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1.
Nature ; 617(7962): 785-791, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37165193

RESUMEN

Different plant species within the grasses were parallel targets of domestication, giving rise to crops with distinct evolutionary histories and traits1. Key traits that distinguish these species are mediated by specialized cell types2. Here we compare the transcriptomes of root cells in three grass species-Zea mays, Sorghum bicolor and Setaria viridis. We show that single-cell and single-nucleus RNA sequencing provide complementary readouts of cell identity in dicots and monocots, warranting a combined analysis. Cell types were mapped across species to identify robust, orthologous marker genes. The comparative cellular analysis shows that the transcriptomes of some cell types diverged more rapidly than those of others-driven, in part, by recruitment of gene modules from other cell types. The data also show that a recent whole-genome duplication provides a rich source of new, highly localized gene expression domains that favour fast-evolving cell types. Together, the cell-by-cell comparative analysis shows how fine-scale cellular profiling can extract conserved modules from a pan transcriptome and provide insight on the evolution of cells that mediate key functions in crops.


Asunto(s)
Productos Agrícolas , Setaria (Planta) , Sorghum , Transcriptoma , Zea mays , Secuencia de Bases , Regulación de la Expresión Génica de las Plantas/genética , Sorghum/citología , Sorghum/genética , Transcriptoma/genética , Zea mays/citología , Zea mays/genética , Setaria (Planta)/citología , Setaria (Planta)/genética , Raíces de Plantas/citología , Análisis de Expresión Génica de una Sola Célula , Análisis de Secuencia de ARN , Productos Agrícolas/citología , Productos Agrícolas/genética , Evolución Molecular
2.
Clin Immunol ; 264: 110234, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38740111

RESUMEN

BACKGROUND: Natural anti-cytokine autoantibodies can regulate homeostasis of infectious and inflammatory diseases. The anti-cytokine autoantibody profile and relevance to the pathogenesis of asthma are unknown. We aim to identify key anti-cytokine autoantibodies in asthma patients, and reveal their immunological function and clinical significance. METHODS: A Luciferase Immunoprecipitation System was used to screen serum autoantibodies against 11 key cytokines in patients with allergic asthma and healthy donors. The antigen-specificity, immunomodulatory functions and clinical significance of anti-cytokine autoantibodies were determined by ELISA, qPCR, neutralization assays and statistical analysis, respectively. Potential conditions for autoantibody induction were revealed by in vitro immunization. RESULTS: Of 11 cytokines tested, only anti-IL-33 autoantibody was significantly increased in asthma, compare to healthy controls, and the proportion positive was higher in patients with mild-to-moderate than severe allergic asthma. In allergic asthma patients, the anti-IL-33 autoantibody level correlated negatively with serum concentration of pathogenic cytokines (e.g., IL-4, IL-13, IL-25 and IL-33), IgE, and blood eosinophil count, but positively with mid-expiratory flow FEF25-75%. The autoantibodies were predominantly IgG isotype, polyclonal and could neutralize IL-33-induced pathogenic responses in vitro and in vivo. The induction of the anti-IL-33 autoantibody in blood B-cells in vitro required peptide IL-33 antigen along with a stimulation cocktail of TLR9 agonist and cytokines IL-2, IL-4 or IL-21. CONCLUSIONS: Serum natural anti-IL-33 autoantibodies are selectively induced in some asthma patients. They ameliorate key asthma inflammatory responses, and may improve lung function of allergic asthma.


Asunto(s)
Asma , Autoanticuerpos , Interleucina-33 , Humanos , Asma/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Interleucina-33/inmunología , Femenino , Adulto , Masculino , Persona de Mediana Edad , Animales , Anticuerpos Neutralizantes/inmunología , Citocinas/inmunología , Citocinas/sangre , Ratones , Adulto Joven , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Receptor Toll-Like 9/inmunología , Receptor Toll-Like 9/agonistas , Índice de Severidad de la Enfermedad , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre
3.
Chemistry ; 30(47): e202401565, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-38864572

RESUMEN

We present a protocol for the on-surface synthesis of polyboroxine molecules derived from boroxine molecules precursors. This process is promoted by oxygen species present on the Au(111) surface: oxygen atoms facilitate the detachment of naphthalene units of trinaphthyl-boroxine molecules and bridge two unsaturated boroxine centers to form a boroxine-O-boroxine chemical motif. X-ray spectroscopic characterization shows that, as the synthesis process proceeds, it progressively tunes the electronic properties of the interface, thus providing a promising route to control the electron level alignment.

4.
BMC Infect Dis ; 24(1): 947, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256663

RESUMEN

PURPOSE: To evaluate the diagnosis and management of bacterial meningitis in adult Sudanese patients in accordance with the Infectious Diseases Society of America (IDSA) guidelines for bacterial meningitis management. PATIENTS AND METHODS: A cross-sectional, retrospective study design was used to recruit all patients aged > 18 years who were diagnosed with or suspected of having bacterial meningitis and admitted to Wad Medani Teaching Hospital, Gezira State, Sudan, between January 2017 and October 2022. RESULTS: In total, 201 patients were included in the analysis. The mean age of the participants was 44.1 ± 21.4 years, and 107 (53.2%) were male. Community-acquired bacterial meningitis accounted for 193 (96%) of the studied patients, and only 8 (4%) of the patients had healthcare-associated meningitis. Neuroimaging was utilized appropriately in 148 (73.6%) patients, blood cultures were not performed entirely, and lumbar puncture was seldom performed in 1 (0.5%) patient. Corticosteroids were appropriately administered to 65 (32.3%) patients, and antibiotics were administered appropriately to only 5 (2.5%) patients. Ceftriaxone 185 (76.1%) was the most frequently utilized antibiotic, followed by vancomycin 23 (9.5%). In terms of overall adherence, this study demonstrated that the IDSA guidelines were not followed at all in the treatment of patients with suspected bacterial meningitis. CONCLUSION: The results of this study contradict the IDSA guidelines for the standard of care for bacterial meningitis. Antibiotic regimens are often incorrect, corticosteroids are administered appropriately in approximately one-third of patients, and neuroimaging is reasonably utilized. This study raises attention to several important issues regarding the diagnosis of bacterial meningitis, including the lack of confirming microbiological tests and the reliance of the diagnosis primarily on CT and clinical examination.


Asunto(s)
Antibacterianos , Meningitis Bacterianas , Humanos , Estudios Transversales , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/microbiología , Sudán , Adulto , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Adulto Joven , Anciano , Adolescente , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/microbiología , Corticoesteroides/uso terapéutico
5.
Br J Anaesth ; 132(5): 1041-1048, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38448274

RESUMEN

BACKGROUND: Regional anaesthesia use is growing worldwide, and there is an increasing emphasis on research in regional anaesthesia to improve patient outcomes. However, priorities for future study remain unclear. We therefore conducted an international research prioritisation exercise, setting the agenda for future investigators and funding bodies. METHODS: We invited members of specialist regional anaesthesia societies from six continents to propose research questions that they felt were unanswered. These were consolidated into representative indicative questions, and a literature review was undertaken to determine if any indicative questions were already answered by published work. Unanswered indicative questions entered a three-round modified Delphi process, whereby 29 experts in regional anaesthesia (representing all participating specialist societies) rated each indicative question for inclusion on a final high priority shortlist. If ≥75% of participants rated an indicative question as 'definitely' include in any round, it was accepted. Indicative questions rated as 'definitely' or 'probably' by <50% of participants in any round were excluded. Retained indicative questions were further ranked based on the rating score in the final Delphi round. The final research priorities were ratified by the Delphi expert group. RESULTS: There were 1318 responses from 516 people in the initial survey, from which 71 indicative questions were formed, of which 68 entered the modified Delphi process. Eleven 'highest priority' research questions were short listed, covering themes of pain management; training and assessment; clinical practice and efficacy; technology and equipment. CONCLUSIONS: We prioritised unanswered research questions in regional anaesthesia. These will inform a coordinated global research strategy for regional anaesthesia and direct investigators to address high-priority areas.


Asunto(s)
Anestesia de Conducción , Investigación Biomédica , Humanos , Técnica Delphi , Encuestas y Cuestionarios , Proyectos de Investigación
6.
Surg Endosc ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39269481

RESUMEN

BACKGROUND: Concurrent neoadjuvant chemo-radiation (nCRT) with total mesorectal excision (TME) alone sometimes fails to cure lateral lymph node metastasis (LLNM). Therefore, additional lateral lymph node dissection (LLND) can help in the treatment of these patients. This is what we refer to as extended total mesorectal excision (eTME). Such operations (TME alone or eTME) can be performed using conventional laparoscopic techniques and robotic-assisted techniques as well. Our meta-analysis aims to compare the results of robot-assisted (R-eTME) versus laparoscopic-assisted extended mesorectal excision (L-eTME) in terms of short- and long-term outcomes. METHODOLOGY: Databases searched using title and abstract included Medline (via PubMed), Web of Science, Scopus, and Embase, up to February 20, 2024. All studies that documented robotic versus laparoscopic procedures for extended total mesorectal excision (R-eTME versus L-eTME) and reported more than two relevant outcomes, were included in the study. RESULTS: Our meta-analysis demonstrates four significant outcomes (operative time, urinary complications, overall recurrence, and admission days) between the laparoscopic and robotic groups. The robotic approach shows advantages over the laparoscopic approach in these outcomes except for the operative time (minute), which was longer in the robotic group compared to the laparoscopic group. The laparoscopic group is associated with a higher overall recurrence than the robotic group with an Odds Ratio of 2(95% CI, 1-4, p = 0.05). CONCLUSION: This meta-analysis study showed that the R-eTME group had a lower recurrence rate compared to the L-eTME group. Additionally, hospital admission days increased significantly in the laparoscopic group. Other long-term outcomes did not differ significantly between the two groups. Short-term outcomes were similar, except for more urinary complications in the laparoscopic group. In conclusion, the study suggests that robotic surgery may offer advantages over laparoscopic surgery for eTME. Further research and analysis could provide further insight into the potential benefits of robotic surgery in this procedure, particularly when surgeon experience, center volume, and learning curve are taken into consideration.

7.
J Am Pharm Assoc (2003) ; 64(1): 9-26.e6, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37844733

RESUMEN

BACKGROUND: The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of diabetic ketoacidosis (DKA). As more drugs of this class are approved and their indications are expanded, this serious adverse effect has been increasingly reported. OBJECTIVE: This review evaluated observational studies to inform the prevalence of SGLT2-inhibitor-associated DKA compared with other antihyperglycemic agents. METHODS: A systematic review was conducted in PubMed and EMBASE until 19 July 2022 (PROSPERO: CRD42022385425). We included published retrospective cohort active comparator/new user (ACNU) and prevalent new user studies assessing SGLT2-inhibitor-associated DKA prevalence in adult patients with type 2 diabetes mellitus (T2DM) against active comparators. We excluded studies which lacked 1:1 propensity score matching. The JBI Checklist for Cohort Studies guided the risk-of-bias assessments. Meta-analysis was conducted based on the inverse variance method in R software. RESULTS: Sixteen studies with a sample of 2,956,100 nonunique patients met the inclusion criteria. Most studies were conducted in North America (n = 9) and adopted the ACNU design (n = 15). Meta-analysis of 14 studies identified 33% higher DKA risk associated with SGLT2 inhibitors (HR = 1.33, 95% CI: 1.14-1.55, P < 0.01). Meta-regression analysis identified the study location (P = 0.02), analysis principle (P < 0.001), exclusion of chronic comorbidities (P = 0.007), and canagliflozin (P = 0.04) as significant moderator variables. CONCLUSIONS: Despite limitations related to heterogeneity, generalizability, and misclassification, the results of this study show that SGLT2 inhibitors increase the prevalence of DKA among adult T2DM patients in the real world. The findings supplement evidence from randomized controlled trials (RCTs) and call for continued vigilance.


Asunto(s)
Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Adulto , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Cetoacidosis Diabética/inducido químicamente , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/complicaciones , Prevalencia , Transportador 2 de Sodio-Glucosa , Nimustina , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos
8.
BMC Nurs ; 23(1): 81, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38291420

RESUMEN

BACKGROUND: One of the global issues facing the nursing profession is work-related stress because it interferes with care quality and organisational competency. These kinds of stressful situations can cause damage to the mental ability of the affected individual resulting in low job productivity. In a Nigerian healthcare setting, patient safety is under-researched. AIM: This study aimed to assess the influence of work-related stress on patient safety culture among nurses in a tertiary hospital. MATERIALS AND METHODS: The study adopted a descriptive cross-sectional survey. The Population of the study was nurses who are currently serving as employees at Federal Medical Center Birnin-Kebbi. Proportional and systematic sampling methods were used in the selection of the sample of the study. The tools used for this study were adapted Hospital Survey on Patient Safety (HSOPS) and Nurses' Occupational Stressor Scale. Ethical approval was obtained from the research ethical committee of the hospital. RESULTS: The moderate stress experience was having the highest percentage (45.0%). The highest percentage of the nurses (69.9%) practised a moderate safety culture. There were weak or very weak significant negative correlations (P < 0.01) between patient safety culture practices and occupational stress across all the subscales of the nurses' occupational stressors scale except in the occupational hazards subscale in which there was extremely weak and non-significant negative correlation. Work-family conflict was a significant predictor of patient safety culture, t (208) = -2.341, P < 0.05. Difficulty in taking leave was a significant predictor of patient safety culture, t (208) = -2.190, P < 0.05. CONCLUSION: There was a significant negative correlation between stress and safety practice which implies that as stress increased safety practice decreased. These study findings can be used to develop ongoing strategies and targeted interventions in addressing work-related stress.

9.
Can Assoc Radiol J ; 75(1): 54-68, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37411043

RESUMEN

Colon cancer is the third most common malignancy in Canada. Computed tomography colonography (CTC) provides a creditable and validated option for colon screening and assessment of known pathology in patients for whom conventional colonoscopy is contraindicated or where patients self-select to use imaging as their primary modality for initial colonic assessment. This updated guideline aims to provide a toolkit for both experienced imagers (and technologists) and for those considering launching this examination in their practice. There is guidance for reporting, optimal exam preparation, tips for problem solving to attain high quality examinations in challenging scenarios as well as suggestions for ongoing maintenance of competence. We also provide insight into the role of artificial intelligence and the utility of CTC in tumour staging of colorectal cancer. The appendices provide more detailed guidance into bowel preparation and reporting templates as well as useful information on polyp stratification and management strategies. Reading this guideline should equip the reader with the knowledge base to perform colonography but also provide an unbiased overview of its role in colon screening compared with other screening options.


Asunto(s)
Pólipos del Colon , Colonografía Tomográfica Computarizada , Neoplasias Colorrectales , Humanos , Pólipos del Colon/diagnóstico por imagen , Inteligencia Artificial , Canadá , Colonografía Tomográfica Computarizada/métodos , Colonoscopía , Radiólogos , Tomografía , Neoplasias Colorrectales/diagnóstico por imagen
10.
Can Assoc Radiol J ; 75(4): 743-750, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38813997

RESUMEN

Imaging of pregnant patients who sustained trauma often causes fear and confusion among patients, their families, and health care professionals regarding the potential for detrimental effects from radiation exposure to the fetus. Unnecessary delays or potentially harmful avoidance of the justified imaging studies may result from this understandable anxiety. This guideline was developed by the Canadian Emergency, Trauma and Acute Care Radiology Society (CETARS) and the Canadian Association of Radiologists (CAR) Working Group on Imaging the Pregnant Trauma Patient, informed by a literature review as well as multidisciplinary expert panel opinions and discussions. The working group included academic subspecialty radiologists, a trauma team leader, an emergency physician, and an obstetriciangynaecologist/maternal fetal medicine specialist, who were brought together to provide updated, evidence-based recommendations for the imaging of pregnant trauma patients, including patient safety aspects (eg, radiation and contrast concerns) and counselling, initial imaging in maternal trauma, specific considerations for the use of fluoroscopy, angiography, and magnetic resonance imaging. The guideline strives to achieve clarity and prevent added anxiety in an already stressful situation of injury to a pregnant patient, who should not be imaged differently.


Asunto(s)
Complicaciones del Embarazo , Heridas y Lesiones , Humanos , Embarazo , Femenino , Complicaciones del Embarazo/diagnóstico por imagen , Canadá , Heridas y Lesiones/diagnóstico por imagen , Diagnóstico por Imagen/métodos , Sociedades Médicas
11.
J Ethn Subst Abuse ; : 1-10, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39146033

RESUMEN

BACKGROUND: Hookah or waterpipe smoking use is a developing trend in the many populations, especially among the young age group. Hookah users are exposed to many of the same toxic compounds or by-products as cigarette users with a higher level of harmful effects. AIM OF THE STUDY: To assess frequency, knowledge, attitude health behavior toward the risks and complication of cigarettes smoking and hookah in particular of Al-Kindy medical students. MATERIALS AND METHODS: A cross-sectional study was conducted from December 2022 to April 2023 to assess frequency of Hookah smoking among 507 medical students at Al-Kindy Medical College. An online questionnaire by Google forms was used to collect the data. RESULTS: The total participants students were 507 who studied at Al-kindy College of Medicine in different stages. Males were constituted 63.1% and the rest were females (36.9%). Regarding smoking habit, 31.95% (162) of them were smoker and the rest 68.05% (345) were not smoker(p = 0.000). Most of them had mixed type of smoking (cigar, hookah, and vape) (14.19%). (0.000) that it had an effect on general health (46.1%), lung (68.8%), larynx (67.1%), heart, blood pressure, diabetes but not bladder, stomach, COVID-19 transmission. There is a significant increase (63.5%) (p = 0.000) regarding their attitude that hookah had a significant amount of tobacco, no benefit of fruity flavors (62.3%), and no relaxation effect (90.53%). CONCLUSIONS: There is a significant decrease in smoking habits among medical students due to their knowledge of its negative effects on health.

12.
Pol Merkur Lekarski ; 52(2): 178-188, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38642353

RESUMEN

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Isatin derivatives as cap group joined by mono amide linker as required to act as HDAC inhibitors. PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group joined by N-alkylation reaction with ethyl-bromo hexanoate as linker group that joined by amide reaction with Isatin derivatives as cap groups which known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. the compounds were synthesized and characterized by successfully by ART-FTIR, NMR and ESI- Ms. Assessed for their cytotoxic activity against human colon adenocarcinoma MCF-7 (IC50, I=105.15, II=60.00, III=54.11, IV=56.57, vorinostat=28.41) and hepatoblastoma HepG2 (IC50, I=63.91, II=135.18, III=118.85, IV=51.46, vorinostat=37.50). Most of them exhibited potent HDAC inhibitory activity and significant cytotoxicity. CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed cytotoxicity toward MCF-7 and HepG2 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.


Asunto(s)
Adenocarcinoma , Antineoplásicos , Neoplasias del Colon , Isatina , Humanos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/química , Vorinostat/farmacología , Isatina/farmacología , Línea Celular Tumoral , Amidas/farmacología , Diseño de Fármacos , Antineoplásicos/farmacología , Sulfonamidas/farmacología , Zinc/metabolismo , Zinc/farmacología , Proliferación Celular , Estructura Molecular
13.
Wiad Lek ; 77(3): 514-525, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38691794

RESUMEN

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Coumarin as cap groups. PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group and Coumarin as cap groups known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. The synthesized compound assessed for their cytotoxic activity against hepatoblastoma HepG2 (IC50, I=0.094, II=0.040, III=0.032, IV=0.046, SAHA=0.141) and human colon adenocarcinoma MCF-7 (IC50, I=0.135, II=0.050, III= 0.065, IV=0.059, SAHA=0.107). The binding mode to the active site of [HDAC6] were determined by docking study which give results that they might be good inhibitors for [HDAC6]. CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed a comparable cytotoxic result with FDA approved drug (SAHA) toward HepG2 and MCF-7 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.


Asunto(s)
Antineoplásicos , Cumarinas , Inhibidores de Histona Desacetilasas , Simulación del Acoplamiento Molecular , Sulfonamidas , Humanos , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/química , Sulfonamidas/química , Sulfonamidas/farmacología , Sulfonamidas/síntesis química , Cumarinas/química , Cumarinas/farmacología , Cumarinas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Células Hep G2 , Células MCF-7
14.
Ann Hematol ; 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37736806

RESUMEN

Gene therapy represents a significant potential to revolutionize the field of hematology with applications in correcting genetic mutations, generating cell lines and animal models, and improving the feasibility and efficacy of cancer immunotherapy. Compared to different genetic engineering tools, clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 9 (Cas9) emerged as an effective and versatile genetic editor with the ability to precisely modify the genome. The applications of genetic engineering in various hematological disorders have shown encouraging results. Monogenic hematological disorders can conceivably be corrected with single gene modification. Through the use of CRISPR-CAS9, restoration of functional red blood cells and hemostasis factors were successfully attained in sickle cell anemia, beta-thalassemia, and hemophilia disorders. Our understanding of hemato-oncology has been advanced via CRIPSR-CAS9 technology. CRISPR-CAS9 aided to build a platform of mutated genes responsible for cell survival and proliferation in leukemia. Therapeutic application of CRISPR-CAS9 when combined with chimeric antigen receptor (CAR) T cell therapy in multiple myeloma and acute lymphoblastic leukemia was feasible with attenuation of CAR T cell therapy pitfalls. Our review outlines the latest literature on the utilization of CRISPR-Cas9 in the treatment of beta-hemoglobinopathies and hemophilia disorders. We present the strategies that were employed and the findings of preclinical and clinical trials. Also, the review will discuss gene engineering in the field of hemato-oncology as a proper tool to facilitate and overcome the drawbacks of chimeric antigen receptor T cell therapy (CAR-T).

15.
Bioorg Chem ; 132: 106358, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36642021

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high recurrence and mortality rate. In this study, a series of ß-cyclocitral-derived mono-carbonyl curcumin analogs were synthesized and their anticancer properties were evaluated. Among the series, A19 exhibited the strongest cytotoxic activity by inhibiting cell viability and colony formation, inducing cell cycle G2/M phase arrest and cell apoptosis of HCC HepG2 and Huh-7 cells, while having almost no cytotoxicity on normal liver MIHA cells. Mechanistically, our results demonstrated that A19 triggered intense DNA damage via suppression of the ERK/JNK/p38 MAPK signaling pathway. Additionally, a combination of A19 with sorafenib significantly induced synergistic cytotoxicity in HCC cells. Overall, our results indicate the potential of A19 as a novel chemotherapeutic drug administered either separately or in combined therapy for HCC treatment.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Curcumina/farmacología , Curcumina/uso terapéutico , Células Hep G2 , Transducción de Señal , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Proliferación Celular , Línea Celular Tumoral
16.
BMC Geriatr ; 23(1): 166, 2023 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-36959598

RESUMEN

BACKGROUND: Older inpatients, particularly those with frailty, have increased exposure to complex medication regimens. It is not known whether frailty and complexity of medication regimens influence attitudes toward deprescribing. This study aimed to investigate (1) older inpatients' attitudes toward deprescribing; (2) if frailty and complexity of medication regimen influence attitudes and willingness to deprescribe - a relationship that has not been investigated in previous studies. METHODS: In this cross-sectional study, older adults (≥ 65 years) recruited from general medicine and geriatric services in a New Zealand hospital completed the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. Hospital frailty risk score (HFRS) was calculated using diagnostic codes and other relevant information present at the time of index hospital admission; higher scores indicate higher frailty risk. Medication regimen complexity was quantified using the medication regimen complexity index (MRCI); higher scores indicate greater complexity. Logistic regression analysis was used to identify predictors of attitudes and willingness to deprescribe. RESULTS: A total of 222 patients were included in the study, the median age was 83 years and 63% were female. One in two patients reported feeling they were taking too many medications, and 1 in 5 considered their medications burdensome. Almost 3 in 4 (73%) wanted to be involved in decision-making about their medications, and 4 in 5 (84%) were willing to stop one or more of their medications if their prescriber said it was possible. Patients with higher MRCI had increased self-reported medication burden (adjusted odds ratio (AOR) 2.6, 95% CI 1.29, 5.29) and were more interested in being involved in decision-making about their medications (AOR 1.8, CI 0.99, 3.42) than those with lower MRCI. Patients with moderate HFRS had lower odds of willingness to deprescribe (AOR 0.45, CI 0.22,0.92) compared to the low-risk group. Female patients had a lower desire to be involved in decision-making. The oldest old age group( > 80 years) had lower self-reported medication burden and were less likely to want to try stopping their medications. CONCLUSION: Most older inpatients wanted to be involved in decision-making about their medications and were willing to stop one or more medications if proposed by their prescriber. Medication complexity and frailty status influence patients' attitudes toward deprescribing and thus should be taken into consideration when making deprescribing decisions. Further research is needed to investigate the relationship between frailty and the complexity of medication regimens.


Asunto(s)
Deprescripciones , Fragilidad , Anciano de 80 o más Años , Humanos , Femenino , Anciano , Masculino , Pacientes Internos , Estudios Transversales , Fragilidad/diagnóstico , Fragilidad/tratamiento farmacológico , Fragilidad/epidemiología , Nueva Zelanda/epidemiología , Polifarmacia , Actitud , Encuestas y Cuestionarios
17.
BMC Health Serv Res ; 23(1): 1194, 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37919707

RESUMEN

OBJECTIVES: To assess the relative productivity of primary medical services in England and the impact of the COVID-19 pandemic on productivity levels. SETTING: Primary medical services for 59 million patients (98% of the population in England), in 101 clinical commissioning groups (CCGs), across two time periods: period 1, pre-pandemic, April to December 2019 and period 2, pandemic, April to December 2020. METHODS: We use data envelopment analysis (DEA) to assess relative productivity with four input measures (the number of full-time equivalent general practitioners, nurses, other direct patient contact staff and administrators), and five output measures (face-to-face appointments, remote consultations, home visits, referrals to secondary care and prescriptions). Our units of analysis were CCGs. DEA assigns an efficiency score to a CCG, taking a value between 0 and 100%, by benchmarking it against the most productive CCGs. We use Tobit regression to examine the association between productivity and other factors. RESULTS: The mean bias-corrected efficiency score of primary medical services in CCGs was 92.9% (interquartile range 92.0% to 95.7%) in period 1, falling to 90.6% (interquartile range 86.8% to 95.2%) in period 2. In period 1, CCGs with a higher proportion of registered patients aged over 65 years, higher levels of deprivation, lower levels of disease prevalence, higher nurse to GP ratios and higher GP to other direct patient contact staff ratios, achieved statistically significantly higher general practice efficiency scores (p < 0.05). In period 2, only the ratio of GP to other direct patient contact staff was associated with efficiency scores (p > 0.05). CONCLUSIONS: Our analysis indicates only modest geographic variation in productivity of primary medical services when measured at the level of clinical commissioning groups and a small reduction in productivity during the pandemic. Further work to establish relative productivity of individual GP practices is warranted once sufficient data on appointment rates by GP practice is available.


Asunto(s)
COVID-19 , Consulta Remota , Humanos , Anciano , Pandemias , Atención Primaria de Salud , Medicina Estatal , COVID-19/epidemiología , Inglaterra/epidemiología
18.
World J Surg Oncol ; 21(1): 266, 2023 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-37626332

RESUMEN

BACKGROUND: The number of patients with non-palpable breast lesions has increased gradually. This is because of the technological development in imaging techniques and the screening programs that lead to early detection of breast lesions. The number of patients with non-palpable breast lesions has increased gradually. This is because of the technological development in imaging techniques and the screening programs that lead to early detection of breast lesions. The aim of marking the non-palpable breast lesions is to achieve accurate lesion localization, to obtain the better cosmetic result with less tissue loss and to provide negative surgical margin. AIM OF THE STUDY: In the current study, we aimed to compare the wire-guided localization (WGL) technique with the radio-guided occult lesion localization (ROLL) technique to assess their accuracy and efficacy in non-palpable breast lesions localization. METHODS: This is a retrospective study conducted at Baheya center for Early Detection and Treatment of Breast Cancer from January 2018 and June2022,where 670 patients with non-palpable breast lesions underwent an excision were enrolled randomly in ROLL group (n = 320) and WGL (n = 350). RESULTS: Both the localization time and the time of operation were significantly decreased with the ROLL in comparison to WGL(P < 0.001). Complete lesion excision with clear margins were reported in 119/135(88.2%) of ROLL group and in 130/159 (81.8%) of WGL group and the difference was significant (P < 0.001). Reoperations (re-lumpectomy or mastectomy) were done as a second procedure on 16(11.8%) of the ROLL patients compared with 29(18.2%) in the WGL patients(P < 0.001). CONCLUSION: This study shows that ROLL is as effective as WGL for non-palpable breast lesions excision. Also, ROLL improve the outcomes by decreasing the duration of surgery, localization time, achieving a higher percentage of clear margin in spite of lower specimen size and scar length.


Asunto(s)
Neoplasias de la Mama , Mastectomía , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Estudios Retrospectivos , Mama/diagnóstico por imagen , Mama/cirugía , Reoperación
19.
Surgeon ; 21(4): 230-234, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35953433

RESUMEN

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) is the most common management of gallstones combined with common bile duct (CBD) stones. This study aims to evaluate the impact of routine insertion of nasobiliary catheter during ERCP in cases of difficult LC. PATIENTS & METHODS: From total 110 patients who underwent ERCP followed by LC in the period from April 2019 to April 2020, nasobiliary (NB) catheter was inserted during ERCP in 55 patients after CBD clearance (NB group). In the other 55 patients, only CBD clearance was done (Control group). In the NB group, dynamic trans-nasobiliary intraoperative cholangiography (TN-IOC) was done during dissection of Calot's triangle. At the end of the procedure, trans-nasobiliay methylene blue (MB) test was done to detect any missed biliary injury. The primary outcome to be analyzed was the incidence and severity of bile duct injury (BDI), secondary outcomes were the operative time, conversion to open surgery, and hospital stay. RESULTS: Of the 110 patients, 57 patients (51.8%) were males and 53 (48.2%) were females. Median age was 55 years. One case of biliary leak was reported in the NB group (1.8%), while 2 cases (3.6%) were reported in the Control group. The average operative time in the NB group was 115 min versus 128 min in the Control group (P value < 0.001). No cases were converted to open cholecystectomy in the NB group (0%) with 5 cases (9.1%) converted to open in the Control group. The average postoperative hospital stay was 2 ± 0.1 days in the NB group versus 3.6 ± 5.3 days in the Control group (P value = 0.037). CONCLUSION: Routine insertion of nasobiliary tube during ERCP, in patients with combined gallbladder and CBD stones, is a simple, safe and dynamic method for IOC. This maneuver does not statistically decrease the incidence of BDI but can diagnose, minimize and treat BDI with shorter operative time and hospital stay.


Asunto(s)
Colecistectomía Laparoscópica , Cálculos Biliares , Masculino , Femenino , Humanos , Persona de Mediana Edad , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomía Laparoscópica/efectos adversos , Resultado del Tratamiento , Cálculos Biliares/cirugía , Colangiografía/métodos
20.
Nano Lett ; 22(1): 164-171, 2022 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-34936370

RESUMEN

Open-shell graphene nanoribbons have become promising candidates for future applications, including quantum technologies. Here, we characterize magnetic states hosted by chiral graphene nanoribbons (chGNRs). The substitution of a hydrogen atom at the chGNR edge by a ketone effectively adds one pz electron to the π-electron network, producing an unpaired π-radical. A similar scenario occurs for regular ketone-functionalized chGNRs in which one ketone is missing. Two such radical states can interact via exchange coupling, and we study those interactions as a function of their relative position, which includes a remarkable dependence on the chirality, as well as on the nature of the surrounding ribbon, that is, with or without ketone functionalization. Besides, we determine the parameters whereby this type of system with oxygen heteroatoms can be adequately described within the widely used mean-field Hubbard model. Altogether, we provide insight to both theoretically model and devise GNR-based nanostructures with tunable magnetic properties.

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