FoxO1, a member of the Forkhead transcription factor family subgroup O (FoxO), is expressed in a range of cell types and is crucial for various pathophysiological processes, such as apoptosis and inflammation. While FoxO1’s roles in multiple diseases have been recognized, the target has remained largely unexplored due to the absence of cost-effective and efficient inhibitors. Therefore, there is a need for natural FoxO1 inhibitors with minimal adverse effects. In this study, docking, MMGBSA, and ADMET analyses were performed to identify natural compounds that exhibit strong binding affinity to FoxO1. The top candidates were then subjected to molecular dynamics (MD) simulations. A natural product library was screened for interaction with FoxO1 (PDB ID-3CO6) using the Glide module of the Schrödinger suite. In Silico ADMET profiling was conducted using SwissADME and pkCSM web servers. Binding free energies of the selected compounds were assessed with the Prime-MMGBSA module, while the dynamics of the top hits were analyzed using the Desmond module of the Schrödinger suite. Several natural products demonstrated high docking scores with FoxO1, indicating their potential as FoxO1 inhibitors. Specifically, the docking scores of neochlorogenic acid and fraxin were both below -6.0. These compounds also exhibit favorable drug-like properties, and a 25 ns MD study revealed a stable interaction between fraxin and FoxO1. Our findings highlight the potential of various natural products, particularly fraxin, as effective FoxO1 inhibitors with strong binding affinity, dynamic stability, and suitable ADMET profiles.

Purpose: The purpose of this study was to determine the pattern of human leukocyte antigen (HLA)-DQ genotype in children diagnosed with celiac disease (CD) (biopsy proven), and to compare this with a control group; and secondarily, to correlate HLA genotypes with clinical profiles of CD. Methods: This cross-sectional comparative observational study included 26 controls and 52 patients diagnosed with CD who presented at Sir Padampat Mother and Child Health Institute, Jaipur, from May, 2017 to October, 2018. HLA DQ genotype was assessed for each patients and correlated with clinical profiles. Results: HLA DQ2/DQ8 genotypes were significantly more common in CD (present in 100.0% cases) than in controls (23.1%) in Northern India (Rajasthan). When HLA DQ2.5 and DQ8 were present together, individuals had significantly more atypical presentations and severe findings on duodenal biopsy. Similarly, patients with the HLA DQ 2.5 genotype were also predisposed to more severe endoscopic findings, while HLA DQ2.2 predisposed them to less severe biopsy findings. HLA DQ8 was significantly associated with later age at diagnosis (>5 years) and shorter stature. The highest HLA DQ relative risk (RR) for CD development was associated with HLA DQ2.5 and DQ2.2 in combination, followed by HLA DQ2.5 and DQ8 in combination, while HLA DQx.5 and HLA DQ2.2 together had the lowest risk. Conclusion HLA DQ2/DQ8 genotypes are strongly associated with pediatric CD patients in northern India. These genotypes and their combinations may be associated with different clinical presentations of CD, and may help predict severity of CD.

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 med-icines 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.

Background: In order to assess the effectiveness of various analgesio-sedative combinations for pain relief and sedation in pediatric dental patients, a thorough evaluation of clinical studies and patient outcomes is necessary. Methods: A total of 128 healthy, uncooperative pediatric dental patients were randomly allocated to receive one of the four combinations of drugs via the intranasal (IN) route: Group I received midazolam-ketamine (MK), Group II received dexmedetomidine-ketamine (DK), Group III received midazolam-fentanyl (MF), and Group IV received dexmedetomidine-fentanyl (DF) in a parallel-arm study design. The efficacy and safety of the combinations were evaluated using different parameters. Results: The onset of sedation was significantly faster in the DF group than in the DK, MF, and MK groups (P < 0.001). The depth of sedation was significantly higher in the DK and DF groups than in the MK and MF groups (P < 0.01). DK and DF produced significant intra- and postoperative analgesia when compared with combinations of MK and MF. No significant adverse events were observed for any of the combinations. Conclusions The DK and DF groups showed potential as analgesio-sedatives in view of their anxiolytic and analgesic effects.

Methods: The study was conducted on 100 adult patients. The patients were randomly allocated into two groups of 50 patients each: group A, autologous fat group, and group B, Gelfoam group. The postoperative follow-up was conducted at intervals of 6 weeks, 3 months, 6 months, and 12 months. Both groups were evaluated clinically (Oswestry Low Back Pain Disability Questionnaire [ODI], Visual Analog Scale [VAS], Straight Leg Raising Test [SLRT]) and radiologically (using Ross grading by contrast magnetic resonance imaging [MRI]) for development of radicular pain and hence EF. Results: Based on the analysis, improvement in mean values of ODI score, VAS score, and SLRT were found to be statistically significant postoperatively at intervals of 6 weeks, 3 months, 6 months, and 12 months when compared individually in both groups. However, improvement was greater in the autologous fat group than in the Gelfoam group. Based on contrast-enhanced MRI, the number of patients who developed EF was smaller in the autologous fat group than in the Gelfoam group. Conclusions In the present study, on clinical and radiological assessment, we conclude that both groups prevent radicular pain and postoperative EF individually but relatively autologous fat was found to be more effective than Gelfoam in the prevention of EF and hence radicular pain.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

As of August 16,2021,there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease(COVID-19),and the pandemic remains a global challenge.To date,no effective and approved drugs are available for the treatment of COVID-19.Angiotensin-converting enzyme 2(ACE2)plays a crucial role in the invasion into host cells by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiological agent of COVID-19.Notably,ACE2 density is influenced by medical con-ditions,such as hypertension,or by drugs,including angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs),which can change the fate of SARS-CoV-2 infectivity.ACE2 is a target for these drugs and can be manipulated to limit the viral entry and replication within the cells.Different strategies aimed at blocking ACE2 with small molecules,peptides,and antibodies,or by neutralizing the virus through its competitive binding with human recombinant soluble ACE2(hrsACE2)are currently under investigation.In this article,we review the current state of knowledge that em-phasizes the need to find effective therapeutic agents against COVID-19 by exploiting ACE2 as a potential target.The increased soluble ACE2 levels and the application of hrsACE2 in patients with COVID-19 can be implemented to control the disease.It has not yet been established whether hypertension and other comorbidities,independent of age,have a direct role in COVID-19.Therefore,the use of renin-angiotensin system inhibitors,ACEls and ARBs,should not be discontinued during COVID-19 treatment.

Background: The emergence of drug-resistant tuberculosis (TB), is a major menace to cast off TB worldwide. Line probe assay (LPA; GenoType MTBDRplus ver. 2) and Xpert MTB/RIF assays are two rapid molecular TB detection/diagnostic tests. To compare the performance of LPA and Xpert MTB/RIF assay for early diagnosis of rifampicin-resistant (RR) TB in acid-fast bacillus (AFB) smear-positive and negative sputum samples. Methods: A total 576 presumptive AFB patients were selected and subjected to AFB microscopy, Xpert MTB/RIF assay and recent version of LPA (GenoType MTBDRplus assay version 2) tests directly on sputum samples. Results were compared with phenotypic culture and drug susceptibility testing (DST). DNA sequencing was performed with rpoB gene for samples with discordant rifampicin susceptibility results. Results: Among culture-positive samples, Xpert MTB/RIF assay detected Mycobacterium tuberculosis (Mtb) in 97.3% (364/374) of AFB smear-positive samples and 76.5% (13/17) among smear-negative samples, and the corresponding values for LPA test (valid results with Mtb control band) were 97.9% (366/374) and 58.8% (10/17), respectively. For detection of RR among Mtb positive molecular results, the sensitivity of Xpert MTB/RIF assay and LPA (after resolving discordant phenotypic DST results with DNA sequencing) were found to be 96% and 99%, respectively. Whereas, specificity of both test for detecting RR were found to be 99%. Conclusion We conclude that although Xpert MTB/RIF assay is comparatively superior to LPA in detecting Mtb among AFB smear-negative pulmonary TB. However, both tests are equally efficient in early diagnosis of AFB smear-positive presumptive RR-TB patients.

Introduction: Bicondylar tibial plateau fractures account for 10-30% of tibial plateau fractures. Despite recent advancements in the management of unstable bicondylar tibial plateau fractures, the outcomes are often poor. The present study aimed to evaluate the functional outcomes and complications of internal fixation of bicondylar tibial plateau fractures with the dual plating using two incisions. Materials and methods: The present study included 30 patients (26 males; 4 females, mean age 35.6 years; range, 19 to 65 years) with bicondylar tibial plateau fractures who were treated with dual plating between January 2017 to August 2019. Out of 30 patients, 5 patients had Schatzker type (V) and 25 patients had Schatzker type (VI) bicondylar tibial plateau fracture. All patients were treated with dual plating using two incisions. In all patient’s similar standard physical rehabilitation therapy was followed. All complications including intra and post-operative were assessed and recorded. The patients were followed-up for over 24 months. Functional outcomes were assessed with Rasmussen’s functional grading system, Oxford knee score, and range of motion of knee joint. Radiological outcomes were evaluated using Rasmussen’s radiological scoring system. Result: All fractures united with a mean time of 18 weeks. The average knee range of motion was 1.5° - 130° (range: 0° - 10° for extension lag, range: 100° -135° for flexion). Mean Rasmussen's functional grading score at the final follow-up was 26.75. All patients showed excellent or good radiographic results according to Rasmussen’s radiological scoring with a mean score of 8.5 (range 6-10). The postoperative radiographs showed mean MPTA was 84.3° and the mean PPTA was 6.2°. In the present study, complications were encountered in five patients. However, there were no cases of secondary loss of reduction, failure of the implant, malunion, or non-union. Conclusion: The surgical treatment of bicondylar tibial plateau fractures with dual locking represents a significant treatment option and provides rigid fixation in these fractures with good functional and radiological outcomes.

Background: The emergence of drug-resistant tuberculosis (TB), is a major menace to cast off TB worldwide. Line probe assay (LPA; GenoType MTBDRplus ver. 2) and Xpert MTB/RIF assays are two rapid molecular TB detection/diagnostic tests. To compare the performance of LPA and Xpert MTB/RIF assay for early diagnosis of rifampicin-resistant (RR) TB in acid-fast bacillus (AFB) smear-positive and negative sputum samples. Methods: A total 576 presumptive AFB patients were selected and subjected to AFB microscopy, Xpert MTB/RIF assay and recent version of LPA (GenoType MTBDRplus assay version 2) tests directly on sputum samples. Results were compared with phenotypic culture and drug susceptibility testing (DST). DNA sequencing was performed with rpoB gene for samples with discordant rifampicin susceptibility results. Results: Among culture-positive samples, Xpert MTB/RIF assay detected Mycobacterium tuberculosis (Mtb) in 97.3% (364/374) of AFB smear-positive samples and 76.5% (13/17) among smear-negative samples, and the corresponding values for LPA test (valid results with Mtb control band) were 97.9% (366/374) and 58.8% (10/17), respectively. For detection of RR among Mtb positive molecular results, the sensitivity of Xpert MTB/RIF assay and LPA (after resolving discordant phenotypic DST results with DNA sequencing) were found to be 96% and 99%, respectively. Whereas, specificity of both test for detecting RR were found to be 99%. Conclusion We conclude that although Xpert MTB/RIF assay is comparatively superior to LPA in detecting Mtb among AFB smear-negative pulmonary TB. However, both tests are equally efficient in early diagnosis of AFB smear-positive presumptive RR-TB patients.