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1.
Cureus ; 16(6): e62174, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38993431

RESUMEN

INTRODUCTION: Surgical intervention for rectal cancer is widely recognized for its potential to significantly impact quality of life, chiefly due to the high probability of permanent colostomy and the associated postoperative complications. OBJECTIVE: This study aimed to evaluate the short-term outcomes and morbidity associated with total mesorectal excision for middle and lower rectal cancer within an Iraqi cohort, in a prospective setting. METHODS: This study prospectively collected and analyzed data from 89 patients who underwent a standardized radical rectal resection, with a follow-up period extending to one month post-surgery. RESULTS: The mean age of patients was 54.4 ± 12.9 years, with a gender distribution of 46 males and 43 females. A total of 33 patients presented with preoperative comorbidities, which heightened the risk of adverse short-term outcomes by a factor of 7.51. The most prevalent comorbidities were hypertension and diabetes mellitus, affecting 22 and 20 patients, respectively. Patients aged 60 years and above were at a 3.97 times greater risk of developing complications. The overall complication rate was 21.35%, with wound infections (9.0%) and cardiovascular events (3.4%) being the most common. Mortality during the follow-up was 1.1%. CONCLUSION: The findings indicate that increased age and the presence of comorbidities are significant risk factors for morbidity and mortality post-surgery. Neoadjuvant chemoradiotherapy or radiotherapy was shown to reduce morbidity and mortality rates while improving survival. The morbidity and mortality rates observed in this study concur with existing literature.

2.
Cureus ; 16(4): e58516, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38957818

RESUMEN

BACKGROUND: Among the patient population in Basrah, Iraq, prolactinoma is the most commonly found pituitary tumor. Impulse control disorders (ICDs) were reportedly associated with these patients being treated with cabergoline. This study aimed to assess the prevalence of ICDs in cabergoline-treated prolactinoma patients versus healthy, matched controls. METHODS: This cross-sectional case-control study was conducted at the Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) in Basrah, southern Iraq, from January 2023 to May 2023. It included 30 cabergoline-treated prolactinoma patients and 30 healthy, matched controls. The questionnaire for ICDs in Parkinson's disease was used as a screening tool. Following this, positively screened patients were evaluated using validated criteria accordingly to diagnose impulse control disorders. RESULTS: The ICDs were diagnosed in nine (30%) cabergoline-treated prolactinoma patients versus two (6.7%) in control (p = 0.02). The most frequent ICD types were hypersexuality and binge eating, while no patient reported pathological gambling. Three patients reported multiple types of ICDs. The patients' sociodemographic characteristics, prolactinoma duration and size, and cabergoline dose did not correlate significantly with ICD diagnosis. CONCLUSIONS: Treatment with cabergoline is associated with the development of ICDs. Therefore, clinicians should be aware of this disabling side effect to ensure its early detection and treatment.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38973528

RESUMEN

INTRODUCTION: The USA has the highest age-standardized prevalence of inflammatory bowel disease (IBD). Both genetic and environmental factors have been implicated in IBD flares and multiple strategies are centered around avoiding dietary triggers to maintain remission. Chat-based artificial intelligence (CB-AI) has shown great potential in enhancing patient education in medicine. We evaluate the role of CB-AI in patient education on dietary management of IBD. METHODS: Six questions evaluating important concepts about the dietary management of IBD which then were posed to three CB-AI models - ChatGPT, BingChat, and YouChat three different times. All responses were graded for appropriateness and reliability by two physicians using dietary information from the Crohn's and Colitis Foundation. The responses were graded as reliably appropriate, reliably inappropriate, and unreliable. The expert assessment of the reviewing physicians was validated by the joint probability of agreement for two raters. RESULTS: ChatGPT provided reliably appropriate responses to questions on dietary management of IBD more often than BingChat and YouChat. There were two questions that more than one CB-AI provided unreliable responses to. Each CB-AI provided examples within their responses, but the examples were not always appropriate. Whether the response was appropriate or not, CB-AIs mentioned consulting with an expert in the field. The inter-rater reliability was 88.9%. DISCUSSION: CB-AIs have the potential to improve patient education and outcomes but studies evaluating their appropriateness for various health conditions are sparse. Our study showed that CB-AIs have the ability to provide appropriate answers to most questions regarding the dietary management of IBD.

4.
Am J Surg Pathol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38989701

RESUMEN

A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56 y). They predominantly affected the upper lobes and measured 1.3 to 9 cm in greatest diameter (mean: 4.6 cm). The tumor cells were characterized by large pleomorphic nuclei with prominent nucleoli, ample cytoplasm, and frequent abnormal mitoses, and were surrounded by a dense inflammatory cell infiltrate, often associated with emperipolesis. Immunohistochemical stains were positive in the tumor cells for cytokeratin AE1/AE3 and CK8/18 and negative for TTF1, napsin A, p40, and CK5/6. Next-generation sequencing was performed in all cases using the Oncomine Precision Assay; the most common abnormalities found included TP53 mutations (9 cases) and AKT1 amplification (8 cases), followed by KRAS mutations (4 cases) and MAP2K1/2 mutations (4 cases). Clinical follow-up was available in 13 patients. Three patients presented with metastases as the initial manifestation of disease; 8 patients died of their tumors from 6 months to 8 years (mean: 2.7 y); 3 patients were alive and well from 4 to 6 years; and 2 patients had metastases when last seen but were lost to follow-up thereafter. The importance of recognizing this distinctive and aggressive variant of non-small cell lung carcinoma lies in avoiding confusion with a sarcoma or other types of malignancy.

5.
Public Health ; 233: 193-200, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38941682

RESUMEN

OBJECTIVES: COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic. STUDY DESIGN: Retrospective cohort study. METHODS: This international retrospective cohort study, led by a large Academic Medical Centre (AMC), was conducted via YouTube and the AMC's online learning platform. From 2020 to 2021, multidisciplinary experts developed and deployed six online training courses based on the latest evidence-based management guidelines. Participants were selected through a voluntary sample following an electronic campaign. Training outcomes were assessed using pre-and post-test questionnaires, evaluation forms, and post-training assessment surveys. Kirkpatrick's Model guided training evaluation to measure self-reported knowledge, clinical skills, and confidence improvement. We also captured the number and type of COVID-19 patients managed by HCWs after the trainings. RESULTS: Every 22.8 reach/impression and every 1.2 engagements led to a course registration. The 10,425 registrants (56.8% female, 43.1% male) represented 584 medical facilities across 154 cities. The largest segments of participants were students/interns (20.6%) and medical officers (13.4%). Of the 2169 registered participants in courses with tests, 66.9% completed post-tests. Test scores from all courses increased from the initial baseline to subsequent improvement post-course. Participants completing post-training assessment surveys reported that the online courses improved their knowledge and clinical skills (83.5%) and confidence (89.4%). Respondents managed over 19,720 COVID-19 patients after attending the courses, with 47.7% patients being moderately/severely ill. CONCLUSIONS: Participants' confidence in handling COVID-19 patients is increased by rapidly deploying mass training to a substantial target population through digital tools. The findings present a virtual education and assessment model that can be leveraged for future global public health issues, and estimates for future electronic campaigns to target.

6.
Asian Pac J Cancer Prev ; 25(6): 2051-2058, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38918667

RESUMEN

OBJECTIVE: Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities. METHODS: In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient. RESULTS: Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF. CONCLUSION: This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.


Asunto(s)
Ácido Aminolevulínico , Neoplasias de la Mama , Proliferación Celular , Dimetilfumarato , FN-kappa B , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Fotoquimioterapia/métodos , FN-kappa B/metabolismo , Fármacos Fotosensibilizantes/farmacología , Ácido Aminolevulínico/farmacología , Femenino , Proliferación Celular/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Dimetilfumarato/farmacología , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Células Tumorales Cultivadas , Línea Celular Tumoral
7.
Sci Total Environ ; 942: 173403, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38844217

RESUMEN

With 24 million inhabitants and 6.6 million vehicles on the roads, Karachi, Pakistan ranks among the world's most polluted cities due to high levels of fine particulate matter (PM2.5). This study aims to investigate PM2.5 mass, seasonal and temporal variability, chemical characterization, source apportionment, and health risk assessment at two urban sites in Karachi. Samples were analyzed using ion chromatography and dual-wavelength optical transmissometer for various inorganic components (anions, cations, and trace elements) and black carbon (BC). Several PM2.5 pollution episodes were frequently observed, with annual mean concentrations at Kemari (140 ± 179 µg/m3) and Malir (95 ± 40.9 µg/m3) being significantly above the World Health Organization's guidelines of 5 µg/m3. Chemical composition at both sites exhibited seasonal variability, with higher pollution levels in winter and fall and lower concentrations in summer. The annual average BC concentrations were 4.86 ± 5.29 µg/m3 and 4.52 ± 3.68 µg/m3, respectively. A Positive Matrix Factorization (PMF) analysis identified 5 factors, crustal, sea salt, vehicular exhaust, fossil-fuel combustion, and industrial emission. The health risk assessment indicated a higher number of deaths in colder seasons (fall and winter) at the Kemari (328,794 and 287,814) and Malir (228,406 and 165,737) sites and potential non-carcinogenic and carcinogenic risks to children from metals. The non-carcinogenic risk of PM2.5 bound Pb, Fe, Zn, Mn, Cr, Cu and Ni via inhalation exposure were within the acceptable level (<1) for adults. However, potential non-carcinogenic and carcinogenic health risk posed by Pb and Cr through inhalation were observed for children. The findings exhibit critical levels of air pollution that exceed the safe limits in Karachi, posing significant health risks to children and sensitive groups. Our study underscores the urgent need for effective emission control strategies and policy interventions to mitigate these air pollution risks.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Monitoreo del Ambiente , Material Particulado , Contaminación del Aire/estadística & datos numéricos , Humanos , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Pakistán , Medición de Riesgo , Ciudades , Exposición a Riesgos Ambientales/estadística & datos numéricos
8.
Talanta ; 276: 126219, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38733936

RESUMEN

This study presents a potent paper-based analytical device (PAD) for quantifying various sugars using an innovative bi-nanozyme made from a 2-dimensional Fe/Ce metal-organic framework (FeCe-BTC). The MOF showed excellent bifunctional peroxidase-oxidase activities, efficiently catalyzing luminol's chemiluminescence (CL) reaction. As a peroxidase-like nanozyme, FeCe-BTC could facilitate the dissociation of hydrogen peroxide (H2O2) into hydroxyl radicals, which then oxidize luminol. Additionally, it was also discovered that when reacting with H2O2, the MOF turns into a mixed-valence MOF, and acts as an oxidase nanozyme. This activity is caused by the generated Ce4+ ions in the structure of MOF that can directly oxidize luminol. The MOF was directly synthesized on the PAD and cascaded with specific natural enzymes to establish simple, rapid, and selective CL sensors for the measurement of different sugars. A cell phone was also used to record light intensities, which were then correlated to the analyte concentration. The designed PAD showed a wide linear range of 0.1-10 mM for glucose, fructose, and sucrose, with detection limits of 0.03, 0.04, and 0.04 mM, respectively. It showed satisfactory results in food and biological samples with recovery values ranging from 95.8 to 102.4 %, which makes it a promising candidate for point-of-care (POC) testing for food control and medicinal purposes.


Asunto(s)
Mediciones Luminiscentes , Luminol , Estructuras Metalorgánicas , Papel , Teléfono Inteligente , Luminol/química , Estructuras Metalorgánicas/química , Mediciones Luminiscentes/métodos , Hierro/química , Hierro/análisis , Cerio/química , Peroxidasa/química , Peroxidasa/metabolismo , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Oxidorreductasas/química , Oxidorreductasas/metabolismo , Azúcares/análisis , Azúcares/química , Materiales Biomiméticos/química , Luminiscencia
9.
Virchows Arch ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38814477

RESUMEN

Non-small cell lung carcinoma with predominantly clear cell features is a rare histologic presentation of lung carcinoma. We have examined 31 cases of lung carcinomas showing extensive clear cell features. The patients were 10 women and 21 men aged 47-92 years (mean: 70 years). The tumors showed a predilection for the right upper and lower lobes and measured from 0.8 to 9.5 cm (mean: 4.2 cm). By immunohistochemistry, 9 cases were typed as adenocarcinoma, 19 cases as squamous cell carcinoma, and 3 showed a "null" phenotype with complete loss of markers for adenocarcinoma or squamous cell carcinoma. Most cases that typed as adenocarcinoma showed a solid growth pattern. A subset of the solid adenocarcinoma cases showed a distinctive "pseudosquamous" morphology. Next-generation sequencing was performed in 20 cases and showed a variety of molecular alterations. The most common abnormalities were found in the TP53 gene (9 cases), FGFR gene family (8 cases), KRAS (5 cases), AKT1 (5 cases), and BRAF (3 cases). Clinical follow-up was available in 21 patients; 16/21 patients died of their tumors from 6 months to 12 years after initial diagnosis (mean: 4.2 years, median: 1.5 years). Four patients were alive and well from 4 to 27 years (mean: 11.5 years, median: 7.5 years); all were pathologic stage 1 or 2. NSCLC with clear cell features can display aggressive behavior and needs to be distinguished from various other tumors of the lung that can show clear cell morphology. The identification of targetable molecular alterations in some of these tumors may be of value for therapeutic management.

10.
Cureus ; 16(4): e58370, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38756268

RESUMEN

BACKGROUND:  Hypothyroidism is one of the most common endocrine disorders with a simple therapy, that is levothyroxine (LT4). A normal thyroid-stimulating hormone (TSH) measurement is used as a marker of optimal replacement. But, many patients still have symptoms. Triiodothyronine (T3), thyroxine (T4), and their ratio may correlate with clinical improvement. The study aims to assess the T3/T4 ratio as a marker of clinical response in patients with hypothyroidism.  Method: A cross-sectional study was conducted from June to November 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, southern Iraq. We included 48 adult patients with primary hypothyroidism on LT4 treatment only and TSH within the target reference range for at least within the last six months. Each patient was subjected to a questionnaire that was designed to capture hypothyroidism-related complaints in the form of a five-point Likert scale. Biochemical assessments were done with the measurement of TSH, T3, and T4. RESULTS: Despite having a normal TSH level, nearly all the patients had persistent and varying severity of clinical complaints of hypothyroidism. Tiredness, hair problems, weight gain, and cold intolerance were the most severely persistent symptoms. Patients with scores of two and more for weight gain, cold intolerance, and skin problems had significantly lower T3/T4 ratios (P = 0.04, 0.002, and 0.02, respectively), while in the remaining clinical symptoms, the T3/T4 ratio did not differ significantly. CONCLUSION: A low T3/T4 ratio was significantly associated with resistant symptoms of hypothyroidism and may be used as a marker for treatment efficacy with TSH rather than TSH value alone.

11.
Cureus ; 16(3): e55783, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38586779

RESUMEN

Objective The objective was to evaluate the modified frailty index as a predictor of early (within 30 days) postoperative complications in total joint arthroplasty patients, in a low middle-income country. Material and methods A cross-sectional study was carried out which included patients with ages ranging from 23 to 86 years, who underwent elective primary Total Hip or Knee Arthroplasties (TKA or THA) between December 2021 and February 2023. Modified frailty index (mFI-5) was calculated and 30-day morbidity and mortality were recorded. Post-operative complications were categorized as either surgical or medical and recorded. Results A total of 175 patients were included, amongst whom the majority were females (68.6%, n=120) and the mean age was 60.5 ± 13.2 years. 85 patients (48.6%) had a mFI-5 score of one while 48 patients (27.4%) had a score of two. Superficial surgical site infection was the most common complication overall in 6 patients (3.4%); however, no case of prosthetic joint infection was noted. Deep vein thrombosis (DVT) was the most common medical complication (1.7%, n=3). 5 patients (2.9%) required re-admission and two mortalities were recorded within the 30-day interval. A significant association was noted between post-operative surgical complications and mFI-5 score (p-value = < 0.001), with the risk of complications increasing with a higher mFI-5 score. Smoking was noted to be a risk factor for post-operative medical complications as well as 30-day mortality. Conclusion The current study shows that the mFI-5 index can effectively be used as a predictor of postoperative complications in the South Asian region such as Pakistan. This should be calculated routinely and can be used as a tool for pre-operative assessment and counseling.

12.
ACG Case Rep J ; 11(4): e01311, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38560020

RESUMEN

Systemic amyloidosis is a multiorgan deposition of misfolded amyloid protein fibrils. The systemic amyloid A protein (AA) amyloidosis type predominantly involves the kidney and is mostly an under-recognized complication among persons who inject drugs. Gastrointestinal involvement in systemic AA amyloidosis that is associated with illicit drug use is uncommon. In this report, we present a case of a 40-year-old man with history of injection drug use, recurrent skin and soft-tissue infection, and renal AA amyloidosis that presented with painless bloody bowel movement, which initially resolved with conservative management. Upon further evaluation, the patient was found to have empyema that required antibiotic therapy and bilateral pleural drain. His hospital course was further complicated by multiple episodes of hematochezia requiring gastrointestinal consultation. Subsequent gastrointestinal biopsy revealed amyloid deposit.

13.
Ann R Coll Surg Engl ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38563065

RESUMEN

We present a case of a 70-year-old gentleman who was referred to our tertiary 2-week-wait penile cancer clinic with a penile mass that was ulcerated, painful and discharging. This was suspicious for penile cancer and a radical circumcision was performed to remove the diseased foreskin en bloc with the lesion that was arising from the inner foreskin. Histopathology did not reveal cancer; however, we identified spirochaetes in keeping with syphilis. This was confirmed on serology. The patient was referred to the genitourinary medicine team and treated with antibiotics. This case demonstrates a rare presentation of genital syphilis in an elderly gentleman initially referred with concerns of penile cancer. Although, rare, especially in this age group, syphilis should be considered as a differential diagnosis in a patient presenting with an ulcerated, discharging, firm penile mass, especially given that the incidence of syphilis has been rising in recent years.

14.
Cureus ; 16(3): e56393, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38633939

RESUMEN

Objective This study aimed to assess the rate of patient satisfaction after primary total joint arthroplasty (TJA) using a validated satisfaction measure. Materials and methods A cross-sectional study was conducted, including all patients who underwent primary TJA between December 2021 and February 2023. The age of the study population was found to range from 23 to 86 years. Patient satisfaction was assessed using a validated tool comprising four questions and a quality of life (QoL) question. Results A total of 197 patients were included, with a mean age of 60.9 ± 12.7 years. Total knee replacement (TKR) was performed in 124 patients (62.9%), and total hip replacement (THR) in 73 patients (37.1%). The mean patient satisfaction score was 86.6 ± 14.4 out of a maximum of 100. A significant negative correlation was observed between the Charlson Comorbidity Index (CCI) and the overall satisfaction score (p-value = 0.029). The majority of the patients (52.3%, n = 103) answered that their QoL had greatly improved, and a similar level of improvement was noted in elderly vs. adult patients (p-value = 0.17). A significantly higher proportion of male patients reported improvement more than they ever expected compared to female patients, the majority of whom reported their QoL was greatly improved (p-value = 0.025). Conclusion Total joint arthroplasty has been shown to achieve good patient satisfaction and an improvement in QoL. However, an increased comorbidity index and female gender were identified as factors for reduced satisfaction. Hence, it is recommended to consider these factors and counsel patients accordingly based on local patient data.

15.
Luminescence ; 39(4): e4745, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38644416

RESUMEN

This study introduces a novel chemiluminescence (CL) approach utilizing FeS2 nanosheets (NSs) catalyzed luminol-O2 CL reaction for the measurement of three pharmaceuticals, namely venlafaxine hydrochloride (VFX), imipramine hydrochloride (IPM), and cefazolin sodium (CEF). The CL method involved the phenomenon of quenching induced by the pharmaceuticals in the CL reaction. To achieve the most quenching efficacy of the pharmaceuticals in the CL reaction, the concentrations of reactants comprising luminol, NaOH, and FeS2 NSs were optimized accordingly. The calibration curves demonstrated exceptional linearity within the concentration range spanning from 4.00 × 10-7 to 1.00 × 10-3 mol L-1, 1.00 × 10-7 to 1.00 × 10-4 mol L-1, and 4.00 × 10-6 to 2.00 × 10-4 mol L-1 with detection limits (3σ) of 3.54 × 10-7, 1.08 × 10-8, and 2.63 × 10-6 mol L-1 for VFX, IPM, and CEF, respectively. This study synthesized FeS2 NSs using a facile hydrothermal approach, and then the synthesized FeS2 NSs were subjected to a comprehensive characterization using a range of spectroscopic methods. The proposed CL method was effective in measuring the aforementioned pharmaceuticals in pharmaceutical formulations as well as different water samples. The mechanism of the CL system has been elucidated.


Asunto(s)
Cefazolina , Compuestos Ferrosos , Imipramina , Mediciones Luminiscentes , Luminol , Clorhidrato de Venlafaxina , Cefazolina/análisis , Cefazolina/química , Clorhidrato de Venlafaxina/análisis , Clorhidrato de Venlafaxina/química , Imipramina/análisis , Imipramina/química , Mediciones Luminiscentes/métodos , Luminol/química , Nanoestructuras/química , Luminiscencia
17.
Nature ; 627(8002): 130-136, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38355793

RESUMEN

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.


Asunto(s)
Inestabilidad Genómica , Micronúcleos con Defecto Cromosómico , Animales , Humanos , Ratones , Cromosomas/genética , Daño del ADN , Inestabilidad Genómica/genética , Fenotipo , Sirtuina 1 , Mutaciones Letales Sintéticas
18.
J Mol Model ; 30(3): 86, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38413404

RESUMEN

CONTEXT: In this study, we investigated the mechanical responses of molybdenum ditelluride (MoTe2) using molecular dynamics (MD) simulations. Our key focus was on the tensile behavior of MoTe2 with trigonal prismatic phase (2H-MoTe2) which was investigated under uniaxial tensile stress for both armchair and zigzag directions. Crack formation and propagation were examined to understand the fracture behavior of such material for varying temperatures. Additionally, the study also assesses the impact of temperature on Young's modulus and fracture stress-strain of a monolayer of 2H-MoTe2. METHOD: The investigation was done using molecular dynamics (MD) simulations using Stillinger-Weber (SW) potentials. The tensile behavior was simulated for temperature for 10 K and then from 100 to 600 K with a 100-K interval. The crack propagation and formation of 10 K and 300 K 2H-MoTe2 for both directions at different strain rates was analyzed using Ovito visualizer. All the simulations were conducted using a strain rate of 10-4 ps-1. The results show that the fracture strength of 2H-MoTe2 in the armchair and zigzag direction at 10 K is 16.33 GPa (11.43 N/m) and 13.71429 GPa (9.46 N/m) under a 24% and 18% fracture strain, respectively. The fracture strength of 2H-MoTe2 in the armchair and zigzag direction at 600 K is 10.81 GPa (7.56 N/m) and 10.13 GPa (7.09 N/m) under a 12.5% and 12.47% fracture strain, respectively.

19.
Int J Surg Pathol ; : 10668969241229330, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38304953

RESUMEN

The diagnosis of low-grade fibroblastic/myofibroblastic tumors of acral sites can be challenging. These tumors encompass a diverse group of neoplasms with a spectrum of biologic potential ranges from benign to overtly malignant. They often demonstrate significant clinical, radiologic, and immunophenotypic overlap, in which the molecular phenotype may play an important diagnostic role to arrive at the final diagnosis. Herein, we report a case of soft tissue mass lesion presented on the palm of an adult patient for four months. Histologically, the tumor consisted of primarily low-grade spindle cells expressing smooth muscle actin. Molecular testing revealed a novel SREBF1::USP6 fusion gene, confirming the final diagnosis of nodular fasciitis and ultimately expanding its molecular profile. This case highlights the diagnostic value of single, cost-effective, targeted molecular panel to arrive at an accurate diagnosis and provide helpful therapeutic information.

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