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Minimal change disease represents a common cause of nephrotic syndrome in both pediatric and adult patients. Although much remains to be discovered, there have been significant recent advancements in our understanding of the pathophysiology of minimal change disease, including the discovery of antinephrin antibodies as a marker for diagnosis of disease. Here we will review what is known about the pathophysiology, treatment, and prognosis of minimal change disease and the differences between pediatric and adult patients. Recent advances in our understanding of the mechanisms of disease will be noted. We will discuss how this may change the treatment of minimal change disease going forward and what remains to be studied.
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Nefrose Lipoide , Humanos , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/fisiopatologia , Nefrose Lipoide/imunologia , Criança , Adulto , PrognósticoRESUMO
In genetic disease, an accurate expression landscape of disease genes and faithful animal models will enable precise genetic diagnoses and therapeutic discoveries, respectively. We previously discovered that variants in NOS1AP , encoding nitric oxide synthase 1 (NOS1) adaptor protein, cause monogenic nephrotic syndrome (NS). Here, we determined that an intergenic splice product of N OS1AP / Nos1ap and neighboring C1orf226/Gm7694 , which precludes NOS1 binding, is the predominant isoform in mammalian kidney transcriptional and proteomic data. Gm7694 -/- mice, whose allele exclusively disrupts the intergenic product, developed NS phenotypes. In two human NS subjects, we identified causative NOS1AP splice variants, including one predicted to abrogate intergenic splicing but initially misclassified as benign based on the canonical transcript. Finally, by modifying genetic background, we generated a faithful mouse model of NOS1AP -associated NS, which responded to anti-proteinuric treatment. This study highlights the importance of intergenic splicing and a potential treatment avenue in a mendelian disorder.
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Malakoplakia is a rare, chronic granulomatous disease that mainly affects the genitourinary system of immunocompromised adults. It is caused by a bactericidal deficit in macrophages and, therefore, the treatment includes antimicrobials that reach high concentrations in macrophages. To our knowledge, we present the first case of malakoplakia in a pediatric solid organ transplant recipient. Our patient is a 15-year-old male renal transplant recipient who presented with recurrent diarrhea. Blood, urine, and gastrointestinal pathogen panel testing were positive for enteroaggregative Escherichia coli. A colonoscopy revealed diffuse malakoplakia. He had a complete resolution of symptoms with trimethoprim-sulfamethoxazole therapy. Unfortunately, his malakoplakia recurred after 9 months prompting the transition of therapy to oral gentamicin with subsequent remission. Malakoplakia should be considered in the differential of solid organ transplant recipients with recurrent gastrointestinal infections.
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Currently, in developing countries, parasitic and bacterial diseases as amebiasis, giardiasis, trichonomiasis, leishmaniasis, trypanosomiasis, tuberculosis, and nocardiasis are a public health problem. The pharmacological treatment for these diseases is not completely effective and causes several side effects in patients. Therefore, the search for new compounds with biological activity is very important to develop new drugs safely and more efficiently. In this study, different organic extracts obtained from thirty-seven species of the Salvadoran flora were evaluated in several in vitro models to determine their potential activity against five protozoa (Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, Leishmania mexicana, and Trypanosoma cruzi) and three bacteria (Acinetobacter baumanni, Mycobacterium tuberculosis, and Nocardia brasiliensis). The results showed the activity of eight extracts with IC50values of less than 100 µg/mL against L. mexicanaand five extracts with MICs values less than <50 µg/mL against M. tuberculosis. Besides, seven plant species showed MICs ≤3.125 µg/mL against N. brasiliensis. Additionally, secondary metabolites (flavonoids and monoterpene oxygenate) previously reported as active were fingerprint by UPLC-MS to establish a potential correlation with the biological activity showed.
Actualmente, en los países en vías de desarrollo, enfermedades parasitarias y bacterianas como la amebiasis, giardiasis, trichonomiasis, leishmaniasis, tripanosomiasis, tuberculosis y nocardiasis son un problema de salud pública. El tratamiento farmacológico de estas enfermedades no es del todo eficaz y provoca varios efectos secundarios en los pacientes. Por lo tanto, la búsqueda de nuevos compuestos con actividad biológica es muy importante para desarrollar nuevos fármacos, seguros y eficaces. En este estudio se evaluaron diferentes extractos orgánicos obtenidos de treinta y siete especies de la flora salvadoreña en varios modelos in vitro para determinar su actividad potencial contra cinco parásitos (Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, Leishmania mexicana y Trypanosoma cruzi) y tres bacterias (Acinetobacter baumanni, Mycobacterium tuberculosis y Nocardia brasiliensis). Los resultados mostraron la actividad de ocho extractos con valores de CI50 menores a 100 µg/mL contra L. mexicana y cinco extractos con valores de CIMs <50 µg/mL contra M. tuberculosis. Además, siete especies de plantas presentaron CIM ≤3,125 µg/mL frente a N. brasilienses. Finalmente, los metabolitos secundarios (flavonoides y monoterpenos oxigenados) previamente reportados como activos fueron determinados por UPLC-MS para establecer una posible correlación con la actividad biológica mostrada.
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Extratos Vegetais/farmacologia , Flora , Antibacterianos/uso terapêutico , Antiparasitários/uso terapêutico , Plantas Medicinais , Doenças Transmissíveis/tratamento farmacológico , El SalvadorRESUMO
Purpose: To determine the prevalence and factors associated with computer vision syndrome in medical students at a private university in Paraguay. Methods: A survey study was conducted in 2021 in a sample of 228 medical students from the Universidad del Pacífico, Paraguay. The dependent variable was CVS, measured with the Computer Visual Syndrome Questionnaire (CVS-Q). Its association with covariates (hours of daily use of notebook, smartphone, tablet and PC, taking breaks when using equipment, use of preventive visual measures, use of glasses, etc.) was examined. Results: The mean age was 22.3 years and 71.5% were women. CVS was present in 82.5% of participants. Higher prevalence of CVS was associated with wearing a framed lens (PR = 1.11, 95% CI: 1.03-1.20). In contrast, taking a break when using electronic equipment at least every 20 min and every 1 h reduced 7% (PR = 0.93, 95% CI: 0.87-0.99) and 6% (PR = 0.94, 95% CI: 0.89-0.99) the prevalence of CVS, respectively. Conclusion: Eight out of 10 students experienced CVS during the COVID-19 pandemic. The use of framed lenses increased the presence of CVS, while taking breaks when using electronic equipment at least every 20 min and every 1 h reduced CVS.
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COVID-19 , Doenças Profissionais , Estudantes de Medicina , Adulto , Computadores , Estudos Transversais , Ergonomia , Feminino , Humanos , Masculino , Doenças Profissionais/epidemiologia , Pandemias , Paraguai/epidemiologia , Inquéritos e Questionários , Síndrome , Universidades , Adulto JovemRESUMO
Triggers of innate immune signaling in the CNS of patients with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD) remain elusive. We report the presence of cytoplasmic double-stranded RNA (cdsRNA), an established trigger of innate immunity, in ALS-FTD brains carrying C9ORF72 intronic hexanucleotide expansions that included genomically encoded expansions of the G4C2 repeat sequences. The presence of cdsRNA in human brains was coincident with cytoplasmic TAR DNA binding protein 43 (TDP-43) inclusions, a pathologic hallmark of ALS/FTD. Introducing cdsRNA into cultured human neural cells induced type I interferon (IFN-I) signaling and death that was rescued by FDA-approved JAK inhibitors. In mice, genomically encoded dsRNAs expressed exclusively in a neuronal class induced IFN-I and death in connected neurons non-cell-autonomously. Our findings establish that genomically encoded cdsRNAs trigger sterile, viral-mimetic IFN-I induction and propagated death within neural circuits and may drive neuroinflammation and neurodegeneration in patients with ALS/FTD.
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Esclerose Lateral Amiotrófica , Proteína C9orf72 , Demência Frontotemporal , Esclerose Lateral Amiotrófica/genética , Animais , Encéfalo/metabolismo , Proteína C9orf72/genética , Expansão das Repetições de DNA , Demência Frontotemporal/genética , Humanos , Camundongos , RNA de Cadeia DuplaRESUMO
An intravenous (IV) formulation of meloxicam is being studied for moderate to severe pain management. This phase 3, randomized, multicenter, double-blind, placebo-controlled trial evaluated the safety of once-daily meloxicam IV 30 mg in subjects following major elective surgery. Eligible subjects were randomized (3:1) to receive meloxicam IV 30 mg or placebo administered once daily. Safety was evaluated via adverse events, clinical laboratory tests, vital signs, wound healing, and opioid consumption. The incidence of adverse events was similar between meloxicam IV- and placebo-treated subjects (63.0% versus 65.0%). Investigators assessed most adverse events as mild or moderate in intensity and unrelated to treatment. Adverse events of interest (injection-site reactions, bleeding, cardiovascular, hepatic, renal, thrombotic, and wound-healing events) were similar between groups. Over the treatment period, meloxicam IV was associated with a 23.6% (P = .0531) reduction in total opioid use (9.2 mg morphine equivalent) compared to placebo-treated subjects. The results suggest that meloxicam IV had a safety profile similar to that of placebo with respect to numbers and frequencies of adverse events and reduced opioid consumption in subjects with moderate to severe postoperative pain following major elective surgery.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Meloxicam/efeitos adversos , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Injeções Intravenosas , Masculino , Meloxicam/administração & dosagem , Meloxicam/uso terapêutico , Pessoa de Meia-Idade , Medição da Dor , Adulto JovemRESUMO
While diminishing nephrology fellow recruitment is a known issue, more work is needed to evaluate possible interventions to reverse this trend. We designed and implemented a curriculum to increase exposure to ambulatory nephrology among internal medicine interns. The curriculum focused on key aspects of outpatient nephrology practice, including supervised clinic visits, formal themed didactic content, and an online interactive forum with assigned evidence-based readings and small-group responses to relevant cases. We obtained postcourse surveys from all participating interns. Of the 43 interns who took part in the first year of the ambulatory nephrology curriculum, 100% reported a positive didactic experience and 91% reported a positive interactive online experience. 77% reported an improvement in their familiarity with clinical nephrology practice (median 2-point increase in familiarity score on a 7-point scale, P<0.001 by signed rank testing). Qualitative feedback included praise for the high-yield topics covered by the lectures and energizing teachers. In conclusion, we successfully implemented an ambulatory nephrology curriculum using a framework that integrated formal didactics, interactive online learning, and key clinical components of outpatient nephrology care. Future investigation will evaluate whether early implementation of this curriculum is associated with increased pursuit of nephrology as a career.
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Assistência Ambulatorial/métodos , Medicina Interna , Nefrologia , Acreditação , Competência Clínica , Currículo , Humanos , Medicina Interna/educação , Medicina Interna/métodos , Internato e Residência/métodos , Nefrologia/educação , Nefrologia/métodos , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários , EnsinoRESUMO
Cardiovascular disease (CVD) is a global epidemic, currently representing the worldwide leading cause of morbidity and mortality. Atherosclerosis is the fundamental pathophysiologic component of CVD, where the immune system plays an essential role. Monocytes and macrophages are key mediators in this aspect: due to their heterogeneity and plasticity, these cells may act as either pro- or anti-inflammatory mediators. Indeed, monocytes may develop heterogeneous functional phenotypes depending on the predominating pro- or anti-inflammatory microenvironment within the lesion, resulting in classic, intermediate, and non-classic monocytes, each with strikingly differing features. Similarly, macrophages may also adopt heterogeneous profiles being mainly M1 and M2, the former showing a proinflammatory profile while the latter demonstrates anti-inflammatory traits; they are further subdivided in several subtypes with more specialized functions. Furthermore, macrophages may display plasticity by dynamically shifting between phenotypes in response to specific signals. Each of these distinct cell profiles is associated with diverse biomarkers which may be exploited for therapeutic intervention, including IL-10, IL-13, PPAR-γ, LXR, NLRP3 inflammasomes, and microRNAs. Direct modulation of the molecular pathways concerning these potential macrophage-related targets represents a promising field for new therapeutic alternatives in atherosclerosis and CVD.
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The amyloid beta peptide aggregates into amyloid plaques at presymptomatic stages of Alzheimer's disease, but the temporal relationship between plaque formation and neuronal dysfunction is poorly understood. Here we demonstrate that the connectivity of the peripheral olfactory neural circuit is perturbed in mice overexpressing human APPsw (Swedish mutation) before the onset of plaques. Expression of human APPsw exclusively in olfactory sensory neurons also perturbs connectivity with associated reductions in odour-evoked gene expression and olfactory acuity. By contrast, olfactory sensory neuron axons project correctly in mice overexpressing wild-type human amyloid precursor protein throughout the brain and in mice overexpressing M671V human APP, a missense mutation that reduces amyloid beta production, exclusively in olfactory sensory neurons. Furthermore, expression of Aß40 or Aß42 solely in the olfactory epithelium disrupts the olfactory sensory neuron axon targeting. Our data indicate that altering the structural connectivity and function of highly plastic neural circuits is one of the pleiotropic actions of soluble human amyloid beta.
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Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Condução Nervosa , Percepção Olfatória , Células Receptoras Sensoriais/fisiologia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Animais , Axônios/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Placa Amiloide/metabolismoRESUMO
Although feeding is an essential component of life, it is only recently that the actions of foods on brain plasticity and function have been scrutinized. There is evidence that select dietary factors are important modifiers of brain plasticity and can have an impact on central nervous system health and disease. Results of new research indicate that dietary factors exert their effects by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Recent study results show that select dietary factors have mechanisms similar to those of exercise, and that, in some cases, dietary factors can complement the action of exercise. Abundant research findings in animal models of central nervous system injury support the idea that nutrients can be taken in through whole foods and dietary supplements to reduce the consequences of neural damage. Therefore, exercise and dietary management appear as a noninvasive and effective strategy to help counteract neurologic and cognitive disorders.
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Lesões Encefálicas/dietoterapia , Sistema Nervoso Central/fisiologia , Suplementos Nutricionais , Metabolismo Energético/fisiologia , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica , Lesões Encefálicas/metabolismo , Lesões Encefálicas/reabilitação , HumanosRESUMO
Se realizó una investigación exploratoria, analítica y transversal en la Facultad de Estomatología de la Universidad de Ciencias Médicas de Camagüey, en el período comprendido entre enero de 2009 y enero de 2010. El objetivo fue determinar cuáles fueron las urgencias bucomaxilofaciales que se atendieron con periodicidad a nivel de la atención primaria de salud, cómo autoevaluaron los estomatólogos generales y estomatólogos generales integrales su competencia y desempeño para enfrentar estas complicaciones, las principales dificultades encontradas por los especialistas de la atención secundaria y las formas organizativas de la superación profesional más eficaces acorde a los resultados. Se utilizó un cuestionario autoevaluativo, se encuestaron 84 estomatólogos, estos manifestaron que las urgencias bucomaxilofaciales que con mayor periodicidad se presentaron fueron las fracturas dentoalveolares y las complicaciones de las exodoncias. La autoevaluación teórica ofreció resultados favorables en todos los grupos. Las respuestas relacionadas con el desempeño práctico mostraron un incremento hacia las autoevaluaciones de regular, principalmente en el de las complicaciones de la exodoncia y los procesos sépticos odontógenos. Los casos referidos a la atención secundaria de salud por complicaciones de las exodoncias, procesos sépticos odontógenos y traumas bucomaxilofaciales, presentaron mayores dificultades en su manejo y tratamiento inicial a nivel de la atención primaria estomatológica. Por sus características formativas, se determinó que en los entrenamientos y diplomados, encontramos las modalidades de superación profesional más adecuadas a las dificultades encontradas(AU)
An exploratory, analytical and cross-sectional research was carried out in the Stomatology Faculty of the Medical Sciences University of Camagüey from January, 2009 to January, 2010. The objective of present paper was to determine the buccomaxillofacial emergences frequently cared at level of the primary health care, how the general stomatologists and integral general stomatologists self-evaluated their capability and performance to confront these complications, the major difficulties founded by the secondary care specialists and the organization ways of the more efficient professional overcoming to be used in keeping with results. We used a self-evaluation questionnaire, 84 stomatologists were polled declaring that the buccomaxillofacial emergences frequently cared were the dentoalveolar fractures and the exodontias complications. The theoretical self-evaluation achieved favorable results in all groups. The responses related to practical performance showed an increase in self-evaluations qualified as regular, mainly in that of exodontias complications and the odontogeny septic processes. The cases referred to secondary health care by exodontias complications, the odontogeny septic processes and buccomaxillofacial traumata showed the higher difficulties in management and initial treatment at level of Stomatology primary care. Due to its formative features, we determined that in training and in granting a diploma were present the modalities of professional overcoming more suitable to be used in keeping with the difficulties founded(AU)
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Humanos , Cirurgia Bucal/métodos , Assistência Odontológica/efeitos adversos , Serviços Médicos de Emergência/métodos , Estudos TransversaisRESUMO
Se realizó un estudio descriptivo prospectivo a 88 pacientes enfermos con diabetes mellitus mayores de 15 años procedentes de la consulta de endocrinología del Hospital General Docente Martín Chang Puga de Nuevitas, Camagüey, desde el 1ro de febrero al 8 de marzo de 2002 para determinar la presencia de la gravedad periodontal y su relación con el grado de higiene bucal, así como el tiempo de evolución de la enfermedad y el grado de control metabólico. Se constató que el 18.10 por ciento no tenían enfermedad periodontal. En los pacientes con diabetes controlada la gingivitis se observó en un 52,20 por ciento y en los de descontrol ligero en un 83.80 por ciento. Todos tenían higiene bucal inadecuada. El descontrol metabólico, la edad y el grado de higiene bucal se correlacionó positivamente con la severidad de la enfermedad periodontal
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Adulto , Humanos , Diabetes Mellitus , Saúde Bucal , Doenças Periodontais , Epidemiologia Descritiva , Estudos ProspectivosRESUMO
Se describen en este trabajo algunos aspectos sobre el diagnóstico clínico y detección precoz del cáncer bucal. El cáncer bucal puede debutar como una pequeña mancha blanquecina o eritematosa, una úlcera plana, en forma exofítica, excavada, infiltrante o nodular. Actualmente la vía más efectiva para disminuir la morbimortalidad del cáncer bucal es el diagnóstico precoz seguido por un tratamiento adecuado. La citología exfoliatríz, el azul de toluidina y el lugol son técnicas adjuntas al examen clínico que pueden utilizarse para la detección precoz de lesiones potencialmente malignas de la cavidad bucal. Se concluye planteando, que los estomatólogos y médicos en general juegan un papel importante en el diagnóstico clínico y la detección precoz del cáncer bucal
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Humanos , Neoplasias Bucais , Diagnóstico ClínicoRESUMO
Se presenta una niña de dos años de edad con quistes dermoides en ambas colas de cejas. Los quistes dermoides derivan de restos de epitelio atrapados por la fusión de procesos embrionarios. Pueden existir ya en el nacimiento o no aparecer hasta algunos años después. Aparecen como tumoraciones lisas, redondeadas, indoloras, variando en tamaño de 1 a 2 cm o más y pueden ser blandos, pastosos, elásticos y fluctuantes. La piel situada por encima es movible. En nuestro paciente se realizó tratamiento quirúrgico (exéresis) convencional, evolucionó satisfactoriamente Este es el primer caso de quiste dermoide bilateral en cola de ceja que se reporta en la literatura nacional y extranjera
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Criança , Cisto Dermoide , SobrancelhasRESUMO
La enfermedad de Sutton, conocida también como periadenitis mucosa necrótica recurrente, aftas de Mikulicz o gran estomatitis aftosa cicatrizal consiste en ulceraciones profundas que al desaparecer dejan siempre cicatrices que pueden ocasionar mutilación o deformidad de la zona afectada, con una prevalencia mayor en el sexo femenino, a pesar de ser poco común. Se presentó un paciente con esta afección, se enfatizó en sus características clínicas e histológicas, diagnóstico diferencial y tratamiento. De esta forma se concluyó que, de tener dudas en el diagnóstico, se realizaría biopsia antes de imponer el tratamiento, el cual debe estar dirigido fundamentalmente a eliminar la causa, la que se ha dicho, es desconocida, pero aceptada su relación con trastornos nerviosos; por lo que recomendamos una consulta con Psiquiatría.
Sutton`s disease know also as recurrent necrotic mucosal aphthous cicatricial stomatitis, it consists in drep ulcerations which always create scars that may cause mutilation or deformities in the affected zone, with a higher incidence in the femenine sex, although it is less common. A patient with this affection is pressented, its clinical, histologic characteristics differential diagnosis and treatment are emphasiged concluding, if there is doubt with the diagnosis, biopsy will be performed before estabishing treatment which may be directed mainly to the elimination of the cause that is unknow but their relationship with nervous disorders is accepted; so we recomended a psychiatric consultation.
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Se realizó un estudio observacional analítico transversal de 120 pacientes atendidos en el Servicio de Cirugía Maxilofacial del Hospital Provincial Clinicoquirúrgico Docente" Manuel Ascunce Domenech" de Camagüey, por el sistema de cirugía mayor ambulatoria, en el período de enero 1998 a diciembre 1999, con el objetivo de evaluar sus resultados en intervenciones complejas. Predominó el sexo masculino con el 59,2(por ciento) y dicha cirugía se realizó con mayor frecuencia entre los 25 y 34 años de edad. Las intervenciones más frecuentes fueron la reducción de fracturas orbitocigomáticas y nasales, cirugía sinusal y rinoplasia correctora, y los procederes quirúrgico y anestésico fueron satisfactorios, con escasas complicaciones posoperatorias no inherentes a estos. El proceder proporcionó un alto grado de satisfacción al paciente. El ahorro a la institución fue de $ 61 757.04 MN, lo que demuestra lo necesario de incrementar esta modalidad en nuestra institución(AU)
A crosswise, analytical and observational study was performed on 120 patients that underwent ambulatory major surgery in the maxillofacial surgery department of "Manuel Ascunce" Provincial Teaching Clinical and Surgical Hospital in Camaguey from January 1998 to December 1999. The objective was to evaluate the results of these complex interventions. Males prevailed (59,2 percent) and this type of surgery was mostly applied in the 25-34y age group. The most frequent interventions were the setting of orbito-zygomatic and nasal fractures, sinus surgery and corrective rhinoplasty. The surgical and anesthetic procedures were satisfactory with little post-operative complications no related to them. Ambulatory major surgery offered a high level of satisfaction to the patients. The institution saved 61 757.04 pesos, which showed that this modality should be more applied in our institution(AU)