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Objectives: The GOSR2 gene is a Golgi vesicle transport gene that encodes for the Golgi SNAP receptor complex member 2 protein. This protein mediates transport between the medial and trans-Golgi compartments. The homozygous missense variant in the GOSR2 gene, c.430G>T, has been associated with progressive myoclonus epilepsy (PME). There have been reports suggesting that compound heterozygous GOSR2 variants are associated with the congenital muscular dystrophy (CMD) phenotype. Methods: In this article, we report a pediatric case with congenital hypotonia, motor delay, elevated creatine kinase, and abnormal muscle biopsy consistent with CMD who subsequently developed PME. Whole-exome sequencing identified pathogenic compound heterozygous variants in the GOSR2 gene, one of which was the previously described PME-related c.430G>T(p.Gly144Trp), and a novel variant, c.22dup(p.Thr8fs). Result: To our knowledge, this is a novel case of compound heterozygous variants in GOSR2 associated with both CMD and PME phenotypes. Discussion: This case adds to the expanding clinical phenotype of GOSR2-related neurologic diseases.
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BACKGROUND: Although the metabolic equivalents (METs) system is a common procedure to quantify the intensity of physical activity in older adults, it remains unclear whether the conventional METs intensity thresholds (CTs) used for this purpose are appropriate in this population. Therefore, this study aimed (i) to derive overall and fitness-specific METs intensity thresholds in older adults ≥ 60 years old (OATs) expressed both in standard METs (VO2/3.5 mL O2·kg-1·min-1) and older adults METs60+ (VO2/2.7 mL O2·kg-1·min-1), and (ii) to compare them with the CTs. METHODS: A total of 93 subjects were assessed for cardiorespiratory fitness. Graded exercise test protocols using indirect calorimetry were performed to calculate individual VO2max and categorize subjects as "very poor/fair" or "good/superior" fitness. Overall and fitness-specific OATs expressed in standard METs (OATsstandard) and METs60+ (OATs60+) were derived based on the %VO2max and the ventilatory thresholds (VTs) physical intensity categories. RESULTS: Significantly higher VO2max, VO2 at VT1 and VO2 at VT2 (p < 0.001) were obtained in the "good/superior" subgroup compared to the "very poor/fair" fitness subgroup. Accordingly, OATs were approximately 69% higher in individuals with a "good/superior" fitness compared to those with a "very poor/fair" fitness. Furthermore, this study showed that OATsstandard were approximately 21-24% lower than OATs60+, and 10-22% higher OATs were observed when following the VTs intensity categories (heavy-intensity physical activity [HPA] and severe-intensity physical activity [SPA]) compared to the %VO2max categories (moderate-intensity physical activity [MPA] and vigorous-intensity physical activity [VPA]). When compared with the CTs, similar or higher OATsstandard and OATs60+ for MPA, and HPA were obtained compared to the conventional MPA threshold (3.0 METs). Conversely, for VPA and SPA, lower, similar, or higher OATs were obtained depending on the METs derivation approach (OATsstandard or OATs60+) or the intensity categories (VO2max or VTs), compared to the conventional VPA threshold (6.0 METs). CONCLUSIONS: None of the derived OATs were concurrently similar to the CTs, suggesting that fitness-specific METs intensity thresholds adapted to the METs derivation approach should be used in older adults. TRIAL REGISTRATION: FenotipAGING (Non-health-care intervention study), PRO-Training (NCT05619250).
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BACKGROUND: Although supervised exercise is frequently recommended for older adults, its superiority over unsupervised exercise remains uncertain. Furthermore, whether motivational techniques could help to enhance the effectiveness of the latter remains to be elucidated. The present randomized controlled trial aims to determine the role of supervision and motivational strategies on the safety, adherence, efficacy, and cost-effectiveness of different exercise programs for improving physical and mental health in older adults. METHODS: Participants (n = 120, aged 60-75 years) will be randomly allocated into five groups: 1-Control (CON), 2-Supervised exercise without motivational intervention (SUP), 3- Supervised exercise with motivational intervention (SUP +), 4- Unsupervised exercise without motivational intervention (UNSUP) and 5- Unsupervised exercise with motivational intervention (UNSUP +). Over 24 weeks, all exercise groups will participate in a multicomponent exercise program three times/week (performed in group classes at a center for SUP and SUP + , or home without supervision but with the help of a mobile app for UNSUP and UNSUP +), while the CON group will maintain their usual lifestyle. The motivational intervention (for SUP + and UNSUP + groups) will be based on the self-determination theory, including strategies such as phone calls, interactive workshops, motivational messages, informative infographics and videos. Primary outcomes will include safety, adherence, costs, and lower-body muscular function using a leg press machine. Secondary outcomes will include upper-body muscular function, physical and cardiorespiratory function, blood pressure and heart rate, body composition, health-related quality of life, cognitive performance, anxiety, depression, physical activity levels, sleep and sedentarism, biochemical markers, motivators and barriers to exercise. Assessments will be conducted at baseline, mid-intervention (i.e., week 13), at the end of the intervention (i.e., week 25), and 24 weeks later (i.e., week 49). DISCUSSION: The findings of this trial might provide valuable insights into the role of supervision and motivational strategies on the effectiveness of exercise programs for older adults. Additionally, the study could contribute to developing cost-effective interventions, supporting the design of future public policies for healthy aging. TRIAL REGISTRATION: NCT05619250. Registered 16 November 2022.
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Salud Mental , Motivación , Humanos , Anciano , Calidad de Vida , Ejercicio Físico/fisiología , Terapia por Ejercicio/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Objetivo: Conocer el uso de opioides en el paciente con enfermedad crónica avanzada en los últimos días de vida. Métodos: Estudio retrospectivo, multicéntrico, descriptivo y analítico. Se recogieron datos de los servicios de Geriatría del Hospital Universitario La Paz, Medicina Interna del Complejo Hospitalario de Toledo, Unidad de Hospital a Domicilio del Hospital Marina Baixa de la Vila Joiosa y del Hospital Centro de Cuidados Laguna. Se incluyeron en el estudio los pacientes ingresados con enfermedad avanzada no oncológica fallecidos entre el 1 de marzo de 2019 y el 29 de febrero de 2020. Se estudiaron distintas variables: edad, sexo, enfermedad principal, motivo de ingreso, valoración por cuidados paliativos, uso previo de opioides, uso de opioides en situación de últimos días, opioide, dosis, vías de administración e indicación. Resultados: En el estudio se incluyeron 261 pacientes, 143 (55 %) mujeres y 118 (45 %) hombres, con una edad media de 84 años. La enfermedad principal más frecuente fue la demencia, seguido de insuficiencia cardiaca y patología respiratoria. El motivo de ingreso más frecuente fue deterioro debido a la enfermedad de base seguido de infección respiratoria y sepsis. En la situación de últimos días, la mayoría de los pacientes tenían pauta de opioide basal (94 % morfina) y de rescate (98 % morfina). La vía de administración más utilizada fue la subcutánea (98 %) y la indicación más frecuente fue la disnea (42 %). La mediana de dosis equivalente de morfina oral diaria por enfermedad principal y por motivo de ingreso fue de 30 mg/día. Conclusiones: El uso de opioides en las enfermedades crónicas avanzadas en situación de últimos días está ampliamente extendido. La morfina es el opioide más usado, independientemente de la enfermedad. La vía de administración más utilizada es la subcutánea. No encontramos diferencias entre pacientes con diferentes patologías. (AU)
Objective: To determine the use of opioids in patients with advanced chronic disease in the last days of life. Methods: A retrospective, multicenter, descriptive, analytical study. Data were collected from the Geriatrics Department of Hospital La Paz, Internal Medicine Department of Complejo Hospitalario de Toledo, Hospital at Home Unit of Hospital Marina Baixa in0 La Vila Joiosa, and Hospital Centro de Cuidados Laguna. The study included patients with advanced non-oncological disease who died between 1 March 2019 and 29 February 2020. Different variables were studied: age, sex, main disease, reason for admission, palliative care assessment, previous opioid use, opioid use in last days, opioid, dose, routes of administration, and indication. Results: The study included 261 patients, 143 (55 %) women and 118 (45 %) men, with a mean age of 84 years. The most frequent main disease was dementia, followed by heart failure and respiratory pathology. The most frequent reason for admission was deterioration due to the underlying disease followed by respiratory infection and sepsis. In the last-day situation, most patients had a baseline (94 % morphine) and rescue (98 % morphine) opioid regimen. The most common route of administration was subcutaneous (98 %) and the most common indication was dyspnea (42 %). The median daily oral morphine equivalent dose per main disease and reason for admission was 30 mg/day. Conclusions: The use of opioids in advanced chronic illness in the last days situation is widespread. Morphine is the most commonly used opioid regardless of disease. The most used route of administration is subcutaneous. We found no differences between patients with different pathologies. (AU)
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Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/uso terapéutico , Enfermedad Crónica/tratamiento farmacológico , Cuidados Paliativos al Final de la Vida , Estudios Retrospectivos , Epidemiología Descriptiva , Analgésicos Opioides/administración & dosificaciónRESUMEN
Non-small cell lung cancer (NSCLC) is the most frequent form of lung cancer and represents a set of histological entities that have an ominous long-term prognosis, for example, adenocarcinoma, squamous carcinoma and large cell carcinoma. Both small cell and non-small cell lung cancer are the main causes of oncological death and the oncological diseases with the highest incidence worldwide. With regard to clinical approaches for NSCLC, several advances have been achieved in diagnosis and treatment; the analysis of different molecular markers has led to the development of new targeted therapies that have improved the prognosis for selected patients. Despite this, most patients are diagnosed in an advanced stage, presenting a limited life expectancy with an ominous short-term prognosis. Numerous molecular alterations have been described in recent years, allowing for the development of therapies directed against specific therapeutic targets. The correct identification of the expression of different molecular markers has allowed for the individualization of treatment throughout the disease course, expanding the available therapeutic arsenal. The purpose of this article is to summarize the main characteristics of NSCLC and the advances that have occurred in the use of targeted therapies, thus explaining the limitations that have been observed in the management of this disease.
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Lung cancer represents one of the most common neoplasms and the main cause of cancerassociated death worldwide. Its relationship with different risk factors such as tobacco, which is its main etiological factor, has been clearly established and despite the numerous advances achieved in the diagnosis, treatment and followup of these patients, the life expectancy of these patients is notably limited. Furthermore, its treatment is not exempt from comorbidities and frequently it neither provides optimal control of the disease nor improve the quality of life of these patients. Despite the possibility of performing screening tests in patients at risk, their implementation in daily clinical practice is complex and most of them are diagnosed at an advanced stage of their disease where systemic radiotherapy or chemotherapy treatments slightly improve their prognosis. Lung adenocarcinoma is the most representative type of lung cancer, with specific epidemiological, molecular and clinical features. Thus, a growing number of studies are being conducted to find potential therapeutic targets based on the study of different molecular pathways, improving the outcome for these patients. In addition, a broad spectrum of serological, immunohistochemical and genetic markers are being evaluated for use in the screening and followup of these patients in daily clinical practice, but unlike for other tumors, they are currently not implemented in the early diagnosis of the disease. Therefore, the aim of the present review was to summarize the main advances that have occurred in the development of serological and histological markers and their therapeutic implications in patients diagnosed with lung adenocarcinoma, explaining the limitations that have been observed and analyzing the future perspectives in the clinical management of this disease.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Calidad de Vida , Marcadores Genéticos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/genética , Pronóstico , Biomarcadores de Tumor/genéticaRESUMEN
BACKGROUND: Coats plus syndrome or cerebroretinal microangiopathy with calcifications and cysts (CMCC) is an exceedingly rare autosomal recessive disorder that predominantly affects the microvasculature in the retina, brain, bones, and gastrointestinal system. Unlike Coats disease, CMCC is bilateral and affects multiple organ systems. MATERIALS AND METHODS: Case report. RESULTS: We report the case of two brothers with Coats Plus syndrome who presented with variable phenotypic expression. One sibling (Patient 1) was thought to have atypical retinopathy of prematurity and was only diagnosed with Coats plus after his older brother (Patient 2) presented with a seizure and a left upper extremity tremor at 4 years of age. The CTC1 mutation was confirmed in both patients. Aggressive treatment with laser photocoagulation and intravitreal bevacizumab dramatically improved the retinal vascular and exudative changes. CONCLUSION: Coats Plus syndrome can have a variable phenotypic presentation, including retinal vascular findings. This rare genetic disease should be in the differential diagnosis in patients who present with atypical retinal pathology, including Retinopathy of Prematurity, Familial Exudative Vitreoretinopathy, or Coats disease associated with non-specific multiorgan abnormalities.
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Quistes del Sistema Nervioso Central , Leucoencefalopatías , Telangiectasia Retiniana , Retinopatía de la Prematuridad , Ataxia , Neoplasias Encefálicas , Calcinosis , Quistes del Sistema Nervioso Central/genética , Humanos , Recién Nacido , Coagulación con Láser , Leucoencefalopatías/genética , Masculino , Espasticidad Muscular , Enfermedades de la Retina , Telangiectasia Retiniana/diagnóstico , Telangiectasia Retiniana/genética , Telangiectasia Retiniana/terapia , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/genética , ConvulsionesRESUMEN
BACKGROUND AND OBJECTIVE: Research has documented the stigma that individuals with degenerative neurological diseases experience, but caregivers also experience stigma by association (i.e., affiliate stigma). In order to shed light on the stigma of caregivers of people with degenerative neurological diseases, the current study aimed to explore cross-cultural differences in the prevalence of Parkinson's disease (PD) caregiver affiliate stigma, as well as the relationship between PD symptoms and caregiver affiliate stigma. Applications for Alzheimer's disease are discussed. METHODS: Survey data were collected in PD clinics at public, academic medical centers. Informal caregivers of an individual with PD from the US (n = 105) and from Mexico (n = 148) participated in the study. Caregivers completed a questionnaire that included the MDS Unified PD Rating Scale to describe the symptoms of the individual with PD, as well as the Affiliate Stigma Scale and demographic information. RESULTS: A series of multiple regressions was run to examine whether PD symptoms were associated with affiliate stigma and if these differed by country. These regressions suggested that different patterns of PD symptoms predicted affiliate stigma in each country. Stigma was higher in the US compared to Mexico, and the relationship between bowel/bladder symptoms and affiliate stigma was significantly stronger in the US. CONCLUSION: Symptoms of individuals with neurodegenerative diseases are related to affiliate stigma experienced by caregivers, and these relationships may differ cross-culturally. Negative public attitudes concerning bowl and bladder issues and the physical symptoms that accompany PD remain a source of stigma for caregivers and families, particularly in the US. Interventions for caregivers of individuals with neurodegenerative diseases should include strategies for coping with stigma concerning bladder and bowel problems, as well as other physical and mental health issues.
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Cuidadores/psicología , Comparación Transcultural , Enfermedad de Parkinson/psicología , Estigma Social , Enfermedad de Alzheimer/psicología , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Encuestas y Cuestionarios/estadística & datos numéricos , Estados UnidosRESUMEN
Cancer is a complex disease affecting millions of people worldwide, with over a hundred clinically approved drugs available. In order to improve therapy, treatment, and response, it is essential to draw better maps of the targets of cancer drugs and possible side interactors. This study presents a large-scale screening method to find associations of cancer drugs with human genes. The analysis is focused on the current collection of Food and Drug Administration (FDA)-approved drugs (which includes about one hundred chemicals). The approach integrates global gene-expression transcriptomic profiles with drug-activity profiles of a set of 60 human cell lines obtained for a collection of chemical compounds (small bioactive molecules). Using a standardized expression for each gene versus standardized activity for each drug, Pearson and Spearman correlations were calculated for all possible pairwise gene-drug combinations. These correlations were used to build a global bipartite network that includes 1007 gene-drug significant associations. The data are integrated into an open web-tool called GEDA (Gene Expression and Drug Activity) which includes a relational view of cancer drugs and genes, disclosing the putative indirect interactions found for FDA-approved drugs as well as the known targets of these drugs. The results also provide insight into the complex action of pharmaceuticals, presenting an alternative view to address predicted pleiotropic effects of the drugs.
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Resistencia a Antineoplásicos , Redes Reguladoras de Genes , Neoplasias/genética , Transcriptoma , Línea Celular Tumoral , Biología Computacional/métodos , HumanosRESUMEN
BACKGROUND/OBJECTIVE: Given the growing population of individuals with Parkinson's disease (PD) worldwide and the growing need for family members to take on a caregiving role, it is critical that cross-cultural differences be examined in order to better meet the needs of PD caregivers. The purpose of this study was to examine the connections between the unmet needs and mental health of PD caregivers differentially in Mexico and the United States. METHODS: In Parkinson's clinics at public, academic medical centers, PD caregivers from Mexico (nâ=â148) and the United States (nâ=â105) completed measures of unmet family needs and mental health. RESULTS: Caregivers in the United States had higher unmet needs for emotional support and for a community support network than caregivers in Mexico, although caregivers at the two sites had comparable levels of anxiety and depression. Unmet family needs explained 29.5% of the variance in caregiver anxiety in the United States (pâ<â0.001) but only 5.7% in Mexico (pâ=â0.209). Unmet family needs explained 30.4% of the variance in caregiver depression in the United States (pâ<â0.001) and 14.0% in Mexico (pâ=â0.001). In the United States, unmet needs for emotional support and for instrumental support uniquely predicted caregiver anxiety and depression, and in Mexico only the unmet need for instrumental support was a unique predictor. CONCLUSIONS: PD caregivers in the United States are at increased risk for poor emotional and community support, and these unmet needs channel directly into caregiver anxiety and depression. In Mexico, where caregivers have stronger emotional and community support, caregivers' unmet need for instrumental support generates anxiety and depression. Important targets for PD caregiver interventions may differ between Mexico and the United States.
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Cuidadores/psicología , Comparación Transcultural , Familia/psicología , Enfermedad de Parkinson/psicología , Adulto , Anciano , Ansiedad/epidemiología , Ansiedad/psicología , Depresión/epidemiología , Depresión/psicología , Emociones , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/enfermería , Estados UnidosRESUMEN
Fetal Magnetic Resonance Imaging (MRI) is increasingly used in prenatal evaluations. OBJECTIVE: Identify common brain malformations on fetal MRI and evaluate perinatal course. METHODS: Fetal consultations from 10/2016 to 12/2017 reviewed. RESULTS: Hundred consultations were requested; 94 were completed. Findings included: posterior fossa malformations (19%), agenesis/dysgenesis of corpus callosum (15%), congenital aqueductal stenosis (CAS) (14%), ventriculomegaly (11%), isolated cortical malformations (8.5%), and holoprosencephaly (6%). Posterior fossa malformations were more likely to be associated with genetic conditions and cardiac malformations. Patients with CAS all required intensive care unit admission. Overall, few patients with congenital brain malformations required feeding or respiratory support at discharge. None had seizures as neonates except two with early epileptic encephalopathy syndromes. CONCLUSIONS: Even though long term neurological prognosis is poor for many conditions including high lifetime risk of epilepsy, most are discharged with no feeding or respiratory support. Seizures are rarely seen in the neonatal period.
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Encéfalo/diagnóstico por imagen , Feto/diagnóstico por imagen , Imagen por Resonancia Magnética , Malformaciones del Sistema Nervioso/diagnóstico por imagen , Diagnóstico Prenatal , Agenesia del Cuerpo Calloso/diagnóstico por imagen , Agenesia del Cuerpo Calloso/embriología , Encéfalo/anomalías , Encéfalo/embriología , Feto/anomalías , Holoprosencefalia/diagnóstico por imagen , Holoprosencefalia/embriología , Humanos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/embriología , Recién Nacido , Malformaciones del Sistema Nervioso/embriología , Estudios Retrospectivos , Convulsiones/etiologíaRESUMEN
BACKGROUND AND PURPOSE: To examine prenatal MRI and postnatal imaging in fetuses with congenital aqueductal stenosis (CAS) to determine the frequency of association of rhombencephalosynapsis (RES) and how it may affect neonatal intensive care unit (NICU) course. MATERIALS AND METHODS: A single center IRB-approved retrospective study of children with CAS was performed. Prenatal MRI, postnatal images, and clinical data were reviewed. Statistical analysis was performed with SAS statistical software package version 9.3. RESULTS: Aqueduct obstruction was confirmed for all 30 participants. Hydrocephalus required shunting in all but one (97%). Fifteen neonates had CAS with rhomboencephalosynapsis (RES) (50%). Although neonatal course between the two groups was comparable, 53% of CAS with RES neonates required feeding assistance versus 20% in CAS only (P = 0.128). Shunting in the CAS with RES group occurred at average of 6 days of life versus CAS group at 55 days (P = 0.196). Biometry measurements showed a statistically significant decrease in pons antero-posterior diameter in both groups (CAS only P = 0.0049 and CAS with RES P = 0.0003) when compared with norms for gestational age. CONCLUSION: CAS has a high association with RES. Feeding assistance in the NICU and earlier neurosurgical intervention may be required in patients with CAS who also have RES.
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Cerebelo/anomalías , Hidrocefalia/diagnóstico por imagen , Malformaciones del Sistema Nervioso/diagnóstico por imagen , Adulto , Métodos de Alimentación , Femenino , Humanos , Hidrocefalia/complicaciones , Hidrocefalia/congénito , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Cuidado Intensivo Neonatal , Imagen por Resonancia Magnética , Masculino , Malformaciones del Sistema Nervioso/complicaciones , Procedimientos Neuroquirúrgicos , Puente/diagnóstico por imagen , Embarazo , Diagnóstico Prenatal , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
PURPOSE: To evaluate the effects of progressive hydrocephalus on the developing brain in a cohort of fetuses diagnosed with congenital aqueduct stenosis by comparing prenatal magnetic resonance imaging and postnatal imaging. METHODS: This IRB approved single center retrospective review of prenatally diagnosed children with congenital aqueduct stenosis interrogated changes in the brain between prenatal and postnatal imaging and analyzed statistics using SAS software package version 9.3. RESULTS: Thirty fetuses imaged at a mean gestational age of 26 weeks had aqueduct obstruction confirmed by postnatal imaging. Progressive hydrocephalus required shunting in all but one patient (97%). Those patients with increasing hydrocephalus showed increase in ventricular rupture (60%), loss of septal leaflets (47%), and reduction in white matter and corpus callosum volume (43%). Cerebellar ectopia developed in 27% with 6% meeting the criteria for Chiari I malformation. CONCLUSION: Hydrocephalus in the fetus results in enlarging ventricular rupture, loss of the septum pellucidum leaflets, volume reduction of brain parenchyma including corpus callosum, and risk for Chiari I anomaly. Given advances in fetal surgery and imaging in the last 3 decades, there may be cause to revisit the idea of in utero cerebral spinal fluid diversion as a means to potentially ameliorate progressive loss of the developing brain.
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Feto/cirugía , Edad Gestacional , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/cirugía , Imagen por Resonancia Magnética , Diagnóstico Prenatal/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/embriología , Ventrículos Cerebrales/diagnóstico por imagen , Derivaciones del Líquido Cefalorraquídeo , Estudios de Cohortes , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Rotura Espontánea/epidemiologíaRESUMEN
Unraveling the protein interaction wiring that occurs in human cells as a scaffold of biological processes requires the identification of all elements that constitute such molecular interaction networks. Proteome-wide experimental studies and bioinformatic comprehensive efforts have provided reliable and updated compendiums of the human protein interactome. In this work, we present a current view of available databases of human protein-protein interactions (PPIs) that allow building protein interaction networks. We also investigate human proteins as targets of specific drugs to analyze how chemicals interact with different target proteins, placing also the study in a network relational space. Hence, we undertake a description of several major drug-target resources to provide a present perspective of the associations between human proteins and specific chemicals. The identification of molecular targets for specific drugs is a critical step to improve disease therapy. As different diseases have different biomolecular scenarios, we addressed the identification of drug-targeted genes focusing our investigations on cancer and cancer genes. So, a description of resources that provide curated compendiums of human cancer genes is presented. Cancer is a complex disease where multiple genetic changes rewire cellular networks during carcinogenesis. This indicates that cancer drug therapy needs the implementation of network-driven studies to reveal multiplex interactions between cancer genes and drugs. To make progress in this direction, in the last part of this work we provide a bipartite network of cancer genes and their drugs shown in a graph landscape that disclose the existence of specific drug-target modules.
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Antineoplásicos/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Mapas de Interacción de Proteínas , Antineoplásicos/química , Humanos , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Neoplasias/química , Neoplasias/metabolismoRESUMEN
BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are slow-growing tumors, which can cause obstructive hydrocephalus in patients with tuberous sclerosis complex (TSC). These tumors require routine surveillance with magnetic resonance imaging. Current consensus guidelines recommend treatment of asymptomatic SEGAs with an mechanistic target of rapamycin (mTOR) inhibitor because these medications have demonstrated efficacy and safety in multiple prospective clinical trials. For symptomatic SEGAs, standard therapy typically involves surgical resection of the tumor to relieve mass effect and resolve hydrocephalus. However, resection can be associated with significant perioperative morbidity and complications. There are anecdotal reports of using mTOR inhibitors to reduce tumor size in preparation for surgery, but prospective studies comparing sole mTOR inhibitor therapy with surgical management have not been completed. METHODS: Here, we present a seven-year-old boy with a large, symptomatic SEGA which was treated acutely with everolimus. RESULTS: Everolimus treatment resulted in rapid reduction in tumor size, symptomatic improvement, and decrease in cerebrospinal fluid protein. CONCLUSIONS: Everolimus can effectively reduce tumor size, decrease cerebrospinal fluid protein, and allow successful ventriculoperitoneal shunt placement without the need for surgical resection of a symptomatic SEGA.
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Antineoplásicos/uso terapéutico , Astrocitoma/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Everolimus/uso terapéutico , Hidrocefalia/tratamiento farmacológico , Astrocitoma/complicaciones , Astrocitoma/diagnóstico por imagen , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Niño , Preescolar , Humanos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/etiología , Imagen por Resonancia Magnética , Masculino , Resultado del TratamientoAsunto(s)
Eosinofilia/parasitología , Púrpura/parasitología , Toxocariasis/complicaciones , Toxocariasis/diagnóstico , Albendazol/uso terapéutico , Animales , Antihelmínticos/uso terapéutico , Preescolar , Diagnóstico Diferencial , Humanos , Masculino , Toxocara canis , Toxocariasis/tratamiento farmacológicoRESUMEN
OBJECTIVE: Given reports of high pain thresholds and reduced auditory response in individuals with agenesis of the corpus callosum (AgCC), this study investigated whether affected participants report atypical experiences and behaviors on a well-established sensory processing measure. METHODS: Fourteen participants with AgCC (ages 11-59) completed the Adolescent/Adult Sensory Profile (Brown & Dunn, 2001). Sensory profile scales were classified as "Atypical" if they were more than 1 standard deviation from the mean. RESULTS: Fifty-seven percent of participants with AgCC reported reduced sensory registration as compared to an expected 16% of the normative sample. Similarly, 50% of the AgCC participants reported atypically increased auditory processing difficulties. CONCLUSIONS: Using a well-established sensory processing questionnaire, participants with AgCC reported measurable differences in multiple aspects of sensory processing. The most notable difference was in the quadrant of low sensory registration, suggesting that individuals with AgCC may require sensory information to be presented more slowly or at a higher intensity for adequate processing. The sensory modality that was most affected was the auditory system, which is consistent with increased rates of language disorders and autism spectrum disorders in this population. Understanding sensory processing in individuals with AgCC can both elucidate the role of interhemispheric transfer in the development of intact sensory processing as well as contribute to our knowledge of the role of the corpus callosum in a range of disorders in which sensory processes are impacted. (PsycINFO Database Record
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Agenesia del Cuerpo Calloso/psicología , Percepción , Sensación , Adolescente , Adulto , Agenesia del Cuerpo Calloso/complicaciones , Agenesia del Cuerpo Calloso/epidemiología , Percepción Auditiva , Trastorno Autístico/epidemiología , Trastorno Autístico/etiología , Trastorno Autístico/psicología , Niño , Cognición , Femenino , Humanos , Trastornos del Lenguaje/epidemiología , Trastornos del Lenguaje/etiología , Trastornos del Lenguaje/psicología , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Drugs use at party contexts has increased in recent decades. Drugs dealing facilitates consumer access to substances, whose sales practices vary according to drugs use, places for the consumption and the drug social function. Drug dealing is socially constructed from a set of practices ranging from reasons to dealing and those related to the consolidation as a common practice. The aim of this research was to describe and analyze the drugs users' experience in party contexts, about their dealer's construction process. An interpretative multiple-case study with the snowball technique was carried out to get the participants. The information was obtained by a semi-structured interview and nonparticipant observation at the dealing places. The information obtained points out the group's participation on the selection of the dealer as the initiation of drugs dealing, the extroversion features and communication skills as an important profile to be a dealer; specially, the capability to satisfy the group's emotional request through the drugs. Also, benefits as acceptation, protection and the warmth from the group and the economical earning. The dealer/businessmen consolidation is socially constructed according to the new identity assumed, the group participation and the specific activities as a business.
El uso de drogas en contextos de fiesta se ha incrementado en las últimas décadas. El narcomenudeo facilita el acceso a sustancias de consumo, cuyas prácticas de venta varían conforme a la droga de uso, los espacios de consumo y la función de la droga en los grupos que la consumen. La venta de drogas implica una serie de prácticas que la construyen y que incluyen los motivos del inicio de venta, el proceso de desarrollo y las relacionadas con la consolidación de la venta como práctica habitual. El objetivo de esta investigación fue describir y analizar la experiencia de usuarios de drogas en contextos de fiesta respecto al proceso en que se construyen como dealers. Para lo anterior, se realizó un estudio interpretativo de casos múltiples, empleando la técnica de "bola de nieve" para captar a los participantes. La observación se obtuvo por medio de una entrevista semiestructurada y la observación no participante en escenarios de venta. Se obtuvo información relacionada con los elementos del salto del uso a la venta como la elección del dealer por el grupo, su perfil para ser elegido como la extroversión y habilidades de comunicación; y sobre todo su capacidad para satisfacer la demanda de emociones de los miembros de su grupo por medio de las drogas de venta. Además, de la aceptación, protección y afecto del grupo y las ganancias económicas. La consolidación como dealer/empresario se construye conforme se asumen una nueva identidad, la participación del grupo y las actividades específicas de la empresa.