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1.
J Wound Care ; 33(Sup4a): xci-xcviii, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38588058

RESUMEN

OBJECTIVE: A diabetic foot ulcer (DFU) is a complication of type 2 diabetes that is difficult to treat. Buerger-Allen exercise has shown effectiveness in improving foot circulation and neuropathy in several studies; however, to the best of our knowledge, no randomised controlled study has investigated its effectiveness for DFU healing. Therefore, this study aimed to assess the effects of Buerger-Allen exercise on the healing of DFUs in patients with type 2 diabetes. METHOD: This is a parallel-group randomised controlled trial (RCT). Of 50 patients with neuropathic DFUs, 41 completed the study. They were assigned randomly to a study group (n=21) and a control group (n=20). Patients in the study group received the standard medical treatment and semi-supervised Buerger-Allen exercise for three sessions per week for four weeks, while patients in the control group only received the standard medical treatment. The outcome measures were: ankle-brachial pressure index (ABPI); ulcer size; ulcer depth; SINBAD score; and ulcer risk for poor outcomes (based on the SINBAD score). RESULTS: The study group's mean age was 49.48±6.45 years and the control group's mean age was 49.15±5.85. The study group's ABPI increased significantly compared to the baseline (1.17±0.04 versus 1.11±0.05, respectively; p<0.001) and the control group (1.17±0.04 versus 1.14±0.05, respectively; p=0.04) post-intervention. Ulcer size also reduced significantly in the study group compared to the baseline (2.63±2.0 versus 7.48±5.55cm2, respectively; p<0.001) and the control group (2.63±2.0 versus 6.43±4.45cm2, respectively; p<0.001) post-intervention. Ulcer depth decreased significantly in the study group compared to the baseline (1.71±1.05 versus 4.19±1.74mm, respectively; p<0.001) and the control group (1.71±1.05 versus 2.80±1.57mm, respectively; p=0.01) post-intervention. Furthermore, the SINBAD score in the study group decreased significantly compared to the baseline (1.38±0.86 versus 2.14±1.06, respectively; p<0.001) and the control group (1.38±0.86 versus 2.0±0.79, respectively; p=0.02) post-intervention. Moreover, the ulcer risk for poor outcomes, based on the SINBAD score, reduced significantly only in the study group, compared to the baseline (p=0.041). The control group showed non-significant changes compared to the baseline in all outcome measures (p>0.05). CONCLUSION: From the findings of this RCT, Buerger-Allen exercise, in combination with standard wound care, may help accelerate the healing of neuropathic DFUs in patients with type 2 diabetes, and could be suggested as part of the management plan for such conditions as an easy-to-perform offloading exercise intervention.


Asunto(s)
Diabetes Mellitus Tipo 2 , Pie Diabético , Humanos , Adulto , Persona de Mediana Edad , Pie Diabético/terapia , Pie Diabético/complicaciones , Pie , Ejercicio Físico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Cicatrización de Heridas
2.
Pediatr Hematol Oncol ; 41(1): 15-29, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37773584

RESUMEN

Sickle cell disease (SCD), a chronic debilitating disorder that may negatively affect health-related quality-of-life (HRQoL). In this observational, case-control study, we aim to assess the prevalence of impaired psychosocial profile and poor HRQoL among SCD patients and their caregivers as well as to determine the association of such impairment with parameters of disease severity. Sixty-five children and adolescents with SCD and 65 age- and sex-matched healthy controls and their caregivers were recruited. Demographic and clinical characteristics were collected, and a thorough clinical and psychiatric assessments and HR QoL were conducted. Recruited children and adolescents with SCD were 34 (52.3%) boys and 31 (47.7%) girls, and their mean age was 11.40 ± 3.55. Most of them (n = 44, 67.7%) had sickle HbSß+, and vaso-occlusive crises were the most common causes for hospital admission (n = 24, 36.9%). Children with SCD and their caregivers had depression and anxiety symptoms scores higher than reported in the control group. Children with SCD had significantly less self-esteem and less QoL scores with the least scores were in the communication domain. This adverse psychological profile was significantly negatively correlated with the age of the child, duration of illness, number and duration of hospitalizations, disease severity score, and occurrence of complications. We conclude that HRQoL of children suffering from SCD, and their caregivers are adversely affected necessitating implementation of interventions which focus on reducing depressive symptoms, enhancing self-esteem and QoL.


Asunto(s)
Anemia de Células Falciformes , Calidad de Vida , Masculino , Niño , Femenino , Adolescente , Humanos , Calidad de Vida/psicología , Cuidadores , Estudios de Casos y Controles , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/psicología , Ansiedad
3.
BMC Nurs ; 23(1): 249, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632551

RESUMEN

BACKGROUND: Nursing education presents unique challenges, including high levels of academic stress and varied learning approaches among students. Understanding the relationship between academic stress and learning approaches is crucial for enhancing nursing education effectiveness and student well-being. AIM: This study aimed to investigate the prevalence of academic stress and its correlation with learning approaches among nursing students. DESIGN AND METHOD: A cross-sectional descriptive correlation research design was employed. A convenient sample of 1010 nursing students participated, completing socio-demographic data, the Perceived Stress Scale (PSS), and the Revised Study Process Questionnaire (R-SPQ-2 F). RESULTS: Most nursing students experienced moderate academic stress (56.3%) and exhibited moderate levels of deep learning approaches (55.0%). Stress from a lack of professional knowledge and skills negatively correlates with deep learning approaches (r = -0.392) and positively correlates with surface learning approaches (r = 0.365). Female students showed higher deep learning approach scores, while male students exhibited higher surface learning approach scores. Age, gender, educational level, and academic stress significantly influenced learning approaches. CONCLUSION: Academic stress significantly impacts learning approaches among nursing students. Strategies addressing stressors and promoting healthy learning approaches are essential for enhancing nursing education and student well-being. NURSING IMPLICATION: Understanding academic stress's impact on nursing students' learning approaches enables tailored interventions. Recognizing stressors informs strategies for promoting adaptive coping, fostering deep learning, and creating supportive environments. Integrating stress management, mentorship, and counseling enhances student well-being and nursing education quality.

4.
J Biochem Mol Toxicol ; 37(3): e23284, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36541377

RESUMEN

Coronary heart disease (CHD) is the most prevalent cause of cardiovascular mortality in the world. It is well established that microRNAs (miRNAs) and their variants have an essential role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. This study was designed to determine the possible association of miRNA polymorphisms (miRNA-146a rs2910164C/G and miR-4513 rs2168518G/A) with susceptibility to CHD in Egyptian patients and their correlation with different biochemical parameters. The study comprised 300 participants, including 200 unrelated patients with CHD and 100 healthy controls. Anthropometric and blood biochemical parameters were measured as well genetic analysis for rs2910164C/G and rs2168518G/A polymorphisms were performed for all subjects using TaqMan real-time PCR assay. Our results revealed that the biomedical parameters have a significant correlation between CHD patients and healthy controls with a p < 0.05. Analyses of genotype distribution for (rs2910164 and rs2168518) revealed a significant association with CHD [odd ratio = 4.54, confidence interval (CI 95%) = (2.41-8.53)] and [odd ratio = 0.88, (CI 95%) = (0.83-0.92)], respectively. Furthermore, a statistically significant difference was detected between lipid profile levels and both rs2910164 and rs2168518 polymorphisms. The present study's findings indicated that the selected polymorphisms, miR-146a rs2910164 and miR-4513 rs2168518 could represent a useful biomarker for susceptibility to CHD in the Egyptian population. These genetic characteristics and personal habits and environmental factors may contribute to the development of CHD.


Asunto(s)
Enfermedad Coronaria , MicroARNs , Humanos , MicroARNs/genética , Egipto , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Genotipo , Polimorfismo de Nucleótido Simple
5.
FASEB J ; 35(6): e21585, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33960026

RESUMEN

While the neural circuits mediating normal, adaptive defensive behaviors have been extensively studied, substantially less is currently known about the network mechanisms by which aberrant, pathological anxiety is encoded in the brain. Here we investigate in mice how deletion of Neuroligin-2 (Nlgn2), an inhibitory synapse-specific adhesion protein that has been associated with pathological anxiety and other psychiatric disorders, alters the communication between key brain regions involved in mediating defensive behaviors. To this end, we performed multi-site simultaneous local field potential (LFP) recordings from the basolateral amygdala (BLA), centromedial amygdala (CeM), bed nucleus of the stria terminalis (BNST), prefrontal cortex (mPFC) and ventral hippocampus (vHPC) in an open field paradigm. We found that LFP power in the vHPC was profoundly increased and was accompanied by an abnormal modulation of the synchrony of theta frequency oscillations particularly in the vHPC-mPFC-BLA circuit. Moreover, deletion of Nlgn2 increased beta and gamma frequency synchrony across the network, and this increase was associated with increased center avoidance. Local deletion of Nlgn2 in the vHPC and BLA revealed that they encode distinct aspects of this avoidance phenotype, with vHPC linked to immobility and BLA linked to a reduction in exploratory activity. Together, our data demonstrate that alterations in long-range functional connectivity link synaptic inhibition to abnormal defensive behaviors, and that both exaggerated activation of normal defensive circuits and recruitment of fundamentally distinct mechanisms contribute to this phenotype. Nlgn2 knockout mice therefore represent a highly relevant model to study the role of inhibitory synaptic transmission in the circuits underlying anxiety disorders.


Asunto(s)
Trastornos de Ansiedad/patología , Conducta Animal , Ritmo beta , Moléculas de Adhesión Celular Neuronal/fisiología , Modelos Animales de Enfermedad , Proteínas del Tejido Nervioso/fisiología , Ritmo Teta , Animales , Trastornos de Ansiedad/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
6.
J Community Health ; 47(2): 344-350, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35020100

RESUMEN

In the U.S., overdoses have become a health crisis in both public and private places. We describe the impact of the overdose crisis in public libraries across five U.S. states, and the front-line response of public library workers. We conducted a cross-sectional survey, inviting one worker to respond at each public library in five randomly selected states (CO, CT, FL, MI, and VA), querying participants regarding substance use and overdose in their communities and institutions, and their preparedness to respond. We describe substance use and overdose patterns, as well as correlates of naloxone uptake, in public libraries. Participating library staff (N = 356) reported witnessing alcohol use (45%) and injection drug use (14%) in their libraries in the previous month. Across states surveyed, 12% of respondents reported at least one on-site overdose in the prior year, ranging from a low of 10% in MI to a high of 17% in FL. There was wide variation across states in naloxone uptake at libraries, ranging from 0% of represented libraries in FL to 33% in CO. Prior on-site overdose was associated with higher odds of naloxone uptake by the library (OR 2.5, 95% CI 1.1-5.7). Although 24% of respondents had attended a training regarding substance use in the prior year, over 90% of respondents wanted to receive additional training on the topic. Public health professionals should partner with public libraries to expand and strengthen substance use outreach and overdose prevention efforts.


Asunto(s)
Sobredosis de Droga , Trastornos Relacionados con Sustancias , Estudios Transversales , Sobredosis de Droga/tratamiento farmacológico , Humanos , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Sustancias/epidemiología , Encuestas y Cuestionarios
7.
Biomed Chromatogr ; 36(11): e5472, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35906747

RESUMEN

A fast, uncomplicated, sensitive and fully validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed for estimating l-amino acids in the plasma of schizophrenic patients. The gradient-elution chromatographic method was implemented with the Luna® PFP column (50 × 2.0 mm, 5 µm), and a mobile phase of 0.1% formic acid in water and methanol was used. The intra- and interday variability of the l-amino acids was <13.11%, their accuracy ranged from 85.14 to 116.75% at the quality control levels and the lower limit of quantification ranged from 2.5 to 15 nm. The extraction efficiency (apparent recovery) of amino acids from healthy plasma was employed by spiking the plasma with standard amino acids at the quality control levels. Their percentage recoveries ranged from 80.4 to 119.94%. Our method has a short run time and fast sample preparation compared with existing methods, which suffer from long preparative steps and/or time-consuming analysis, restricted reagents and the suboptimal performance characteristics of presently available technologies. Therefore, the proposed HPLC-MS/MS method was effectively applied for monitoring the l-amino acids in the plasma of schizophrenic patients and healthy volunteers.


Asunto(s)
Esquizofrenia , Espectrometría de Masas en Tándem , Aminas , Aminoácidos , Cromatografía Líquida de Alta Presión/métodos , Formiatos , Humanos , Metanol , Espectrometría de Masas en Tándem/métodos , Agua
8.
Financ Res Lett ; 46: 102493, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34658678

RESUMEN

This paper examines how the COVID-19 pandemic affects corporate dividend policy. Utilizing a sample of 8889 firms listed in the G-12 countries, the findings show that although the proportion of dividend cuts and omissions is significantly higher during the pandemic, yet the majority of firms could either maintain or increase dividends. By doing so, firms might aim to purse more stable dividend policies and signal their financial prospects during the crisis, as posited by dividend signaling theory. Logit regression findings reveal that firm profitability, earnings prospects, size and leverage appear to be important determinants of dividend policy decisions during the pandemic.

9.
J Pharmacol Exp Ther ; 377(3): 326-335, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33707301

RESUMEN

Combined neprilysin (NEP) inhibition (sacubitril) and angiotensin type 1 receptor (AT1R) antagonism (valsartan) is used in the treatment of congestive heart failure and is gaining interest for other angiotensin II (AngII)-related cardiovascular diseases. In addition to heart failure, AngII promotes hypertension, atherosclerosis, and abdominal aortic aneurysms (AAAs). Similarly, NEP substrates or products have broad effects on the cardiovascular system. In this study, we examined NEP inhibition (with sacubitril) and AT1R antagonism (with valsartan) alone or in combination on AngII-induced hypertension, atherosclerosis, or AAAs in male low-density lipoprotein receptor-deficient mice. Preliminary studies assessed drug delivery via osmotic minipumps for simultaneous release of sacubitril and/or valsartan with AngII over 28 days. Mice were infused with AngII (1000 ng/kg per minute) in the absence (vehicle) or presence of sacubitril (1, 6, or 9 mg/kg per day), valsartan (0.3, 0.5, 1, 6, or 20 mg/kg per day), or the combination thereof (1 and 0.3, or 9 or 0.5 mg/kg per day of sacubitril and valsartan, respectively). Plasma AngII and renin concentrations increased 4-fold at higher valsartan doses, indicative of removal of AngII negative feedback on renin. Sacubitril doubled plasma AngII concentrations at lower doses (1 mg/kg per day). Valsartan dose-dependently decreased systolic blood pressure, aortic atherosclerosis, and AAAs of AngII-infused mice, whereas sacubitril had no effect on atherosclerosis or AAAs but reduced blood pressure of AngII-infused mice. Combination therapy with sacubitril and valsartan did not provide additive benefits. These results suggest limited effects of combination therapy with NEP inhibition and AT1R antagonism against AngII-induced hypertension, atherosclerosis, or AAAs. SIGNIFICANCE STATEMENT: The combination of valsartan (angiotensin type 1 receptor antagonist) and sacubitril (neprilysin inhibitor) did not provide benefit above valsartan alone on AngII-induced hypertension, atherosclerosis, or abdominal aortic aneurysms in low-density lipoprotein receptor-deficient male mice. These results do not support this drug combination in therapy of these AngII-induced cardiovascular diseases.


Asunto(s)
Antihipertensivos , Aminobutiratos , Angiotensina II , Aterosclerosis , Compuestos de Bifenilo , Neprilisina , Animales , Ratones
10.
J Fish Biol ; 95(3): 820-832, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31215642

RESUMEN

Species-specific disturbance calls of five commercially-important characiform species are described, the Curimatidae commonly called branquinhas: Potamorhina latior, Potamorhina altamazonica and Psectrogaster amazonica; Prochilodontidae: jaraquí Semaprochilodus insignis and curimatã Prochilodus nigricans. All species have a two-chambered swimbladder and the sonic mechanism, present exclusively in males, utilises hypertrophied red muscles between ribs that adhere to the anterior chamber. The number of muscles is unusually plastic across species and varies from 1 to 4 pairs suggesting considerable evolution in an otherwise conservative system. Advertisement calls are produced in river confluences in the Madeira Basin during the high-water mating season (January-February). Disturbance calls and sampling allowed recognition of underwater advertisement choruses from P. latior, S. insignis and P. nigricans. The advertisement calls of the first two species have largely similar characteristics and they mate in partially overlapping areas in the Guaporé River. However, P. latior sounds have a lower dominant frequency and it prefers to call from river confluences whereas S. insignis shoals occur mostly in the main river channel adjacent to the confluence. These results help identify and differentiate underwater sounds and evaluate breeding areas during the courtship of commercially important characids likely to be affected by two hydroelectric dams.


Asunto(s)
Comunicación Animal , Characiformes/fisiología , Conducta Sexual Animal , Acústica , Sacos Aéreos/anatomía & histología , Sacos Aéreos/fisiología , Animales , Characiformes/anatomía & histología , Masculino , Músculos/anatomía & histología , Músculos/fisiología , Reproducción , Ríos , Especificidad de la Especie
11.
Proc Biol Sci ; 283(1841)2016 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-27798293

RESUMEN

Despite rapid damping, fish swimbladders have been modelled as underwater resonant bubbles. Recent data suggest that swimbladders of sound-producing fishes use a forced rather than a resonant response to produce sound. The reason for this discrepancy has not been formally addressed, and we demonstrate, for the first time, that the structure of the swimbladder wall will affect vibratory behaviour. Using the oyster toadfish Opsanus tau, we find regional differences in bladder thickness, directionality of collagen layers (anisotropic bladder wall structure), material properties that differ between circular and longitudinal directions (stress, strain and Young's modulus), high water content (80%) of the bladder wall and a 300-fold increase in the modulus of dried tissue. Therefore, the swimbladder wall is a viscoelastic structure that serves to damp vibrations and impart directionality, preventing the expression of resonance.


Asunto(s)
Sacos Aéreos/anatomía & histología , Batrachoidiformes/anatomía & histología , Animales , Sonido , Vibración
12.
Lasers Surg Med ; 47(5): 388-95, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25946210

RESUMEN

BACKGROUND: Primary cutaneous amyloidosis (PCA) comprises three main forms: macular, lichen, and nodular amyloidosis. The current available treatments are quite disappointing. OBJECTIVES: Assess and compare the clinical and histological changes induced by different modes of Fractional CO2 laser in treatment of PCA. PATIENTS AND METHODS: Twenty five patients with PCA (16 macular and 9 lichen amyloidosis) were treated by fractional CO2 using; superficial ablation (area A) and deep rejuvenation (area B). Each patient received 4 sessions with 4 weeks intervals. Skin biopsies were obtained from all patients at baseline and one month after the last session. Patients were assessed clinically and histologically (Congo red staining, polarized light). Patients were followed-up for 3 months after treatment. RESULTS: Both modes yielded significant reduction of pigmentation, thickness, itching, and amyloid deposits (P-value < 0.001). However, the percentage of reduction of pigmentation was significantly higher in area A (P-value = 0.003). Pain was significantly higher in area B. Significant reduction in dermal amyloid deposits denotes their trans-epidermal elimination induced by fractional photothermolysis. CONCLUSION: Both superficial and deep modes of fractional CO2 laser showed comparable efficacy in treatment of PCA. Superficial mode being better tolerated by patients, is recommended as a valid therapeutic option.


Asunto(s)
Amiloidosis Familiar/cirugía , Terapia por Láser/métodos , Láseres de Gas/uso terapéutico , Enfermedades Cutáneas Genéticas/cirugía , Adulto , Amiloidosis Familiar/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Método Simple Ciego , Enfermedades Cutáneas Genéticas/patología , Resultado del Tratamiento , Adulto Joven
13.
Br J Psychiatry ; 204(2): 129-36, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24357572

RESUMEN

BACKGROUND: Changes in corpus callosum area and thickness have been reported in bipolar disorder. Imaging and limited neuropathological data suggest possible abnormalities in myelination and/or glial function. AIMS: To compare corpus callosum area, thickness and magnetic resonance imaging (MRI) T1 signal intensity in patients with bipolar disorder and healthy controls. METHOD: A total of 48 patients with euthymic bipolar disorder and 46 healthy controls underwent MRI analysis of callosal midsagittal area, callosal thickness and T1 signal intensity. RESULTS: The bipolar group had smaller overall and subregional callosal areas and correspondingly reduced callosal width than the control group. Age correlated negatively with callosal area in the control group but not in the bipolar group. Signal intensity was higher in women than in men in both groups. Signal intensity was reduced in women, but not in men, in the bipolar group. CONCLUSIONS: Observed differences probably relate to diagnosis rather than mood state and bipolar disorder appears to result in morphometric change that overrides changes seen in normal ageing. Intensity changes are consistent with possible altered myelination or glial function. A gender-dependent factor appears to operate and to interact with diagnosis.


Asunto(s)
Trastorno Bipolar/patología , Cuerpo Calloso/patología , Adolescente , Adulto , Factores de Edad , Envejecimiento/fisiología , Antimaníacos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Estudios de Casos y Controles , Niño , Cuerpo Calloso/crecimiento & desarrollo , Femenino , Humanos , Compuestos de Litio/uso terapéutico , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/patología , Escalas de Valoración Psiquiátrica , Caracteres Sexuales , Adulto Joven
14.
Trends Mol Med ; 30(5): 429-442, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38453529

RESUMEN

Glioma is a type of aggressive and incurable brain tumor. Patients with glioma are highly resistant to all types of therapies, including immunotherapies. Epigenetic reprogramming is a key molecular hallmark in tumors across cancer types, including glioma. Mounting evidence highlights a pivotal role of epigenetic regulation in shaping tumor biology and therapeutic responses through mechanisms involving both glioma cells and immune cells, as well as their symbiotic interactions in the tumor microenvironment (TME). In this review, we discuss the molecular mechanisms of epigenetic regulation that impacts glioma cell biology and tumor immunity in both a cell-autonomous and non-cell-autonomous manner. Moreover, we provide an overview of potential therapeutic approaches that can disrupt epigenetic-regulated tumor-immune symbiosis in the glioma TME.


Asunto(s)
Neoplasias Encefálicas , Epigénesis Genética , Glioma , Microambiente Tumoral , Humanos , Glioma/genética , Glioma/inmunología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Animales , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica
15.
Nat Commun ; 15(1): 1987, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443336

RESUMEN

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase inhibitor stiripentol emerges as the top hit. Combined profiling and functional studies demonstrate that lactate dehydrogenase A (LDHA)-directed extracellular signal-regulated kinase (ERK) pathway activates yes-associated protein 1 (YAP1)/ signal transducer and activator of transcription 3 (STAT3) transcriptional co-activators in glioblastoma cells to upregulate C-C motif chemokine ligand 2 (CCL2) and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.


Asunto(s)
Glioblastoma , Animales , Humanos , Ratones , Glioblastoma/genética , L-Lactato Deshidrogenasa/genética , Lactato Deshidrogenasa 5 , Ácido Láctico , Simbiosis , Microambiente Tumoral
16.
Expert Rev Hematol ; 17(4-5): 153-163, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38597207

RESUMEN

BACKGROUND: Hemophagocyticlymphohistiocytosis (HLH) is a spectrum of immune activation which could be genetically determined, or secondary to an underlying illness. Our aim was to present the clinico-genetic aspects of HLH among Egyptian children and to evaluate the patterns of reactivation and outcome with illustrations of overlap manifestations. RESEARCH DESIGNAND METHODS: We retrospectively collected the data of 55 patients with HLH, registered at Ain Shams University Children's Hospital,Cairo, Egypt. RESULTS: Median age at diagnosis was 19 months (range 2-180), 33 patients (60%) fulfilled the diagnostic HLH criteria at presentation. Fourteen (25.45%) patients had secondary HLH, 15 (27.27%) patients had genetically documented familial HLH (11 had variants in UNC13D gene and one in PRF1 gene), 3 had Griscelli and Chediak-Higashi syndromes. Sixteen patients (29.1%) had reactivations, 8 (50%) of them had molecularly confirmed HLH. We report the death of 40 patients, the median duration from the diagnosis to death of 5 months mostly due to disease activity. CONCLUSIONS: This study confirms that the nonspecific signs and symptoms of HLH are challenging. Genetic testing, though expensive and sophisticated, is integral for the diagnosis. The difficulty in finding non-related donors for stem cell transplantation and the early reactivations are the causes of the inferior outcome.


Asunto(s)
Linfohistiocitosis Hemofagocítica , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/terapia , Linfohistiocitosis Hemofagocítica/mortalidad , Linfohistiocitosis Hemofagocítica/genética , Egipto/epidemiología , Niño , Masculino , Preescolar , Femenino , Lactante , Estudios Retrospectivos , Adolescente , Resultado del Tratamiento , Manejo de la Enfermedad
18.
Pediatr Hematol Oncol ; 30(2): 93-103, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23301991

RESUMEN

BACKGROUND: The improvement of quality and duration of life of transfusion-dependent B thalassemia patients over the last years discloses several complications due to the underling disorder, iron overload and the treatment with iron chelators. Our Aim was to assess the morbidity patterns and mortality rate of transfusion-dependent thalassemia patients, and compare the outcomes in relation to age of onset, type, duration, and compliance to iron chelation therapy and frequency of blood transfusion. PROCEDURE: This retrospective study included 447 transfusion-dependent ß-thalassemia patients who attended the Thalassemia Center, Ain Shams University Children's Hospital over the last 10 years in the period between January 2000 and January 2010. Data were collected from the patients or their caregivers, as well as by reviewing follow up sheets for examinations and investigations done to detect morbidities as well as iron chelation therapies given. Determination of mortality rate and the causes of death were also done. RESULTS: Results revealed that the most common morbidities were endocrinologic (44.7%) followed by cardiovascular (41.3%) and hepatic (40.5%), then renal (4%). The different iron chelation therapy groups showed a comparable prevalence of different morbidities. The mortality rate was 1.5% and infection was the most common cause of death. The 5, 10, 20 years' survival rate among the studied patients was 80%, 50%, 20%, respectively. CONCLUSION: In the past 10 years, the survival and morbidity rates in our center have markedly improved as a result of regular blood transfusion, new iron chelators, and better compliance of the patients.


Asunto(s)
Transfusión Sanguínea , Talasemia beta/mortalidad , Talasemia beta/terapia , Adolescente , Adulto , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/terapia , Niño , Preescolar , Supervivencia sin Enfermedad , Enfermedades del Sistema Endocrino/etiología , Enfermedades del Sistema Endocrino/mortalidad , Enfermedades del Sistema Endocrino/terapia , Femenino , Humanos , Lactante , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/mortalidad , Sobrecarga de Hierro/terapia , Enfermedades Renales/etiología , Enfermedades Renales/mortalidad , Enfermedades Renales/terapia , Hepatopatías/etiología , Hepatopatías/mortalidad , Hepatopatías/terapia , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Talasemia beta/complicaciones
19.
Pulm Med ; 2023: 4159651, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37179531

RESUMEN

Background: Although SARS-CoV-2 infection primarily affects adults, the increasing emergence of infected pediatric patients has been recently reported. However, there is a paucity of data regarding the value of imaging in relation to the clinical severity of this pandemic emergency. Objectives: To demonstrate the relationships between clinical and radiological COVID-19 findings and to determine the most effective standardized pediatric clinical and imaging strategies predicting the disease severity. Patients and Methods. This observational study enrolled eighty pediatric patients with confirmed COVID-19 infection. The studied patients were categorized according to the disease severity and the presence of comorbidities. Patients' clinical findings, chest X-ray, and CT imaging results were analyzed. Patients' evaluations using several clinical and radiological severity scores were recorded. The relations between clinical and radiological severities were examined. Results: Significant associations were found between severe-to-critical illness and abnormal radiological findings (p = 0.009). In addition, chest X-ray score, chest CT severity score, and rapid evaluation of anamnesis, PO2, imaging disease, and dyspnea-COVID (RAPID-COVID) score were significantly higher among patients with severe infection (p < 0.001, <0.001, and 0.001) and those with comorbidities (p = 0.005, 0.002, and <0.001). Conclusions: Chest imaging of pediatric patients with COVID-19 infection may be of value during the evaluation of severe cases of infected pediatric patients and in those with underlying comorbid conditions, especially during the early stage of infection. Moreover, the combined use of specific clinical and radiological COVID-19 scores are likely to be a successful measure of the extent of disease severity.


Asunto(s)
COVID-19 , Adulto , Humanos , Niño , COVID-19/diagnóstico por imagen , SARS-CoV-2 , Tomografía Computarizada por Rayos X/métodos , Disnea , Tórax , Estudios Retrospectivos
20.
Artículo en Inglés | MEDLINE | ID: mdl-36767388

RESUMEN

Hospitals' operational performance during disasters varies from failing, to being responsive and resilient, to dealing with disruption and surprise. Transformational leaders enable continuously learning hospitals that are resilient in the face of disasters by adapting regeneratively and evolving beyond undertaking conventional lesson-learning after each disaster. However, learning from successful transformational leaders in healthcare is still ad hoc with a lack of guidance on how to develop such leaders. Hence, this study sought to identify key competencies of transformational leaders by exploring hospital leaders' actions in dealing with disasters, considering the disaster cycle of prevention, preparedness, response, and recovery (PPRR). A qualitative case-study design was adopted comprising in-depth semi-structured interviews with twelve senior hospital staff with operational leadership experience with disasters. Three significant categories (themes) and seven key component competencies (sub-themes, in brackets) of transformational leaders were revealed through the analysis of transcripts: (1) 'Governance and leadership' ('transformative agency' and 'decisive accountability'); (2) 'Planning and risk assessment' ('risk navigation', 'disaster attunement', and 'planning agility'); and (3) 'Communication and network engagement' ('communication accelerator' and 'collaboration innovator'). The authors propose a transformational leadership model for hospital disaster resilience and an assessment checklist for leaders' self-reflection to support hospitals in their transition to resilient operations.


Asunto(s)
Planificación en Desastres , Desastres , Humanos , Liderazgo , Hospitales , Atención a la Salud , Personal de Hospital
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