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1.
Life Sci Alliance ; 7(9)2024 Sep.
Article in English | MEDLINE | ID: mdl-38925866

ABSTRACT

In Caenorhabditis elegans, inter-cellular transport of the small non-coding RNA causing systemic RNAi is mediated by the transmembrane protein SID1, encoded by the sid1 gene in the systemic RNAi defective (sid) loci. SID1 shares structural and sequence similarity with cholesterol uptake protein 1 (CHUP1) and is classified as a member of the ChUP family. Although systemic RNAi is not an evolutionarily conserved process, the sid gene products are found across the animal kingdom, suggesting the existence of other novel gene regulatory mechanisms mediated by small non-coding RNAs. Human homologs of sid gene products-hSIDT1 and hSIDT2-mediate contact-dependent lipophilic small non-coding dsRNA transport. Here, we report the structure of recombinant human SIDT1. We find that the extra-cytosolic domain of hSIDT1 adopts a double jelly roll fold, and the transmembrane domain exists as two modules-a flexible lipid binding domain and a rigid transmembrane domain core. Our structural analyses provide insights into the inherent conformational dynamics within the lipid binding domain in ChUP family members.


Subject(s)
Membrane Proteins , Humans , Membrane Proteins/genetics , Membrane Proteins/metabolism , Membrane Proteins/chemistry , Protein Binding , Protein Domains/genetics , Models, Molecular , Protein Conformation , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Animals , Amino Acid Sequence , Binding Sites , Lipids/chemistry , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/chemistry , RNA Interference
2.
Med Chem ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38918990

ABSTRACT

The most common heterocyclic aromatic molecule with potential uses in industry and medicine is quinoline. Its chemical formula is C9H7N, and it has a distinctive double-ring structure with a pyridine moiety fused with a benzene ring. Various synthetic approaches synthesize quinoline derivatives. These approaches include solvent-free synthetic approach, mechanochemistry, ultrasonic, photolytic synthetic approach, and microwave and catalytic synthetic approaches. One of the important synthetic approaches is a catalyst-based synthetic approach in which different catalysts are used such as silver-based catalysts, titanium-based nanoparticle catalysts, new iridium catalysts, barium-based catalysts, iron-based catalysts, gold-based catalysts, nickel-based catalyst, some metal-based photocatalyst, α-amylase biocatalyst, by using multifunctional metal-organic framework-metal nanoparticle tandem catalyst etc. In the present study, we summarized different catalyst-promoted reactions that have been reported for the synthesis of quinoline. Hopefully, the study will be helpful for the researchers.

3.
ACS Appl Bio Mater ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848346

ABSTRACT

Critical limb ischemia (CLI) refers to a severe condition resulting from gradual obstruction in the supply of blood, oxygen, and nutrients to the limbs. The most promising clinical solution to CLI is therapeutic angiogenesis. This study explored the potency of pro-angiogenic terbium hydroxide nanorods (THNR) for treatment of CLI, with a major focus on their impact on ischemia-induced maladaptive alterations in endothelial cells as well as on vascularization in ischemic limbs. This study demonstrated that, in hypoxia-exposed endothelial cells, THNR improve survival and promote proliferation, migration, restoration of nitric oxide production, and regulation of vascular permeability. Based on molecular studies, these attributes of THNR can be traced to the stimulation of PI3K/AKT/eNOS signaling pathways. Besides, Wnt/GSK-3ß/ß-catenin signaling pathways may also play a role in the therapeutic actions of THNR. Furthermore, in the murine model of CLI, THNR administration can integrally re-establish blood perfusion with concomitant reduction of muscle damage and inflammation. Additionally, improvement of locomotor activities and motor coordination in ischemic limbs in THNR treated mice is also evident. Overall, the study demonstrates that THNR have the potential to be developed as an efficacious and cost-effective alternative clinical therapy for CLI, using a nanomedicine approach.

4.
Chem Biol Drug Des ; 103(6): e14537, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888058

ABSTRACT

The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six-membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure-activity relationship concerning different biological activities of various piperazine-containing drugs has also been highlighted to provide a good understanding to researchers for future research on piperazines.


Subject(s)
Chemistry, Pharmaceutical , Piperazines , Piperazines/chemistry , Piperazines/chemical synthesis , Humans , Structure-Activity Relationship , Animals
5.
ACS Chem Neurosci ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902941

ABSTRACT

Chronic hypoxic exposure triggers the onset and progression of cognitive dysfunction; however, the mechanisms underlying chronic hypoxia-induced neuroinflammation and its contribution to cognitive dysfunction remain poorly understood. Although inflammation and hypoxia are interdependent, numerous recent studies have linked the development of various human diseases to hypoxia-induced inflammation. In this study, we focused on the NLRP3 inflammasome with novel analogues of cytokine release inhibitory drug 3 (CRID3), a class of small molecule inhibitors for the NLRP3 inflammasome, to investigate their potential contribution to alleviating chronic hypoxia-induced neuroinflammation using the zebrafish model. The designed CRID3 analogues 6a-q were prepared from 2-methyl furan-3-carboxylate, following a four-step reaction sequence and fully characterized by NMR and mass spectral analysis. The administration of CRID3 analogues 6a-q led to a notable reduction in neuroinflammation and an increase in glial proliferation markers in both sexes. In addition, we investigated the potential effects of CRID3 analogues 6a-q through various behavioral tasks to assess their role in ameliorating post-hypoxic behavioral deficits and cognitive impairment. Notably, the study revealed that post-chronic hypoxia, male zebrafish exhibited significantly higher levels of inflammatory marker expression than females. Furthermore, we observed that the neurogenic response to treatment with CRID3 derivative 6o varied depending on the sex, with females showing a sex-specific differential increase in neurogenesis compared to males. This work emphasizes the significance of considering sex differences into account in developing therapeutic strategies for neurological disorders, as shown by the sex-specific molecular and behavioral changes in zebrafish cognitive impairment and neuroinflammation.

6.
Cureus ; 16(5): e59508, 2024 May.
Article in English | MEDLINE | ID: mdl-38826983

ABSTRACT

Background Dyspepsia is one of the most common GI complaints encountered in clinical practice. Histopathological assessment of endoscopic gastric mucosa biopsy is crucial to delineate the exact cause of dyspepsia to guide patients' management. Objectives The aim of this study was to determine the histopathological spectrum of upper gastrointestinal (GI) tract endoscopic biopsies and to study the age and sex distribution of the predominant upper GI lesions. Methods A cross-sectional study was conducted in the Department of Pathology, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India, from January 2022 to December 2023. All endoscopic mucosal biopsies of the esophagus, stomach, and duodenum (first and second parts) lesions were examined under a microscope for histopathological findings. Results Out of 250 endoscopic biopsies studied, there were 76 cases of esophageal biopsies, 149 cases of gastric biopsies, and 25 cases of duodenal biopsies. The male-to-female ratio was 1.2:1. Non-neoplastic lesions were more common than neoplastic lesions. The most common lesions encountered were esophagitis in the esophagus, gastritis in the stomach, and duodenitis in the duodenum. Conclusion The main organic cause of dyspepsia in our setting was chronic gastritis. We conclude that endoscopy of the upper GI tract and histopathological examination help in the earlier detection of both benign and malignant lesions. This aids in better timely management of the patients and improves the overall treatment provided resulting in a better prognosis.

7.
Indian J Surg Oncol ; 15(2): 341-348, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38741642

ABSTRACT

Prostate cancer is a significant cause of cancer-related mortality among men worldwide, necessitating the exploration of prognostic biomarkers to aid in accurate risk assessment and treatment decision-making. This cross-sectional study aimed to comprehensively evaluate the role of Ki-67 as a prognostic marker in prostate cancer by examining its association with clinicopathological parameters. A total of 102 archived cases of prostate core biopsy specimens, histopathologically reported as prostate carcinoma, were included in this study. Histopathological grading was conducted using Gleason's scoring and grading system based on morphology. The statistical software "R" was utilized for data analysis. Kruskal-Wallis test and Fisher's exact test were employed to analyze the association between Ki-67 expression and clinicopathological parameters. The study revealed significant correlations between Ki-67 expression and various clinicopathological parameters in prostate cancer cases. High Ki-67 expression levels were associated with higher Gleason scores, increased incidence of perineural invasion, advanced T stages, lymph node metastasis, presence of distant metastasis, and higher prognostic stage groups. The findings of this cross-sectional study support the potential of Ki-67 as a prognostic marker in prostate cancer. The significant associations observed between Ki-67 expression and clinicopathological parameters indicate its usefulness in risk stratification and treatment decision-making. The incorporation of histopathological grading, including Gleason scoring, and analysis of perineural invasion strengthens the validity of the study. Ki-67, in combination with morphological assessments, provides valuable prognostic information for prostate cancer patients.

8.
Lung India ; 41(3): 230-248, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38704658

ABSTRACT

Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.

9.
Rice (N Y) ; 17(1): 33, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727876

ABSTRACT

BACKGROUND: The lack of stable-high yielding and direct-seeded adapted varieties with better germination ability from deeper soil depth and availability of molecular markers are major limitation in achieving the maximum yield potential of rice under water and resource limited conditions. Development of high-throughput and trait-linked markers are of great interest in genomics-assisted breeding. The aim of present study was to develop and validate novel KASP (Kompetitive Allele-Specific PCR) markers associated with traits improving germination and seedling vigor of deep sown direct seeded rice (DSR). RESULTS: Out of 58 designed KASP assays, four KASP assays did not show any polymorphism in any of the eleven genetic backgrounds considered in the present study. The 54 polymorphic KASP assays were then validated for their robustness and reliability on the F1s plants developed from eight different crosses considered in the present study. The third next validation was carried out on 256 F3:F4 and 713 BC3F2:3 progenies. Finally, the reliability of the KASP assays was accessed on a set of random 50 samples from F3:F4 and 80-100 samples from BC3F2:3 progenies using the 10 random markers. From the 54 polymorphic KASP, based on the false positive rate, false negative rate, KASP utility in different genetic backgrounds and significant differences in the phenotypic values of the positive (desirable) and negative (undesirable) traits, a total of 12 KASP assays have been selected. These 12 KASP include 5 KASP on chromosome 3, 1 on chromosome 4, 3 on chromosome 7 and 3 on chromosome 8. The two SNPs lying in the exon regions of LOC_Os04g34290 and LOC_Os08g32100 led to non-synonymous mutations indicating a possible deleterious effect of the SNP variants on the protein structure. CONCLUSION: The present research work will provide trait-linked KASP assays, improved breeding material possessing favourable alleles and breeding material in form of expected pre-direct-seeded adapted rice varieties. The marker can be utilized in introgression program during pyramiding of valuable QTLs/genes providing adaptation to rice under DSR. The functional studies of the genes LOC_Os04g34290 and LOC_Os08g32100 possessing two validated SNPs may provide valuable information about these genes.

10.
J Colloid Interface Sci ; 669: 366-382, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38718590

ABSTRACT

In this study, metal-free PO43- enriched g-C3N4/g-C3N4 (PGCN) homojunction alginate 3D beads were developed for in-situ H2O2 production under visible light. Later, the photocatalytic-self-Fenton system was integrated with peroxymonosulfate for tetracycline degradation. Initially, the PO43- enriched g-C3N4 (PCN) and a homojunction composed of PCN and g-C3N4 (GCN) were prepared via the wet-impregnation method. Later, PGCN homojunction was formulated into 3D alginate beads through the blend-crosslinking method. The comprehensive characterization of the homojunction beads affirmed the closer contact between the semiconductors, alteration of the bandgap, faster channelization of electron-hole pairs, and improved separation of charge carriers that attributed to higher catalytic efficacy. The PGCN beads exhibited a maximum H2O2 production of 535 ± 12 µM under visible light irradiation for 60 min. The homojunction hydrogels displayed 99 ± 0.25 % tetracycline degradation in 20 min in the photocatalytic-self-Fenton-PMS system. The experimental studies also claimed a maximum chemical oxygen demand removal of 81 ± 3.6 % in 20 min with maximum reusability of beads up to 20 cycles. The Z-scheme electron migration mechanism is proposed based on the results aided by scavenger and electron spin resonance analysis. Overall, the as-synthesized alginate-supported homojunction-based photocatalytic-self-Fenton-peroxymonosulfate system is highly versatile and reusable for energy and environmental remediation.

12.
Indian J Surg Oncol ; 15(Suppl 2): 331-337, 2024 May.
Article in English | MEDLINE | ID: mdl-38818003

ABSTRACT

Adenomyomatous hyperplasia and adenomyoma are rare benign inflammatory pseudotumors of the gallbladder arising from Rokitansky-Aschoff sinuses. Occurrence of these hyperplastic conditions in the Vaterian and biliary system is extremely rare and is a concern for gastroenterologists and surgeons in distinguishing them from primary malignancies of the biliary system. Definitive diagnosis by imaging or cytopathological examination is difficult; thus, surgical resection becomes the only choice in such cases to relieve the obstruction. Here, we report two extremely rare cases of adenomyomatous hyperplasia of the extrahepatic bile duct after an extensive diagnostic workup, followed by Whipple's procedure.

13.
EXCLI J ; 23: 300-334, 2024.
Article in English | MEDLINE | ID: mdl-38655092

ABSTRACT

Cutaneous Squamous Cell Carcinoma (cSCC) is a common and potentially fatal type of skin cancer that poses a significant threat to public health and has a high prevalence rate. Exposure to ultraviolet radiation on the skin surface increases the risk of cSCC, especially in those with genetic syndromes like xerodermapigmentosum and epidermolysis bullosa. Therefore, understanding the molecular pathogenesis of cSCC is critical for developing personalized treatment approaches that are effective in cSCC. This article provides a comprehensive overview of current knowledge of cSCC pathogenesis, emphasizing dysregulated signaling pathways and the significance of molecular profiling. Several limitations and challenges associated with conventional therapies, however, are identified, stressing the need for novel therapeutic strategies. The article further discusses molecular targets and therapeutic approaches, i.e., epidermal growth factor receptor inhibitors, hedgehog pathway inhibitors, and PI3K/AKT/mTOR pathway inhibitors, as well as emerging molecular targets and therapeutic agents. The manuscript explores resistance mechanisms to molecularly targeted therapies and proposes methods to overcome them, including combination strategies, rational design, and optimization. The clinical implications and patient outcomes of molecular-targeted treatments are assessed, including response rates and survival outcomes. The management of adverse events and toxicities in molecular-targeted therapies is crucial and requires careful monitoring and control. The paper further discusses future directions for therapeutic advancement and research in this area, as well as the difficulties and constraints associated with conventional therapies.

14.
Med Chem ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38685782

ABSTRACT

The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six-membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure-activity relationship concerning different biological activities of various piperazine-containing drugs was also highlighted to provide a good understanding to researchers for future research on piperazines.

15.
Plants (Basel) ; 13(8)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38674572

ABSTRACT

Salinity is one of the most significant abiotic stress that affects the growth and development of high-value tree species, including sandalwood, which can also be managed effectively on saline soils with the help of suitable host species. Therefore, the current investigation was conducted to understand the physiological processes and antioxidant mechanisms in sandalwood along the different salinity gradients to explore the host species that could support sandalwood growth in salt-affected agro-ecosystems. Sandalwood seedlings were grown with ten diverse host species with saline water irrigation gradients (ECiw~3, 6, and 9 dS m-1) and control (ECiw~0.82 dS m-1). Experimental findings indicate a decline in the chlorophyll content (13-33%), relative water content (3-23%), photosynthetic (27-61%) and transpiration rate (23-66%), water and osmotic potential (up to 137%), and ion dynamics (up to 61%) with increasing salinity levels. Conversely, the carotenoid content (23-43%), antioxidant activity (up to 285%), and membrane injury (82-205%) were enhanced with increasing salinity stress. Specifically, among the hosts, Dalbergia sissoo and Melia dubia showed a minimum reduction in chlorophyll content, relative water content, and plant water relation and gas exchange parameters of sandalwood plants. Surprisingly, most of the host tree species maintained K+/Na+ of sandalwood up to moderate water salinity of ECiw~6 dS m-1; however, a further increase in water salinity decreased the K+/Na+ ratio of sandalwood by many-fold. Salinity stress also enhanced the antioxidative enzyme activity, although the maximum increase was noted with host plants M. dubia, followed by D. sissoo and Azadirachta indica. Overall, the investigation concluded that sandalwood with the host D. sissoo can be successfully grown in nurseries using saline irrigation water and, with the host M. dubia, it can be grown using good quality irrigation water.

16.
J West Afr Coll Surg ; 14(2): 225-228, 2024.
Article in English | MEDLINE | ID: mdl-38562397

ABSTRACT

Rhabdomyosarcoma (RMS) is the third most common extra-cranial sarcoma occurring in childhood, adolescents, and young adults (AYAs); and is rare in adults. Literature about RMS mainly considers RMS in AYAs, either with that in the children or adults, even though histological, molecular, and clinical characteristics of RMS in AYAs are significantly different from either of the two. Herein, we report a case of prostatic embryonal RMS, in a 17-year-old boy, along with the review of literature of prostatic RMS, with emphasis on AYAs. Our patient presented with clinical complaints of acute urinary retention, Grade IV prostatomegaly and, low serum prostate-specific-antigen (0.11ng/dl). The diagnosis was clinched by prostatic biopsy, which revealed diffuse 'small round blue cell' tumour admixed with larger rhabdomyoblasts, displaying positivity for desmin and myogenin, on immunohistochemistry. Clinicians should be mindful that RMS is found in all age groups ranging from childhood to adults; however, the clinical, histological, and molecular features are different. RMS in AYAs is often treated according to the guidelines provided for the paediatric age group. Treatment mostly comprises a multimodality approach, including surgery with/without chemo- and radiotherapy. Prognosis in AYAs is worse than in children but is better than in adults. Thus, early diagnosis gains utmost importance to provide comparatively more probability of rendering treatment and, hopefully, a better quality of life.

17.
Cureus ; 16(3): e55532, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38576643

ABSTRACT

Lipedematous scalp is a rare cutaneous disorder, characterized by subtle but conspicuous scalp swelling, usually associated with dysesthesia. The chronic recalcitrant nature of this condition can be extremely debilitating for the patient. We report a case of boggy scalp swelling and dysesthesia in a 37­year­old female present for five years. Magnetic resonance imaging (MRI) brain showed thickening of subcutaneous tissue of the scalp. Histopathological examination revealed thickened and edematous subcutaneous tissue, reaching up to the upper dermis. A diagnosis of lipedematous scalp was made. The patient was reassured about the benign nature of the disease and given symptomatic treatment for dysesthesia. Herein we discuss the approach to a case of boggy dysesthetic scalp swelling and the available treatment options.

18.
Indian J Crit Care Med ; 28(4): 336-342, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38585308

ABSTRACT

Aim and background: High-quality cardiopulmonary resuscitation (CPR) is associated with improved patient outcomes, but healthcare workers (HCWs) may be frequently undertrained. This study aimed to assess baseline knowledge and skills among HCWs about basic and advanced life support and the effect of simulation-based training on it. Methods: It was a single-center prospective quasi-interventional study among resident doctors and nurses at a Tertiary Center in New Delhi, India. A questionnaire-based assessment was done to assess baseline knowledge. The participants then underwent simulation-based training followed by questionnaire-based knowledge assessment and skill assessment. A repeat questionnaire-based assessment was done 6 months post-training to assess knowledge retention. Results: A total of 82 HCWs (54 doctors and 28 nurses) were enrolled. The participants scored 22.28 ± 6.06 out of 35 (63.65%) in the pre-training knowledge assessment, with low scores in post-cardiac arrest care, advanced life support, and defibrillation. After the training, there was a significant rise in scores to 28.32 ± 4.08 out of 35 (80.9%) (p < 0.01). The retention of knowledge at 6 months was 68.87% (p < 0.01). The participants scored 92.61 ± 4.75% marks in skill assessment with lower scores in chest compressions and team leadership roles. There was a positive correlation (r = 0.35) between knowledge and skills scores (p < 0.01). Conclusion: There is a progressive decrease in baseline knowledge of HCWs with the further steps in the adult chain of survival. The simulation training program had a positive impact on the knowledge of HCWs. The training programs should focus on defibrillation, advanced life support, post-cardiac arrest care, and leadership roles. How to cite this article: Agarwal A, Baitha U, Ranjan P, Swarnkar NK, Singh GP, Baidya DK, et al. Knowledge and Skills in Cardiopulmonary Resuscitation and Effect of Simulation Training on it among Healthcare Workers in a Tertiary Care Center in India. Indian J Crit Care Med 2024;28(4):336-342.

19.
3 Biotech ; 14(4): 108, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38476643

ABSTRACT

IRS1 is a cytoplasmic adaptor protein that helps in cellular growth, glucose metabolism, proliferation, and differentiation. Highly disordered (insulin receptor substrate 1) IRS1 protein sequence (mol.wt- 131,590.97 da) has been used to develop model using ab initio modeling technique by I-Tassar tool and Discovery Studio/ DogSite Server to decipher a novel active site. The constructed protein model has been submitted with PMDB Id- PM0082210. GRAVY index of IRS1 model ( - 0.675) indicated surface protein-water interaction. Protparam tool instability index (75.22) demonstrated disorderedness combined with loops owing to prolines/glycines. After refinement, the Ramachandran plot showed that 88 percent of AAs were present in the allowed region and only 0.5% in the disallowed region. Novel IRS1 model protein has 10 α-helices, 22 ß-sheets, 20 ß-hairpins, 5 ß-bulges, 47 strands, 105 ß-turns, and 8 γ-turns. Docking of IRS1 with drug MH demonstrated interaction of Ser-70, Thr-18, and Pro-69 with C-H bonds; Gln-71, and Glu-113 with hydrogen bonds; while both Glu-114 and Glu-113 with salt-bridge connection. Permissible 1.0-1.5 Å range of RMSD fluctuation between 20 and 45 ns was obtained in simulation of IRS1 and IRS1-met complex confirmed that both complexes were stable during whole simulation process. RMSF result showed that except positions 57AA and 114AA, the binding of drug had no severe effects on the flexibility of the IRS1 and IRS1-met complex. The RoG value of compactness and rigidity showed little change in IRS1 protein. SASA value of IRS1 indicated non-significant fluctuation between IRS1 and drug MH means ligand (drug) and IRS1 receptor form stable structure. Hydrogen bond strength of IRS1 and IRS1-met was 81.2 and 76.4, respectively, which suggested stable interaction.

20.
Head Neck ; 46(7): 1589-1600, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38482913

ABSTRACT

BACKGROUND: In 2018, the National Comprehensive Cancer Network treatment guidelines began recommending the use of neck dissection during surgical management of stage I-II supraglottic laryngeal squamous cell carcinoma (LSCC). METHODS: Trends and factors associated with the use of neck dissection during larynx-preserving surgery for patients with cT1-2, N0, M0 supraglottic LSCC in the National Cancer Database (2004-2020) were evaluated using multivariable-adjusted logistic regression. RESULTS: Of the 2080 patients who satisfied study eligibility criteria, 633 (30.4%) underwent neck dissection. Between 2018 and 2020, the rate of neck dissection was 39.0% (114/292). After multivariable adjustment, academic facility type, undergoing biopsy prior to surgery, and more radical surgery were significant predictors of receiving neck dissection. CONCLUSIONS: The results of this national analysis suggest that the utilization of guideline-concordant neck dissection for management of stage I-II supraglottic LSCC remains low and highlight the need to promote the practice of neck dissection for this patient population.


Subject(s)
Laryngeal Neoplasms , Neck Dissection , Neoplasm Staging , Humans , Laryngeal Neoplasms/surgery , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/mortality , Male , Female , Middle Aged , Aged , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , United States , Retrospective Studies , Databases, Factual , Laryngectomy/methods
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