Objective: To compile epidemiological characteristics of traumatic spinal cord injury (TSCI) in the Northern Indian Himalayan regions and Sub-Himalayan planes. Methods: The present study is a retrospective, cross-sectional descriptive analysis based on hospital data conducted at the Department of Physical Medicine and Rehabilitation and Spine Unit of Trauma Centre in a tertiary care hospital in Uttarakhand, India. People hospitalized at the tertiary care center between August 2018 and November 2021 are included in the study sample. A prestructured proforma was employed for the evaluation, including demographic and epidemiological characteristics. Results: TSCI was found in 167 out of 3,120 trauma patients. The mean age of people with TSCI was 33.5±13.3, with a male-to-female ratio of 2.4:1. Eighty-three participants (49.7%) were from the plains, while the hilly region accounts for 50.3%. People from the plains had a 2.9:1 rural-to-urban ratio, whereas the hilly region had a 6:1 ratio. The overall most prevalent cause was Falls (59.3%), followed by road traffic accidents (RTAs) (35.9%). RTAs (57.2%) were the most common cause of TSCI in the plains’ urban regions, while Falls (58.1%) were more common in rural plains. In both urban (66.6%) and rural (65.3%) parts of the hilly region, falls were the most common cause. Conclusion TSCI is more common in young males, especially in rural hilly areas. Falls rather than RTAs are the major cause.

Cancer drug resistance is associated with metabolic adaptation. Cancer cells have been shown to implicate acetylated polyamines in adaptations during cell death. However, exploring the mimetic of acetylated polyamines as a potential anticancer drug is lacking.We performed intracellular metabolite profiling of human breast cancer MCF-7 cells treated with doxorubicin (DOX), a well known anticancer drug. A novel and in-house vertical tube gel electrophoresis assisted procedure followed by LC-HRMS analysis was employed to detect acetylated polyamines such as N1-acetylspermidine. We designed a mimetic N1-acetylspermidine (MINAS) which is a known substrate of histone deacetylase 10 (HDAC10). Molecular docking and molecular dynamics (MDs) simulations were used to evaluate the inhibitory potential of MINAS against HDAC10. The inhibitory potential and the ADMET profile of MINAS were compared to a known HDAC10 inhibitor Tubastatin A. N1-acetylspermidine, an acetylated form of polyamine, was detected intracellularly in MCF-7 cells treated with DOX over DMSO-treated MCF-7 cells. We designed and curated MINAS (PubChem CID 162679241). Molecular docking and MD simulations suggested the strong and comparable inhibitory potential of MINAS (–8.2 kcal/ mol) to Tubastatin A (–8.4 kcal/mol). MINAS and Tubastatin A share similar binding sites on HDAC10, including Ser138, Ser140, Tyr183, and Cys184. Additionally, MINAS has a better ADMET profile compared to Tubastatin A, with a high MRTD value and lower toxicity. In conclusion, the data show that N1-acetylspermidine levels rise during DOX-induced breast cancer cell death. Additionally, MINAS, an N1-acetylspermidine mimetic compound, could be investigated as a potential anticancer drug when combined with chemotherapy like DOX.

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.

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.

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.

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.

Diabetes mellitus, a very common and multifaceted metabolic disorder is considered as one of the fastest growing public health problems in the world. It is characterized by hyperglycemia, a condition with high glucose level in the blood plasma resulting from defects in insulin secretion or its action and in some cases both the impairment in secretion and also action of insulin coexist. Historically, animal models have played a critical role in exploring and describing malady pathophysiology and recognizable proof of targets and surveying new remedial specialists and in vivo medicines. In the present study, we reviewed the experimental models employed for diabetes and for its related complications. This paper reviews briefly the broad chemical induction of alloxan and streptozotocin and its mechanisms associated with type 1 and type 2 diabetes. Also we highlighted the different models in other species and other animals.

Diabetes mellitus, a very common and multifaceted metabolic disorder is considered as one of the fastest growing public health problems in the world. It is characterized by hyperglycemia, a condition with high glucose level in the blood plasma resulting from defects in insulin secretion or its action and in some cases both the impairment in secretion and also action of insulin coexist. Historically, animal models have played a critical role in exploring and describing malady pathophysiology and recognizable proof of targets and surveying new remedial specialists and in vivo medicines. In the present study, we reviewed the experimental models employed for diabetes and for its related complications. This paper reviews briefly the broad chemical induction of alloxan and streptozotocin and its mechanisms associated with type 1 and type 2 diabetes. Also we highlighted the different models in other species and other animals.

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.