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1.
Blood Cells Mol Dis ; 109: 102885, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39182343

RESUMEN

OBJECTIVE: To document the results of outpatient hematopoietic stem cell transplantation (HSCT) from the peripheral blood (PB) of sibling donors without anti-thymocyte globulin (ATG) in the conditioning regimen. MATERIAL AND METHODS: Patients from a low-income population with severe AA who received a PB, unmanipulated sibling HLA-identical HSCT between 2000 and 2020 at a single institution were studied. Survival was the primary outcome. RESULTS: Forty-one transplants were performed. Time between diagnosis and transplant was five months (1-104). Median age was 37 (range, 4-61) years; 25 (61 %) recipients were males and 32 (78 %) had treatment failure, 9 (22 %) have not received treatment. ATG was administered in 5 (12.2 %) cases; the graft source was PB in 38 (92.7 %) transplants. Twenty-six (63.4 %) transplants were carried out in the outpatient setting. Infections developed in 14 (34.1 %) patients. Primary graft failure (GF) occurred in 3 (7.3 %) patients. The 15-year OS was 81 %, EFS was 77.4 %. Patients with high pre-HSCT transfusion burden had lower OS (p = 0.035) and EFS (p = 0.026). Previous treatment failure and age were not associated with lower OS (p = 0.115, p = 0.069) or EFS (p = 0.088, p = 0.5, respectively). CONCLUSIONS: HLA-identical T-cell replete outpatient HSCT from the PB of sibling donors for AA patients using ATG-free conditioning offers excellent long-term survival.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39166415

RESUMEN

BACKGROUND AND AIM: Recommendations on pregnancy, lactation, and contraception in women with Wilson disease are briefly stated in international guidelines but are not entirely homogeneous. Data regarding the management of these special events among patients with Wilson disease in Spain are lacking. We used the Wilson Registry platform of the Spanish Association for the Study of the Liver to question patients on their reproductive and gestational lives. METHODS: This was a multicentre ambispective study including adult women with Wilson disease in the Spanish Wilson Registry interviewed about their contraception, childbearing, pregnancy, and lactation experiences. Clinical and analytical data were extracted from the registry. RESULTS: The study included 92 women from 17 centres in Spain. Most (63%) reported having a previous pregnancy history. The rate of spontaneous miscarriages was 21.6%, mainly occurring in the first trimester and up to one third among undiagnosed patients. Most pregnant women received chelator therapy during pregnancy, but dose reduction was recommended in less than 10%. After delivery, artificial lactation predominated (60.3%) and its use was mainly based on physician's recommendations (68%). Up to 40% of the women included reported some concerns about their reproductive lives, mainly related to the potential drug toxicity to their children. Most of the patients considered the information given by specialists to be sufficient. CONCLUSION: Gestational management among women with Wilson disease in Spain was found to be highly heterogeneous and frequently different from what is described in international guidelines. Education on rare liver diseases should be a priority for scientific societies in order to homogenize patient follow-up and recommendations.

3.
Genome Med ; 16(1): 107, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187844

RESUMEN

BACKGROUND: Poly (ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors (PARPi) are targeted therapies approved for homologous recombination repair (HRR)-deficient breast, ovarian, pancreatic, and prostate cancers. Since inhibition of PARP1 is sufficient to cause synthetic lethality in tumors with homologous recombination deficiency (HRD), PARP1 selective inhibitors such as saruparib (AZD5305) are being developed. It is expected that selective PARP1 inhibition leads to a safer profile that facilitates its combination with other DNA damage repair inhibitors. Here, we aimed to characterize the antitumor activity of AZD5305 in patient-derived preclinical models compared to the first-generation PARP1/2 inhibitor olaparib and to identify mechanisms of resistance. METHODS: Thirteen previously characterized patient-derived tumor xenograft (PDX) models from breast, ovarian, and pancreatic cancer patients harboring germline pathogenic alterations in BRCA1, BRCA2, or PALB2 were used to evaluate the efficacy of AZD5305 alone or in combination with carboplatin or an ataxia telangiectasia and Rad3 related (ATR) inhibitor (ceralasertib) and compared it to the first-generation PARPi olaparib. We performed DNA and RNA sequencing as well as protein-based assays to identify mechanisms of acquired resistance to either PARPi. RESULTS: AZD5305 showed superior antitumor activity than the first-generation PARPi in terms of preclinical complete response rate (75% vs. 37%). The median preclinical progression-free survival was significantly longer in the AZD5305-treated group compared to the olaparib-treated group (> 386 days vs. 90 days). Mechanistically, AZD5305 induced more replication stress and genomic instability than the PARP1/2 inhibitor olaparib in PARPi-sensitive tumors. All tumors at progression with either PARPi (39/39) showed increase of HRR functionality by RAD51 foci formation. The most prevalent resistance mechanisms identified were the acquisition of reversion mutations in BRCA1/BRCA2 and the accumulation of hypomorphic BRCA1. AZD5305 did not sensitize PDXs with acquired resistance to olaparib but elicited profound and durable responses when combined with carboplatin or ceralasertib in 3/6 and 5/5 models, respectively. CONCLUSIONS: Collectively, these results show that the novel PARP1 selective inhibitor AZD5305 yields a potent antitumor response in PDX models with HRD and delays PARPi resistance alone or in combination with carboplatin or ceralasertib, which supports its use in the clinic as a new therapeutic option.


Asunto(s)
Proteína BRCA1 , Proteína BRCA2 , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Ratones , Proteína BRCA1/genética , Proteína BRCA2/genética , Femenino , Ftalazinas/farmacología , Ftalazinas/uso terapéutico , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Piperazinas/farmacología , Piperazinas/uso terapéutico , Indoles/uso terapéutico , Indoles/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Carboplatino/farmacología , Carboplatino/uso terapéutico , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética
4.
World J Transplant ; 14(2): 91052, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38947965

RESUMEN

BACKGROUND: The impact of social determinants of health in allogeneic transplant recipients in low- and middle-income countries is poorly described. This observational study analyzes the impact of place of residence, referring institution, and transplant cost coverage (out-of-pocket vs government-funded vs private insurance) on outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) in two of Mexico's largest public and private institutions. AIM: To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in Mexico. METHODS: In this retrospective cohort study, we included adolescents and adults ≥ 16 years who received a matched sibling or haploidentical transplant from 2015-2022. Participants were selected without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in Mexico. Three payment groups were compared: Out-of-pocket (OOP), private insurance, and a federal Universal healthcare program "Seguro Popular". Outcomes were compared between referred and institution-diagnosed patients, and between residents of Nuevo Leon and out-of-state. Primary outcomes included overall survival (OS), categorized by residence, referral, and payment source. Secondary outcomes encompassed early mortality, event-free-survival, graft-versus-host-relapse-free survival, and non-relapse-mortality (NRM). Statistical analyses employed appropriate tests, Kaplan-Meier method, and Cox proportional hazard regression modeling. Statistical software included SPSS and R with tidycmprsk library. RESULTS: Our primary outcome was overall survival. We included 287 patients, n = 164 who lived out of state (57.1%), and n = 129 referred from another institution (44.9%). The most frequent payment source was OOP (n = 139, 48.4%), followed by private insurance (n = 75, 26.1%) and universal coverage (n = 73, 25.4%). No differences in OS, event-free-survival, NRM, or graft-versus-host-relapse-free survival were observed for patients diagnosed locally vs in another institution, nor patients who lived in-state vs out-of-state. Patients who covered transplant costs through private insurance had the best outcomes with improved OS (median not reached) and 2-year cumulative incidence of NRM of 14% than patients who covered costs OOP (Median OS and 2-year NRM of 32%) or through a universal healthcare program active during the study period (OS and 2-year NRM of 19%) (P = 0.024 and P = 0.002, respectively). In a multivariate analysis, payment source and disease risk index were the only factors associated with overall survival. CONCLUSION: In this Latin-American multicenter study, the site of residence or referral for alloHSCT did not impact outcomes. However, access to healthcare coverage for alloHSCT was associated with improved OS and reduced NRM.

5.
J Drugs Dermatol ; 23(7): 519-524, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38954624

RESUMEN

Despite growing diversity in the United States population, studies show that medical education lacks representation of conditions in darker skin tones. Given that medical conditions present differently in different skin tones, limited exposure to images of darker tones in medical training may contribute to incorrect or delayed diagnoses, perpetuating health inequities. This study examines the preclinical curriculum at the Georgetown University School of Medicine (GUSOM) to report on its image representation with respect to skin tone and to assess the impact of a student-driven initiative in achieving visual learning equity (VLE). Of 1050 preclinical images, 58.2% depicted conditions in light/white skin tones, 31.3% in medium/brown, and 10.5% in dark/black. The microbiology and pathology courses had the highest percentages of dark/black and medium/brown images. Infectious disease images made up 36.3% of all images with 54.6% light/white, 31.5% medium/brown, and 13.9% dark/black. Overall, the first images representing conditions were 63.5% light/white, 30.0% medium/brown, and 6.6% dark/black. When dark/black images were presented first, 64.3% were of infectious diseases, compared to 35.1% for medium/brown and only 28.4% for white/light first images that were infectious diseases. A significant increase in images of conditions in darker skin tones was observed in the IRD course 2022 compared to the IRD course 2020 (P<.001). Our study highlights an underrepresentation of darker skin tones compared to lighter skin tones in the GUSOM preclinical curriculum. A student-led initiative significantly increased the representation of darker skin tones in dermatologic images, demonstrating the potential impact of such efforts in achieving VLE in medical education.J Drugs Dermatol. 2024;23(7):519-524.  doi:10.36849/JDD.7992.


Asunto(s)
Curriculum , Dermatología , Enfermedades de la Piel , Humanos , Estudios Transversales , Dermatología/educación , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/terapia , Pigmentación de la Piel , Educación de Pregrado en Medicina/métodos , Estados Unidos , Estudiantes de Medicina/estadística & datos numéricos
6.
Cell Cycle ; : 1-12, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984667

RESUMEN

Colorectal cancer (CRC) is the third most common cancer worldwide. In the United States alone, CRC was responsible for approximately 52,550 deaths in 2023, with an estimated 153,020 new cases. CRC presents with synchronous peritoneal spread in 5-10% of patients, and up to 20-50% of patients with recurrent disease will develop metachronous colorectal cancer peritoneal metastatic (CRC-PM) disease. Eradication of the tumor, tumor margins and microscopic residual disease is paramount, as microscopic residual disease is associated with local recurrences, with 5-year survival rates of less than 35%. The success of resection and reduction of residual disease depends on the accuracy with which cancer cells and normal tissue can be intra-operatively distinguished. Fluorescence Molecular Imaging (IFMI) and tumor-targeted contrast agents represent a promising approach for intraoperative detection and surgical intervention. Proper target selection, the development of scalable imaging agents and enhanced real-time tumor and tumor microenvironment imaging are critical to enabling enhanced surgical resection. LGR5 (leucine-rich repeat-containing G-protein-coupled receptor 5), a colonic crypt stem cell marker and the receptor for the R-spondins (RSPO) in the Wnt signaling pathway, is also expressed on colorectal cancer stem cells (CSC) and on CRC tumors and metastases, suggesting it could be a useful target for imaging of CRC. However, there are numerous diverging reports on the role of LGR5 in CRC therapy and outcomes. Herein, we report on the synthesis and validation of a 37 amino acid RSPO1-mimetic peptide, termed RC18, that was specifically designed to access the R-spondin binding site of LGR5 to potentially be used for interoperative imaging of CRC-PM. The receptor-binding capabilities of the RC18 indicate that direct interactions with LGR5 neither significantly increased LGR5 signaling nor blocked RSPO1 binding and signal transduction, suggesting that the RSPO1-mimetic is functionally inert, making it an attractive contrast agent for intraoperative CRC-PM imaging.

7.
BMC Pregnancy Childbirth ; 24(1): 500, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054429

RESUMEN

OBJECTIVE: To assess the prevalence of anxiety and depression and their associated risk factors throughout the pregnancy and postpartum process using a new screening for the early detection of mental health problems. DESIGN: A prospective cross-sectional descriptive multicentred study. Participants were consecutively enrolled at ≥ 12 weeks' gestation and followed at three different time points: at 12-14 weeks of pregnancy, at 29-30 weeks of pregnancy, and 4-6 weeks postpartum. All women completed a mental screening at week 12-14 of pregnancy consisting of two questions from the Generalised Anxiety Disorder Scale (GAD-2) and the two Whooley questions. If this screening was positive, the woman completed the Edinburgh Postnatal Depression Scale (EPDS). SETTING: Seven primary care centres coordinated by a Gynaecology and Obstetrics Department in the city of Terrassa (Barcelona) in northern Spain. PARTICIPANTS: Pregnant women (N = 335, age 18-45 years), in their first trimester of pregnancy, and receiving prenatal care in the public health system between July 2018 and July 2020. FINDINGS: The most relevant factors associated with positive screening for antenatal depression or anxiety during pregnancy, that appear after the first trimester of pregnancy, are systematically repeated throughout the pregnancy, and are maintained in the postpartum period were: a history of previous depression, previous anxiety, abuse, and marital problems. In weeks 12-14 early risk factors for positive depression and anxiety screening and positive EPDS were: age, smoking, educational level, employment status, previous psychological/psychiatric history and treatment, suicide in the family environment, voluntary termination of pregnancy and current planned pregnancy, living with a partner and partner's income. In weeks 29-30 risk factors were: being a skilled worker, a history of previous depression or anxiety, and marital problems. In weeks 4-6 postpartum, risk factors were: age, a history of previous depression or anxiety or psychological/psychiatric treatment, type of treatment, having been mistreated, and marital problems. CONCLUSIONS: Early screening for anxiety and depression in pregnancy may enable the creation of more effective healthcare pathways, by acting long before mental health problems in pregnant women worsen or by preventing their onset. Assessment of anxiety and depression symptoms before and after childbirth and emotional support needs to be incorporated into routine practice.


Asunto(s)
Ansiedad , Depresión , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Adulto , Estudios Transversales , Estudios Prospectivos , Factores de Riesgo , Prevalencia , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , Ansiedad/epidemiología , Depresión/epidemiología , Depresión/diagnóstico , Depresión/psicología , Adulto Joven , Periodo Posparto/psicología , España/epidemiología , Adolescente , Depresión Posparto/epidemiología , Depresión Posparto/diagnóstico , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Atención Prenatal
8.
Animals (Basel) ; 14(12)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38929349

RESUMEN

Organic livestock farming is committed to high environmental and animal welfare standards, although pathologies such as post-weaning diarrhoea (PWD) may appear. The main objective of this study was to assess nutritional strategies to prevent PWD in organic piglets. A total of 134 weaned piglets were fed one of three diets: high crude protein (17.8%, HCP), low crude protein (16.8%, LCP), and low crude protein supplemented with liquid whey (LCP+W). Piglets were assessed weekly for four weeks on the following parameters: diarrhoea incidence, additional health parameters, average daily gain, and behaviour. Faecal samples were taken to analyse the intestinal microbiota composition. Data were analysed using LMM and GLMM models and Shannon and Whittaker indexes. No significant effect of diet on diarrhoea incidence was found, but the LCP+W diet increased average daily gain. Pigs fed the LCP+W diet presented a lower percentage of drinking and negative social behaviour compared with the HCP diet, and LCP pigs presented higher exploration compared with HCP. In addition, LCP+W piglets showed a higher abundance of the beneficial genus Frisingicoccus. Although liquid whey did not reduce diarrhoea incidence, the benefits found in growth, microbiota composition, and reduced negative social behaviour indicate that it could be an optimal supplement to organic diets.

9.
Pediatr Infect Dis J ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38920379

RESUMEN

BACKGROUND: Since the end of 2023, an elevated incidence and severity of Mycoplasma pneumoniae infections among children in Asia has been noted. Subsequently, this trend was observed in several European countries although limited data are currently available. We conducted a national study to delineate the ongoing M. pneumoniae outbreak in our country. METHODS: A multicenter retrospective observational study was conducted across 32 hospitals in Spain, encompassing patients under 18 years old hospitalized for M. pneumoniae infection from January 2023 to March 2024. Infection was confirmed by positive polymerase chain reaction and/or by 2 serological tests. RESULTS: A total of 623 children were included, with 79% of cases diagnosed in the final 3 months of the study period. Pneumonia was the most common diagnosis (87%). Respiratory symptoms were present in 97% of cases, with 62% requiring oxygen supplementation and 14% requiring admission to the pediatric intensive care unit (PICU). Risk factors for PICU admission included the presence of neurological symptoms, hypoxemia and a history of prematurity. Children admitted to the PICU exhibited significantly higher neutrophil counts upon admission. CONCLUSIONS: We have observed a notable increase in hospital admissions, including PICU support by up to 14%, due to M. pneumoniae infection in our country since November 2023, indicative of a more severe clinical course associated with this pathogen.

11.
Cureus ; 16(4): e59080, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38800203

RESUMEN

Castleman´s disease (CD) is a rare lymphoproliferative disorder. Concurrent autoimmune disease and CD are uncommon, but even more so, comorbid CD and autoimmune hemolytic anemia (AIHA). To the best of our knowledge, this case represents the first successful AIHA and multicentric CD (MCD) treatment using rituximab as first-line treatment. We present the case of a 53-year-old woman with a 10-year history of plasma cell variant CD who arrived at the emergency department with signs and symptoms of anemia. On admission, we made a preliminary diagnosis of hemolytic anemia and initiated immunosuppressive therapy with rituximab and steroids. After seven days, the patient recovered according to clinical and laboratory parameters, and we discharged her early. We portray a rare occurrence of CD and AIHA successfully treated with rituximab and steroid therapy, which makes our case unique.

12.
Cytotherapy ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38775773

RESUMEN

BACKGROUND: Hematopoietic cell transplantation (HCT) is a promising treatment for hematological diseases, yet access barriers like cost and limited transplant centers persist. Telemedicine-based patient navigation (PN) has emerged as a solution. This study presents a cost-free PN telemedicine clinic (TC) in collaboration with the National Marrow Donor Program. AIM: to assess its feasibility and impac on HCT access determined by the cumulative incidence of transplantation. METHODS: In this single-center cohort study, patients of all ages and diagnoses referred for HCT participated. Two transplant physician-navigators established patient relationships via video calls, collecting medical history, offering HCT education and recommending pretransplant tests. The analysis involved descriptive statistics and intent-to-transplant survival assessment. RESULTS: One hundred and three patients were included of whom n = 78 were referred for allogeneic HCT (alloHCT), with a median age of 28 years. The median time from initial contact to the first consult was 5 days. The cumulative incidence of transplantation was 50% at 6 months and 61% at 12 months, with varying outcomes based on HCT type. Notably, 49 patients were not transplanted, primarily due to refractory disease, progression or relapse (57.1%). Autologous HCT candidates and physician referrals were correlated with higher transplant success compared to alloHCT candidates and patients who were not referred by a physician. CONCLUSION: Our pretransplant TC was feasible, facilitating access to HCT. Disease relapse posed a significant barrier. Enhancing timely physician referrals should be a focus for future efforts.

13.
Protein Expr Purif ; 220: 106490, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38697589

RESUMEN

The production of fermentable sugars from lignocellulosic biomass is achieved by the synergistic action of a group of enzymes called cellulases. Cellulose is a long chain of chemically linked glucoses by ß-1,4 bonds. The enzyme ß-1,4-endoglucanase is the first cellulase involved in the degradation, breaking the bond of the amorphous regions. A ß-1,4-endoglucanase enzyme with high activity was obtained from a Bacillus subtilis strain isolated from wastewater of a pulp and paper mill. Sequencing and bioinformatic analysis showed that the gene amplified by PCR consisting of 1407 nucleotides and coding for a ß-1,4-endoglucanase enzyme of approximately 55 kDa. The open reading frame (ORF) encoding the mature endoglucanase (eglS) was successfully inserted in a modified cloning plasmid (pITD03) and into the pYD1 plasmid used for its expression in yeast. Carboxymethylcellulose (CMC) plate assay, SDS-PAGE, and zymogram confirmed the production and secretion by the transformed E. coli BL21-SI strain of a 39 kDa ß-1,4-endoglucanase consistent with the catalytic domain without the cellulose-binding module (CBM). The results showed that the truncated ß-1,4-endoglucanase had higher activity and stability.


Asunto(s)
Bacillus subtilis , Celulasa , Papel , Proteínas Recombinantes , Aguas Residuales , Bacillus subtilis/genética , Bacillus subtilis/enzimología , Bacillus subtilis/aislamiento & purificación , Aguas Residuales/microbiología , Aguas Residuales/química , Celulasa/genética , Celulasa/química , Celulasa/biosíntesis , Celulasa/aislamiento & purificación , Celulasa/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/aislamiento & purificación , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Clonación Molecular , Expresión Génica
14.
Am J Physiol Cell Physiol ; 326(4): C1272-C1290, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38602847

RESUMEN

Sodium-glucose cotransporter, type 2 inhibitors (SGLT2i) are emerging as the gold standard for treatment of type 2 diabetes (T2D) with renal protective benefits independent of glucose lowering. We took a high-level approach to evaluate the effects of the SGLT2i, empagliflozin (EMPA) on renal metabolism and function in a prediabetic model of metabolic syndrome. Male and female 12-wk-old TallyHo (TH) mice, and their closest genetic lean strain (Swiss-Webster, SW) were treated with a high-milk-fat diet (HMFD) plus/minus EMPA (@0.01%) for 12-wk. Kidney weights and glomerular filtration rate were slightly increased by EMPA in the TH mice. Glomerular feature analysis by unsupervised clustering revealed sexually dimorphic clustering, and one unique cluster relating to EMPA. Periodic acid Schiff (PAS) positive areas, reflecting basement membranes and mesangium were slightly reduced by EMPA. Phasor-fluorescent life-time imaging (FLIM) of free-to-protein bound NADH in cortex showed a marginally greater reliance on oxidative phosphorylation with EMPA. Overall, net urine sodium, glucose, and albumin were slightly increased by EMPA. In TH, EMPA reduced the sodium phosphate cotransporter, type 2 (NaPi-2), but increased sodium hydrogen exchanger, type 3 (NHE3). These changes were absent or blunted in SW. EMPA led to changes in urine exosomal microRNA profile including, in females, enhanced levels of miRs 27a-3p, 190a-5p, and 196b-5p. Network analysis revealed "cancer pathways" and "FOXO signaling" as the major regulated pathways. Overall, EMPA treatment to prediabetic mice with limited renal disease resulted in modifications in renal metabolism, structure, and transport, which may preclude and underlie protection against kidney disease with developing T2D.NEW & NOTEWORTHY Renal protection afforded by sodium glucose transporter, type 2 inhibitors (SGLT2i), e.g., empagliflozin (EMPA) involves complex intertwined mechanisms. Using a novel mouse model of obesity with insulin resistance, the TallyHo/Jng (TH) mouse on a high-milk-fat diet (HMFD), we found subtle changes in metabolism including altered regulation of sodium transporters that line the renal tubule. New potential epigenetic determinants of metabolic changes relating to FOXO and cancer signaling pathways were elucidated from an altered urine exosomal microRNA signature.


Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Glucósidos , Enfermedades Renales , MicroARNs , Neoplasias , Estado Prediabético , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Masculino , Femenino , Ratones , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estado Prediabético/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Riñón , Glucosa/farmacología , MicroARNs/farmacología , Sodio
15.
Medicine (Baltimore) ; 103(7): e36941, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38363946

RESUMEN

Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting pulmonary pathology in immunosuppressed patients. We conducted a single-center prospective study. Consecutive patients with febrile neutropenia who underwent CT (Computerized Tomography) underwent TUS evaluation within 24h of CT. Both studies were performed by an expert who was blinded to the clinical information and results of the alternative imaging modalities. 34 patients met the inclusion criteria. The median age was 39.9 years (±17 standard deviation). TUS as a diagnostic test had a sensitivity of 92.9% and specificity of 83.3%, negative predictive value of 71.4%, and positive predictive value of 96.3%. Substantial between-method agreement was demonstrated with a kappa of 0.71 (P = .001) between the TUS and chest CT findings. We obtained a kappa of 1 (P = .001) for the final diagnosis of Pleural Effusion (PE). We concluded that TUS is a promising screening test for immunocompromised individuals. The results showed good diagnostic performance of TUS compared to CT for the detection of pulmonary findings highly suggestive of pathology with high accuracy and reproducibility.


Asunto(s)
Neutropenia Febril , Sistemas de Atención de Punto , Humanos , Adulto , Estudios de Cohortes , Estudios Prospectivos , Reproducibilidad de los Resultados , Ultrasonografía/métodos , Tomografía Computarizada por Rayos X , Sensibilidad y Especificidad
16.
Expert Rev Hematol ; 17(1-3): 77-86, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38226642

RESUMEN

BACKGROUND: HLA compatibility predicts allogeneic hematopoietic cell transplant (allo-HCT) and graft-versus-host disease (GvHD) outcomes. There is insufficient information regarding GvHD outcomes for outpatient HLA-identical and haploidentical-HCT employing reduced-intensity conditioning (RIC). RESEARCH DESIGN AND METHODS: We compare GvHD outcomes between donor types and report risk factors associated with GvHD. Stem cell source was T-cell replete peripheral blood. GvHD prophylaxis was post-transplant cyclophosphamide (PT-CY), mycophenolic acid, and calcineurin inhibitors for haploidentical (n = 107) and oral cyclosporine (CsA) plus methotrexate i.v. for HLA-identical (n = 89) recipients. RESULTS: One hundred and ninety-six HCT transplant patients were included. aGvHD and cGvHD frequency were similar between HCT types. aGvHD severity was comparable, but severe cGvHD was less frequent in the haploidentical group (p = .011). One-hundred-day cumulative incidence (CI) of aGvHD for haploidentical and HLA-identical was 31% and 33% (p = .84); 2-year CI of cGvHD was 32% and 38% (p = .6), respectively. Haploidentical recipients had less steroid-refractory cGvHD (p = .043). Patients with cGvHD had less 2-year relapse (p = .003); both aGvHD and cGvHD conferred higher OS (p = .010 and p = .001), respectively. Male sex was protective for steroid-refractory cGvHD (p = .028). CONCLUSIONS: Acute and chronic GvHD rates were comparable between HLA-identical and haploidentical transplant groups. cGvHD severity was lower in the haploidentical group.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Pacientes Ambulatorios , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/epidemiología , Ciclofosfamida/uso terapéutico , Esteroides , Acondicionamiento Pretrasplante/efectos adversos
17.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1563737

RESUMEN

Introducción: Los actores del ámbito educativo deben gestionar procesos adecuados y coherentes con la movilidad social que acontece en la sociedad. Objetivo: Exponer los resultados del diagnóstico del estado inicial de la gestión didáctica de los docentes de la asignatura Ginecología y Obstetricia en situaciones de contingencia. Métodos: Se realizó un estudio cualitativo en el Hospital Universitario Ginecobstétrico Provincial Ana Betancourt de Mora durante el año 2022. Se tuvieron en cuenta las siguientes dimensiones: cognitiva, instrumental y actitudinal con sus respectivos indicadores e índices a medir en el diagnóstico de necesidades. El diagnóstico efectuado se aplicó a 17 docentes de dicha asignatura que laboran en la mencionada institución. Resultados: La dimensión cognitiva fue evaluada de regular, aunque la mayoría de los docentes conocían lo relativo al programa vigente de la asignatura Ginecología y Obstetricia, la mayor cantidad de ellos desconocían los reajustes realizados en situaciones de contingencia. La dimensión instrumental fue evaluada de mal porque los dos indicadores que la componen fueron evaluados de igual modo; mientras que la dimensión actitudinal fue evaluada de regular. Conclusiones: La determinación de la situación inicial de la gestión didáctica de los docentes de la asignatura Ginecología y Obstetricia en situaciones de contingencia, confirmó la presencia de insuficiencias en la gestión didáctica de dicha asignatura en las condiciones señaladas. Ello refleja la necesidad de instrumentar vías para su perfeccionamiento.


Introduction: The actors in the educational field must manage adequate and coherent processes with the social mobility that occurs in society. Objective: To present the results of the diagnosis of the initial state of the didactic management of the teachers of the subject Gynecology and Obstetrics in contingency situations. Methods: A qualitative study was carried out at the Ana Betancourt de Mora Provincial Gynecobstetric University Hospital during the year 2022. The following dimensions were taken into account: cognitive, instrumental and attitudinal with their respective indicators and indices to be measured in the diagnosis of needs. The diagnosis made was applied to 17 teachers of the said subject who work in the aforementioned institution. Results: The cognitive dimension was evaluated as regular, although most of the teachers knew about the current program of the Gynecology and Obstetrics subject, most of them were unaware of the readjustments made in contingency situations. The instrumental dimension was evaluated poorly because the two indicators that comprise it were evaluated in the same way; while the attitudinal dimension was evaluated as regular. Conclusions: The determination of the initial situation of the didactic management of the teachers of the Gynecology and Obstetrics subject in contingency situations, confirmed the presence of insufficiencies in the didactic management of said subject under the indicated conditions. This reflects the need to implement ways for its improvement.

18.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1564476

RESUMEN

Introducción: En el contexto de la pandemia por COVID-19 surgen las secuelas discapacitantes, aún por dimensionar, que acompañarán los próximos años. En relación con esta temática deben dirigirse acciones con enfoque multidisciplinario, donde la salud pública y el sistema educativo aporten el conocimiento y la metodología para su enfrentamiento. Objetivo: Elevar el nivel de conocimiento sobre las secuelas discapacitantes pos-COVID-19 en estudiantes de medicina. Métodos: Se realizó un estudio cuasi-experimental de intervención educativa en estudiantes de quinto año de medicina de la Universidad de Ciencias Médicas de Camagüey, desde la asignatura Salud Pública, durante el período abril-mayo de 2023. Del universo de 23 estudiantes se seleccionó una muestra de 20. Fueron estudiadas las variables grupos de edades, sexo, nivel de conocimiento sobre la epidemiología de las secuelas discapacitantes pos-COVID-19, clasificación por sistemas, identificación, seguimiento, tratamiento y nivel de conocimiento global acerca de estas. Resultados: Predominaron el grupo de 21-25 años (50 %) y el sexo femenino (65 %). En el tema sobre la epidemiología de las secuelas discapacitantes pos-COVID-19 el nivel de conocimiento aumentó entre 5-95 %; mientras, en lo referente a la clasificación por sistemas alcanzó 20-90 %. En cuanto a la identificación, el seguimiento y el tratamiento, el nivel de conocimiento suficiente fue de un 15-75 %. La evaluación global suficiente transitó de un 5 % a un 90 %. Conclusiones: Se logró elevar el nivel de conocimiento sobre las secuelas discapacitantes pos-COVID-19 en estudiantes de medicina. Esto permitirá identificar, conducir y seguir los casos durante la educación en el trabajo.


Introduction: In the context of the COVID-19 pandemic, the disabling sequelae emerge, still to be measured, which will accompany the coming years. With respect to this issue, actions with a multidisciplinary approach should be targeted, in which public health and the educational system provide the knowledge and methodology for their confrontation. Objective: To raise the level of knowledge about post-COVID-19 disabling sequelae in medical students. Methods: A quasiexperimental study of educational intervention was carried out with fifth-year medical students from Universidad de Ciencias Médicas de Camagüey, as part of the Public Health course, during the period April-May 2023. From the study universe of 23 students, a sample of 20 was selected. The following variables were studied: age groups, sex, level of knowledge about the epidemiology of post-COVID-19 disabling sequelae, classification by systems, identification, follow-up, treatment and overall level of knowledge about these. Results: The group aged 21-25 years (50 %) and the female sex (65 %) predominated. The level of knowledge about the epidemiology of post-COVID-19 disabling sequelae increased between 5 % and 95%, while it reached 20 %-90% regarding the classification by systems. With respect to identification, follow-up and treatment, the level of sufficient knowledge was 15 %-75 %. The overall sufficient assessment moved from 5 % to 90 %. Conclusions: The level of knowledge about post-COVID-19 disabling sequelae was managed to be raised in medical students. This will allow identifying, conducting and following up cases during education at work.

19.
Humanidad. med ; 23(3)dic. 2023.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1534556

RESUMEN

El desarrollo científico tecnológico caracterizado, entre otros por los avances en el campo de las ciencias biomédicas, trascienden a la educación, especialmente se denotan los nexos entre la genética médica y la educación especial. En la provincia de Camagüey se desarrolla una investigación entre los servicios de Genética y el Centro de Diagnóstico y Orientación de la educación especial. A partir del análisis de la interrelación entre ambas ciencias se proyectan en la práctica de la atención de educandos con necesidades educativas especiales enfoques multi, inter y transdisciplinarios con el fin de contribuir al perfeccionamiento del diagnóstico sicopedagógico. El estudio se desarrolla con la colaboración de la Benemérita Universidad Autónoma de Puebla.


Scientific and technological development, characterized among cons by advances in the field of biomedical sciences, transcend education, especially the links between medical genetics and special education. In the province of Camagüey, research is being carried out between the Genetics services and the Diagnosis and Guidance Center for special education. Based on the analysis of the interrelation between both sciences, multi, inter and transdisciplinary approaches are projected into the practice of caring for students with special educational needs, in order to contribute to the improvement of psychopedagogical diagnosis. The study is developed with the collaboration of the Benemérita Universidad Autónoma de Puebla.

20.
Artículo en Español | LILACS, CUMED | ID: biblio-1565504

RESUMEN

Introducción: Durante la primera década de la Revolución cubana se produjeron importantes transformaciones en el sistema de salud y, en especial, en la formación médica. Objetivo: Caracterizar la formación médica durante la primera década posterior al triunfo de la Revolución cubana. Métodos: Se realizó un estudio de revisión de literatura científica en el Hospital Pediátrico de Camagüey, durante el mes de junio de 2023, en las bases de datos Scopus, SciELO, DOAJ y Latindex. Se consultaron artículos originales, de revisión y de posición, en su mayoría de los últimos 5 años. La formación médica se caracterizó en dependencia de la implementación y modificación de los primeros planes de estudio. Desarrollo: Durante el período analizado se realizaron cambios sustanciales en la enseñanza de los contenidos médico-sociales en la carrera de Medicina, a saber: fue sustituido el enfoque biologisista por el preventivo; la salud fue declarada de carácter gratuito y acceso universal el servicio médico rural; el inicio de la docencia en varias provincias del país; y la integración de las distintas disciplinas, entre otros. Estas novedades marcaron una transformación sin precedentes. Conclusiones: La investigación permitió caracterizar los principales cambios ocurridos en la formación médica en los primeros diez años posteriores a 1959. En este sentido se abogó por un médico con alto grado de sensibilidad y principios; se apostó por un modelo promocional y preventivo; comenzó la preparación en los hospitales y policlínicos, y se tuvieron en cuenta modernos ensayos médico-pedagógicos a nivel mundial para la creación de los primeros planes de estudio(AU)


Introduction: During the first decade of the Cuban Revolution, important transformations took place in the health system and, especially, in medical training. Objective: To characterize medical education during the decade following the triumph of the Cuban Revolution. Methods: A scientific literature review study was conducted at the Pediatric Hospital of Camagüey, during the month of June 2023, in the Scopus, SciELO, DOAJ and Latindex databases. Original, review and position articles were consulted, mostly from the last five years. Medical training was characterized by the implementation and modification of the first curricula. Development: During the analyzed period, substantial changes were made in the teaching of medico-social content in the medical career, namely: the biological approach was replaced by the preventive one; health care was declared free and universally accessible, as well as other medical services and the rural service; it began teaching in several provinces of the country; and the different disciplines, among others, were integrated. These developments marked an unprecedented transformation. Conclusions: The research allowed us to characterize the main changes that occurred in medical education in the first ten years after 1959. In this sense, a physician with a high degree of sensitivity and principles was advocated, a promotional and preventive model was chosen, preparation began in hospitals and polyclinics, and modern medical-pedagogical trials worldwide were taken into account for the creation of the first curricula(AU)


Asunto(s)
Humanos
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