Incidence of Different Characters of Neuropathic Pain in Cancer Patients Coming to Tertiary Care Centre in North India Over A Period of 1 Year - An Observational Study.

Objectives: Pain is classified as nociceptive, neuropathic, or nociplastic. Neuropathic pain presents as variable phenotypes (characters) based on specific aetiology and pathophysiology. This study aimed to find out among cancer patients the incidence of different phenotypes of neuropathic pain and form specific phenotypic clusters based on the underlying neurophysiology and association of sensory profile with various organ systems - A prospective observational study. Materials and methods: The Institutional Ethical Committee clearance (IEC code: 2020-49-MD-EXP-15) https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=44886&EncHid=88651.15716&userName=CTRI/2020/09/027964 approval was obtained. After written and informed consent, patients of age group 18-80 years, registering in the pain and palliative outpatient department or radiotherapy department with complaints of pain and not taking any anti-neuropathic pain medications, were enrolled. They were assessed using Leeds assessment of neuropathic symptoms and signs (LANSS) pain score, and a score of >12 was eligible for assessment of neuropathic pain phenotypes. Results: Out of 210 cancer patients complaining of pain, a neuropathic component with LANSS >12 was found in 73 (34.76%). The most predominant phenotypes, allodynia> tingling> pricking = burning, were found in 72.60%, 56.16%, and 43.84% of patients, respectively. Phenotypes were clustered into Nodes 1 and 2 based on clinically significant separation of phenotypes. Node 1 had neuropathic pain of spontaneous origin found predominantly in gastrointestinal tract (GIT) and genitourinary tract (GUT) cancers. Node 2 had stimulus-evoked negative and positive characters which occurred in head and neck, thoracic, and spinal metastatic cancers. Conclusion: Careful patient assessment reveals the incidence of neuropathic pain in 34.76%; allodynia and tingling astable the most prominent phenotypes. Broadly, sensory characters were clustered into spontaneous and stimulus-evoked sensations with GIT and GUT cancers presenting with Node 1 symptoms.

Impact of Flaxseed Oil Supplementation on Tobacco Dependence, Craving, and Haematological Parameters in Tobacco-Dependent Subjects.

Background Tobacco is prevalently used in smoking or smokeless forms and remains a major public health concern worldwide, with its adverse effects on overall health. Omega-3 fatty acid (FA) has shown its promising effects in various health conditions. Objective The purpose of this study was to evaluate the effect of flaxseed oil (omega-3 supplementation) on tobacco dependence, craving, withdrawal symptoms, and haematological parameters in tobacco users. Methods In this randomised, single-blind, placebo-controlled study, 104 tobacco users (54 in the omega-3 group and 50 in the placebo group) were supplemented with 10 ml of food-grade flaxseed oil and 10 ml of placebo for six months, respectively. Their demographics, frequency of daily tobacco use, tobacco dependence, tobacco craving, tobacco withdrawal symptoms, and complete blood count (CBC) were assessed at baseline (before intervention) and after a six-month intervention. Results The demographic characteristics of the two groups were similar except for gender at baseline. There were 50 males and four females in the omega-3 group, while there were 42 males and eight females in the placebo group. After a six-month flaxseed oil intervention, BMI values showed a significant reduction (p = 0.0081) in the omega-3 group when compared to baseline; however, CBC parameters did not show any significant changes when comparing baseline to follow-up values. On the contrary, haemoglobin and red blood cells (RBCs) showed significant changes when comparing the follow-ups of the omega-3 group with the placebo group, indicating p = 0.0016 and p = 0.0163, respectively. Also, omega-3 effectively decreased daily tobacco use frequency (p<0.0001), tobacco dependence (p<0.0001), and craving (p<0.0001). Conclusion Supplementation of 10 ml of flaxseed oil per day (omega-3 FA) for six months significantly reduced tobacco dependence and cravings. Additionally, the flaxseed oil supplementation effectively reduced the frequency of daily tobacco intake and modulated tobacco withdrawal symptoms. Thus, our results suggest that flaxseed oil supplementation is a useful adjunct for tobacco users who intend to quit tobacco use.

Next-generation therapeutics for rare genetic disorders.

The therapeutic potential of the human genome has been explored through the development of next-generation therapeutics, which have had a high impact on treating genetic disorders. Classical treatments have traditionally focused on common diseases that require repeated treatments. However, with the recent advancements in the development of nucleic acids, utilizing DNA and RNA to modify or correct gene expression in genetic disorders, there has been a paradigm shift in the treatment of rare diseases, offering more potential one-time cure options. Advanced technologies that use CRISPR-Cas 9, antisense oligonucleotides, siRNA, miRNA, and aptamers are promising tools that have achieved successful breakthroughs in the treatment of various genetic disorders. The advancement in the chemistry of these molecules has improved their efficacy, reduced toxicity, and expanded their clinical use across a wide range of tissues in various categories of human disorders. However, challenges persist regarding the safety and efficacy of these advanced technologies in translating into clinical practice. This review mainly focuses on the potential therapies for rare genetic diseases and considers how next-generation techniques enable drug development to achieve long-lasting curative effects through gene inhibition, replacement, and editing.

CRAFT: a web-integrated cavity prediction tool based on flow transfer algorithm.

Numerous computational methods, including evolutionary-based, energy-based, and geometrical-based methods, are utilized to identify cavities inside proteins. Cavity information aids protein function annotation, drug design, poly-pharmacology, and allosteric site investigation. This article introduces "flow transfer algorithm" for rapid and effective identification of diverse protein cavities through multidimensional cavity scan. Initially, it identifies delimiter and susceptible tetrahedra to establish boundary regions and provide seed tetrahedra. Seed tetrahedron faces are precisely scanned using the maximum circle radius to transfer seed flow to neighboring tetrahedra. Seed flow continues until terminated by boundaries or forbidden faces, where a face is forbidden if the estimated maximum circle radius is less or equal to the user-defined maximum circle radius. After a seed scanning, tetrahedra involved in the flow are clustered to locate the cavity. The CRAFT web interface integrates this algorithm for protein cavity identification with enhanced user control. It supports proteins with cofactors, hydrogens, and ligands and provides comprehensive features such as 3D visualization, cavity physicochemical properties, percentage contribution graphs, and highlighted residues for each cavity. CRAFT can be accessed through its web interface at http://pitools.niper.ac.in/CRAFT , complemented by the command version available at https://github.com/PGlab-NIPER/CRAFT/ .Scientific contribution: Flow transfer algorithm is a novel geometric approach for accurate and reliable prediction of diverse protein cavities. This algorithm employs a distinct concept involving maximum circle radius within the 3D Delaunay triangulation to address diverse van der Waals radii while existing methods overlook atom specific van der Waals radii or rely on complex weighted geometric techniques.

Intracellular Iron Accumulation Induces Inflammatory and Oxidative Status of the Host After Japanese Encephalitis Viral Infection.

The factors mitigating the microglia/macrophage activation and inflammatory damage in Japanese encephalitis (JE) virus infected CNS are still being ascertained. We aim to characterize the changes in iron transporter and iron storage proteins along with inflammatory and oxidative stress-mediated signaling during the JE viral infection. Cortical tissue samples from mice with JE viral infection were processed for biochemical, histological, and molecular analysis. Iron storage protein, i.e., ferritin, was found significantly increased post-JE viral infection, and iron accumulation was noted in cortical tissue. Key proinflammatory associated markers, such as TNF-α, IL-6, and its regulator TLR4, were found to be increased, while SOCS1 (anti-inflammatory regulator) transcription decreased with increased levels of oxidative stress markers NOX2-mediated NF-ΚB/p65 and protein carbonyl. Furthermore, it is noted that hepcidin level increased and ferroportin level decreased, and iron transporter gene expression got imbalanced after JE viral infection. This observation was further confirmed by deferoxamine (DFO) treatment to JE viral infection mice model, where the decline in hepcidin transcription level and iron load in cortical tissue of JE viral infected animals was noted. However, no change was found in the ferroportin level compared to JE viral infected animals. Together, these findings suggest that iron overload and hepcidin-ferroportin regulation are involved in JE viral infection disease pathologies and associated with the inflammatory and oxidative status of the host during infection.

Mental health during the COVID-19 pandemic in children and adolescents with ADHD: A systematic review of controlled longitudinal cohort studies.

Prior studies reported mixed effects of the COVID-19 pandemic on the mental health of children and adolescents with ADHD, but they were mainly cross-sectional and without controls. To clarify the impact, we searched Web of Science, EMBASE, Medline, and PsychINFO until 18/11/2023 and conducted a systematic review of controlled longitudinal cohort studies (Prospero: CRD42022308166). The Newcastle-Ottawa scale was used to assess quality. We identified 6 studies. Worsening of mental health symptoms was more evident in ADHD or control group according to symptom considered and context. However, those with ADHD had more persistent elevated symptoms and remained an at-risk population. Sleep problems deteriorated more significantly in those with ADHD. Lower pre-COVID emotion regulation skills and greater rumination were associated with worse mental health outcomes, and longer screen time with poorer sleep. Quality was rated as low in most studies, mainly due to self-report outcome measures and no information on attrition rates. Despite these limitations, results suggest a predominantly negative impact on youths with ADHD and may guide clinical practice and policy.

Comparative Evaluation of the Antimicrobial Efficacy of Chemical and Phytomedicinal Agents When Used As Intracanal Irrigants: An In Vitro Study.

AIM: This study aimed to compare and evaluate the antimicrobial efficacy of chemical and phytomedicinal agents when used as intracanal irrigants against Candida albican (C. albican) and Enterococcus faecalis (E. faecalis). Materials and methods: This study was conducted at Kothiwal Dental College and Research Centre, Moradabad, India. One-hundred human tooth roots with a standardized length of 12±0.5 mm were divided into two groups (A and B, 50 each) inoculated with C. albican and E. faecalis, respectively. The groups were further divided according to the irrigants: A1 (11% ethanolic extract of propolis), A2 (2% chlorhexidine gluconate (CHX)), A3 (0.5% metronidazole), A4 (10% babool), and A5 (sterile saline (control) for the C. albican group and E. faecalis group (B1 to B5, respectively). The samples of different specimens were taken at subsequent intervals. The first collection was taken two days and 21 days after inoculation in group A and group B, respectively. The second collection was taken post irrigation, and the third collection seven days after different irrigants were used in both the groups. Microbiological samples were grown in a culture medium and incubated at 37°C for 24 hours for C. albican and 48 hours for E. faecalis (Sabouraud dextrose agar for C. albican and brain heart fusion for E. faecalis). The results were submitted for analysis of variance (ANOVA) and post-hoc test for statistical analysis. RESULTS: In group A, 2% chlorhexidine gluconate showed a highly significant percentage reduction of colony-forming unit (CFU) count (p≤0.001) with respect to the time interval against C. albican, followed by metronidazole, babool, propolis, and saline, whereas in group B, propolis showed a significant percentage reduction of CFU count (p<0.001) with respect to time interval against E. faecalis, followed by 2% CHX, metronidazole, babool, and saline. CONCLUSION: Two percent chlorhexidine gluconate showed the highest antimicrobial efficacy against C. albican, whereas propolis showed the highest antimicrobial efficacy against E. faecalis. Chemical irrigants proved effective over herbal irrigants against C. albican, whereas herbal irrigants showed better antimicrobial efficacy over chemical irrigants against E. faecalis.

Applications of some advanced sequencing, analytical, and computational approaches in medicinal plant research: a review.

The potential active chemicals found in medicinal plants, which have long been employed as natural medicines, are abundant. Exploring the genes responsible for producing these compounds has given new insights into medicinal plant research. Previously, the authentication of medicinal plants was done via DNA marker sequencing. With the advancement of sequencing technology, several new techniques like next-generation sequencing, single molecule sequencing, and fourth-generation sequencing have emerged. These techniques enshrined the role of molecular approaches for medicinal plants because all the genes involved in the biosynthesis of medicinal compound(s) could be identified through RNA-seq analysis. In several research insights, transcriptome data have also been used for the identification of biosynthesis pathways. miRNAs in several medicinal plants and their role in the biosynthesis pathway as well as regulation of the disease-causing genes were also identified. In several research articles, an in silico study was also found to be effective in identifying the inhibitory effect of medicinal plant-based compounds against virus' gene(s). The use of advanced analytical methods like spectroscopy and chromatography in metabolite proofing of secondary metabolites has also been reported in several recent research findings. Furthermore, advancement in molecular and analytic methods will give new insight into studying the traditionally important medicinal plants that are still unexplored.

Increased IL-6 Levels and the Upregulation of Iron Regulatory Biomarkers Contribute to the Progression of Japanese Encephalitis Virus Infection's Pathogenesis.

Integrated analysis of iron regulatory biomarkers and inflammatory response could be an important strategy for Japanese encephalitis viral (JEV) infection disease management. In the present study, the inflammatory response was assessed by measuring serum Interleukin-6 (IL-6) levels using ELISA, and the transcription levels of iron homeostasis regulators were analyzed via RT-PCR. Furthermore, inter-individual variation in the transferrin gene was analyzed by PCR-RFLP and their association with clinical symptoms, susceptibility, severity, and outcomes was assessed through binary logistic regression and classification and regression tree (CART) analysis. Our findings revealed elevated levels of IL-6 in serum as well as increased expression of hepcidin (HAMP), transferrin (TF), and transferrin receptor-1 (TFR1) mRNA in JEV infection cases. Moreover, we found a genetic variation in TF (rs4481157) associated with clinical symptoms of meningoencephalitis. CART analysis indicates that individuals with the wild-type TF genotype are more susceptible to moderate JEV infection, while those with the homozygous type are in the high-risk group to develop a severe JEV condition. In summary, the study highlights that JEV infection induces alteration in both IL-6 levels and iron regulatory processes, which play pivotal roles in the development of JEV disease pathologies.

Rapid metabolic fingerprinting with the aid of chemometric models to identify authenticity of natural medicines: Turmeric, Ocimum, and Withania somnifera study.

Herbal medicines are popular natural medicines that have been used for decades. The use of alternative medicines continues to expand rapidly across the world. The World Health Organization suggests that quality assessment of natural medicines is essential for any therapeutic or health care applications, as their therapeutic potential varies between different geographic origins, plant species, and varieties. Classification of herbal medicines based on a limited number of secondary metabolites is not an ideal approach. Their quality should be considered based on a complete metabolic profile, as their pharmacological activity is not due to a few specific secondary metabolites but rather a larger group of bioactive compounds. A holistic and integrative approach using rapid and nondestructive analytical strategies for the screening of herbal medicines is required for robust characterization. In this study, a rapid and effective quality assessment system for geographical traceability, species, and variety-specific authenticity of the widely used natural medicines turmeric, Ocimum, and Withania somnifera was investigated using Fourier transform near-infrared (FT-NIR) spectroscopy-based metabolic fingerprinting. Four different geographical origins of turmeric, five different Ocimum species, and three different varieties of roots and leaves of Withania somnifera were studied with the aid of machine learning approaches. Extremely good discrimination (R2 > 0.98, Q2 > 0.97, and accuracy = 1.0) with sensitivity and specificity of 100% was achieved using this metabolic fingerprinting strategy. Our study demonstrated that FT-NIR-based rapid metabolic fingerprinting can be used as a robust analytical method to authenticate several important medicinal herbs.

Modulation of various host cellular machinery during COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) emerged in December 2019, causing a range of respiratory infections from mild to severe. This resulted in the ongoing global COVID-19 pandemic, which has had a significant impact on public health. The World Health Organization declared COVID-19 as a global pandemic in March 2020. Viruses are intracellular pathogens that rely on the host's machinery to establish a successful infection. They exploit the gene expression machinery of host cells to facilitate their own replication. Gaining a better understanding of gene expression modulation in SARS-CoV2 is crucial for designing and developing effective antiviral strategies. Efforts are currently underway to understand the molecular-level interaction between the host and the pathogen. In this review, we describe how SARS-CoV2 infection modulates gene expression by interfering with cellular processes, including transcription, post-transcription, translation, post-translation, epigenetic modifications as well as processing and degradation pathways. Additionally, we emphasise the therapeutic implications of these findings in the development of new therapies to treat SARS-CoV2 infection.

Microfluidic Isolation of Disseminated Tumor Cells from the Bone Marrow of Breast Cancer Patients.

Disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer (BC) patients are putative precursors of metastatic disease, and their presence is associated with an adverse clinical outcome. To achieve the personalization of therapy on a clinical routine level, the characterization of DTCs and in vitro drug testing on DTCs are of great interest. Therefore, biobanking methods, as well as novel approaches to DTC isolation, need to be developed. In this study, we established a protocol for the biobanking of BM samples and evaluated a microfluidic-based separation system (Parsortix®) for the enrichment of cryopreserved DTCs. We were able to successfully isolate viable DTCs after the prior cryopreservation of BM samples. We calculated a significant increase of up to 90-fold in harvested DTCs with the proposed method compared to the current standard techniques, opening up new analysis possibilities for DTCs. Our advanced method further presents options for 3D DTC cultures, enabling the individualized testing of targeted therapies for BC patients. In conclusion, we present a novel approach for DTC enrichment, with possibilities for future clinical implications.

A review on accelerated orthodontics.

When the duration of orthodontic treatment is shortened, the patient may have a number of benefits, including an increase in the number of dental cavities, root resorption, and gingival irritation, all of which are associated to a higher degree of decalcification. In addition to drugs, magnets, and other therapies, they include surgical methods (corticotomies, piezosurgery), mechanical/physical stimulation techniques (vibration, lasers), and other forms of therapy. These methods, each of which has been validated by extensive research, have been shown to reduce treatment times.

Proteins with amino acid repeats constitute a rapidly evolvable and human-specific essentialome.

Protein products of essential genes, indispensable for organismal survival, are highly conserved and bring about fundamental functions. Interestingly, proteins that contain amino acid homorepeats that tend to evolve rapidly are enriched in eukaryotic essentialomes. Why are proteins with hypermutable homorepeats enriched in conserved and functionally vital essential proteins? We solve this functional versus evolutionary paradox by demonstrating that human essential proteins with homorepeats bring about crosstalk across biological processes through high interactability and have distinct regulatory functions affecting expansive global regulation. Importantly, essential proteins with homorepeats rapidly diverge with the amino acid substitutions frequently affecting functional sites, likely facilitating rapid adaptability. Strikingly, essential proteins with homorepeats influence human-specific embryonic and brain development, implying that the presence of homorepeats could contribute to the emergence of human-specific processes. Thus, we propose that homorepeat-containing essential proteins affecting species-specific traits can be potential intervention targets across pathologies, including cancers and neurological disorders.

Impact of learning effect on reliability factors and global indices in visual field testing by standard automated perimetry in normal healthy subjects and primary open-angle glaucoma patients to obtain an accurate baseline perimetry chart.

Purpose: To record and evaluate the reliability parameters (fixation loss (FL) %, false positive (FP) %) and global indices (mean sensitivity (MS), mean deviation (MD), pattern standard deviation in dB) in three visual field test sessions within two weeks to assess the learning effect in normal healthy subjects and POAG patients and comparison of learning effect gender wise and age wise in primary open-angle glaucoma (POAG) patients. Methods: This study was a prospective observational study. An oculus visual field testing was done and analyzed in 30 eyes of POAG patients and 30 eyes of normal healthy subjects in three visits. Results: There were 16 (53.3%) males and 14 (46.6%) females in the POAG group and 16 (53.33%) males and 14 (46.66%) females in the normal healthy subject group. A significant difference in data change between each visit in FL, FP, MD, MS was found though the difference was more pronounced in the second visit than in the third visit. The pattern standard deviation does not change significantly in subsequent visits in both groups. Gender wise and age wise no significant difference was found in the POAG group. Conclusion: Significant improvement in reliability parameters and global indices with each subsequent visit in both the POAG group and normal patients signifies the importance of learning effect on these parameters and the need to perform at least three tests to get the baseline perimetry chart, especially in POAG patients, while in normal subjects, second perimetric result can be accepted. It was also concluded that the learning effect is not influenced by age and gender.

Optimizing the Immunogenicity of HIV Vaccines by Adjuvants - NIAID Workshop Report.

This report summarizes the highlights of a workshop convened by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), on April 4-5, 2022, to provide a discussion forum for sharing insights on the current status, key challenges, and next steps to advance the current landscape of promising adjuvants in preclinical and clinical human immunodeficiency virus (HIV) vaccine studies. A key goal was to solicit and share recommendations on scientific, regulatory, and operational guidelines for bridging the gaps in rational selection, access, and formulation of clinically relevant adjuvants for HIV vaccine candidates. The NIAID Vaccine Adjuvant Program working group remains committed to accentuate promising adjuvants and nurturing collaborations between adjuvant and HIV vaccine developers.

The SARS-CoV-2 UTR's Intrudes Host RBP's and Modulates Cellular Splicing.

SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of post-transcriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3'UTRs of the viral genomic RNAs, results in reduced mRNA levels possibly due to modulation of host cell pre-mRNA splicing. Further, we have investigated the potential RNA-binding proteins interacting with the 5' and 3'UTRs, using in-silico approaches. Our results suggest that 5' and 3'UTRs indeed interact with many RNA-binding proteins. Our results provide a primer for further investigations into the UTR-mediated regulation of splicing and related molecular mechanisms in host cells.

Advances in Drug Discovery based on Genomics, Proteomics and Bioinformatics in Malaria.

Malaria is one of the neglected infectious diseases, and drugs are the first line of action taken against the onset of malaria as therapeutics. The drugs can be of either natural or artificial origin. Drug development has multiple impediments grouped under three categories, a. drug discovery and screening, b. the drug's action on the host and the pathogen, and c. clinical trials. Drug development takes coon's age from discovery to the market after FDA approval. At the same time, targeted organisms develop drug resistance quicker than drug approval, raising the requirement for advancement in drug development. The approach to explore drug candidates using the classical methods from natural sources, computation-based docking, mathematical and machine learningbased high throughput in silico models or drug repurposing has been investigated and developed. Also, drug development with information about the interaction between Plasmodium species and its host, humans, may facilitate obtaining an efficient drug cohort for further drug discovery or repurposing expedition. However, drugs may have side effects on the host system. Hence, machine learning and systems-based approaches may provide a holistic view of genomic, proteomic, and transcriptomic data and their interaction with the selected drug candidates. This review comprehensively describes the drug discovery workflows using drug and target screening methodologies, followed by possible ways to check the binding affinity of the drug and targets using various docking software.

Bio-removal of rare earth elements from hazardous industrial waste of CFL bulbs by the extremophile red alga Galdieria sulphuraria.

In recent decades, a shift has been seen in the use of light-emitting diodes over incandescent lights and compact fluorescent lamps (CFL), which eventually led to an increase in wastes of electrical equipment (WEE), especially fluorescent lamps (FLs) and CFL light bulbs. These widely used CFL lights, and their wastes are good sources of rare earth elements (REEs), which are desirable in almost every modern technology. Increased demand for REEs and their irregular supply have exerted pressure on us to seek alternative sources that may fulfill this demand in an eco-friendly manner. Bio-removal of wastes containing REEs, and their recycling may be a solution to this problem and could balance environmental and economic benefits. To address this problem, the current study focuses on the use of the extremophilic red alga, Galdieria sulphuraria, for bioaccumulation/removal of REEs from hazardous industrial wastes of CFL bulbs and the physiological response of a synchronized culture of G. sulphuraria. A CFL acid extract significantly affected growth, photosynthetic pigments, quantum yield, and cell cycle progression of this alga. A synchronous culture was able to efficiently accumulate REEs from a CFL acid extract and efficiency was increased by including two phytohormones, i.e., 6-Benzylaminopurine (BAP - Cytokinin family) and 1-Naphthaleneacetic acid (NAA - Auxin family).