Gender Representation in Academic Publications of Tourette Syndrome Research: An Analysis of Authorship Trends.

Tourette syndrome, characterized by phonic and motor tics, is a neurodevelopmental disorder that significantly affects the quality of life of people with the condition. With over 1500 articles published in the last decade alone, this study aims to analyze the gender trends in publications related to Tourette syndrome from 2013 to 2022, examining the number of female authors as first authors and predicting future changes in female participation. The aim of this study is to analyze the gender trends of the first author in publications related to "Tourette Syndrome" from PubMed-indexed publications from January 2013 to December 2022. A bibliometric analysis was conducted by the search engine PubMed for articles pertaining to "Tourette Syndrome". NamSor app V.2 (Namsor™ Applied Onomastics, NamSor SAS, Versailles, France), an application programming interface (API), was used to identify the gender of the first publishing author. Statistical analysis and graphic models were produced using R software (R Foundation for Statistical Computing, Vienna, Austria), ARIMA (Autoregressive Integrated Moving Average) model, and DataWrapper (Datawrapper GmbH, Berlin Prenzlauer Berg, Germany). Based on the analysis of 1052 publications on Tourette Syndrome, it was found that 54.8% (n=576) of the first authors were females. A significant association was observed between gender ratios and country of publication. Statistical forecasting models suggest that female participation in Tourette research is expected to rise to approximately 60 by the year 2027. Therefore, the study highlights the progress made in achieving gender parity in Tourette syndrome research, with female-led publications being on par with male-led publications. However, there is still a need to address the global gender gap and geographical disparities in research to work towards a more inclusive and diverse academic environment.

Tofacitinib in dermatology: a potential opportunity for topical applicability through novel drug-delivery systems.

Tofacitinib is a first-generation JAK inhibitor approved by the US FDA for treating rheumatoid arthritis. It exhibits a broad-spectrum inhibitory effect with abilities to block JAK-STAT signalling. The primary objective of this review is to obtain knowledge about cutting-edge methods for effectively treating a variety of skin problems by including tofacitinib into formulations that are based on nanocarriers. The review also highlights clinical trials and offers an update on published clinical patents. Nanocarriers provide superior performance compared to conventional treatments in terms of efficacy, stability, drug bioavailability, target selectivity and sustained drug release. Current review has the potential to make significant contributions to the ongoing discussion involving dermatological treatments and the prospective impact of nanotechnology on transforming healthcare within this field.

Decoding the therapeutic landscape of alpha-linolenic acid: a network pharmacology and bioinformatics investigation against cancer-related epigenetic modifiers.

Omega-3 (n - 3) and omega-6 (n - 6) polyunsaturated fatty acids (PUFAs) are vital for human health, but an imbalance between these types is associated with chronic diseases, including cancer. Alpha-linolenic acid (ALA), a n - 3 PUFA, shows promise as an anticancer agent in both laboratory and animal studies. However, the precise molecular mechanisms underlying ALA's actions against cancer-related epigenetic modifiers (CaEpM) remain unclear. To understand this, we employed network pharmacology (NP) and molecular docking techniques. Our study identified 51 potential ALA targets and GO and KEGG pathway analysis revealed possible molecular targets and signaling pathways of ALA against CaEpM. From PPI analysis, EZH2, KAT2B, SIRT1, KAT2A, KDM6B, EHMT2, WDR5, SETD7, SIRT2, and HDAC3 emerged as the top 10 potential targets. Additionally, GeneMANIA functional association (GMFA) network analysis of these top 10 targets was performed to enhance NP insights and explore ALA's multi-target approach. After an exhaustive analysis of the core FGN subnetwork, it became evident that 9 out of the 15 targets-namely EZH2, SUZ12, EED, PARP1, HDAC3, DNMT1, NCOR2, KAT2B, and TRRAP-manifested evidently strong and abundant interconnections among each other. Molecular docking of both top 10 targets and core FGN targets confirmed strong binding affinity between ALA and SIRT2, WDR5, KDM6B, EHMT2, HDAC3, EZH2, PARP1, and KAT2B, underscoring their roles in ALA's anti-CaEpM mechanism. Our findings suggest that ALA may target key signaling pathways related to transcriptional regulation, microRNA involvement, stem cell pluripotency and cellular senescence in cancer epigenetics. These findings illuminate ALA's potential as a multi-target agent against CaEpM.Communicated by Ramaswamy H. Sarma.

Exploring the therapeutic potential of sodium deoxycholate tailored deformable-emulsomes of etodolac for effective management of arthritis.

The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (- 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.

Nature to Nurture: Chitosan nanopowder a natural carbohydrate polymer choice of egg parasitoid, Trichogramma Japonicum Ashmead.

Chitosan is a naturally occurring linear biopolymer made of partially deacetylated acetyl and N-acetyl glucosamine. Its biocompatible physiochemical and biochemical properties are unmatched. Chitosan is transformed to nanopowder for use in agriculture and associated industries as nanocarriers for existing agrochemicals, ensuring the delayed release of chemicals with better solubility. Chitosan nanopowder applied to leaves or soil can activate a plant's natural defences against insects and pathogens. These studies were carried out because there is a potential for toxicological risk linked with products created utilizing nanotechnology, such as chitosan nanopowder, and therefore researchers felt the need to investigate this. The egg parasitoides Trichogramma Japonicum Ashmead was used as a low-cost biomarker to determine the potential toxicity of chitosan nanopowder. This study looked into the possibility that the adult stage of the egg parasitoids, Trichogramma Japonicum Ashmead might be negatively impacted by chitosan nanopowder (80-100 nm). Unpaired t-test statistical analysis has been carried out. According to the statistical analysis, host eggs exposed to chitosan nanopowder showed noticeably greater parasitization than the control group. As a natural supply of carbohydrate polymers chitosan nanopowder promotes the parasitization of T. Japonicum. The findings showed that T. Japonicum favoured chitosan nanopowder. Through Y dual choice, eight-arm multiple choice, and no-choice olfactometer experiments, as well as images from a stereozoom microscope and a scanning electron microscope (SEM), the data was thoroughly supported. Future agricultural applications of chitosan nanopowder will benefit from a deeper understanding of our findings.

From the inside out: understanding the gut-heart connection.

The gut microbiome was first termed as 'Animalcules' by Antonie van Leeuwenhoek in the 17th century. The diverse composition and complex interactions of gut microbes are essential for good human health. They play a crucial role in inflammation, which by itself leads to the development of cardiovascular diseases. Although the mechanisms are not fully understood, it has been studied that the gut microbiota produce several bioactive metabolites impacting cardiovascular health mainly through TMAO pathway, SCFA pathway and bile acid pathway. Moreover, studies have found that using dietary interventions like high fiber diet and probiotics to re-establish a healthy equilibrium show promising results on improving cardiovascular health and thus, could be potentially used for prevention and management of cardiovascular diseases.

Awareness about Tobacco Causing Head and Neck Cancers via Mass Media: A Case-Control Study from India.

OBJECTIVE: This study aimed to assess the awareness of people about the adverse effects of tobacco (smoking and chewing) consumption causing head and neck cancers (HNCs) via mass media channels like television, cinema, radio and newspapers or magazines, wall painting or billboards / hoardings, public transportation and packets of chewing tobacco, bidis or cigarettes. METHODS: Hospital-based case-control was conducted in Pune, Maharashtra, India. Face to face interviews were conducted for the purpose of data collection on 225 cases and 240 controls. The relationship between two categorical variables were estimated using chi-square test with a  2-tailed P value of <.05.  SPSS software was used for data analysis. RESULTS: Controls as compared to cases had good awareness scores for chewing (59.9%) and smoking tobacco (63.7%), P<0.001. The most common form of mass media was television where the cases (60.4%) and controls (77.9%) had heard messages about tobacco in chewing and smoking form causing HNCs. Level of awareness of tobacco causing HNCs amongst tobacco users, stratified by their status (cases versus controls) showed that cases were 1.68 times less likely than controls to have heard or seen messages about the association between chewing tobacco and HNCs via radio. Males (61.3% and 61.0%) had significantly (P<0.001) more awareness as compared to females (46.9% and 43.5%) about chewing and smoking tobacco as a causal factor for  HNCs. CONCLUSION: Mass media needs to create a social environment which discourages tobacco consumption and promotes oral health at the population level. Additionally, there should be easy access to the availability of support services like Quitline and other community support services.

cGAS-STING pathway targeted therapies and their applications in the treatment of high-grade glioma.

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches in gliomas.

Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers chromosomal instability and bone metastasis in Ewing sarcoma.

Adverse prognosis in Ewing sarcoma (ES) is associated with the presence of metastases, particularly in bone, tumor hypoxia and chromosomal instability (CIN). Yet, a mechanistic link between these factors remains unknown. We demonstrate that in ES, tumor hypoxia selectively exacerbates bone metastasis. This process is triggered by hypoxia-induced stimulation of the neuropeptide Y (NPY)/Y5 receptor (Y5R) pathway, which leads to RhoA over-activation and cytokinesis failure. These mitotic defects result in the formation of polyploid ES cells, the progeny of which exhibit high CIN, an ability to invade and colonize bone, and a resistance to chemotherapy. Blocking Y5R in hypoxic ES tumors prevents polyploidization and bone metastasis. Our findings provide evidence for the role of the hypoxia-inducible NPY/Y5R/RhoA axis in promoting genomic changes and subsequent osseous dissemination in ES, and suggest that targeting this pathway may prevent CIN and disease progression in ES and other cancers rich in NPY and Y5R.

Spherical Nucleic Acids as Precision Therapeutics for the Treatment of Cancer-From Bench to Bedside.

Spherical Nucleic Acids (SNAs) emerged as a new class of nanotherapeutics consisting of a nanoparticle core densely functionalized with a shell of radially oriented synthetic oligonucleotides. The unique three-dimensional architecture of SNAs protects the oligonucleotides from nuclease-mediated degradation, increases oligonucleotide bioavailability, and in the absence of auxiliary transfection agents, enables robust uptake into tumor and immune cells through polyvalent association with cell surface pattern recognition receptors. When composed of gene-regulatory small interfering (si)RNA or immunostimulatory DNA or RNA oligonucleotides, SNAs silence gene expression and induce immune responses superior to those raised by the oligonucleotides in their "free" form. Early phase clinical trials of gene-regulatory siRNA-based SNAs in glioblastoma (NCT03020017) and immunostimulatory Toll-like receptor 9 (TLR9)-agonistic SNAs carrying unmethylated CpG-rich oligonucleotides in solid tumors (NCT03086278) have shown that SNAs represent a safe, brain-penetrant therapy for inhibiting oncogene expression and stimulating immune responses against tumors. This review focuses on the application of SNAs as precision cancer therapeutics, summarizes the findings from first-in-human clinical trials of SNAs in solid tumors, describes the most recent preclinical efforts to rationally design next-generation multimodal SNA architectures, and provides an outlook on future efforts to maximize the anti-neoplastic activity of the SNA platform.

Pluronic F127-tailored lecithin organogel of acyclovir: preclinical evidence of antiviral activity using BALB/c murine model of cutaneous HSV-1 infection.

Herpes is a well-known contagious infection equally affecting both sexes. Among many antiviral drugs employed for its treatment, acyclovir (ACY) is the drug of choice. The currently available therapies of ACY suffer from limitations like poor oral bioavailability (10-15%) and high-dose requirement. The present scientific study aims to explore pluronic lecithin organogel (PLO) as a novel drug delivery platform for ACY to bring an improvement in its delivery through topical route. The properties of organogel like biocompatibility and amphiphilic nature which facilitates dissolution of various drugs of different solubility characteristics along with enhancing the permeation potential of active molecules make it a favorable drug delivery platform for the management of topical diseases. The developed PLO formulations were characterized for micromeritic characteristics, viz., zeta potential, percentage drug content, organogel morphology, skin permeation, retention, and stability studies. The selected topical formulation was further compared with the marketed one for its therapeutic efficacy by inducing cutaneous Herpes simplex virus type 1 infection followed by confirmation of viral load by immunofluorescence and PCR analyses. The developed formulation showed significant improvement over the marketed product as reflected in lesion scoring index and PCR analysis. Further, it proved better to the marketed formulation in t.i.d. treatment regimen in comparison to control. The improvement in overall performance leading to enhanced bioavailability and safety is attributed to the synergism between excipient properties and formulation characteristics. The drug ACY in this micro environment not only finds an improved delivery vehicle but it also offers enhanced drug-target interactions.

Profile of Children with Kawasaki Disease Associated with Tropical Infections.

OBJECTIVE: To describe various infectious triggers for Kawasaki disease (KD) in India. METHODS: A series of 10 children with diagnosed infections who developed KD during their course of illness has been presented. They were diagnosed by the American Heart Association (AHA) 2017 guidelines. Echocardiography was done to check for coronary artery dilation. Treatment was instituted as per standard protocol. RESULTS: Kawasaki disease was diagnosed in 8 boys and 2 girls, aged 1 mo to 11 y. These children were being treated for dengue, chikungunya, SARS-CoV-2, hepatitis A, tuberculosis, brucellosis, disseminated staphylococcal sepsis, scrub typhus, and enteric fever. CONCLUSIONS: Kawasaki disease has been associated with infectious triggers. It should be considered in febrile patients with mucocutaneous involvement or in nonresponsive sepsis, despite adequate therapy.

Delayed Tibial Shaft Fracture Healing Associated with Smoking: A Systematic Review and Meta-Analysis of Observational Studies Conducted Worldwide.

Tibial fractures represent a great burden of disease globally, being the most common long-bone fracture; smoking is a known risk factor for delayed skeletal healing and post-fracture complications. This systematic review and meta-analysis aims to analyse the effect of smoking on healing of tibial shaft fractures. PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched from inception to March 2021, with no limitation on language, to find relevant research. All observational studies that assessed the association between cigarette smoking and tibial shaft fracture healing in adults (≥18 years) were included. The quality of studies was evaluated using the Newcastle Ottawa Quality Assessment Scale. A random effects model was used to conduct meta-analysis. Tobacco smoking was associated with an increased rate of non-union and delayed union as well as an increase in time to union in fractures of the tibial shaft. Among the 12 included studies, eight reported an increased rate of non-union, three reported delayed union, and five reported an increase in time to union. However, the results were statistically significant in only three studies for non-union, one for delayed union, and two studies for increased time to union. This review confirms the detrimental impact of smoking on tibial shaft fracture healing and highlights the importance of patient education regarding smoking cessation.

Role of Cissus quadrangularis in the Management of Osteoporosis: An Overview.

This article aims to provide a comprehensive review of Cissus quadrangularis (CQ), which is a traditional medicinal herb and has a potential osteoprotective effect. CQ is a perennial climber of family Vitaceae that is commonly found in the hotter parts of India. It is most widely used in India for improving bone health and is well known as "hadjod." It shows an anti-osteoporotic effect through different pathways mechanisms. It is natural matrices of excellence with proven bioactivity. Several cell line and animal studies demonstrated its protective nature against many diseases such as osteoporosis, arthritis, gastric ulcers etc. This review also highlights the phytochemicals identified to the date and related pharmacological applications. The discussion has also expanded to its oral formulations, which has been proven for its efficacy practically. However, the scientific information of CQ is not in the proper documentation for reference, and so availability of scientific knowledge of this climber is limited. Therefore, this review might be provided a platform to those who will be interested in studying further this herb, either for analyzing phytochemical profiling or its anti-osteoporotic usage. This is a crucial platform as several productive results have been reported on this herb, which likely to be beneficial for new drug discovery in future. Here we also discuss the bone remodeling and related factors influenced by the intake of CQ.

Co-delivery of isotretinoin and clindamycin by phospholipid-based mixed micellar system confers synergistic effect for treatment of acne vulgaris.

BACKGROUND: The combination therapy of Isotretinoin (ITR) and antibacterial formulations administered through topical route suffer from several limitations including reduced therapeutic efficacy and low patient-compliance. EXPERIMENT: The present study aimed to develop biocompatible lipid-based mixed micelles of ITR in combination with Clindamycin phosphate (CLIN) employing self-assembly method to improve its skin delivery, photostability, biocompatibility and pharmacodynamic efficacy. RESULTS: The MTT assay and cellular uptake studies showed non-cytotoxic effect to HaCat cell lines. The zone of inhibition studies conducted in Propionibacterium acnes provides the first literature evidence to support the antimicrobial property of Isotretinoin and Tretinioin. The nano-sized carriers offered (19.3 ± 1.03 nm particle size with -3.12 mV zeta potential) enhanced permeation, skin retention, pre-clinical efficacy and significant skin biocompatibility. The testosterone-induced acne model proved superior pharmacodynamic efficacy of lab developed formulation vis-à-vis marketed products of both the drugs. The results were further confirmed by the histopathological studies of respective skin samples treated with different formulations. CONCLUSION: The lab developed lipid-based micellar formulation of ITR and CLIN offers a better strategy for the combined delivery of unstable molecules like ITR and CLIN in acne management.

Impact of COVID-19 pandemic on orthopaedic surgeons in terms of anxiety, sleep outcomes and change in management practices: A cross-sectional study from India.

PURPOSE: The aim of this study was to assess the effects of the COVID-19 pandemic on anxiety, sleep outcomes and change in clinical management practices among orthopaedic surgeons following a nation-wide lockdown. METHODS: We conducted an online cross-sectional study using piloted structured questionnaires with self-reported responses from Indian orthopaedic surgeons. Study participants were identified through social networking sites: Facebook and WhatsApp. The extent of anxiety and sleep quality was assessed by the standardised seven-item Generalised Anxiety Disorder (GAD-7) scale, single-item sleep quality scale, questions on unavailability of personal protective equipment, training module on COVID-19 and change in orthopaedic patient management. RESULTS: One hundred male orthopaedic surgeons responded to the survey with majority (79%) in 30-44 years age group. Severe anxiety scores were observed in 8%; moderate, mild and minimal anxiety was observed in 12%, 27% and 53% surgeons respectively. Changes in management practice due to the pandemic was admitted by 65% respondents. We also observed an association between higher anxiety among surgeons and primary or secondary level of healthcare facility: (p = 0.04). Sleep disturbance was significantly associated with change in management practice to non-operative procedures (p = 0.03). CONCLUSION: Anxiety among orthopaedic surgeons during the COVID-19 pandemic is related to factors like younger age group, working in a primary or secondary healthcare facility. Early recognition of anxiety is essential to prevent serious psychological sequelae.

Anxiety and Sleep Disturbances Among Health Care Workers During the COVID-19 Pandemic in India: Cross-Sectional Online Survey.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 has become a serious concern among the global medical community and has resulted in an unprecedented psychological impact on health care workers, who were already working under stressful conditions. OBJECTIVE: In this study, we aimed to evaluate and measure the effects of the COVID-19 pandemic on the anxiety levels and sleep quality among health care workers in India, as well as to determine how the unavailability of personal protective equipment affects their willingness to provide patient-related care. METHODS: We conducted an online cross-sectional study using piloted, structured questionnaires with self-reported responses from 368 volunteer male and female health care workers in India. Study participants were identified through social networking platforms such as Facebook and WhatsApp. The survey evaluated the participants' degree of signs and symptoms of anxiety and sleep quality based on the 7-item Generalized Anxiety Disorder (GAD-7) scale and single-item Sleep Quality Scale, respectively. Information on the availability of personal protective equipment was collected based on responses to relevant survey questions. RESULTS: The majority of health care workers (126/368, 34.2%) were in the age group 45-60 years, and 52.2% (192/368) were doctors. Severe anxiety (ie, GAD-7 score >10) was observed among 7.3% (27/368) health care workers, whereas moderate, mild, and minimal anxiety was observed among 12.5% (46/368), 29.3% (108/368), and 50.8% (187/368) health care workers, respectively. Moreover, 31.5% (116/368) of the health care workers had poor-to-fair sleep quality (ie, scores <6). Univariate analysis showed female gender and inadequate availability of personal protective equipment was significantly associated with higher anxiety levels (P=.01 for both). Sleep disturbance was significantly associated with age <30 years (P=.04) and inadequate personal protective equipment (P<.001). Multivariable analysis showed that poorer quality of sleep was associated with higher anxiety levels (P<.001). CONCLUSIONS: The COVID-19 pandemic has potentially caused significant levels of anxiety and sleep disturbances among health care workers, particularly associated with the female gender, younger age group, and inadequate availability of personal protective equipment. These factors put health care workers at constant risk of contracting the infection themselves or transmitting it to their families. Early identification of at-risk health care workers and implementation of situation-tailored mitigation measures could help alleviate the risk of long-term, serious psychological sequelae as well as reduce current anxiety levels among health care workers.

The orphan nuclear receptor estrogen-related receptor beta (ERRß) in triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC)/basal-like breast cancer (BLBC) is a highly aggressive form of breast cancer. We previously reported that a small molecule agonist ligand for the orphan nuclear receptor estrogen-related receptor beta (ERRß or ESRRB) has growth inhibitory and anti-mitotic activity in TNBC cell lines. In this study, we evaluate the association of ESRRB mRNA, copy number levels, and protein expression with demographic, clinicopathological, and gene expression features in breast tumor clinical specimens. METHODS: ESRRB mRNA-level expression and clinical associations were analyzed using RNAseq data. Array-based comparative genomic hybridization determined ESRRB copy number in African-American and Caucasian women. Transcription factor activity was measured using promoter-reporter luciferase assays in TNBC cell lines. Semi-automatic quantification of immunohistochemistry measured ERRß protein expression on a 150-patient tissue microarray series. RESULTS: ESRRB mRNA expression is significantly lower in TNBC/BLBC versus other breast cancer subtypes. There is no evidence of ESRRB copy number loss. ESRRB mRNA expression is correlated with the expression of genes associated with neuroactive ligand-receptor interaction, metabolic pathways, and deafness. These genes contain G/C-rich transcription factor binding motifs. The ESRRB message is alternatively spliced into three isoforms, which we show have different transcription factor activity in basal-like versus other TNBC cell lines. We further show that the ERRß2 and ERRßsf isoforms are broadly expressed in breast tumors at the protein level. CONCLUSIONS: Decreased ESRRB mRNA expression and distinct patterns of ERRß isoform subcellular localization and transcription factor activity are key features in TNBC/BLBC.