Introduction: Congenital talipes equino-varus (CTEV) is amongst one of the most common paediatric foot deformities. Ponseti’s method is the standard way of treatment, however, some patients are left with residual or partially corrected deformities. Dynamic supination is one amongst them, where the foot supinates in swing phase of the gait cycle. It is due to a strong tibialis anterior and its weak antagonist. Materials and methods: We undertook a prospective interventional study in thirty patients of CTEV with residual dynamic supination deformity and treated them with tibialis anterior tendon transfer (TATT) using a button anchor. Minimum follow-up was six months after the surgery. Functional, subjective and objective evaluation was done using foot posture index (FPI), disease specific instrument (DSI) for clubfoot, clinician satisfaction grading and videotaped functional gait analysis. Statistical analysis was done using paired ‘t’ test and calculating p values. Results: We achieved good to excellent results in 93.3% of our patients and fair in 6.66%. None of our patients had poor results. Mean FPI improved from -1.93 to +0.3, DSI values also showed a significant reduction from 18.17 +/- 1.09 to 13.37 +/- 1.54 after surgery. A total of 90% had satisfactory gait post-surgery at 6 months follow-up. Conclusion: Tibialis anterior tendon transfer using a button anchor is effective in treatment of residual dynamic supination deformity.

Background/Aims: Inflammatory bowel disease (IBD) is increasing across the globe, more so in populous countries like India. We aimed to study the disease burden and epidemiological trends of IBD in India and look closer into the disease pattern across the country from 1990 to 2019. Methods: The burden of IBD was estimated in India using the data from the Global Burden of Disease estimate for 2019, which is a comprehensive worldwide project. The analysis included various parameters like incidence, prevalence, mortality, disability-adjusted life years, years lived with disability, and years of life lost as age-adjusted rates (per 100,000 population). Using modeling, the prediction was also made for 2050 in India. Results: The age-standardized incidence, prevalence, mortality, and disability rates of IBD in India for 2019 were 2.34, 20.34, 0.40, and 13.04, respectively. These are lower than the global incidence, prevalence, mortality, and disability rates of 4.97, 59.25, 0.54, and 20.15, respectively. The annual rates of change in incidence, prevalence, mortality, and disability rates in India from 1990 to 2019 were 0.05, –0.02, –0.36, and –0.35, respectively. The annual rates of change in incidence and prevalence are higher than the global rate of –0.18 and –0.19, while the annual rates of change in mortality and disability are lower than the global rate of –0.19 and –0.26. Conclusions The incidence and prevalence of IBD in India are lower compared to the global population but are increasing at a faster rate than the global population.

During liver injury, intrahepatic macrophage compartment is augmented by circulating monocytes that infiltrate the liver driven by C-C motif chemokine ligand/C-C motif chemokine receptor (CCL/CCR) axis including CCL1‒CCR8 axis, thereby contributing to liver inflammation. Numerous small molecular receptor antagonists, including R243, have been developed for targeting CCR8; however, these agents face challenges in clinical translation, potentially attributed to their poor pharmacokinetic profiles, lack of target specificity, and potential adverse effects. In this study, we designed four CCR8 antagonizing peptides (AP8i-AP8iv) and performed molecular characterization in silico and therapeutic investigation in vitro and in vivo. Based on in silico docking, molecular dynamic simulation using homology build model and in-vitro (competitive) binding studies, AP8ii (YEWRFYHG) evidenced highly favorable and selective interactions at the CCR8-active site. AP8ii inhibited CCL1-driven chemotaxis and LPS/IFNγ-induced pro-inflammatory activation of monocytes-macrophages in vitro. In a CCl₄-induced acute liver injury mouse model, AP8ii treatment decreased intrahepatic infiltration of circulating monocytes. Moreover, AP8ii reduced liver inflammation, as indicated by decreased F4/80, IL6 and iNOS expression, diminished ALT levels, and attenuated fibrosis, as indicated by reduced collagen-I expression. In conclusion, we report a novel CCR8-antagonizing peptide that inhibited CCL1-driven intrahepatic monocytes infiltration and differentiation into pro-inflammatory phenotype, consequently ameliorating liver inflammation and fibrogenesis in an acute liver injury mouse model.

Oral squamous cell carcinoma (OSCC) progresses from preneoplastic precursors via genetic and epigenetic alterations. Previous studies have focused on the treatment of terminally developed OSCC. However, the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied. Our study identified lysine-specific demethylase 1 (LSD1) as a crucial promoter of OSCC, demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia. LSD1 inhibition by SP2509 disrupted cell cycle, reduced immunosuppression, and enhanced CD4+ and CD8+ T-cell infiltration. In a feline model of spontaneous OSCC, a clinical LSD1 inhibitor (Seclidemstat or SP2577) was found to be safe and effectively inhibit the STAT3 network. Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling, which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4. Notably, LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422, offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition. This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
STAT3 Transcription Factor/metabolism* ; Animals ; Histone Demethylases/genetics* ; Phosphorylation ; Mouth Neoplasms/immunology* ; Mice ; Carcinoma, Squamous Cell/immunology* ; Disease Progression ; Cyclin-Dependent Kinase-Activating Kinase ; Precancerous Conditions/metabolism* ; Humans ; Cyclin-Dependent Kinases/metabolism* ; Disease Models, Animal

Dental implants have restored masticatory function to over 100 000 000 individuals, yet almost 1 000 000 implants fail each year due to peri-implantitis, a disease triggered by peri-implant microbial dysbiosis. Our ability to prevent and treat peri-implantitis is hampered by a paucity of knowledge of how these biomes are acquired and the factors that engender normobiosis. Therefore, we combined a 3-month interventional study of 15 systemically and periodontally healthy adults with whole genome sequencing, fine-scale enumeration and graph theoretics to interrogate colonization dynamics in the pristine peri-implant sulcus. We discovered that colonization trajectories of implants differ substantially from adjoining teeth in acquisition of new members and development of functional synergies. Source-tracking algorithms revealed that this niche is initially seeded by bacteria trapped within the coverscrew chamber during implant placement. These pioneer species stably colonize the microbiome and exert a sustained influence on the ecosystem by serving as anchors of influential hubs and by providing functions that enable cell replication and biofilm maturation. Unlike the periodontal microbiome, recruitment of new members to the peri-implant community occurs on nepotistic principles. Maturation is accompanied by a progressive increase in anaerobiosis, however, the predominant functionalities are oxygen-dependent over the 12-weeks. The peri-implant community is easily perturbed following crown placement, but demonstrates remarkable resilience; returning to pre-perturbation states within three weeks. This study highlights important differences in the development of the periodontal and peri-implant ecosystems, and signposts the importance of placing implants in periodontally healthy individuals or following the successful resolution of periodontal disease.
Humans ; Dental Implants/microbiology* ; Microbiota ; Male ; Adult ; Female ; Biofilms ; Middle Aged ; Peri-Implantitis/microbiology*

Ganoderma lucidum, a medicinal mushroom renowned for its production of a diverse array of compounds, accounts for the pharmacological effects including anti-inflammatory, antioxidant, immunomodulatory, and anticancer characteristics. Thus, it is recognized as a valuable species of interest in the pharmaceutical and nutraceutical industries due to its important medicinal properties. Recent advances in omics technologies such as genomes, transcriptomics, proteomics, and metabolomics have considerably increased our understanding of the bioactives in G. lucidum. This review explores the application of molecular breeding techniques to enhance both the yield and quality of G. lucidum across the food, pharmaceutical, and industrial sectors. The article discusses the current state of research on the use of contemporary omics technologies which studies and highlights future research directions that may increase the production of bioactive compounds for their therapeutic potential. Additionally, predictive methods with computational studies have recently emerged as effective tools for investigating bioactive constituents in G. lucidum, providing an organized and cost-effective strategy for understanding their bioactivity, interactions, and possible therapeutic uses. Omics and machine learning techniques can be applied to identify the candidates for pharmaceutical applications and to enhance the production of bioactive compounds in G. lucidum. The quantification and production of the bioactive compounds can be streamlined by the integrating computational study of bioactive compounds with non-destructive predictive machine learning models of the same. Synergistically, these techniques have the potential to be a promising approach for the future prediction of the bioactive constituents, without compromising the integrity of the fungal organism.

Introduction: The purpose of this study is to assess the outcomes of patients that underwent single-stage revision ACL reconstruction (ACLR) with peroneus longus tendon (PLT), augmented with lateral extra-articular tenodesis (LET) using the modified Lemaire technique. Materials and methods: All the 18 patients underwent arthroscopic single-stage revision ACLR using autologous PLT with an additional modified Limier LET procedure. Patients were thoroughly assessed pre- and post-operatively by the Lachman test, the pivot shift test, and the side-to-side difference by the Rolimeter. Functional evaluation was done with the help of the Lysholm score, the IKDC subjective score, Tegner score, VAS score, MARX activity rating scale and The American Orthopaedic Foot and Ankle Society (AOFAS) score. Post-operatively, patient satisfaction, return to sport, and physical activity were also recorded. SPSS ver. 22.0 software was used. Wilcoxon test, paired and unpaired t-tests were used to compare variables. Statistical significance was determined by a two-sided p-value <0.05. Results: Regarding subjective evaluations; post-operative residual laxity, and return to sport and physical activity, all of the patients demonstrated excellent results. Post-operatively, there was significant improvement in the anterior knee laxity. According to the Marx Activity Rating Scale, the extent of sports engagement was significantly increased at 18 months following surgery (p<0.001). According to the AOFAS score (p=0.38), there were no documented significant donor site morbidities. Conclusions: Single-stage revision ACLR using PLT with an additional modified Lemaire LET procedure results in a significant reduction in residual knee laxity with good clinical outcomes and a high return to play and physical activity

Objective: Colony-stimulating factor 1 receptor-related leukoencephalopathy (CSF1R-L) is a rare adult-onset leukoencephalopathy. Reports of CSF1R-L patients from the Indian subcontinent remain limited. We aimed to report four patients with genetically confirmed CSF1R-L from four Asian Indian families and described their clinical, molecular, and radiological features. Methods: All patients underwent clinical examination, brain magnetic resonance imaging, and whole-exome sequencing to identify causative variants in the CSF1R gene. We also reviewed published reports of Indian patients with CSF1R-L. Results: The age at enrollment ranged from 34 to 40 years. The duration of symptoms ranged from 11 months to 2 years. The chief clinical phenotype in three patients was a rapidly evolving cognitive-behavioral syndrome combined with atypical parkinsonism, and asymmetrical spastic tetraparesis was observed in one patient. We identified four different variants (three missense variants and one in-frame deletion). Radiological findings revealed white matter involvement and diffusion restriction involving the subcortical white matter and pyramidal tracts. Conclusion We expand the literature on CSF1R-L patients from India by reporting four new cases.

Objective: To explore sleep patterns in individuals with essential tremor (ET) and essential tremor plus (ET-Plus) compared with healthy controls and assess differences between ET and ET-Plus, given the lack of established polysomnography (PSG) data on these groups and the potential for sleep disturbances to serve as clinical markers. Methods: We conducted a prospective cross-sectional study at National Institute of Mental Health and Neurosciences, Bengaluru, from November 2021 to August 2023 on 45 patients (26 ET, 19 ET-Plus) and 45 controls. Tremor severity was assessed using The Essential Tremor Rating Assessment Scale (TETRAS) and Fahn‐Tolosa‐Marin Clinical Rating Scale (FTMRS). Sleep symptoms were assessed via the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Mayo Sleep Questionnaire, restless legs syndrome questionnaire, Berlin questionnaire, Generalized Anxiety Disorder Scale 7, and Patient Health Questionnaire-9. All patients and controls underwent overnight video PSG. Sleep scoring was manually performed by a trained sleep research technician and the first author following the American Academy of Sleep Medicine (2017) guidelines, with data analyzed using R studio. Results: Compared with ET-Plus patients, ET patients had a younger onset age (46.8±11.1 years versus 30.8±16.7 years, respectively). Compared with ET patients, ET-Plus patients had higher TETRAS and FTMRS scores (p<0.005). Compared with controls, both ET patients and ET-Plus patients presented poorer sleep quality, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, and restless legs syndrome symptoms. PSG findings supported these clinical observations, showing an elevated apnea‒hypopnea index, reduced total sleep time, prolonged REM latency, decreased sleep efficiency, increased N1 stage duration, and reduced N2/N3 durations and percentages in patients versus controls. Conclusion The study highlights significant sleep architecture abnormalities in both ET and ET-Plus patients compared with healthy controls, with no differences between the ET groups.