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2.
Biomacromolecules ; 25(3): 1429-1438, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38408372

RESUMO

We applied solid- and solution-state nuclear magnetic resonance spectroscopy to examine the structure of multidomain peptides composed of self-assembling ß-sheet domains linked to bioactive domains. Bioactive domains can be selected to stimulate specific biological responses (e.g., via receptor binding), while the ß-sheets provide the desirable nanoscale properties. Although previous work has established the efficacy of multidomain peptides, molecular-level characterization is lacking. The bioactive domains are intended to remain solvent-accessible without being incorporated into the ß-sheet structure. We tested for three possible anticipated molecular-level consequences of introducing bioactive domains to ß-sheet-forming peptides: (1) the bioactive domain has no effect on the self-assembling peptide structure; (2) the bioactive domain is incorporated into the ß-sheet nanofiber; and (3) the bioactive domain interferes with self-assembly such that nanofibers are not formed. The peptides involved in this study incorporated self-assembling domains based on the (SL)6 motif and bioactive domains including a VEGF-A mimic (QK), an IGF-mimic (IGF-1c), and a de novo SARS-CoV-2 binding peptide (SBP3). We observed all three of the anticipated outcomes from our examination of peptides, illustrating the unintended structural effects that could adversely affect the desired biofunctionality and biomaterial properties of the resulting peptide hydrogel. This work is the first attempt to evaluate the structural effects of incorporating bioactive domains into a set of peptides unified by a similar self-assembling peptide domain. These structural insights reveal unmet challenges in the design of highly tunable bioactive self-assembling peptide hydrogels.


Assuntos
Nanofibras , Peptídeos , Conformação Proteica em Folha beta , Peptídeos/química , Nanofibras/química , Hidrogéis/química , Materiais Biocompatíveis
3.
Nat Commun ; 15(1): 1142, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326301

RESUMO

The lasting threat of viral pandemics necessitates the development of tailorable first-response antivirals with specific but adaptive architectures for treatment of novel viral infections. Here, such an antiviral platform has been developed based on a mixture of hetero-peptides self-assembled into functionalized ß-sheets capable of specific multivalent binding to viral protein complexes. One domain of each hetero-peptide is designed to specifically bind to certain viral proteins, while another domain self-assembles into fibrils with epitope binding characteristics determined by the types of peptides and their molar fractions. The self-assembled fibrils maintain enhanced binding to viral protein complexes and retain high resilience to viral mutations. This method is experimentally and computationally tested using short peptides that specifically bind to Spike proteins of SARS-CoV-2. This platform is efficacious, inexpensive, and stable with excellent tolerability.


Assuntos
COVID-19 , Humanos , Peptídeos/química , SARS-CoV-2/metabolismo , Antivirais/farmacologia , Proteínas Virais , Glicoproteína da Espícula de Coronavírus/metabolismo
4.
Biomacromolecules ; 25(2): 1319-1329, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38291600

RESUMO

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide, especially in aging and metabolically unhealthy populations. A major target of regenerative tissue engineering is the restoration of viable cardiomyocytes to preserve cardiac function and circumvent the progression to heart failure post-MI. Amelioration of ischemia is a crucial component of such restorative strategies. Angiogenic ß-sheet peptides can self-assemble into thixotropic nanofibrous hydrogels. These syringe aspiratable cytocompatible gels were loaded with stem cells and showed excellent cytocompatibility and minimal impact on the storage and loss moduli of hydrogels. Gels with and without cells were delivered into the myocardium of a mouse MI model (LAD ligation). Cardiac function and tissue remodeling were evaluated up to 4 weeks in vivo. Injectable peptide hydrogels synergized with loaded murine embryonic stem cells to demonstrate enhanced survival after intracardiac delivery during the acute phase post-MI, especially at 7 days. This approach shows promise for post-MI treatment and potentially functional cardiac tissue regeneration and warrants large-scale animal testing prior to clinical translation.


Assuntos
Hidrogéis , Infarto do Miocárdio , Camundongos , Animais , Hidrogéis/farmacologia , Infarto do Miocárdio/terapia , Miocárdio , Peptídeos/farmacologia , Células-Tronco Embrionárias
5.
Indian J Pediatr ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270753

RESUMO

OBJECTIVES: To explore the magnitude of sex bias and determinants of treatment abandonment (TA) in childhood cancer in India. METHODS: Individual data of children (0-19 y) registered between January 1, 2017 and July 31, 2022, was compiled. TA was defined as defaulting curative intent treatment ≥4 wk. Defaulting treatment irrespective of intent ≥4 wk was defined as Treatment Default (TD). The primary outcome was the proportion of male-to-female children with TA. Secondary outcomes included the proportion of male-to-female children with upfront TA, TA at relapse, TD, TD-p (TD only in the palliative setting). The impact of clinico-demographic factors on TA was analysed using multivariable regression and propensity score matching (PSM). RESULTS: Three thousand two hundred eighty four patients were analysed. The overall male-to-female ratio (MFR) was 2.08 (95% CI 1.94-2.24). Of 2906 patients treated with curative intent, 415 (14·3%) abandoned treatment. TA was higher in females than males (16·4% vs. 13·3%; p = 0·022) with adjusted MFR of 0·81 (0·66-0·98). The adjusted MFR of TA for treatment-naïve and relapsed patients and TD were 0·73 (0·59-0·91), 1·13 (0·65-1·96) and 0·84 (0·71-1·00) respectively. Sex independently predicted TA on multivariable analysis. However, on PSM analysis including socio-economic variables, lower maternal education predicted higher TA in children with cancer (10·1% vs. 6%, p = 0·015). CONCLUSIONS: Child sex predicted TA in childhood cancer in India with more females abandoning treatment. Maternal education is a more crucial factor predicting TA over child sex, when socio-economic factors were considered. Hence, policies promoting female education and gender equality may mitigate sex-based gaps in childhood cancer care.

6.
Eur Urol ; 85(3): 257-273, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37208237

RESUMO

CONTEXT: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease. OBJECTIVE: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer. EVIDENCE ACQUISITION: EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included. EVIDENCE SYNTHESIS: We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2-3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2-3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2-3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases. CONCLUSIONS: Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2-3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting. PATIENT SUMMARY: Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team.


Assuntos
Neoplasias Penianas , Humanos , Masculino , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Neoplasias Penianas/patologia
7.
Childs Nerv Syst ; 40(3): 919-924, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37930424

RESUMO

A 13-year-old female patient presented with painless vision loss and proptosis for 18 months. Imaging findings were highly suggestive of a supraorbital aneurysmal bone cyst (ABC) for which she underwent complete surgical excision. Postoperatively, she developed left hemiparesis. Computed tomography angiography (CTA) revealed right complete internal carotid arterial (ICA) thrombosis. This was managed conservatively, and she improved in hemiparesis over the next 3 weeks. Histopathology report revealed osteosarcoma with secondary ABC, for which she was referred for radiotherapy. At 1.5 months follow-up, the patient's left lower limb power improved to 4 + /5. She was walking without support, and her left upper limb power was 4/5.


Assuntos
Cistos Ósseos Aneurismáticos , Neoplasias Ósseas , Osteossarcoma , Adolescente , Feminino , Humanos , Cistos Ósseos Aneurismáticos/complicações , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Neoplasias Ósseas/complicações , Angiografia por Tomografia Computadorizada , Paresia
8.
ACS Appl Mater Interfaces ; 16(1): 364-375, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38145951

RESUMO

Growth factor (GF) mimicry involves recapitulating the signaling of larger molecules or cells. Although GF mimicry holds considerable promise in tissue engineering and drug design applications, difficulties in targeting the signaling molecule to the site of delivery and dissociation of mimicking peptides from their target receptors continue to limit its clinical application. To address these challenges, we utilized a self-assembling peptide (SAP) platform to generate synthetic insulin-like growth factor (IGF)-signaling, self-assembling GFs. Our peptide hydrogels are biocompatible and bind target IGF receptors in a dose-dependent fashion, activate proangiogenic signaling, and facilitate formation of angiogenic microtubules in vitro. Furthermore, infiltrated hydrogels are stable for weeks to months. We conclude that the enhanced targeting and long-term stability of our SAP/GF mimicry implants may improve the efficacy and safety of future GF mimic therapeutics.


Assuntos
Peptídeos Semelhantes à Insulina , Peptídeos , Peptídeos/química , Peptídeos e Proteínas de Sinalização Intercelular , Engenharia Tecidual , Hidrogéis/química
9.
Sci Rep ; 13(1): 21643, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38062163

RESUMO

Breast cancer is a highly aggressive type of cancer and has several subtypes, including triple-negative breast cancer (TNBC), which accounts for 25% of morbidity related to breast cancer. miRNAs are small non-coding RNA molecules that regulate 60% of human genes. Dysregulated expression of miRNA in liquid biopsy of TNBC patients has the potential as a minimally invasive diagnostic biomarker. The Association of miRNA with TNBC was evaluated using in-silico analysis. Highly enriched miRNAs were selected for functional analysis to evaluate the role of miRNA in the progression of TNBC. The qRT-PCR-based expression analysis of miRNA was performed in 190 serum samples (139 TNBC and 51 healthy). Revealed the elevated expression of miRNA-155 and miRNA-21 in TNBC compared to control samples (P < 0.0001), while miRNA-205 was significantly downregulated in TNBC (P < 0.0001). The combined diagnostic value of the miRNA-205, miRNA-155 and miRNA-21 in cohort-I, cohort-II, and cohort-III was AUC of 96.1% (P < 0.0001), 94.9% (P < 0.0001), and 97.1% (P < 0.0001), respectively. Our study revealed that dysregulated expression of miRNA could be used as an independent indicator for discriminating TNBC from healthy patients. In addition, the combined predictive value of miRNA-205 + miRNA - 155 + miRNA-21 has higher AUC, sensitivity, and specificity in the diagnosis of TNBC in all three cohorts.


Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética
10.
Curr Rheumatol Rev ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38018201

RESUMO

Arthritis is a medical condition that affects the joints and causes inflammation, pain, and stiffness. There are different types of arthritis, and it can affect people of all ages, even infants and the elderly. Recent studies have found that individuals with diabetes, heart disease, and obesity are more likely to experience arthritis symptoms. According to the World Health Organization, over 21% of people worldwide suffer from musculoskeletal problems. Roughly 42.19 million individuals in India, constituting around 0.31% of the populace, have been documented as having Rheumatic Artheritis (RA). Compared to other common diseases like diabetes, cancer, and AIDS, arthritis is more prevalent in the general population. Unfortunately, there is no specific cure for arthritis, and treatment plans usually involve non-pharmacological methods, surgeries, and medications that target specific symptoms. Plant-based remedies have also been shown to be effective in managing inflammation and related complications. In addition to therapies, maintaining a healthy diet, exercise, and weight management are essential for managing arthritis. This review discusses the causes, prevalence, diagnostic methods, current and prospective future treatments, and potential medicinal plants that may act as anti-inflammatory or anti-rheumatic agents. However, more research is necessary to identify the underlying mechanisms and active molecules that could improve arthritis treatment.

11.
J Orthop Case Rep ; 13(10): 163-167, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37885625

RESUMO

Introduction: Tuberculosis (TB) of pubic symphysis is an extremely uncommon condition accounting <1% of all musculoskeletal TB. Further recurrence of TB of symphysis pubis is a rare clinical scenario requiring a high level of suspicion for diagnosing the condition. Recurrence of tuberculosis can occur either be due to relapse of the original infection or reinfection due to exogenous Mycobacterium tuberculosis strain. There have only been nine case reports on TB of the pubic symphysis in the last three decades and only 40 patients were identified in English language medical literature so to the best of our knowledge this is the first case report on the recurrence of TB of pubic symphysis. Case Report: A 26-year-old female patient presented with pain over symphyseal area for 2 months. Laboratory and radiological investigations were suggestive of TB of symphysis pubis. She was started on oral, category I anti-tubercular therapy (ATT) from DOTS center. Patient on improvement in symptoms discontinued taking ATT after 6 months. About 7 months after stopping ATT, she again presented with pain over symphyseal area and difficulty in walking. Laboratory, radiological investigation, and biopsy were obtained to rule out multidrug-resistant (MDR) TB. The patient improved on 12 months' oral daily ATT regime (HRZES2+HRZE4+HRE6). She was followed up for another 1 year with clinical examination and laboratory investigation after stopping ATT. At present, she is asymptomatic with no signs of recurrence after 1 year of completion of treatment. Conclusion: ATT intake should be continued for 12 months for musculoskeletal TB for preventing recurrence. The biopsy needs to be taken from the affected region in recurrence TB to rule out MDR.

12.
Indian J Otolaryngol Head Neck Surg ; 75(3): 2334-2337, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37636780

RESUMO

Infraorbital nerve schwannoma is an infrequent entity that is rarely reported in the paediatric population. This case report is a summed-up report of this infrequent diagnosis, its presentation, and management from an otorhinolaryngologist's perspective. It is reported here for its rarity, inherent surgical challenge, and academic interest. We report a case of a 13-year-old boy with infraorbital nerve schwannoma arising from its two terminal branches. We performed its surgical excision without any disabling deformity. The peculiarity of this case gives insight into the varied presentation of schwannoma. It is important to identify such cases with a high degree of suspicion and treat them accordingly.

13.
EMBO Mol Med ; 15(9): e17376, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37534622

RESUMO

SARS-CoV-2 acute respiratory distress syndrome (ARDS) induces uncontrolled lung inflammation and coagulopathy with high mortality. Anti-viral drugs and monoclonal antibodies reduce early COVID-19 severity, but treatments for late-stage immuno-thrombotic syndromes and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases. The myxoma virus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated thrombotic, thrombolytic, and complement proteases as a self-defense strategy to combat clearance. Serp-1 is effective in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp-1 as a therapy for immuno-coagulopathic complications during ARDS. Treatment with PEGSerp-1 in two mouse-adapted SARS-CoV-2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved outcomes. PEGSerp-1 significantly reduced M1 macrophages in the lung and heart by modifying urokinase-type plasminogen activator receptor (uPAR), thrombotic proteases, and complement membrane attack complex (MAC). Sequential changes in gene expression for uPAR and serpins (complement and plasminogen inhibitors) were observed. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for severe viral ARDS, immuno-coagulopathic responses, and Long COVID.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Serpinas , Camundongos , Animais , Humanos , Serpinas/uso terapêutico , Serpinas/metabolismo , Serpinas/farmacologia , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Peptídeo Hidrolases
14.
Artigo em Inglês | MEDLINE | ID: mdl-37537775

RESUMO

BACKGROUND: Lung cancer is a foremost global health issue due to its poor diagnosis. The advancement of novel drug delivery systems and medical devices will aid its therapy. OBJECTIVE: In this review, the authors thoroughly introduce the ideas and methods for improving nanomedicine- based approaches for lung cancer therapy. This article provides mechanistic insight into various novel drug delivery systems (DDSs) including nanoparticles, solid lipid nanoparticles, liposomes, dendrimers, niosomes, and nanoemulsions for lung cancer therapy with recent research work. This review provides insights into various patents published for lung cancer therapy based on nanomedicine. This review also highlights the current status of approved and clinically tested nanoformulations for their treatment. METHODOLOGY: For finding scholarly related data for the literature search, many search engines were employed including PubMed, Science Direct, Google, Scihub, Google Scholar, Research Gate, Web of Sciences, and several others. Various keywords and phrases were used for the search such as "nanoparticles", "solid lipid nanoparticles", "liposomes", "dendrimers", "niosomes", "nanoemulsions", "lung cancer", "nanomedicine", "nanomaterial", "nanotechnology", "in vivo" and "in vitro". The most innovative and cutting-edge nanotechnology-based approaches that are employed in pre-clinical and clinical studies to address problems associated with lung cancer therapies are also mentioned in future prospects. A variety of problems encountered with current lung cancer therapy techniques that frequently led to inadequate therapeutic success are also discussed in the end. CONCLUSION: The development of nanoformulations at the pilot scale still faces some difficulties, but their prospects for treating lung cancer appear to be promising in the future. Future developments and trends are anticipated as the evaluation comes to a close.

15.
J Clin Anesth ; 90: 111238, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37639750

RESUMO

OBJECTIVE: We studied the primary hypothesis that the training level of anesthesiology residents (first clinical anesthesia year, CA1 vs CA2/3 residents) is associated with early postoperative desaturation (oxygen saturation < 90%). We also analyzed the change in the rate (trajectory) of desaturation during the resident's development from CA1 to CA2/3 resident, and its effects on postoperative respiratory complications. DESIGN: Retrospective hospital registry study. SETTING: Two university-affiliated hospitals networks (MA and NY, USA). PATIENTS: 140,818 adults undergoing non-cardiac surgery under general anesthesia and extubation in the operating room by residents (n = 378) between 2005 and 2021. MEASUREMENTS: Multivariate logistic and quantile regression were used in the analyses. The secondary outcome was major respiratory complication within 7 days after surgery. MAIN RESULTS: In 6.5% and 1.6% of cases, early postoperative desaturation to < 90% and 80% occurred. Compared to CA2/3 residents, CA1 residents had higher odds of experiencing early postoperative desaturation to < 90% and 80% (adjusted odds ratio [ORadj], 1.07; 95%CI 1.03-1.12; p = 0.002, and ORadj 1.10; 95%CI 1.01-1.20; p = 0.037, respectively). The change in postoperative desaturation rate during the transition from CA1 to CA2/3 status varied substantially from ORadj 0.80 (decreased risk) to 1.33 (increased risk). Major respiratory complication did not differ between experience levels (p = 0.52). However, a strong decline in improvement regarding the rate of postoperative desaturation during the transition from CA1 to CA2/3, was paralleled by an increased odds of major respiratory complication for CA2/3 residents (ORadj 1.20; 95%CI 1.02-1.42; p = 0.026, p-for-interaction = 0.056). CONCLUSION: Patients treated by CA1 residents have an increased risk of postoperative desaturation. Some residents show an improvement and others a decline in postoperative desaturation rate. Our secondary analysis suggests that there should be more focus on those residents who had a declining performance in postoperative desaturation despite becoming more experienced.


Assuntos
Internato e Residência , Adulto , Humanos , Estudos de Coortes , Estudos Retrospectivos , Anestesia Geral , Hospitais Universitários , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
16.
Cureus ; 15(5): e39792, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37398752

RESUMO

Background Portal hypertension leads to the formation of portosystemic collateral veins, of which esophageal varices (EV) are the most severe complications and have the greatest clinical impact. The possibility of identifying cirrhotic patients with varices by non-invasive tests is appealing, as they can lead to reduced healthcare costs and can be done in resource-limited settings. In this study, we investigated ammonia as a potential non-invasive predictor of EV. Methods This was a single-center cross-sectional observational study that was done at a tertiary health care hospital in north India. It included 97 chronic liver disease patients irrespective of etiology after excluding patients with portal vein thrombosis and hepatocellular carcinoma to participate in endoscopic screening for the presence of EV and correlate it with various non-invasive markers like serum ammonia levels, thrombocytopenia and aspartate aminotransferase to platelet ratio index (APRI ). On the basis of endoscopy, enrolled patients were divided into two groups, i.e., group A consisting of large varices (grade III and grade IV) and group B consisting of patients with low-grade varices and no varices (grade II, grade I, and no varices). Results This study included 97 patients, out of which 81 patients have varices on endoscopy, and mean serum ammonia levels were found to be significantly higher in cases with varices (135 ±69.70 ) vs. those without varices (94±43) (p value=0.026). Further, on comparing serum ammonia values between patients with large varices (Grade III/IV) (Group A) with a mean value of 176 ± 83 vs. Grade I/II/No varices (Group B) with a mean value of 107±47, which were significantly higher in Group A patients (<0.001). In our study, we also found a correlation between blood urea level as a non-invasive predictor of varices, but no statistically significant relation was found between thrombocytopenia and APRI. Conclusion This study found that serum ammonia can be used as a useful marker for the prediction of EV and can also be used to determine the severity of varices. Apart from ammonia, serum urea levels can also prove to be a good non-invasive marker for the prediction of varices although further multicentric studies are warranted to reach this conclusion.

17.
J Cancer Res Ther ; 19(3): 664-670, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37470591

RESUMO

Purpose: To estimate the fitting parameters of the sigmoidal dose response (SDR) curve of radiation-induced acute proctitis in prostate cancer patients treated with intensity modulated radiation therapy (IMRT) for the calculation of normal tissue complication probability (NTCP). Materials and Methods: Twenty-five prostate cancer patients were enrolled and evaluated weekly for acute radiation-induced (ARI) proctitis toxicity. Their scoring was performed as per common terminology criteria for adverse events version 5.0. The radiobiological parameters namely n, m, TD50, and γ50 were calculated from the fitted SDR curve obtained from the clinical data of prostate cancer patients. Results: ARI toxicity for rectum in carcinoma of prostate patients was calculated for the endpoint of acute proctitis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade 1 and Grade 2 acute proctitis are found to be 0.13, 0.10, 30.48 ± 1.52 (confidence interval [CI] 95%), 3.18 and 0.08, 0.10, 44.37 ± 2.21 (CI 95%), 4.76 respectively. Conclusion: This study presents the fitting parameters for NTCP calculation of Grade-1 and Grade-2 ARI rectum toxicity for the endpoint of acute proctitis. The provided nomograms of volume versus complication and dose versus complication for different grades of acute proctitis in the rectum help radiation oncologists to decide the limiting dose to reduce the acute toxicities.


Assuntos
Carcinoma , Proctite , Neoplasias da Próstata , Lesões por Radiação , Radioterapia de Intensidade Modulada , Masculino , Humanos , Próstata , Proctite/etiologia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/complicações , Lesões por Radiação/etiologia , Reto , Radioterapia de Intensidade Modulada/efeitos adversos , Carcinoma/complicações , Dosagem Radioterapêutica
18.
J Cancer Res Ther ; 19(3): 738-744, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37470603

RESUMO

Purpose: The purpose of the study was to estimate the fitting parameters of the sigmoidal dose response (SDR) curve of radiation-induced acute dermatitis in breast cancer patients treated with intensity-modulated radiation therapy for calculation of normal tissue complication probability (NTCP). Materials and Methods: Twenty-five breast cancer patients were enrolled to model the SDR curve for acute dermatitis. The acute radiation-induced (ARI) dermatitis toxicity was assessed weekly for all the patients, and their scores were determined using the common terminology criterion adverse events version 5.0. The radiobiological parameters n, m, TD50, and γ50 were derived using the fitted SDR curve obtained from breast cancer Patient's clinical data. Results: ARI dermatitis toxicity in carcinoma of breast patients was calculated for the end point of acute dermatitis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade-1 dermatitis are found to be 0.03, 0.04, 28.65 ± 1.43 (confidence interval [CI] 95%) and 1.02 and for Grade-2 dermatitis are found to be 0.026, 0.028, 38.65 ± 1.93 (CI. 95%) and 1.01 respectively. Conclusion: This research presents the fitting parameters for NTCP calculation of Grade-1 and Grade-2 acute radiation-induced skin toxicity in breast cancer for the dermatitis end point. The presented nomograms of volume versus complication probability and dose versus complication probability assist radiation oncologists in establishing the limiting dose to reduce acute toxicities for different grades of acute dermatitis in breast cancer patients.


Assuntos
Neoplasias da Mama , Dermatite , Lesões por Radiação , Radiodermite , Humanos , Feminino , Neoplasias da Mama/patologia , Lesões por Radiação/etiologia , Mama/patologia , Pele/patologia , Radiodermite/etiologia , Dermatite/complicações , Dermatite/patologia , Doença Aguda
19.
Indian J Otolaryngol Head Neck Surg ; 75(2): 249-254, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37275095

RESUMO

Tonsillectomy is one of the most commonly performed surgical procedures worldwide. Postoperative pain remains a significant problem for patients undergoing tonsillectomy and is the most typical reason for readmission after the procedure. We conducted the present study to investigate the efficacy of a single dose of dexamethasone administered intravenously before tonsillectomy on postoperative pain in a group of patients undergoing cold dissection tonsillectomy, using a standardised anaesthetic and surgical procedure.It was a prospective study done in the Department of ENT in a tertiary care centre in eastern India, from 1 st September 2017 to 31 st August 2019 (2 years). Subjects included in the study were patients who attended the OPD of ENT of the tertiary care centre in eastern India, with a history of throat pain,difficulty in deglutition, mouth breathing, snoring. Tonsillectomy operation was recommended to the patients who fit the inclusion criteria. A hundred patients were selected for the study and divided randomly into two groups. Patients in group A (50 patients) were administered preoperative intravenous dexamethasone (0.15 mg/kg)after the induction of anaesthesia, and Group B patients (50 patients)were not administered dexamethasone along with other drugs.RESULTS: A hundred patients were enrolled after excluding the patients not fulfilling the selection criteria. The majority of patients were female, with the majority patients between 9-19 years. There was a noteworthy decreased mean pain score postoperatively of Group A on the first, third, and fifth day. (p-value = < 0.001).The results of this study suggest that a single preoperative injection of dexamethasone for patients undergoing tonsillectomy by cold dissection method significantly reduced postoperative pain.

20.
World J Microbiol Biotechnol ; 39(8): 218, 2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37269502

RESUMO

Owing to the increased population and their overuse, estrogens are being detected in the environment at alarming levels. They act as endocrine disrupting compounds (EDC's) posing adverse effects on animals and humans. In this study, a strain belonging to Enterobacter sp. strain BHUBP7 was recovered from a Sewage Treatment Plant (STP) situated in Varanasi city, U.P., India, and was capable of metabolizing both 17 α-Ethynylestradiol (EE2) and 17 ß-Estradiol (E2) separately as a sole carbon source. The strain BHUBP7 exhibited high rates of E2 degradation as compared to EE2 degradation. The degradation of E2 (10 mg/L) was 94.3% after four days of incubation, whereas the degradation of EE2 (10 mg/L) under similar conditions was 98% after seven days of incubation. The kinetics of EE2 and E2 degradation fitted well with the first-order reaction rate. FTIR analysis revealed the involvement of functional groups like C = O, C-C, C-OH during the degradation process. The metabolites generated during degradation of EE2 and E2 were identified using HRAMS and a plausible pathway was elucidated. It was observed that metabolism of both E2 and EE2 proceeded with the formation of estrone, which was then hydroxylated to 4-hydroxy estrone, followed by ring opening at the C4-C5 position, and was further metabolized by the 4,5 seco pathway leading to the formation of 3-(7a-methyl-1,5-dioxooctahydro-1H-inden-4-yl) propanoic acid (HIP). It is the first report on the complete pathway of EE2 and E2 degradation in Enterobacter sp. strain BHUBP7. Moreover, the formation of Reactive Oxygen Species (ROS) during the degradation of EE2 and E2 was observed. It was concluded that both hormones elicited the generation of oxidative stress in the bacterium during the degradation process.


Assuntos
Estradiol , Poluentes Químicos da Água , Humanos , Estradiol/análise , Estradiol/metabolismo , Estrona/análise , Estrona/metabolismo , Etinilestradiol/análise , Etinilestradiol/metabolismo , Bactérias/metabolismo , Índia , Poluentes Químicos da Água/metabolismo
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