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1.
Ann Surg ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606552

RESUMO

OBJECTIVE: The objective of this study is to explore the patient characteristics and practice patterns of non-certified surgeons who treat Medicare patients in the United States. SUMMARY BACKGROUND DATA: While most surgeons in the United States are board-certified, non-certified surgeons are permitted to practice in many locations. At the same time, surgical workforce shortages threaten access to surgical care for many patients. It is possible that non-certified surgeons may be able to help fill these access gaps. However, little is known about the practice patterns of non-certified surgeons. METHODS: A 100% sample of Medicare claims data from 2014-2019 were used to identify practicing general surgeons. Surgeons were categorized as certified or non-certified in general surgery​​ based on data from the American Board of Surgery. Surgeon practice patterns and patient characteristics were analyzed. RESULTS: A total of 2,097,206 patient cases were included in the study. These patients were treated by 16,076 surgeons, of which 6% were identified as non-certified surgeons. Compared to certified surgeons, non-certified surgeons were less frequently fellowship-trained (20.5% vs. 24.2%, P=0.008) and more likely to be a foreign medical graduate (14.5% vs. 9.2%, P<0.001). Non-certified surgeons were more frequently practicing in for-profit hospitals (21.2% vs. 14.2%, P<0.001) and critical access hospitals (2.2% vs. 1.3%, P<0.001), and were less likely to practice in a teaching hospital (63.2% vs. 72.4%, P<0.001). Compared to certified surgeons, non-certified surgeons treated more non-White patients (19.6% vs. 14%, P<0.001) as well as a higher percentage of patients in the two lowest socioeconomic status (SES) quintiles (36.2% vs. 29.2%, P<0.001). Operations related to emergency admissions were more common amongst non-certified surgeons (68.8% vs. 55.7%, P<0.001). There were no differences in gender or age of the patients treated by certified and non-certified surgeons. CONCLUSION: For Medicare patients, non-certified surgeons treated more patients who are non-White, of lower SES, and in more rural, critical-access hospitals.

2.
Rapid Commun Mass Spectrom ; 38(11): e9745, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38591150

RESUMO

RATIONALE: As per International Council for Harmonization (ICH) drug stability test guideline Q1A(R2), inherent stability characteristics of a drug should be studied. This work was designed to investigate inherent degradation characteristics of the drug idelalisib under ICH prescribed stress conditions, identify its degradation products, and postulate their corresponding degradation pathways. METHODS: Idelalisib was subjected to the ICH prescribed conditions of hydrolytic (neutral, acidic, and alkaline), photolytic, oxidative, and thermal stress according to ICH guideline Q1A(R2). An ultrahigh-performance liquid chromatography with photodiode array (UHPLC-PDA) method was developed to adequately resolve the drug from its degradation products, validated as per the ICH guidelines, and subsequently extended to UHPLC with electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOFMS) studies to identify the degradation products. RESULTS: Significant degradation was noted under conditions of acidic/alkaline hydrolysis, acid photolysis, and oxidative stress. The UHPLC/ESI-QTOFMS studies revealed the generation of four degradation products (I-IV), which were satisfactorily resolved from the drug by UHPLC on a Kinetex® C18 (100 × 4.6 mm; 2.6 µm) column by the developed isocratic elution method. Detection wavelength was selected as 270 nm. All the degradation products (I-IV) could be identified and characterized from their mass spectral data. The degradation pathways for the generation of various products from the drug were postulated. CONCLUSIONS: A UHPLC-PDA method was developed and validated for idelalisib. Four degradation products of idelalisib were revealed through UHPLC/ESI-QTOFMS studies, and corresponding degradation pathways were postulated for the same.


Assuntos
Purinas , Quinazolinonas , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Hidrólise , Estabilidade de Medicamentos , Oxirredução , Fotólise , Cromatografia Líquida de Alta Pressão/métodos
3.
Ann Intern Med ; 177(2): JC15, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38315998

RESUMO

SOURCE CITATION: Ford AC, Wright-Hughes A, Alderson SL, et al; ATLANTIS trialists. Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;402:1773-1785. 37858323.


Assuntos
Síndrome do Intestino Irritável , Humanos , Amitriptilina/uso terapêutico , Método Duplo-Cego , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/diagnóstico , Atenção Primária à Saúde , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como Assunto
4.
Acad Med ; 98(11S): S143-S148, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37983406

RESUMO

PURPOSE: Despite ongoing efforts to improve surgical education, surgical residents face gaps in their training. However, it is unknown if differences in the training of surgeons are reflected in the patient outcomes of those surgeons once they enter practice. This study aimed to compare the patient outcomes among new surgeons performing partial colectomy-a common procedure for which training is limited-and cholecystectomy-a common procedure for which training is robust. METHOD: The authors retrospectively analyzed all adult Medicare claims data for patients undergoing inpatient partial colectomy and inpatient cholecystectomy between 2007 and 2018. Generalized additive mixed models were used to investigate the associations between surgeon years in practice and risk-adjusted rates of 30-day serious complications and death for patients undergoing partial colectomy and cholecystectomy. RESULTS: A total of 14,449 surgeons at 4,011 hospitals performed 340,114 partial colectomy and 355,923 cholecystectomy inpatient operations during the study period. Patients undergoing a partial colectomy by a surgeon in their 1st vs 15th year of practice had higher rates of serious complications (5.22% [95% CI, 4.85%-5.60%] vs 4.37% [95% CI, 4.22%-4.52%]; P < .01) and death (3.05% [95% CI, 2.92%-3.17%] vs 2.83% [95% CI, 2.75%-2.91%]; P < .01). Patients undergoing a cholecystectomy by a surgeon in their 1st vs 15th year of practice had similar rates of 30-day serious complications (4.11% vs 3.89%; P = .11) and death (1.71% vs 1.70%; P = .93). CONCLUSIONS: Patients undergoing partial colectomy faced a higher risk of serious complications and death when the operation was performed by a new surgeon compared to an experienced surgeon. Conversely, patient outcomes following cholecystectomy were similar for new and experienced surgeons. More attention to partial colectomy during residency training may benefit patients.


Assuntos
Medicare , Cirurgiões , Adulto , Humanos , Idoso , Estados Unidos/epidemiologia , Estudos Retrospectivos , Colecistectomia/efeitos adversos , Colectomia/efeitos adversos , Colectomia/educação , Colectomia/métodos
5.
Ann Surg ; 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37830271

RESUMO

OBJECTIVE: To evaluate severe complications and mortality over years of independent practice among general surgeons. SUMMARY BACKGROUND DATA: Despite concerns that newly graduated general surgeons may be unprepared for independent practice, it is unclear whether patient outcomes differ between early and later career surgeons. METHODS: We used Medicare claims for patients discharged between July 1, 2007 and December 31, 2019 to evaluate 30-day severe complications and mortality for 26 operations defined as core procedures by the American Board of Surgery. Generalized additive mixed models were used to assess the association between surgeon years in practice and 30-day outcomes while adjusting for differences in patient, hospital, and surgeon characteristics. RESULTS: The cohort included 1,329,358 operations performed by 14,399 surgeons. In generalized mixed models, the relative risk (RR) of mortality was higher among surgeons in their first year of practice compared to surgeons in their 15th year of practice (5.5% [95% CI 4.1%-7.3%] vs. 4.7% [95% CI 3.5%-6.3%], RR 1.17 [95% CI 1.11-1.22). Similarly, the relative risk of severe complications was higher among surgeons in their first year of practice compared to surgeons in their 15th year of practice (7.5% [95% CI 6.6%-8.5%]) vs. 6.9% [95% CI 6.1%-7.9%], RR 1.08 [95% CI 1.03-1.14]). When stratified by individual operation, 21 operations had a significantly higher relative risk of mortality and all 26 operations had a significantly higher relative risk of severe complications in the first compared to the 15th year of practice. CONCLUSIONS: Among general surgeons performing common operations, rates of mortality and severe complications were higher among newly graduated surgeons compared to later career surgeons.

6.
Science ; 381(6660): 824, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37616373

RESUMO

Denied remote access, astronomers struggling to prevent loss of valuable observing time.

7.
Science ; 381(6657): 471, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37535737

RESUMO

Government says measure is needed to fight climate change, but conservationists have opposed it.

8.
Oecologia ; 201(4): 887-900, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36977811

RESUMO

The question of whether biodiversity conservation and carbon conservation can be synergistic hinges on the form of the biodiversity-productivity relationship (BPR), a fundamental ecological pattern. The stakes are particularly high when it comes to forests, which at a global level comprises a large fraction of both biodiversity and carbon. And yet, in forests, the BPR is relatively poorly understood. In this review, we critically evaluate research on forest BPRs, focussing on the experimental and observational studies of the last 2 decades. We find general support for a positive forest BPR, suggesting that biodiversity and carbon conservation are synergistic to a degree. However, we identify several major caveats: (i) although, on average, productivity may increase with biodiversity, the highest-yielding forests are often monocultures of very productive species; (ii) productivity typically saturates at fewer than ten species; (iii) positive BPRs can be driven by some third variable, in particular stem density, instead of a causal arrow from biodiversity to productivity; (iv) the BPR's sign and magnitude varies across spatial grains and extents, and it may be weak at scales relevant to conservation; and (v) most productivity estimates in forests are associated with large errors. We conclude by explaining the importance of these caveats for both conservation programmes focussed on protection of existing forests and conservation programmes focussed on restoring or replanting forests.


Assuntos
Biodiversidade , Florestas , Conservação dos Recursos Naturais
9.
Acad Med ; 98(7): 813-820, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36724304

RESUMO

PURPOSE: Accurate assessment of clinical performance is essential to ensure graduating residents are competent for unsupervised practice. The Accreditation Council for Graduate Medical Education milestones framework is the most widely used competency-based framework in the United States. However, the relationship between residents' milestones competency ratings and their subsequent early career clinical outcomes has not been established. It is important to examine the association between milestones competency ratings of U.S. general surgical residents and those surgeons' patient outcomes in early career practice. METHOD: A retrospective, cross-sectional study was conducted using a sample of national Medicare claims for 23 common, high-risk inpatient general surgical procedures performed between July 1, 2015, and November 30, 2018 (n = 12,400 cases) by nonfellowship-trained U.S. general surgeons. Milestone ratings collected during those surgeons' last year of residency (n = 701 residents) were compared with their risk-adjusted rates of mortality, any complication, or severe complication within 30 days of index operation during their first 2 years of practice. RESULTS: There were no associations between mean milestone competency ratings of graduating general surgery residents and their subsequent early career patient outcomes, including any complication (23% proficient vs 22% not yet proficient; relative risk [RR], 0.97, [95% CI, 0.88-1.08]); severe complication (9% vs 9%, respectively; RR, 1.01, [95% CI, 0.86-1.19]); and mortality (5% vs 5%; RR, 1.07, [95% CI, 0.88-1.30]). Secondary analyses yielded no associations between patient outcomes and milestone ratings specific to technical performance, or between patient outcomes and composites of operative performance, professionalism, or leadership milestones ratings ( P ranged .32-.97). CONCLUSIONS: Milestone ratings of graduating general surgery residents were not associated with the patient outcomes of those surgeons when they performed common, higher-risk procedures in a Medicare population. Efforts to improve how milestones ratings are generated might strengthen their association with early career outcomes.


Assuntos
Internato e Residência , Idoso , Humanos , Estados Unidos , Estudos Retrospectivos , Estudos Transversais , Competência Clínica , Medicare , Educação de Pós-Graduação em Medicina/métodos , Acreditação , Avaliação Educacional/métodos
10.
J Cancer Res Ther ; 18(4): 1093-1097, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36149166

RESUMO

Background: Hepatosplenic T-cell lymphoma (HSTCL) is a rare fatal T-cell neoplasm with unique clinical and laboratory features. There is, however, significant morphological and immunophenotypic heterogeneity which may lead to diagnostic dilemma. Aims and Objectives: The study was aimed to study the prevalence and clinic-pathological spectrum of this rare variant of T cell lymphoma in the Indian subcontinent. Material and Methods: A retrospective analysis of all consecutive cases of HSTCL diagnosed over a period of 6 years was carried out. The clinical and laboratory parameters of all these patient were reviewed and analysed. Results: A total of 12 cases of HSTCL were diagnosed during this period which accounted for 1.76% of all non-Hodgkin's lymphomas (NHLs) and 9.1% of all T-cell NHLs. The median (range) age of presentation was 23 (16-30) years.Leukocytosis, peripheral blood (PB) involvement, and a blastic morphology were noted in 41%, 67%, and 58% of the cases, respectively. FCI proved these cells to have a mature, dual-negative (CD4-/CD8-) T-cell phenotype with a gamma-delta T-cell receptor restriction. Frequent loss of CD5 expression (84%) was also noted. These patients invariably had a fatal outcome and majority died within a year of diagnosis. Conclusion: The incidence of leukocytosis and a blastoid morphology is quite frequent in HSTCL. Hence, a differential diagnosis of HSTCL should always be considered in young patients presenting with splenomegaly and exhibiting atypical lymphoid/blastoid cells in the PB or a marrow. An FCI can readily diagnose and differentiate them from an acute lymphoblastic leukemia/lymphoma.


Assuntos
Neoplasias Hepáticas , Linfoma de Células T , Neoplasias Esplênicas , Citometria de Fluxo , Humanos , Leucocitose , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Linfoma de Células T/diagnóstico , Linfoma de Células T/epidemiologia , Receptores de Antígenos de Linfócitos T gama-delta/análise , Receptores de Antígenos de Linfócitos T gama-delta/genética , Estudos Retrospectivos , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/epidemiologia
11.
Cancers (Basel) ; 14(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35008377

RESUMO

Since 2019, the SARS-CoV-2 pandemic has caused a huge chaos throughout the world and the major threat has been possessed by the immune-compromised individuals involving the cancer patients; their weakened immune response makes them vulnerable and susceptible to the virus. The oncologists as well as their patients are facing many problems for their treatment sessions as they need to postpone their surgery, chemotherapy, or radiotherapy. The approach that could be adopted especially for the cancer patients is the amalgamation of immunotherapy and nanotherapy which can reduce the burden on the healthcare at this peak time of the infection. There is also a need to predict or analyze the data of cancer patients who are at a severe risk of being exposed to an infection in order to reduce the mortality rate. The use of artificial intelligence (AI) could be incorporated where the real time data will be available to the physicians according to the different patient's clinical characteristics and their past treatments. With this data, it will become easier for them to modify or replace the treatment to increase the efficacy against the infection. The combination of an immunotherapy and nanotherapy will be targeted to treat the cancer patients diagnosed with SARS-CoV-2 and the AI will act as icing on the cake to monitor, predict and analyze the data of the patients to improve the treatment regime for the most vulnerable patients.

12.
Ann Surg ; 276(6): e1095-e1100, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34132692

RESUMO

OBJECTIVE: To examine the alignment between graduating surgical trainee operative performance and a prior survey of surgical program director expectations. BACKGROUND: Surgical trainee operative training is expected to prepare residents to independently perform clinically important surgical procedures. METHODS: We conducted a cross-sectional observational study of US general surgery residents' rated operative performance for Core general surgery procedures. Residents' expected performance on those procedures at the time of graduation was compared to the current list of Core general surgery procedures ranked by their importance for clinical practice, as assessed via a previous national survey of general surgery program directors. We also examined the frequency of individual procedures logged by residents over the course of their training. RESULTS: Operative performance ratings for 29,885 procedures performed by 1861 surgical residents in 54 general surgery programs were analyzed. For each Core general surgery procedure, adjusted mean probability of a graduating resident being deemed practice-ready ranged from 0.59 to 0.99 (mean 0.90, standard deviation 0.08). There was weak correlation between the readiness of trainees to independently perform a procedure at the time of graduation and that procedure's historical importance to clinical practice ( p = 0.22, 95% confidence interval 0.01-0.41, P = 0.06). Residents also continue to have limited opportunities to learn many procedures that are important for clinical practice. CONCLUSION: The operative performance of graduating general surgery residents may not be well aligned with surgical program director expectations.


Assuntos
Cirurgia Geral , Internato e Residência , Humanos , Competência Clínica , Estudos Transversais , Motivação , Inquéritos e Questionários , Cirurgia Geral/educação , Educação de Pós-Graduação em Medicina
13.
Am J Surg ; 223(2): 224-228, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34119330

RESUMO

BACKGROUND: Many US general surgery residents are interested in global surgery, but their competence with key procedures is unknown. METHODS: Using a registry managed by the Society for Improving Medical Professional Learning (SIMPL), we extracted longitudinal operative performance ratings data for a national cohort of US general surgery residents. Operative performance at the time of graduation was estimated via a Bayesian generalized linear mixed model. RESULTS: Operative performance ratings for 12,976 procedures performed by 1584 residents in 52 general surgery programs were analyzed. These spanned 17 of 31 (55%) procedures deemed important for global surgical practice. For these procedures, the probability of a graduating resident being deemed competent to perform a procedure was 0.95 (95% confidence interval 0.86-1.00) but was less than 0.9 for 3 observed procedures. CONCLUSION: Our results highlight gaps in the preparedness of US general surgery trainees to perform procedures deemed most important for global surgery settings.


Assuntos
Cirurgia Geral , Internato e Residência , Teorema de Bayes , Competência Clínica , Estudos de Coortes , Educação de Pós-Graduação em Medicina , Cirurgia Geral/educação , Humanos
14.
Am J Surg ; 222(6): 1072-1078, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34696846

RESUMO

BACKGROUND: A significant roadblock in surgical education research has been the inability to compare trainee performance to the outcomes of those surgeons after they enter independent practice. We describe the feasibility of an innovative method to link trainee performance data with patient outcomes. METHODS: We extracted surgeon NPI numbers from Medicare claims data for common general surgery procedures between 2007 and 2017. Next, American Board of Surgery (ABS) trainee performance data was cross-referenced with additional resources to supplement NPI data. The patient and trainee datasets were linked using NPI number and a linkage rate was calculated. RESULTS: We identified 12,952 unique surgeons in the Medicare file. Medicare surgeons were matched with ABS records by NPI number, with 96.2% (n = 12,460) of surgeons linked successfully. CONCLUSIONS: We demonstrated a novel process to link patient outcomes to trainee performance. This innovation can enable future research investigating the relationship between surgical trainee performance and patient outcomes in independent practice.


Assuntos
Competência Clínica , Educação de Pós-Graduação em Medicina/normas , Cirurgia Geral/educação , Armazenamento e Recuperação da Informação/métodos , Idoso , Idoso de 80 Anos ou mais , Competência Clínica/normas , Competência Clínica/estatística & dados numéricos , Educação de Pós-Graduação em Medicina/estatística & dados numéricos , Avaliação Educacional , Feminino , Cirurgia Geral/normas , Cirurgia Geral/estatística & dados numéricos , Humanos , Masculino , Procedimentos Cirúrgicos Operatórios/educação , Procedimentos Cirúrgicos Operatórios/normas , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Resultado do Tratamento
15.
Indian J Hematol Blood Transfus ; 37(4): 576-585, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34690454

RESUMO

Hypodiploidy with < 40 chromosomes is associated with poor prognosis in B cell precursor acute lymphoblastic leukemia. In some patients, the hypodiploid clone undergoes endoreduplication, resulting in doubling of the number of chromosomes and masquerades as a high hyperdiploid BCP-ALL. Karyotyping reveals metaphases with 50-79 chromosomes masking the hypodiploid clone. Identifying hypodiploidy in such cases requires awareness of non random alterations of chromosomal copy numbers found in hypodiploid BCP-ALL. We used a systematic strategy to identify masked hypodiploidy integrating targeted fluorescence in situ hybridization (FISH) analysis directed towards identifying monosomies of chromosomes 7, 15 and 17 and flow cytometry-based ploidy analysis (FCPA). Of 445 patients diagnosed as BCP ALL, 2.9% (13/445) were classified as hypodiploid including patients with masked hypodiploidy. Karyotype analysis showed hypodiploidy in 3 patients, near triploidy in 4 patients and normal karyotype in 6 patients. Four patients with near triploid clone on karyotype showed either bimodal peak (2 patients) or single low hypodiploid peak (1 patient) or only near triploid peak (1 patient) on FCPA. All 6 patients with normal karyotype revealed either bimodal peak (4 patients) or hypodiploid peak (2 patients) on FCPA. Targeted FISH analysis unmasked hypodiploid clone showing monosomies of chromosomes 7, 15 and 17 in all ten patients. Our algorithm successfully identified masked hypodiploidy in patients, including those with endoreduplication (4 patients) and normal karyotype (6 patients). Integrating FCPA with targeted FISH analysis provides a practical, sensitive and specific approach to identify masked hypodiploidy in low resource settings.

16.
Curr Pharm Biotechnol ; 22(15): 2085-2093, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33430724

RESUMO

AIM: The aim of present investigation is to identify the potential targets for Thymidylate Synthase and Amp-C ß-lactamase from non-alkaloidal fractions of Moringa oleifera leaves. BACKGROUND: Bioactive constituents from medicinal plants, either as pure compounds or as crude forms, provide vast opportunities for new drug discoveries. Due to an increasing demand for chemical diversity in screening programs, seeking therapeutic drugs from natural products, mainly from edible plants, has grown throughout the world. Moringa oleifera has an impressive range of medicinal uses with high nutritional value. Therefore, this medicinal plant has been used widely in traditional Indian medicine for anti-inflammation, anticancer and antibacterial infections. OBJECTIVES: The primary objective is to identify the phytoconstituents present in the maximum proportion in non-alkaloidal fractions of ethanolic leaf extract of Moringa oleifera. Then, the identified phytoconstituents were used to ensure the potential target molecules for binding affinity towards the target proteins viz. Thymidylate Synthase (1HVY) and Amp-C beta-lactamase (1FSY) by docking analysis. METHODS: In present investigation, ethanolic extract of Moringa leaves was prepared and then fractionated on the basis of presence/absence of alkaloids. The antimicrobial activity of different fractions of ethanolic leaf extract was evaluated against various pathogens. Later, after this, bioactive molecules present in the non-alkaloidal fractions of ethanolic leaf extract were accomplished through GC-MS analysis, and finally, the identified phytocompounds were analyzed through docking studies to evaluate their affinity for target proteins viz. Thymidylate Synthase (1HVY) and Amp-C ß-lactamase (1FSY). RESULTS: The antimicrobial activity of non-alkaloidal fractions of ethanolic leaf extract was evaluated against various pathogens which exhibited significant antimicrobial activity. Twenty phytocompounds were identified as gas chromatogram of non-alkaloidal fractions (chloroform and ethyl acetate) of leaf extract of M. oleifera; Four most prominent compounds having highest peak area percentage were identified as Ethane, 1,1,2,2-tetrachloro, (46.45%) 2-Propanone, 1,1,3-trichloro, (13.77%) Heptasiloxane, 1,1,3,3,5,5,7,7,9,9,11,11,13,13-tetradecamethyl (17.87%) and 2,4-Dichlorodiphenylsulfone (17.64%). Other notable compounds were 9,12-Octadecadienoic acid (Z,Z) (14.06%), Oleic acid, 3- (octadecyloxy)propyl ester (12.41%), Fluoranthene (6.98%), Phenol, 2,4-bis( 1,1-dimethylethyl) (4.16%) and Phthalic acid, butyl nonyl ester (3.47%). Only, five compounds viz. 2,6-Bis(1,1- dimethylethyl)phenol(C1), Dodecamethylcyclohexasiloxane(C2), Chlorodimethylethylsilane(C3), Fluoranthene(C4) and Hexadecanoic acid, methyl ester(C5) showed the maximum interaction with 1HVY with highest docking score of -178.51Kcal/mol, - 231.65Kcal/mol, -129.18Kcal/mol, - 173.10Kcal/mol and -220.78Kcal/mol, respectively. In addition, three compounds viz. Dodecamethylcyclohexasiloxane( C2), Fluoranthene(C4) and Hexadecanoic acid, methyl ester(C5) showed the maximum interaction with 1FSY with highest docking score of -137.23Kcal/mol, -54.34Kcal/mol and -153.84Kcal/mol, respectively. CONCLUSION: Moringa plant may provide incredible capabilities to develop pharmacological products. The present finding demonstrated that Moringa oleifera is an excellent plant candidate to be used for improving the health of communities.


Assuntos
Alcaloides , Moringa oleifera , Extratos Vegetais , Timidilato Sintase/antagonistas & inibidores , Inibidores de beta-Lactamases/farmacologia , Alcaloides/farmacologia , Moringa oleifera/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , beta-Lactamases
17.
Artigo em Inglês | MEDLINE | ID: mdl-33178666

RESUMO

Curcumin, very rightly referred to as "a wonder drug" is proven to be efficacious in a variety of inflammatory disorders including cancers. Antiaging, anti-inflammatory, antioxidant, antitumor, chemosensitizing, P-gp efflux inhibiting, and antiproliferative activity are some of the striking features of curcumin, highlighting its importance in chemotherapy. Curcumin inhibits Bcl-2, Bcl-XL, VEGF, c-Myc, ICAM-1, EGFR, STAT3 phosphorylation, and cyclin D1 genes involved in the various stages of breast, prostate, and gastric cancer proliferation, angiogenesis, invasion, and metastasis. The full therapeutic potential of curcumin however remains under explored mainly due to poor absorption, rapid metabolism and systemic elimination culminating in its poor bioavailability. Furthermore, curcumin is insoluble, unstable at various pH and is also prone to undergo photodegradation. Nanotechnology can help improve the therapeutic potential of drug molecules with compromised biopharmaceutical profiles. Solid lipid nanoparticles (SLNs) are the latest offshoot of nanomedicine with proven advantages of high drug payload, longer shelf life, biocompatibility and biodegradability, and industrial amenability of the production process. We successfully developed CLEN (Curcumin encapsulated lipidic nanoconstructs) containing 15 mg curcumin per ml of the SLN dispersion with highest (till date, to our knowledge) increase in solubility of curcumin in an aqueous system by 1.4 × 106 times as compared to its intrinsic solubility of 11 ng/ml and high drug loading (15% w/v with respect to lipid matrix). Zero-order release kinetics observed for CLEN versus first order release for free curcumin establish controlled release nature of the developed CLEN. It showed 69.78 times higher oral bioavailability with respect to free curcumin; 9.00 times higher than a bioavailable marketed formulation (CurcuWIN®). The formulation showed 104, 13.3, and 10-times enhanced stability at pH 6.8, 1.2, and 7.4, respectively. All these factors ensure the efficacy of CLEN in treating cancer and other inflammatory diseases.

19.
Recent Pat Biotechnol ; 14(4): 283-294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32767933

RESUMO

BACKGROUND: Sclerotinia sclerotiorum is a ubiquitous fungal pathogen infecting more than 400 plant species. Sclerotinia stem rot is known to cause as high as 100% crop loss in many cases. Currently, chemical fungicides are the only known solution to this problem. Thus, there is an urgent need for developing environment-friendly alternatives for controlling this pathogen. The review of published articles revealed that a number of mycoviruses with the potential of a biocontrol agent against Sclerotinia had been identified from different parts of the world. OBJECTIVE: The present investigation describes the isolation and characterization of isolates of S. sclerotiorum infecting cauliflower, peas, and mustard for the presence of a potent mycovirus from lower Himachal region of India. METHODS: Various infected fields were visited and samples in the form of sclerotia were collected. Various isolates of S. sclerotiorum were obtained, and putative hypovirulent isolates were screened. Thereafter, hypovirulent strains were chosen and mycovirus isolation was performed. Finally, isolates showing an extra nucleic acid band were used for mycovirus isolation and further characterization. Curing of mycovirus was used to confirm if altered phenotype was due to the presence of this virus. RESULTS: A ssDNA mycovirus was identified and confirmed from the growth defective isolate. CONCLUSION: This mycovirus can in turn act as a biocontrol agent, thus reducing dependency on chemical fungicides and can also be developed in the form of a patent once completely characterized and formulated. To our knowledge, this is the first report on mycovirus isolation from any Sclerotinia sclerotiorumisolate from India.


Assuntos
Ascomicetos , Agentes de Controle Biológico , Brassica/microbiologia , Micovírus , Doenças das Plantas , Ascomicetos/patogenicidade , Ascomicetos/virologia , Índia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle
20.
Bone ; 138: 115505, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32599223

RESUMO

OBJECTIVE: Significant weight loss following treatments for obesity undermines bone metabolism and increases bone turnover and fracture incidence. High resolution peripheral quantitative computed tomography (HR-pQCT) is widely used in skeletal heath assessment research to provide noninvasive bone parameter measurement (e.g. volumetric bone mineral density (vBMD)) with minimal radiation exposure. However, variation in body composition among study groups or longitudinal variations within individuals undergoing significant weight change will generate artifacts and errors in HR-pQCT data. The purpose of this study is to determine the influence of these artifacts on the measurement of vBMD. METHODS: We designed a custom-made hydroxyapatite (HA)-polymer phantom surrounded by layers of reusable gel pack and hydrogenated fat to mimic the distal tibia and the surrounding lean and fat tissue. Four different thicknesses of fat were used to mimic the soft tissue of increasingly overweight individuals. We then evaluated how a change in soft tissue thickness influenced image quality and vBMD quantification within total, trabecular, and cortical bone compartments. Based on these data, we applied a data correction to previously acquired clinical data in a cohort of gastric bypass patients. RESULTS: In the phantom measurements, total, trabecular, and cortical vBMD increased as soft tissue thickness decreased. The impact of soft tissue thickness on vBMD varied by anatomic quadrant. When applying the soft tissue data correction to a set of clinical data, we found that soft tissue reduction following bariatric surgery can lead to a clinically significant underestimation of bone loss in longitudinal data, and that the effect is most severe in the cortical compartment. CONCLUSION: HR-pQCT-based vBMD measurement accuracy is influenced by soft tissue thickness and is spatially inhomogeneous. Our results suggest that variations in soft tissue thickness must be considered in HR-pQCT studies, particularly in studies enrolling cohorts with differing body composition or in studies of longitudinal weight change.


Assuntos
Densidade Óssea , Tomografia Computadorizada por Raios X , Osso e Ossos/diagnóstico por imagem , Humanos , Imagens de Fantasmas , Rádio (Anatomia) , Tíbia/diagnóstico por imagem
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