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1.
Mol Biol Rep ; 51(1): 791, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990430

RESUMEN

BACKGROUND: Heat stress is a detrimental abiotic stress that limits the development of many plant species and is linked to a variety of cellular and physiological problems. Heat stress affects membrane fluidity, which leads to negative effects on cell permeability and ion transport. Research reveals that heat stress causes severe damage to cells and leads to rapid accumulation of reactive oxygen species (ROS), which could cause programmed cell death. METHODS AND RESULTS: This current study aimed to validate the role of Triticum aestivum Salt Stress Root Protein (TaSSRP) in plants' tolerance to heat stress by modulating its expression in tobacco plants. The Relative Water Content (RWC), total chlorophyll content, and Membrane Stability Index (MSI) of the seven distinct transgenic lines (T0 - 2, T0 - 3, T0 - 6, T0 - 8, T0 - 9, T0 - 11, and T0 - 13), increased in response to heat stress. Despite the fact that the same tendency was detected in wild-type (WT) plants, changes in physio-biochemical parameters were greater in transgenic lines than in WT plants. The expression analysis revealed that the transgene TaSSRP expressed from 1.00 to 1.809 folds in different lines in the transgenic tobacco plants. The gene TaSSRP offered resistance to heat stress in Nicotiana tabacum, according to the results of the study. CONCLUSION: These findings could help to improve our knowledge and understanding of the mechanism underlying thermotolerance in wheat, and the novel identified gene TaSSRP could be used in generating wheat varieties with enhanced tolerance to heat stress.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Respuesta al Choque Térmico , Nicotiana , Proteínas de Plantas , Plantas Modificadas Genéticamente , Triticum , Nicotiana/genética , Nicotiana/metabolismo , Triticum/genética , Triticum/metabolismo , Plantas Modificadas Genéticamente/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Respuesta al Choque Térmico/genética , Especies Reactivas de Oxígeno/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Termotolerancia/genética , Clorofila/metabolismo , Tolerancia a la Sal/genética
2.
J Healthc Qual Res ; 39(4): 233-240, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38811301

RESUMEN

INTRODUCTION AND OBJECTIVES: The Scarborough Health Network joined the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) in fiscal year 2017-2018 with interest in tracking surgical outcomes in General and Vascular Surgery patients. Results of the ACS NSQIP program revealed poor outcomes in 30-day urinary tract infection (UTI) rates in this population group. Results were in the lowest quartile compared to peer hospitals. To improve patient care, SHN initiated a multi-pronged quality improvement plan (QIP). METHODS: The QIP focused on several improvements: (1) clarify the current state and conduct a root cause analysis, (2) determine a plan to encourage early removal of catheters in post-surgical patients, (3) enhance team communication in the pre-operative, operative and post-operative care environments, and (4) improve education around UTI prevention and treatment. RESULTS: This study demonstrates the success of the quality improvement plan to improve a peri-operative complication in surgical patients. By 2019, SHN saw a significant decrease in UTI rates, and became a top decile performer in ACS NSQIP. CONCLUSIONS: This study demonstrates the feasibility and success of implementing a quality improvement project, and its methods can be adapted at other hospital sites to improve patient care.


Asunto(s)
Complicaciones Posoperatorias , Mejoramiento de la Calidad , Infecciones Urinarias , Humanos , Infecciones Urinarias/prevención & control , Infecciones Urinarias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Análisis de Causa Raíz
3.
Gene Ther ; 31(7-8): 413-421, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38755404

RESUMEN

Degeneration of the macula is associated with several overlapping diseases including age-related macular degeneration (AMD) and Stargardt Disease (STGD). Mutations in ATP Binding Cassette Subfamily A Member 4 (ABCA4) are associated with late-onset dry AMD and early-onset STGD. Additionally, both forms of macular degeneration exhibit deposition of subretinal material and photoreceptor degeneration. Retinoic acid related orphan receptor α (RORA) regulates the AMD inflammation pathway that includes ABCA4, CD59, C3 and C5. In this translational study, we examined the efficacy of RORA at attenuating retinal degeneration and improving the inflammatory response in Abca4 knockout (Abca4-/-) mice. AAV5-hRORA-treated mice showed reduced deposits, restored CD59 expression and attenuated amyloid precursor protein (APP) expression compared with untreated eyes. This molecular rescue correlated with statistically significant improvement in photoreceptor function. This is the first study evaluating the impact of RORA modifier gene therapy on rescuing retinal degeneration. Our studies demonstrate efficacy of RORA in improving STGD and dry AMD-like disease.


Asunto(s)
Modelos Animales de Enfermedad , Terapia Genética , Ratones Noqueados , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Degeneración Retiniana , Enfermedad de Stargardt , Animales , Humanos , Ratones , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Dependovirus/genética , Terapia Genética/métodos , Atrofia Geográfica/genética , Atrofia Geográfica/metabolismo , Atrofia Geográfica/terapia , Degeneración Macular/genética , Degeneración Macular/metabolismo , Degeneración Macular/terapia , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Miembro 1 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Degeneración Retiniana/genética , Degeneración Retiniana/terapia , Degeneración Retiniana/metabolismo , Enfermedad de Stargardt/genética
4.
J Pharm Pharmacol ; 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38642916

RESUMEN

The Phyllanthus genus is very important plant traded as a raw herbal medicine in India. Commonly known as 'Bhumyamalaki' (Phyllanthus species) has been used for the prevention and treatment of jaundice. Phyllanthus is rich in diversity of bioactive compounds such as lignans, alkaloids, terpenoids, flavonoids, and tannins. Among some metabolites such as phyllanthin, hypophyllanthin, 8, 9-epoxy brevifolin, brevifolin, quercetin, gallic acid, elagic acid, and brevifolin carboxylate have been shown to have hepatoprotective and antioxidant activity found in this genus. The basic objective of this review was to overview the hepatoprotective activity based on the other available data from various plants of the Phyllanthus species including Phyllanthus amarus, Phyllanhtus urinaria, Phyllanthus fraternus, Phyllanthus maderaspatenis, Phyllanthus simplex, Phyllanthus emblica, Phyllanthus debillis, Phyllanthus tenellus, Phyllanthus polyphyllus, Phyllanthus reticulates, Phyllanthus indofischerii, Phyllanthus acidus, Phyllanthus niruri, Phyllanthus rheedii, Phyllanthus kozhikodianus, and Phyllanthus longiflorus. These species studied had considerable hepatoprotective potential. The secondary data, each in vitro and in vivo studies confirm the capacity of Phyllanthus species used as a remedy for jaundice or liver disease in addition to having antioxidants. Furthermore, it could be concluded that herbal drugs have the least side effects and are taken into considered safe for human health, they are able to substantially alternative synthetic drugs in the future.

5.
Appl Radiat Isot ; 202: 111038, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37812857

RESUMEN

Lutetium-177 radio-pharmaceutical has become an important theranostic candidate in cancer treatment. Its availability from bench-to-bed requires strategic implementation of isotope-enrichment, neutron-irradiation and radio-chemical techniques. In this paper, the need for enrichment of lutetium-176 is emphasized by estimating specific activity of lutetium-177 as a function of enrichment percentage for typical neutron flux available at Dhruva reactor, India. A novel Atomic Vapour Laser Isotope Separation (AVLIS) module for lutetium-176 enrichment is designed to meet the above requirement. The paper documents its characteristics and production estimates. The design is carried out after critical assessment and evaluation of available AVLIS-infrastructure in the country. Outline of lutetium-177 enrichment, capable of producing non-carrier-added lutetium is also provided. This work concludes that India has taken a step forward towards self-reliance (Atmanirbhar Bharat) in securing the supply chain of lutetium-177.

6.
Hernia ; 27(5): 1155-1163, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37452974

RESUMEN

INTRODUCTION: The Desarda autologous tissue repair is comparable to the Lichtenstein hernioplasty for inguinal hernia regarding recurrence, chronic groin pain, and return to work activities. This study was designed to establish the outcomes of Desarda's repair versus Lichtenstein's hernioplasty concerning post-operative recovery to normal gait and its feasibility under local anesthesia (LA). MATERIALS AND METHODS: This study was a single-center, prospective, double-blinded, non-inferiority, randomized trial. Patients undergoing open hernia repair for primary inguinal hernia were included. Patients were randomly assigned and followed up for 2 years. The primary endpoint was the time to return to normal gait post-surgery with comfort (non-inferiority margin fixed as 0.5 days). The secondary outcomes studied were post-operative pain score, the time required to return to work (all previously performed activities), and surgical-site occurrences (SSO). RESULTS: One hundred ten eligible patients were randomly assigned [56 patients (50.9%) in the Desarda group and 54 patients (49.1%) in the Lichtenstein group]. All the procedures were safely performed under LA. The median (interquartile range) time for resuming gait post-surgery with comfort was 5 days in the Desarda vs 4 days in Lichtenstein's arm (P = 0.16), thereby failing to demonstrate non-inferiority of Desarda against Lichtenstein hernioplasty. However, there were no significant differences in days to return to work, SSO, chronic groin pain, and recurrence within two years of surgery. CONCLUSIONS AND RELEVANCE: This study could not demonstrate the non-inferiority of the Desarda repair versus Lichtenstein hernioplasty regarding the time taken to return to normal gait. Comparing the days to return to work, pain score, SSO, and chronic groin pain, including recurrence rate, Desarda repair faired equally with Lichtenstein hernioplasty, thereby highlighting its feasibility and efficacy under LA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03512366.


Asunto(s)
Dolor Crónico , Hernia Inguinal , Humanos , Hernia Inguinal/cirugía , Herniorrafia/efectos adversos , Herniorrafia/métodos , Anestesia Local , Resultado del Tratamiento , Estudios Prospectivos , Estudios de Factibilidad , Dolor Postoperatorio/etiología , Dolor Postoperatorio/cirugía , Dolor Crónico/etiología , Dolor Crónico/cirugía , Dolor Pélvico/cirugía , Mallas Quirúrgicas , Recurrencia
7.
Clin Ter ; 174(3): 281-286, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37199365

RESUMEN

Background: During neurosurgeries like resection of interhemispheric lipoma or cyst, surgeon needs to remain within the limits of interhemispheric fissure (IHF). Despite a massive literature search, data regarding the morphometry of IHF is meagre. Therefore, the present study was done to calculate the depth of IHF. Materials and Methods: Twenty-five (fourteen male and eleven female) fresh human cadaveric brain specimens were used. The depth of IHF was measured from frontal pole; three points, anterior to coronal suture (A, B and C); four points, posterior to coronal suture (D, E, F and G) and from two points (via parieto-occipital sulcus and calcarine sulcus) on occipital pole. The measurements were taken from these points up to the floor of IHF. IHF is a midline groove and hence the measurements were taken from each point against both the left and the right cerebral hemispheres. At the end, not much bilateral asymmetry was found, hence the average of the reading for the same point against left and the right cerebral hemisphere was considered for calculation. Result: Maximum depth was found to be 59.60 mm and minimum depth was found to be 19.66 mm among all the points which were considered for evaluation. No statistical difference was found in the depth of IHF among the male and the female groups as well as in the various age groups. Conclusion: This data and knowledge about the depth of interhemispheric fissure will aid the neurosurgeons in order to perform the interhemispheric transcallosal approach as well as surgeries of interhemispheric fissure such as excision of lipoma, cyst, tumor of interhemispheric fissure through the shortest and the safest possible route.


Asunto(s)
Cerebro , Quistes , Lipoma , Humanos , Masculino , Femenino , Encéfalo , Cadáver
8.
Anaesthesia ; 78(8): 1005-1019, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37094792

RESUMEN

Chronic post-surgical pain is known to be a common complication of thoracic surgery and has been associated with a lower quality of life, increased healthcare utilisation, substantial direct and indirect costs, and increased long-term use of opioids. This systematic review with meta-analysis aimed to identify and summarise the evidence of all prognostic factors for chronic post-surgical pain after lung and pleural surgery. Electronic databases were searched for retrospective and prospective observational studies as well as randomised controlled trials that included patients undergoing lung or pleural surgery and reported on prognostic factors for chronic post-surgical pain. We included 56 studies resulting in 45 identified prognostic factors, of which 16 were pooled with a meta-analysis. Prognostic factors that increased chronic post-surgical pain risk were as follows: higher postoperative pain intensity (day 1, 0-10 score), mean difference (95%CI) 1.29 (0.62-1.95), p < 0.001; pre-operative pain, odds ratio (95%CI) 2.86 (1.94-4.21), p < 0.001; and longer surgery duration (in minutes), mean difference (95%CI) 12.07 (4.99-19.16), p < 0.001. Prognostic factors that decreased chronic post-surgical pain risk were as follows: intercostal nerve block, odds ratio (95%CI) 0.76 (0.61-0.95) p = 0.018 and video-assisted thoracic surgery, 0.54 (0.43-0.66) p < 0.001. Trial sequential analysis was used to adjust for type 1 and type 2 errors of statistical analysis and confirmed adequate power for these prognostic factors. In contrast to other studies, we found that age had no significant effect on chronic post-surgical pain and there was not enough evidence to conclude on sex. Meta-regression did not reveal significant effects of any of the study covariates on the prognostic factors with a significant effect on chronic post-surgical pain. Expressed as grading of recommendations, assessment, development and evaluations criteria, the certainty of evidence was high for pre-operative pain and video-assisted thoracic surgery, moderate for intercostal nerve block and surgery duration and low for postoperative pain intensity. We thus identified actionable factors which can be addressed to attempt to reduce the risk of chronic post-surgical pain after lung surgery.


Asunto(s)
Dolor Postoperatorio , Calidad de Vida , Humanos , Pronóstico , Estudios Retrospectivos , Dolor Postoperatorio/tratamiento farmacológico , Pulmón , Estudios Observacionales como Asunto
9.
SAR QSAR Environ Res ; 34(1): 39-64, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36779961

RESUMEN

5-fluorouracil is an essential component of systemic chemotherapy for colon, breast, head, and neck cancer patients. However, tumoral overexpression of the dihydropyrimidine dehydrogenase has rendered 5-FU clinically ineffective by inactivating it to 5'-6'-dihydro fluorouracil. The responses to 5-FU in terms of efficacy and toxicity greatly differ depending upon the population group, because of variability in the DPD activity levels. In the current study, key active site amino acids involved in the 5-FU inactivation were investigated by modelling the 3D structure of human DPD in a complex with 5-FU. The identified amino acids were analyzed for their possible missense mutations available in dbSNP database. Out of 12 missense SNPs, four were validated either by sequencing in the 1000 Genomes project or frequency/genotype data. The recorded validated missense SNPs were further considered to analyze the effect of their respective alterations on 5-FU binding. Overall findings suggested that population bearing the Glu611Val DPD mutation (rs762523739) is highly vulnerable to 5-FU resistance. From the docking, electrostatic complementarity, dynamics, and energy decomposition analyses it was found that the above mutation showed superior scores than the wild DPD -5FU complex. Therefore, prescribing prodrug NUC-3373 or DPD inhibitors (Gimeracil/3-Cyano-2,6-Dihydroxypyridines) as adjuvant therapy may overcome the 5-FU resistance.


Asunto(s)
Dihidrouracilo Deshidrogenasa (NADP) , Polimorfismo de Nucleótido Simple , Humanos , Dihidrouracilo Deshidrogenasa (NADP)/genética , Dihidrouracilo Deshidrogenasa (NADP)/metabolismo , Relación Estructura-Actividad Cuantitativa , Fluorouracilo/metabolismo , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Inhibidores Enzimáticos
10.
Ann R Coll Surg Engl ; 105(6): 501-506, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36688842

RESUMEN

INTRODUCTION: A wandering spleen occurs when laxity or absence of the suspensory ligaments allows migration throughout the abdomen. Gastric outlet obstruction resulting from this abnormality is rare. We present a systematic literature search and a case that was managed successfully with surgical intervention at our centre. METHODS: A systematic search of the PubMed, Embase™, Medline® and Google Scholar™ databases was carried out employing the combined search terms "gastric outlet obstruction" AND "wandering spleen". Six results were included for final analysis. RESULTS: All six search results described a single case each. Patients underwent surgical management (open or laparoscopic) after initial investigation utilising a range of modalities. There were no mortalities reported at 90 days. The single case we present was complicated by gastric perforation; the patient made a successful recovery following open splenopexy and stapled wedge resection of the stomach. CONCLUSIONS: A wandering spleen is a rare diagnosis and there are only six reported cases of gastric outlet obstruction secondary to a wandering spleen in the literature. None report associated gastric perforation. There are a variety of presenting symptoms, intraoperative findings and operative techniques used to address the gastrosplenic abnormality. The case reported by our centre adds to this limited evidence base and demonstrates a successful outcome from definitive surgical management. We highlight the need to seek early gastro-oesophageal expertise if any gastric pathology is found together with anatomical abnormality of the spleen.


Asunto(s)
Obstrucción de la Salida Gástrica , Laparoscopía , Ectopía del Bazo , Humanos , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugía , Laparoscopía/métodos , Esplenectomía/métodos , Ectopía del Bazo/complicaciones , Ectopía del Bazo/diagnóstico por imagen , Ectopía del Bazo/cirugía , Informes de Casos como Asunto
11.
Physiol Mol Plant Pathol ; 122: 101916, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36405863

RESUMEN

Sheath blight (ShB) is one of the most serious diseases in rice, leading to severe yield losses globally. In our study, we evaluated a total of 63 rice genotypes for resistance against sheath blight disease by artificial inoculation over two seasons under field conditions and studied the weather parameters associated with disease incidence. Based on two years of testing, 23 genotypes were found moderately resistant, 38 were moderately susceptible, and 2 exhibited a susceptible reaction to sheath blight disease. Among the specific four genotypes (IC283139, IC283041, IC283038, and IC283023) of the moderately resistant group exhibited less disease reaction in comparison with check variety Tetep. Further, the correlation of percent disease index (PDI) with weather parameters revealed negative associations between PDI and maximum temperature, minimum temperature, low rainfall and the positive association with maximum relative humidity (RH) suggest that very low temperature or high precipitation might have a negative impact on pathogen establishment. In addition, the sheath blight-linked SSRs were assessed using distance and model-based approaches, results of both the models revealed that genotypes distinguished the resistant population from the susceptible one. From the output of two years of principal component analysis, two genotypes from each group of moderately resistant, moderately susceptible and susceptible were studied for their biochemical reaction against the sheath blight pathogen. The biochemical study revealed that the accumulation of defense and antioxidant enzymes, namely, polyphenol oxidase, peroxidase, total phenol, phenylalanine ammonia-lyase, catalase, and superoxide dismutase, were higher in moderately resistant genotypes, but was observed to be lower in moderately susceptible and susceptible genotypes. The statistical analysis revealed the enzyme activities (defense and antioxidant) exhibited a strong negative correlation with area under the disease progress curve (AUDPC) and influence of weather parameter RH. This demonstrates that the environment factor RH plays a major role in imparting the resistance mechanism by decreasing the enzymes activities and increasing PDI. This study found that the identified novel resistant genotype (IC283139) with purple stem base demonstrated improved resistance against sheath blight infection through a defense response and the use of antioxidant machinery.

12.
J Postgrad Med ; 68(4): 199-206, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36255012

RESUMEN

Background: : Risk assessment with prognostic scoring, though important, is scarcely studied in emergency surgical patients with COVID-19 infection. Methods and Material: We conducted a retrospective cohort study on adult emergency surgical patients with COVID-19 infection in our institute from 1 May 2020 to 31 October 2021 to find the 30-day postoperative mortality and predictive accuracy of prognostic scores. We assessed the demographic data, prognostic risk scores (American Society of Anesthesiologists-Physical Classification (ASA-PS), Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) and Portsmouth-POSSUM (P-POSSUM) scores), surgical and anesthetic factors. We assessed the postoperative morbidity using the Clavien-Dindo scale and recorded the 30-day mortality. Correlation of prognostic scores and mortality was evaluated using Univariate Cox proportional hazards regression, receiver operating characteristic curve (ROC), Youden's index and Hosmer- Lemeshow goodness of fit model. Results: Emergency surgery was performed in 67 COVID-19 patients with postoperative complication and 30-day mortality rate of 33% and 19%, respectively. A positive qSOFA and ASAPS IIIE/IVE had a 9.03- and 12.7-times higher risk of mortality compared to a negative qSOFA and ASA-PS IE/IIE (P < 0.001), respectively. Every unit increase of SOFA, POSSUM and P-POSSUM scores was associated with a 50%, 18% and 17% higher risk of mortality, respectively. SOFA, POSSUM and P-POSSUM AUCROC curves showed good discrimination between survivors and non-survivors (AUC 0.8829, 0.85 and 0.86, respectively). Conclusions: SOFA score has a higher sensitivity to predict 30-day postoperative mortality as compared to POSSUM and P-POSSUM. However, in absence of a control group of non-COVID-19 patients, actual risk attributable to COVID-19 infection could not be determined.


Asunto(s)
COVID-19 , Adulto , Humanos , Estudios Retrospectivos , Pronóstico , Periodo Posoperatorio , Medición de Riesgo/métodos , Curva ROC , Complicaciones Posoperatorias/etiología , Índice de Severidad de la Enfermedad
13.
ESMO Open ; 7(5): 100573, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36084396

RESUMEN

BACKGROUND: We conducted a phase I, multicenter, open-label, dose-finding, and expansion study to determine the safety and preliminary efficacy of eprenetapopt (APR-246) combined with pembrolizumab in patients with advanced/metastatic solid tumors (ClinicalTrials.gov NCT04383938). PATIENTS AND METHODS: For dose-finding, requirements were non-central nervous system primary solid tumor, intolerant to/progressed after ≥1 line of treatment, and eligible for pembrolizumab; for expansion: (i) gastric/gastroesophageal junction tumor, intolerant to/progressed after first-line treatment, and no prior anti-programmed cell death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy; (ii) bladder/urothelial tumor, intolerant to/progressed after first-line cisplatin-based chemotherapy, and no prior anti-PD-1/PD-L1 therapy; (iii) non-small-cell lung cancer (NSCLC) with previous anti-PD-1/PD-L1 therapy. Patients received eprenetapopt 4.5 g/day intravenously (IV) on days 1-4 with pembrolizumab 200 mg IV on day 3 in each 21-day cycle. Primary endpoints were dose-limiting toxicity (DLT), adverse events (AEs), and recommended phase II dose (RP2D) of eprenetapopt. RESULTS: Forty patients were enrolled (median age 66 years; range 27-85) and 37 received eprenetapopt plus pembrolizumab. No DLTs were reported and the RP2D for eprenetapopt in combination was 4.5 g/day IV on days 1-4. The most common eprenetapopt-related AEs were dizziness (35.1%), nausea (32.4%), and vomiting (29.7%). AEs leading to eprenetapopt discontinuation occurred in 2/37 patients (5.4%). In efficacy-assessable patients (n = 29), one achieved complete response (urothelial cancer), two achieved partial responses (NSCLC, urothelial cancer), and six patients had stable disease. CONCLUSIONS: The eprenetapopt plus pembrolizumab combination was well tolerated with an acceptable safety profile and showed clinical activity in patients with solid tumors.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Quinuclidinas/uso terapéutico
14.
Iran J Vet Res ; 23(1): 61-68, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35782354

RESUMEN

Background: In mammalian females, the uterine tissue is highly responsive to steroid hormones and their antagonists. Aims: In the present study, topographical, histoarchitectural, and gene expression changes in goat endometrium treated with estradiol, progesterone, and mifepristone for 24 h were investigated, in vitro. Methods: Scanning electron microscopy (SEM) was used for surface topographical analysis; WGA and DBA lectins were used for histochemical analysis; and qRT-PCR was done for the quantification of mRNA levels of MKI67 (marker of proliferation Ki67), ESR1 (estrogen receptor), PGR (progesterone receptor), CASP3 (caspase 3), and PDGFR-ß (platelet derived growth factor receptor-ß). Results: Few topographical alterations were observed in endometrial glands and the presence of scattered mucoid granules. A significant decline in WGA staining was reported only in the progesterone group. However, DBA binding was highest in the progesterone group and lowest in the mifepristone group. The expression of MKI67 gene declined to 79% in the mifepristone group, while in the estradiol and progesterone groups it elevated to 153% and 41%, respectively, than control; a similar trend was observed for PDGFR-ß. The mRNA abundance for ESR1 declined to 59% in the progesterone group and 10% in the mifepristone group. However, a 100% increase occurred in the estradiol group. PGR expression followed the same trend as that of ESR1. CASP3 declined in the estradiol (50%) and progesterone (37%) group, but it showed a 67% increase in the mifepristone group. Conclusion: We concluded that the caprine uterus undergoes dramatic alteration in structure and functions in response to different kinds of steroidal environments.

15.
J Maxillofac Oral Surg ; 21(2): 715-724, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35712411

RESUMEN

Objectives: To assess the role of sialendoscopy as a diagnostic modality and in managing cases of non-neoplastic parotid gland diseases. Secondly, to provide descriptive analysis of intraoperative findings. Methods: The patients of chronic parotid sialadenitis who presented with complaints of recurrent unilateral or bilateral parotid swelling and pain were included in the study. All patients underwent sialendoscopy, and the findings were noted. Intervention was carried out in the same sitting like dilatation of stenosis, stone removal by basket, combined approach, flushing of mucoid flakes, etc. Failed cases were worked up with radiological investigation and managed accordingly. Results: Two hundred and forty-one cases of parotid sialadenitis who underwent sialendoscopy between 2012 and 2018 were included. Diagnostic sialendoscopy was achieved in 100% cases, while intervention was successful in 96.7% (233/241) cases after the first procedure. On diagnostic sialendoscopy, ductal stenosis was the most common pathology present in 177 (73.4%) patients followed by stones (12%) and debris (11.6%). All cases of stenosis were serially dilated with increasing sizes of sialendoscopes followed by stenting in 75% of the cases. The diagnosis of juvenile recurrent parotitis was confirmed in 17 children (mean age 5.6 years) with consistent clinical history and sialendoscopic findings of stenosis along with pale ductal mucosa. There were 18 cases where ductal perforation was seen. One case showed multiple hyperdense foci in bilateral parotid gland along with multiple strictures that underwent repeat sialendoscopy, but the symptoms did not resolve, and finally the patient underwent bilateral superficial parotidectomy. Conclusion: Sialendoscopy is a safe and highly effective modality in managing non-neoplastic parotid gland disorders with low complication rates and resulted in gland preservation in the vast majority of patients. Therefore, it can be concluded that sialendoscopy is the diagnostic and therapeutic modality of choice for parotid obstructive sialadenitis.

16.
J Clin Neurosci ; 100: 7-14, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35367733

RESUMEN

Due to lack of well-designed trials, there is no good evidence on the efficacy of stem cells in spinal cord injury. We aim to study the efficacy and outcome of bone marrow derived stem cells (BMSCs) in acute complete spinal cord injury (SCI). In this prospective study over a 3-year period, 27 patients with acute, complete SCI were randomized to receive BMSCs or placebo (intramedullary route) intraoperatively. Institutional ethics approval was taken and informed consent was taken from all patients. Functional outcome was assessed using ASIA scale, SCIM score and SSEP responses preoperatively, three and six months after surgery. Thirteen patients were available for final analysis of which six were in the stem cell group and seven received placebo. 6 patients had improvement by at least one grade in ASIA score in the stem cell group as compared to only one patient in the placebo group. However, no functional motor improvement in any of the patients. ASIA sensory score improved from a preoperative mean of 124 to 224 at 6 months compared to the static mean of 115 in the control group. Absent SSEP waveform converted to abnormal waveform at 6 months in 3 patients in the stem cell group and one patient in the control group. There was no significant difference in the SCIM scores between the groups at last follow-up. All patients in the stem cell group reported improved bladder sensation, decreased spasticity and improved posture control as compared to nine in the placebo group. BMSCs through intramedullary route are a potential therapy for acute complete SCI and more research is required in this area.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Traumatismos de la Médula Espinal , Médula Ósea , Células de la Médula Ósea , Humanos , Estudios Prospectivos , Recuperación de la Función , Médula Espinal , Traumatismos de la Médula Espinal/cirugía , Células Madre
17.
Eur Rev Med Pharmacol Sci ; 26(2): 710-714, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35113446

RESUMEN

OBJECTIVE: To study the utility of Galactomannan (GM) antigen as a screening marker for diagnosing invasive pulmonary aspergillosis (IPA) in coronavirus disease 2019 (COVID-19) patients. PATIENTS AND METHODS: The serum samples from patients with severe COVID-19 diseases admitted to the Critical Care Unit were collected on the 5th day of admission for GM screening. The samples were analysed by enzyme linked immune sorbent assay (ELISA) and GM index of more than 1 was considered as positive. All GM positive patients were serially followed until discharge or death. RESULTS: The GM was raised in serum of 12 out of 38 patients, indicating an incidence of possible COVID-19 associated IPA (CAPA) in 31.57% of patients. The median age of these CAPA patients was 56.5 years, males were significantly more affected than females. The inflammatory marker serum ferritin was raised in all 12 patients (median value of 713.74 ng/ml), while IL-6 was raised in 9 patients (median value of 54.13 ng/ml). None of these patients received antifungals. Their median length of hospital stay was 20 days (IQR: 12, 34 days). All these patients succumbed to the illness. CONCLUSIONS: The serum GM appears to be sensitive diagnostic tool to identify early IPA in COVID-19 patients and pre-emptive antifungal therapy could play a role in salvaging these patients.


Asunto(s)
COVID-19/diagnóstico , Galactosa/análogos & derivados , Aspergilosis Pulmonar Invasiva/diagnóstico , Mananos/sangre , Adulto , Anciano , COVID-19/complicaciones , COVID-19/virología , Ensayo de Inmunoadsorción Enzimática , Femenino , Galactosa/sangre , Humanos , Interleucina-6/metabolismo , Aspergilosis Pulmonar Invasiva/complicaciones , Tiempo de Internación , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , SARS-CoV-2/aislamiento & purificación , Factores Sexuales
18.
Ann R Coll Surg Engl ; 104(5): e139-e142, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34941460

RESUMEN

Renal cell cancer (RCC) accounts for 3% of all solid malignancies. Synchronous tumour thrombus in the renal vein or inferior vena cava is reported in 4-10% cases and is a surgical challenge. Contemporary imaging modalities that are used to define the presence and extent of venous thrombus include colour Doppler, contrast-enhanced computed tomography and magnetic resonance venography. Surgical management depends upon the degree of tumour thrombus. We report isolated recurrence of RCC in the inferior vena cava 2 years after radical nephrectomy, and discuss its pathophysiology and management.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Primarias Secundarias , Células Neoplásicas Circulantes , Trombosis , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Neoplasias Renales/complicaciones , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Masculino , Neoplasias Primarias Secundarias/patología , Células Neoplásicas Circulantes/patología , Nefrectomía/métodos , Estudios Retrospectivos , Trombectomía , Trombosis/patología , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/patología , Vena Cava Inferior/cirugía
19.
J Laryngol Otol ; 136(2): 146-153, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34588007

RESUMEN

OBJECTIVE: To assess benefits of surgical intervention at an early age and focus on surgical techniques using exclusively autologous cartilage grafts. METHODS: Five children aged 8-15 years, treated between March 2016 and 2020, underwent augmentation rhinoplasty using autologous cartilage, with post-operative follow up ranging from 1.5 to 2 years. Photographs and Rhinoplasty Outcome Evaluation questionnaire scores were examined. RESULTS: Augmentation was achieved without complications. No restricted skin or mucosal pockets were encountered. Patients showed improved confidence and perspective with regard to self-image, and were less socially self-conscious. There was significant improvement in all Rhinoplasty Outcome Evaluation questionnaire scores. CONCLUSION: Early surgery allows augmentation with easier release of skin and mucosal pockets, and without the tension otherwise encountered if primary augmentation is performed at a later age. It offers a chance to improve confidence and self-perception in a growing child conscious about their appearance, which may make them socially withdrawn. Autologous cartilage gives better results than bone grafts, and is comparable with silicone but without its complications.


Asunto(s)
Cartílago/trasplante , Anomalías Maxilofaciales/cirugía , Rinoplastia/métodos , Adolescente , Niño , Intervención Médica Temprana , Femenino , Humanos , Masculino , Trasplante Autólogo
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