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BACKGROUND: Obesity is associated with multiple pregnancy-related complications. Bariatric surgery is frequently performed in women of childbearing age. While the impact of bariatric surgery on fertility and nutritional complications has been characterized, few studies on effects of bariatric surgery on obesity-related pregnancy complications exist. The purpose of this study is to examine the impact of bariatric surgery on pregnancy complications in a US insured population. METHODS: Pregnancy-related claims from 2011-2019 were obtained from MarketScan commercial claims database for bariatric surgical patients and non-surgical patients with no history of obesity. Claims were grouped into 3 time periods: pre-surgery (time of first claim to date of surgery), peri-surgery (date of surgery to 24 month postoperatively), and post-surgery (> 24 month postoperatively). Peri-surgery period was defined based on the recommendation to avoid pregnancy for the first 12-24 months following surgery. Codes for both maternal and fetal pregnancy-related complications were extracted from the database. Standardized incidence rates in person-months (pms) were calculated and generalized estimating equations with Poisson distribution tested for differences in each category at the three time intervals. RESULTS: The final cohort included 163612 female bariatric surgery patients. The rate of successful births was 3/1000 pms in the pre-surgery and peri-surgery period and increased to 4/1000 pms in the post-surgery period, compared to a rate of 7/1000 in the control group. The rate of pregnancy complications in the pre-surgery group was 4/1000 pms and dropped to 2/1000 pms in the peri- and post-surgery periods. The complication rate in the control group was 4/1000 pms. CONCLUSION: After bariatric surgery, the rate of pregnancy complications is lower than non-obese, non-bariatric surgery patients. Compared to before surgery, pregnancy complications decrease by 63% in the peri-surgery period and 57% in the post-surgery period. In the US, bariatric surgery is an important intervention for decreasing pregnancy complications in patients with obesity.
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ABSTRACT: We examined the records of the Connecticut Office of the Chief Medical Examiner for all female homicides from 2012 to 2021 to ascertain the rate of femicide. The investigative data were subcategorized as femicides and nonfemicides. The records included autopsy, toxicology, and investigators' reports. All underwent autopsy examination. The relationship of the perpetrator, cause of death, and special circumstances were examined in conjunction with the United Nations operational criteria. If the death investigation did not identify the suspected perpetrator, news media were searched for a reported homicide or manslaughter arrest. The total number of homicides was 271, and 259 (96%) could be further categorized, of which 181 (70%) were femicides. Differences between the 2 cohorts included causes of death ( P 's < 0.001), age at death ( P < 0.001), and the involvement of murder-suicide ( P < 0.001). No differences were observed for race, and the yearly rate of femicides did not increase during the COVID-19 pandemic.
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COVID-19 , Homicidio , Humanos , Homicidio/estadística & datos numéricos , Femenino , Connecticut/epidemiología , Adulto , Persona de Mediana Edad , Adolescente , COVID-19/mortalidad , COVID-19/epidemiología , Adulto Joven , Anciano , Médicos Forenses , Causas de Muerte , Suicidio Completo/estadística & datos numéricos , Autopsia/estadística & datos numéricos , Niño , Distribución por Edad , Anciano de 80 o más AñosRESUMEN
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions (mean semiquantitative value ≤1) and classify them as cortical-sparing CTE (CSCTE). Of 620 brain donors with pathologically diagnosed CTE, 66 (11%) met criteria for CSCTE. Compared to typical high stage CTE, those with CSCTE had a similar age at death and years of contact sports participation and were less likely to carry apolipoprotein ε4 (p < 0.05). CSCTE had less overall tau pathology severity, but a proportional increase of disease burden in medial temporal lobe and brainstem regions compared to the neocortex (p's < 0.001). CSCTE also had lower prevalence of comorbid neurodegenerative disease. Clinically, CSCTE participants were less likely to have dementia (p = 0.023) and had less severe cognitive difficulties (as reported by informants using the Functional Activities Questionnaire (FAQ); p < 0.001, meta-cognitional index T score; p = 0.002 and Cognitive Difficulties Scale (CDS); p < 0.001,) but had an earlier onset age of behavioral (p = 0.006) and Parkinsonian motor (p = 0.013) symptoms when compared to typical high stage CTE. Other comorbid tauopathies likely contributed in part to these differences: when cases with concurrent Alzheimer dementia or frontal temporal lobar degeneration with tau pathology were excluded, differences were largely retained, but only remained significant for FAQ (p = 0.042), meta-cognition index T score (p = 0.014) and age of Parkinsonian motor symptom onset (p = 0.046). Overall, CSCTE appears to be a distinct subtype of high stage CTE with relatively greater involvement of subcortical and brainstem regions and less severe cognitive symptoms.
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Enfermedad de Alzheimer , Encefalopatía Traumática Crónica , Enfermedades Neurodegenerativas , Humanos , Estudios Transversales , EncéfaloRESUMEN
ABSTRACT: Suicide rapidly increased in the United States by 30% from 2000 to 2020, accounting for more than 800,000 deaths ( Neurosci Res Program Bull . 1972; 10: 384-8). Studies have shown that there are a multitude of underlying issues, including mental illness, that elevate an individual's risk of dying by suicide ( CDC WONDER: Underlying cause of death, 1999-2019 . Atlanta, GA: US Department of Health and Human Services, CDC; 2020). Presented here is a case of Bing Neel syndrome (BNS) found in a 69-year-old man who died by suicide by jumping off a 135' bridge. His medical history was significant for traumatic brain injury, Waldenstrom macroglobulinemia (WM), major depressive disorder, suicidal ideation, and anxiety. Bing Neel syndrome is a rare central nervous system complication of WM. His wife reported an abrupt mental deterioration starting 5 years before his death, characterized by paranoia, depression, and insomnia. He had been a high-functioning university professor. His decline culminated with the loss of independence in his activities of daily living. At autopsy, it was found that he experienced blunt force injuries related to the fall, causing his death. A neuropathologic examination revealed a brisk and fulminant clonal CD20 + /immunoglobulin M+ lymphocytic infiltrate, involving all sampled regions of his brain, consistent with WM. This workup was critical to obtaining an accurate pathologic diagnosis of BNS and understanding his full clinical status before death. Although BNS was not the proximate cause of death, this diagnosis aided the death investigation as a causal factor in his suicidality and was vital to providing his family closure.
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Trastorno Depresivo Mayor , Trastornos Psicóticos , Suicidio , Macroglobulinemia de Waldenström , Humanos , Masculino , Animales , Bovinos , Anciano , Ideación Suicida , Actividades Cotidianas , Macroglobulinemia de Waldenström/complicaciones , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/patología , Trastornos Psicóticos/complicacionesRESUMEN
Meningioma is the most common intracranial neoplasm, yet there is no effective therapy for recurrent/refractory meningiomas after surgery and radiation. Prostate-specific membrane antigen (PSMA) is an enzyme upregulated on endothelial cells of multiple neoplasms and is being investigated as a theranostic target. Until now, PSMA has not been studied in meningiomas. We aimed to verify PSMA endothelial expression in meningiomas, detect tumor grade variability, and investigate the relationship of PSMA signal with tumor recurrence. We analyzed 96 archival meningiomas including 58 de novo and 38 recurrent specimens. All specimens were stained routinely and immunostained for CD31 and PSMA. Slides were scanned and analyzed producing raw data for images of PSMA, CD31, PSMA/CD31, and PSMA/vasculature. PSMA expression was seen within 98.9% of meningioma samples. In the total cohort, higher-grade tumors had increased expression of raw PSMA and PSMA/CD31, and PSMA/vasculature ratios compared to grade 1 tumors. PSMA expression and PSMA/vasculature ratios (p = 0.0015) were higher in recurrent versus de novo tumors among paired samples. ROC curves demonstrated PSMA/CD31, PSMA/vasculature, and raw CD31 as indicators of tumor recurrence. Thus, PSMA is expressed within endothelial cells of meningiomas, is increased with tumor grade and recurrence, and persists with prior irradiation.
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Neoplasias Meníngeas , Meningioma , Humanos , Masculino , Meningioma/cirugía , Recurrencia Local de Neoplasia , Medicina de Precisión , Células Endoteliales , Próstata , Neoplasias Meníngeas/cirugíaRESUMEN
INTRODUCTION: Intraductal tubulopapillary neoplasm (ITPN) is a recently described rare tumor of the pancreas. Diagnostic approach and treatment are based on relatively few cases. PRESENTATION OF CASE: Here we report a case of a 68-year-old male presenting with an ampullary adenoma with high grade dysplasia who underwent pancreaticoduodenectomy and was incidentally found to have an ITPN at the pancreatic resection margin with areas of microinvasion throughout the resected specimen. He went on to rapidly develop an invasive adenocarcinoma arising in association with recurrent ITPN in the remnant pancreas requiring a completion total pancreatectomy. DISCUSSION: Patients with ITPN present with non-specific symptoms and diagnosis can be challenging. Radiographic evaluation will reveal tumor ingrowth into the main pancreatic duct and distal duct dilatation without upstream dilation or mucinous engorgement. ITPNs are treated with formal resection given that determination of an invasive component can be difficult and the risk of malignant transformation. Following resection, recurrences are infrequent and 5-year survival is over 70 % even with microinvasion. CONCLUSIONS: ITPNs can follow a variable clinical course but hold the potential for malignant transformation. When ITPN is incidentally found at a pancreatic resection margin, we recommend completion resection due to the risk of local recurrence.
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Infecciones por Coronavirus/epidemiología , Personas con Mala Vivienda , Neumonía Viral/epidemiología , Rol Profesional , Clínica Administrada por Estudiantes/organización & administración , Estudiantes de Medicina , Telemedicina/organización & administración , Betacoronavirus , COVID-19 , Humanos , New Hampshire/epidemiología , Pandemias , SARS-CoV-2RESUMEN
Increasing evidence suggests a role for inflammation in neuropsychiatric conditions including autism spectrum disorder (ASD), a neurodevelopmental syndrome with higher prevalence in males than females. Here we examined the effects of early-life immune system activation (EIA)-comprising regimens of prenatal, early postnatal, or combined ("two-hit") immune activation-on the core behavioral features of ASD (decreased social interaction, increased repetitive behavior, and aberrant communication) in C57BL/6J mice. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C) on gestational day 12.5 to produce maternal immune activation (MIA). Some offspring also received lipopolysaccharide (LPS) on postnatal day 9 to produce postnatal immune activation (PIA). EIA produced disruptions in social behavior and increases in repetitive behaviors that were larger in males than in females. Ultrasonic vocalizations (USVs) were altered in both sexes. Molecular studies revealed that EIA also produced prominent sex-specific changes in inflammation-related gene expression in the brain. Whereas both sexes showed increases in pro-inflammatory factors, as reflected by levels of mRNA and protein, expression of anti-inflammatory factors was decreased in males but increased in females. Our findings demonstrate that EIA can produce sex-specific behavioral effects and immune responses in the brain, and identify molecular processes that may contribute to resilience in females.
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Trastorno Autístico/etiología , Trastorno Autístico/psicología , Inmunidad , Exposición Materna/efectos adversos , Neuroinmunomodulación , Efectos Tardíos de la Exposición Prenatal , Animales , Conducta Animal , Biomarcadores , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Expresión Génica , Mediadores de Inflamación/metabolismo , Masculino , Ratones , Embarazo , Factores Sexuales , Conducta SocialRESUMEN
Inflammatory processes may be involved in the pathophysiology of neuropsychiatric illnesses including autism spectrum disorder (ASD). Evidence from studies in rodents indicates that immune activation during early development can produce core features of ASD (social interaction deficits, dysregulation of communication, increases in stereotyped behaviors, and anxiety), although the neural mechanisms of these effects are not thoroughly understood. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C), which simulates a viral infection, or vehicle on gestational day 12.5 to produce maternal immune activation (MIA). Male offspring received either vehicle or lipopolysaccharide, which simulates a bacterial infection, on postnatal day 9 to produce postnatal immune activation (PIA). We then used optogenetics to address the possibility that early developmental immune activation causes persistent alterations in the flow of signals within the mPFC to basolateral amygdala (BLA) pathway, a circuit implicated in ASD. We found that our MIA regimen produced increases in synaptic strength in glutamatergic projections from the mPFC to the BLA. In contrast, our PIA regimen produced decreases in feedforward GABAergic inhibitory postsynaptic responses resulting from activation of local circuit interneurons in the BLA by mPFC-originating fibers. Both effects were seen together when the regimens were combined. Changes in the balance between excitation and inhibition were differentially translated into the modified spike output of BLA neurons. Our findings raise the possibility that prenatal and postnatal immune activation may affect different cellular targets within brain circuits that regulate some of the core behavioral signs of conditions such as ASD.SIGNIFICANCE STATEMENT Immune system activation during prenatal and early postnatal development may contribute to the development of autism spectrum disorder (ASD). Combining optogenetic approaches and behavioral assays that reflect core features of ASD (anxiety, decreased social interactions), we uncovered mechanisms by which the ASD-associated behavioral impairments induced by immune activation could be mediated at the level of interactions within brain circuits implicated in control of emotion and motivation (mPFC and BLA, specifically). Here, we present evidence that prenatal and postnatal immune activation can have different cellular targets in the brain, providing support to the notion that the etiology of ASD may be linked to the excitation/inhibition imbalance in the brain affecting the signal flow within relevant behavior-driving neural microcircuits.
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Amígdala del Cerebelo/fisiopatología , Trastorno del Espectro Autista/inmunología , Corteza Prefrontal/fisiopatología , Efectos Tardíos de la Exposición Prenatal/inmunología , Transmisión Sináptica , Amígdala del Cerebelo/inmunología , Animales , Trastorno del Espectro Autista/etiología , Trastorno del Espectro Autista/fisiopatología , Femenino , Neuronas GABAérgicas/metabolismo , Neuronas GABAérgicas/fisiología , Interneuronas/metabolismo , Interneuronas/fisiología , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos C57BL , Corteza Prefrontal/inmunología , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Efectos Tardíos de la Exposición Prenatal/fisiopatologíaRESUMEN
Increasing evidence suggests a role for inflammation in neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous work in rodents has established that immune activation during critical developmental periods can cause phenotypes that reproduce core features of ASD, including decreased social interaction, aberrant communication, and increased repetitive behavior. In humans, ASD is frequently associated with comorbid medical conditions including sleep disorders, motor hyperactivity, and seizures. Here we use a 'two-hit' immune-activation paradigm to determine whether perinatal immune activation can also produce these comorbid features in mice. In this paradigm, we treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C), which simulates a viral infection, on gestational day 12.5 according to an established maternal immune activation regimen. A subset of the offspring also received a second 'hit' of lipopolysaccharide (LPS), which simulates a bacterial infection, on postnatal day 9. At 6 weeks of age, mice were implanted with wireless telemetry transmitters that enabled continuous measurements of electroencephalography (EEG), electromyography (EMG), locomotor activity, and subcutaneous temperature. Effects at 7 and 12 weeks of age were compared. Both prenatal Poly I:C and postnatal LPS produced changes in locomotor activity and temperature patterns, increases in slow-wave sleep, and shifts in EEG spectral power, several of which persisted at 12 weeks of age. Postnatal LPS also produced persistent increases in spontaneous bursts of epileptiform activity (spike-wave discharges) that occurred predominantly during sleep. Our findings demonstrate that early-life immune activation can lead to long-lasting physiologic perturbations that resemble medical comorbidities often seen in ASD and other neuropsychiatric conditions.
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Encéfalo/crecimiento & desarrollo , Encéfalo/inmunología , Epilepsia/inmunología , Inflamación/fisiopatología , Trastornos Mentales/inmunología , Sueño/inmunología , Animales , Animales Recién Nacidos , Temperatura Corporal/inmunología , Modelos Animales de Enfermedad , Electroencefalografía , Femenino , Lipopolisacáridos , Masculino , Trastornos Mentales/etiología , Ratones , Ratones Endogámicos C57BL , Actividad Motora/inmunología , Poli I-C , Embarazo , Complicaciones Infecciosas del Embarazo , Efectos Tardíos de la Exposición PrenatalRESUMEN
AIM: To evaluate the prevalence of hyperglycemia and dyslipidemia in the population of Isabela, Galápagos, Ecuador, across gender and age (above or below 50). METHODS: In this population-based retrospective cross-sectional study among individuals in Isabela, Galápagos, Ecuador, demographic and metabolic factors were evaluated based on World Health Organization (WHO) Global Guidelines. RESULTS: The population overall exceeded the WHO guidelines for cardiovascular health. As to be expected, there was significance in the trend of increasing dyslipidemia and hyperglycemia with age except postprandial glucose. In those individuals below the age of 50, 8.0%, 49% and 26% had hyperglycemia, hypercholesterolemia and hypertriglyceridemia, respectively. However, in those above 50, they measured 24%, 68% and 36% respectively, showing a significant increase. CONCLUSIONS: Hyperglycemia and dyslipidemia appear to be prevalent in Isabela, Galápagos, Ecuador and this pilot study supports further research into metabolic syndrome and diabetes. Such data may help in healthcare planning and screening to ensure not only timely diagnosis, but prevention. The limitations of this data illustrate modalities that data collection can be improved, such as having a linked clinical history to the data itself and better patient follow up for such entities as post prandial glucose, for example. However, this pilot study presents a starting point for future directions of research, such as ascertaining prevalence of diabetes type II, metabolic syndrome and cardiovascular disease.
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Enfermedades Cardiovasculares , Dislipidemias/epidemiología , Hiperglucemia/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/prevención & control , Dislipidemias/complicaciones , Ecuador/epidemiología , Femenino , Humanos , Hiperglucemia/complicaciones , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/prevención & control , Persona de Mediana Edad , Proyectos Piloto , Periodo Posprandial , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVES: To study rates and predictors of hepatitis C virus (HCV) cure among human immunodeficiency virus (HIV)/HCV-coinfected patients, and then to evaluate the effect of attendance at clinic visits on HCV cure. METHODS: Retrospective cohort study of adult HIV/HCV-coinfected patients who initiated and completed treatment for HCV with direct-acting antivirals (DAAs) between January 1, 2014, and June 30, 2015. RESULTS: Eighty-four participants reported completing treatment. The median age was 58 years (interquartile ratio, 50-66); 88% were male and 50% were black. One-third were cirrhotic and half were HCV-treatment-experienced. The most commonly used regimen was sofosbuvir/ledipasvir (40%) followed by simeprevir/sofosbuvir (30%). Cure was achieved in 83.3%, 11.9% relapsed, and 2.3% experienced virological breakthrough. Two patients (2.3%) did not complete treatment based on pill counts and follow-up visit documentation. In multivariable analysis, cure was associated with attendance at follow-up clinic visits (odds ratio [OR], 9.0; 95% CI, 2.91-163) and with use of an integrase-based HIV regimen versus other non-integrase regimens, such as non-nucleoside analogues or protease inhibitors (OR, 6.22; 95% CI 1.81-141). Age, race, genotype, presence of cirrhosis, prior HCV treatment, HCV regimen, and pre-treatment CD4 counts were not associated with cure. CONCLUSIONS: Real-world HCV cure rates with DAAs in HCV/HIV coinfection are lower than those seen in clinical trials. Cure is associated with attendance at follow-up clinic visits and with use of an integrase-based HIV regimen. Future studies should evaluate best antiretroviral regimens, predictors of attendance at follow-up visits, impact of different monitoring protocols on medication adherence, and interventions to ensure adequate models of HIV/HCV care.
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Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Anciano , Coinfección/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Inhibidores de Integrasa VIH/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral/efectos de los fármacos , Carga Viral/estadística & datos numéricosAsunto(s)
Dermatología , Drama , Medicina en las Artes , Música , Canto , Enfermedades de la Piel , Femenino , Humanos , MasculinoRESUMEN
Muscle fat infiltration (MFI) is an expected consequence of incomplete spinal cord injury (iSCI). The MFI magnitude may have clinical value in determining functional recovery. However, there is a lack of understanding of how MFI relates to the volitional muscle activity in people with motor incomplete spinal cord injury (iSCI). Five iSCI and 5 uninjured age-matched control subjects participated in the study. In this preliminary study, we established the reliability of MFI quantification of select lower extremity muscles across different raters. Secondly, we assessed the magnitude and distribution of MFI in the lower legs of iSCI and uninjured control participants. Thirdly, we explored the relationship between MFI in the plantar flexor muscles and the ability to volitionally activate these muscles. High levels of inter-rater reliability were observed. The iSCI group had significantly elevated and a vastly different MFI distribution in the lower leg muscles compared to healthy controls. MFI was negatively correlated with volitional activation in iSCI. Our preliminary results sanction the importance of lower extremity MFI quantification as a potential measure in determining the functional outcomes in iSCI, and the subsequent pathological sequelae.
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Tejido Adiposo , Extremidad Inferior , Imagen por Resonancia Magnética/métodos , Músculo Esquelético , Traumatismos de la Médula Espinal , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/fisiología , Humanos , Extremidad Inferior/diagnóstico por imagen , Extremidad Inferior/fisiopatología , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiopatología , Fenómenos Fisiológicos Musculoesqueléticos , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/fisiopatología , Volición/fisiologíaRESUMEN
PURPOSE: The purpose of this project was to study the relationship between conjunctivochalasis (Cch) and ocular signs and symptoms of dry eye. METHODS: Ninety-six patients with normal eyelid and corneal anatomy were prospectively recruited from a Veterans Administration hospital over 12 months. Symptoms (via the dry eye questionnaire 5 [DEQ5]) and signs of dry eye were assessed along with quality of life implications. Statistical analyses comparing the above metrics among the three groups included χ(2), analysis of variance, and linear regression tests. RESULTS: Participants were classified into three groups: nasal conjunctivochalasis (NCch; n = 31); nonnasal conjunctivochalasis (non-NCch; n = 41); and no conjunctivochalasis (no-Cch; n = 24). Patients with NCch had more dry eye symptoms than those with non-NCch (DEQ5: NCch = 13.8 ± 5.0, non-NCch = 10.2 ± 5.0, no-Cch = 11.6 ± 5.8; P = 0.014), and more ocular pain than those with Non-NCch and no-Cch (numerical rating scale [NRS]: NCch = 4.5 ± 3.0, non-NCch = 2.3 ± 2.8, no-Cch = 3.3 ± 2.6; P = 0.008). They also had worse dry eye signs compared to those with no-Cch measured by Schirmer score with anesthesia (NCch = 14.5 ± 6.9, non-NCch = 16.8 ± 8.2, no-Cch = 19.9 ± 6.4; P = 0.039); meibomian gland dropout (NCch 1.8 ± 0.9, non-NCch = 1.4 ± 1.0, no-Cch = 1.0 ± 1.0; P = 0.020); and eyelid vascularity (NCch = 0.84 ± 0.8, non-NCch = 0.74 ± 0.7, no-Cch = 0.33 ± 0.6; P = 0.019). Moreover, those with NCch more frequently reported that dry eye symptoms moderately to severely impacted their quality of life (NCch = 87%, non-NCch = 51%, no-Cch = 58%; P = 0.005). CONCLUSIONS: The presence of NCch associates with dry eye symptoms, abnormal tear parameters, and impacts quality of life compared with non-NCch and no-Cch. Based on these data, it is important for clinicians to look for Cch in patients with symptoms of dry eye.
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Enfermedades de la Conjuntiva/epidemiología , Síndromes de Ojo Seco/epidemiología , Anciano , Enfermedades de la Conjuntiva/complicaciones , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/rehabilitación , Síndromes de Ojo Seco/terapia , Femenino , Florida/epidemiología , Humanos , Gotas Lubricantes para Ojos/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la EnfermedadRESUMEN
Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some of these children, particularly those with epilepsies classified as Landau-Kleffner Syndrome or continuous spike and wave during sleep, have infrequent seizure activity but frequent focal epileptiform activity. This frequent epileptiform activity is thought to be detrimental to cognitive development; however, it is also possible that these IIS events initiate pathophysiological pathways in the developing brain that may be independently associated with cognitive deficits. These hypotheses are difficult to address due to the previous lack of an appropriate animal model. To this end, we have recently developed a rat model to test the role of frequent focal epileptiform activity in the prefrontal cortex. Using microinjections of a GABA(A) antagonist (bicuculline methiodine) delivered multiple times per day from postnatal day (p) 21 to p25, we showed that rat pups experiencing frequent, focal, recurrent epileptiform activity in the form of interictal spikes during neurodevelopment have significant long-term deficits in attention and sociability that persist into adulthood. To determine if treatment with ACTH, a drug widely used to treat early-life seizures, altered outcome we administered ACTH once per day subcutaneously during the time of the induced interictal spike activity. We show a modest amelioration of the attention deficit seen in animals with a history of early life interictal spikes with ACTH, in the absence of alteration of interictal spike activity. These results suggest that pharmacological intervention that is not targeted to the interictal spike activity is worthy of future study as it may be beneficial for preventing or ameliorating adverse cognitive outcomes.
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Hormona Adrenocorticotrópica/farmacología , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/patología , Modelos Animales de Enfermedad , Epilepsias Parciales/complicaciones , Epilepsias Parciales/patología , Corteza Prefrontal/patología , Hormona Adrenocorticotrópica/administración & dosificación , Hormona Adrenocorticotrópica/uso terapéutico , Análisis de Varianza , Animales , Trastorno por Déficit de Atención con Hiperactividad/etiología , Bicuculina/análogos & derivados , Bicuculina/toxicidad , Epilepsias Parciales/inducido químicamente , Antagonistas de Receptores de GABA-A/toxicidad , Inyecciones Subcutáneas , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
There is a well-described association between childhood epilepsy and pervasive cognitive and behavioral deficits. Often these children not only have ictal EEG events, but also frequent interictal abnormalities. The precise role of these interictal discharges in cognition remains unclear. In order to understand the relationship between frequent epileptiform discharges during neurodevelopment and cognition later in life, we developed a model of frequent focal interictal spikes (IIS). Postnatal day (p) 21 rats received injections of bicuculline methiodine into the prefrontal cortex (PFC). Injections were repeated in order to achieve 5 consecutive days of transient inhibitory/excitatory imbalance resulting in IIS. Short-term plasticity (STP) and behavioral outcomes were studied in adulthood. IIS is associated with a significant increase in STP bilaterally in the PFC. IIS rats did not show working memory deficits, but rather showed marked inattentiveness without significant alterations in motivation, anxiety or hyperactivity. Rats also demonstrated significant deficits in social behavior. We conclude that GABAergic blockade during early-life and resultant focal IIS in the PFC disrupt neural networks and are associated with long-term consequences for behavior at a time when IIS are no longer present, and thus may have important implications for ADHD and autism spectrum disorder associated with childhood epilepsy.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/etiología , Epilepsia/patología , Corteza Prefrontal/fisiopatología , Trastorno de la Conducta Social/etiología , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Electroencefalografía , Epilepsia/complicaciones , Conducta Exploratoria/fisiología , Técnicas In Vitro , Masculino , Memoria a Corto Plazo , Motivación , Plasticidad Neuronal/fisiología , Corteza Prefrontal/crecimiento & desarrollo , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Nuclear imaging using positron emission tomography [PET] is a powerful technique with clinical applications which include oncology, cardiovascular disease and CNS disorders. Conventional chemical syntheses of the short half-life radionuclides used in the process however imposes numerous limitations on scope of available ligands. By utilizing microwave assisted synthesis methods many of these limitations can be overcome, paving the way for the design of diverse families of agents with defined cellular targets. This review will survey recent developments in the field with emphasis on the period 2006-2011. Positron emission tomography [PET] has become one of the most powerful in vivo imaging modalities, capable of delivering mm3 resolution of radiotracer distribution and metabolism [1]. When combined with anatomic imaging methods (MRI, CT) co-registered multimode images offer the potential to track metabolic and physiologic events in diseased states and guide and accelerate clinical trials of investigational new drugs. Also, this same methodology can be used to evaluate first pass pharmacokinetics/pharmacodynamics in early stage drug discovery. Though powerful as a technique only a limited number of drugs have seen clinical use and to date only one drug 2-fluoro-deoxy-D-glucose (FDG) has received FDA approval [2]. One of the drawbacks of PET imaging is the need for tracers labeled with an appropriate nuclide and the half-lives of these agents places special constraints on the chemical synthesis. Among the most popular are 11C (t½ =20.4 min) and 18F (t ½ =109.8 min) labeled compounds and this has resulted in a resurgence of interest in practical application of their chemistries [3,4]. This review will focus on microwave mediated methods of acceleration of organic reactions used for the production of labeled PET image contrast agents, with emphasis on the five year period 2006 to 2011.