and ABCA7 rs115550680 independently influence late-life cognitive outcomes, we know too little about the interplay between these two factors on cognitive function. OBJECTIVE: We investigated the interaction between sleep and ABCA7 rs115550680 on hippocampal-dependent cognitive function in older African Americans. METHODS: One-hundred fourteen cognitively healthy older African Americans were genotyped for ABCA7 risk (n = 57 carriers of risk "G" allele; n = 57 non-carriers), responded to lifestyle questionnaires, and completed a cognitive battery. Sleep was assessed via a self-reported rating of sleep quality (poor, average, good). Covariates included age and years of education. RESULTS: Using ANCOVA, we found that carriers of the risk genotype who reported poor or average sleep quality demonstrated significantly poorer generalization of prior learning-a cognitive marker of AD-compared to their non-risk counterparts. Conversely, there was no genotype-related difference in generalization performance in individuals who reported good sleep quality. CONCLUSION: These results indicate that sleep quality may be neuroprotective against genetic risk for AD. Future studies employing more rigorous methodology should investigate the mechanistic role of sleep neurophysiology in the pathogenesis and progression of AD associated with ABCA7. There is also need for the continued development of non-invasive sleep interventions tailored to racial groups with specific AD genetic risk profiles.

A Comparative Study to Confirm the Endotracheal Tube Placement Using Ultrasonography and Standard Auscultation Method in Children.

BACKGROUND: In pediatric patients due to shorter trachea suboptimal positioning of endotracheal tube (ETT) is seen in 20%-50% of patients triggering grave complications. We compared standard auscultation and ultrasound-guided lung sliding to confirm the position of ETT in children. METHODS: Seventy-five pediatric patients between 2-8 years of age, American Society of Anesthesiologists physical status classification I and II scheduled for surgery under general anesthesia with endotracheal intubation were studied. The position of ETT was confirmed by chest auscultation for the breath sounds bilaterally and by ultrasound on the same sites for lung-sliding signs. The data obtained were compared to findings on waveform capnography. Study outcomes included position of the ETT; tracheal or esophageal, accuracy of diagnosis and time taken till confirming the diagnosis. RESULTS: Compared to waveform capnography findings, an ultrasound revealed a sensitivity of 94.31%, a specificity of 72.33%, and an accuracy of 90.7% while that for standard auscultation were 82.8%, 47.28%, and 74.67%, respectively. The mean time taken for confirmation of ETT position was significantly shorter with waveform capnography (10.29 ± 2.25 s) compared to auscultation (12.96 ± 2.23 s) and ultrasonography (USG) (14.28 ± 3.77 s). CONCLUSION: Confirmation of ETT position using USG or waveform capnography is essential because of high false results using standard auscultation alone. Ultrasound-guided lung sliding method is a simple, fast, and a reliable method used for detecting tube malposition.

Onion (Allium cepa L.) peel: A review on the extraction of bioactive compounds, its antioxidant potential, and its application as a functional food ingredient.

Functional food development is rapidly increasing as a result of consumer consciousness concerning healthy and nutritious foods. In turn, research exploring novel ingredients for formulating functional foods has been accelerated. Onion peel or skin is a byproduct obtained from onion processing that contains abundant phytochemicals, contributing to its antioxidant potential. The main focus of this review is to highlight different extraction techniques (both conventional and nonconventional) that can be implemented to extract the bioactive compounds from onion peel and assess their antioxidant activity. Furthermore, this review highlights the major areas for the application of onion peel and its extract as prospective functional ingredients, thus aiding in the preparation of designer foods with additional health benefits. The use of onion peel could also assist in redesigning popularly consumed processed foods, such as baked products, noodles or pasta, as packaging material, meat quality improvers, colorants, and juice clarifiers. This review serves as a preliminary document that can assist in exploring different ways of incorporating bioactive onion peels or skin into the functional food industry and concludes that future research can assist in the effective and efficient utilization of this resource.

Inhibition of Hepatitis E Virus Replication by Novel Inhibitor Targeting Methyltransferase.

Hepatitis E Virus (HEV) is a quasi-enveloped virus having a single-stranded, positive-sense RNA genome (~7.2 kb), flanked with a 5' methylated cap and a 3' polyadenylated tail. The HEV open reading frame 1 (ORF1) encodes a 186-kDa polyprotein speculated to get processed and produce Methyltransferase (MTase), one of the four essential replication enzymes. In this study, we report the identification of the MTase inhibitor, which may potentially deplete its enzymatic activity, thus causing the cessation of viral replication. Using in silico screening through docking, we identified ten putative compounds, which were tested for their anti-MTase activity. This resulted in the identification of 3-(4-Hydroxyphenyl)propionic acid (HPPA), with an IC50 value of 0.932 ± 0.15 µM, which could be perceived as an effective HEV inhibitor. Furthermore, the compound was tested for inhibition of HEV replication in the HEV culture system. The viral RNA copies were markedly decreased from ~3.2 × 106 in untreated cells to ~4.3 × 102.8 copies in 800 µM HPPA treated cells. Therefore, we propose HPPA as a potential drug-like inhibitor against HEV-MTase, which would need further validation through in vivo analysis using animal models and the administration of Pharmacokinetic and Pharmacodynamic (PK/PD) studies.

Glutamate 1-semialdehyde aminotransferase is connected to GluTR by GluTR-binding protein and contributes to the rate-limiting step of 5-aminolevulinic acid synthesis.

Tetrapyrroles play fundamental roles in crucial processes including photosynthesis, respiration, and catalysis. In plants, 5-aminolevulinic acid (ALA) is the common precursor of tetrapyrroles. ALA is synthesized from activated glutamate by the enzymes glutamyl-tRNA reductase (GluTR) and glutamate-1-semialdehyde aminotransferase (GSAAT). ALA synthesis is recognized as the rate-limiting step in this pathway. We aimed to explore the contribution of GSAAT to the control of ALA synthesis and the formation of a protein complex with GluTR. In Arabidopsis thaliana, two genes encode GSAAT isoforms: GSA1 and GSA2. A comparison of two GSA knockout mutants with the wild-type revealed the correlation of reduced GSAAT activity and ALA-synthesizing capacity in leaves with lower chlorophyll content. Growth and green pigmentation were more severely impaired in gsa2 than in gsa1, indicating the predominant role of GSAAT2 in ALA synthesis. Interestingly, GluTR accumulated to higher levels in gsa2 than in the wild-type and was mainly associated with the plastid membrane. We propose that the GSAAT content modulates the amount of soluble GluTR available for ALA synthesis. Several different biochemical approaches revealed the GSAAT-GluTR interaction through the assistance of GluTR-binding protein (GBP). A modeled structure of the tripartite protein complex indicated that GBP mediates the stable association of GluTR and GSAAT for adequate ALA synthesis.

Thioredoxin-dependent control balances the metabolic activities of tetrapyrrole biosynthesis.

Plastids are specialized organelles found in plants, which are endowed with their own genomes, and differ in many respects from the intracellular compartments of organisms belonging to other kingdoms of life. They differentiate into diverse, plant organ-specific variants, and are perhaps the most versatile organelles known. Chloroplasts are the green plastids in the leaves and stems of plants, whose primary function is photosynthesis. In response to environmental changes, chloroplasts use several mechanisms to coordinate their photosynthetic activities with nuclear gene expression and other metabolic pathways. Here, we focus on a redox-based regulatory network composed of thioredoxins (TRX) and TRX-like proteins. Among multiple redox-controlled metabolic activities in chloroplasts, tetrapyrrole biosynthesis is particularly rich in TRX-dependent enzymes. This review summarizes the effects of plastid-localized reductants on several enzymes of this pathway, which have been shown to undergo dithiol-disulfide transitions. We describe the impact of TRX-dependent control on the activity, stability and interactions of these enzymes, and assess its contribution to the provision of adequate supplies of metabolic intermediates in the face of diurnal and more rapid and transient changes in light levels and other environmental factors.

Insights on COVID-19 impacts, challenges and opportunities for India's biodiversity research: From complexity to building adaptations.

The COVID-19 pandemic has impacted every sphere of human society. The paradigm shift of focus to COVID-related research and management has significantly affected various scientific domains, including biodiversity conservation. We assessed the perceptions of early-career researchers working for biodiversity conservation across India, to understand the impacts of the ongoing pandemic on their research. We administered an online questionnaire survey to 565 respondents, who identified four key areas that are affected by the pandemic: (1) research, (2) conservation (3) education, and (4) communication and networking. Respondents (89.2%) perceived that their fieldwork, followed by travel for meetings and funding were the most affected due to COVID-19 outbreak and subsequent lockdown. Nonetheless, responses on the impact varied between different professional categories and were disproportionate. Our study highlights that majority of the respondents (80%) advocate for stakeholder-driven policies and management practices as the most effective strategy to promote biodiversity conservation, in the post-COVID-19 world. To this end, as a post-pandemic response, we propose holistic solutions such as optimising research funding and collaborations, and supporting and strengthening them by citizen science and big data analytics. Our findings and recommendations will also serve as a paradigm for post-COVID-19 biodiversity policy, advocacy and implementation of the post 2020 biodiversity action plan that supports eco civilization.

Improving resident education through unstable chicken hips: a novel way to teach an infant hip examination.

Current clinical screening for infantile hip dysplasia relies on combined Ortolani and Barlow maneuvers, which have a quoted sensitivity and specificity of 74-98 and 84-99%, respectively. Teaching this delicate physical examination maneuver is difficult as it requires a distinct tactile feel. The purpose of this study is to validate a benchtop learning grocery-bought chicken simulator model of newborn hip instability through a pre- and post-test surveys. This model of hip dysplasia uses whole chickens. A posterior capsulotomy of the chicken's hip joint was performed to create instability. Provocative maneuvers to dislocate and relocate the hip were taught by a pediatric orthopedic surgeon. All participants completed an anonymous pre- and post-training surveys. A total of 58 participants were included in the study: 10 medical students, 13 pediatric residents, 15 orthopedic residents, and 20 orthopedic or pediatric attending physicians. The pediatric residents had performed the Barlow/Ortolani tests more than the orthopedic residents (96.15 ± 83.19 vs. 37.53 ± 60.89; P = 0.01); however, fewer pediatric residents reported feeling a positive examination (31 vs. 67%). The majority of the group agreed that the simulation felt and moved like an infant's hip (3.95 and 4.13; Likert five-point scale). The participants unanimously agreed that the model could be used to teach someone new to pediatrics the basic steps of the examination (4.91; Likert five-point scale) and should be implemented in the teaching curriculum (100%). The current study validates the benchtop model in teaching the clinical steps in detecting hip dysplasia. The model improved confidence and comfort level for all participants and proved to be a valuable tool for resident education in multiple specialties. By improving education with this model, we hope to improve early identification of hip dysplasia with increased accuracy across subspecialties.

Increased dynamic flexibility in the medial temporal lobe network following an exercise intervention mediates generalization of prior learning.

Recent work has conceptualized the brain as a network comprised of groups of sub-networks or modules. "Flexibility" of brain network(s) indexes the dynamic reconfiguration of comprising modules. Using novel techniques from dynamic network neuroscience applied to high-resolution resting-state functional magnetic resonance imaging (fMRI), the present study investigated the effects of an aerobic exercise intervention on the dynamic rearrangement of modular community structure-a measure of neural flexibility-within the medial temporal lobe (MTL) network. The MTL is one of the earliest brain regions impacted by Alzheimer's disease. It is also a major site of neuroplasticity that is sensitive to the effects of exercise. In a two-group non-randomized, repeated measures and matched control design with 34 healthy older adults, we observed an exercise-related increase in flexibility within the MTL network. Furthermore, MTL network flexibility mediated the beneficial effect aerobic exercise had on mnemonic flexibility, as measured by the ability to generalize past learning to novel task demands. Our results suggest that exercise exerts a rehabilitative and protective effect on MTL function, resulting in dynamically evolving networks of regions that interact in complex communication patterns. These reconfigurations may underlie exercise-induced improvements on cognitive measures of generalization, which are sensitive to subtle changes in the MTL.

Analysis of rice nuclear-localized seed-expressed proteins and their database (RSNP-DB).

Nuclear proteins are primarily regulatory factors governing gene expression. Multiple factors determine the localization of a protein in the nucleus. An upright identification of nuclear proteins is way far from accuracy. We have attempted to combine information from subcellular prediction tools, experimental evidence, and nuclear proteome data to identify a reliable list of seed-expressed nuclear proteins in rice. Depending upon the number of prediction tools calling a protein nuclear, we could sort 19,441 seed expressed proteins into five categories. Of which, half of the seed-expressed proteins were called nuclear by at least one out of four prediction tools. Further, gene ontology (GO) enrichment and transcription factor composition analysis showed that 6116 seed-expressed proteins could be called nuclear with a greater assertion. Localization evidence from experimental data was available for 1360 proteins. Their analysis showed that a 92.04% accuracy of a nuclear call is valid for proteins predicted nuclear by at least three tools. Distribution of nuclear localization signals and nuclear export signals showed that the majority of category four members were nuclear resident proteins, whereas other categories have a low fraction of nuclear resident proteins and significantly higher constitution of shuttling proteins. We compiled all the above information for the seed-expressed genes in the form of a searchable database named Rice Seed Nuclear Protein DataBase (RSNP-DB) https://pmb.du.ac.in/rsnpdb . This information will be useful for comprehending the role of seed nuclear proteome in rice.

ABCA7 Genotype Moderates the Effect of Aerobic Exercise Intervention on Generalization of Prior Learning in Healthy Older African Americans.

African Americans are at elevated risk for age-related cognitive decline, with double the prevalence of Alzheimer's disease (AD) compared to Caucasians Americans. Various behavioral, biological, and lifestyle factors may underlie this health disparity, but little is known about the relative importance and interactions among these different risk factors in African Americans. While the neuroprotective effects of aerobic exercise on biomarkers are well established, few studies have examined the differential benefits of exercise based on genetic risk for AD. Furthermore, evidence is limited regarding the potential moderating effects of ABCA7, a gene known to confer significantly greater AD risk in African Americans. In a case-control matched sample of 56 healthy older African Americans, we investigated the effect of an aerobic exercise intervention on a hippocampus-related assessment of generalization following rule learning, in individuals who were carriers of the ABCA7 rs3764650 non-risk (TT) or high-risk (GG) genotype. Following the exercise-intervention, the non-risk group made significantly fewer generalization errors, while there was no improvement in generalization for the high-risk group. For the controls, no changes in generalization scores were observed regardless of genotype status. Our results indicate that the ongoing adverse effects of ABCA7 high-risk genotype may diminish the benefits associated with aerobic exercise. As such, the potential disease-modifying effects of aerobic exercise on AD-related neuropathology may be limited to carriers of the ABCA7 rs3764650 non-risk genotype.