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1.
J Neurosci ; 42(6): 1090-1103, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-34980636

RESUMO

Strong inhibitory synaptic gating of dentate gyrus granule cells (GCs), attributed largely to fast-spiking parvalbumin interneurons (PV-INs), is essential to maintain sparse network activity needed for dentate dependent behaviors. However, the contribution of PV-INs to basal and input-driven sustained synaptic inhibition in GCs and semilunar granule cells (SGCs), a sparse morphologically distinct dentate projection neuron subtype, is currently unknown. In studies conducted in hippocampal slices from mice, we find that although basal IPSCs are more frequent in SGCs and optical activation of PV-INs reliably elicited IPSCs in both GCs and SGCs, optical suppression of PV-INs failed to reduce IPSC frequency in either cell type. Amplitude and kinetics of IPSCs evoked by perforant path (PP) activation were not different between GCs and SGCs. However, the robust increase in sustained polysynaptic IPSCs elicited by paired afferent stimulation was lower in SGCs than in simultaneously recorded GCs. Optical suppression of PV-IN selectively reduced sustained IPSCs in SGCs but not in GCs. These results demonstrate that PV-INs, while contributing minimally to basal synaptic inhibition in both GCs and SGCs in slices, mediate sustained feedback inhibition selectively in SGCs. The temporally selective blunting of activity-driven sustained inhibitory gating of SGCs could support their preferential and persistent recruitment during behavioral tasks.SIGNIFICANCE STATEMENT Our study identifies that feedback inhibitory regulation of dentate semilunar granule cells (SGCs), a sparse and functionally distinct class of projection neurons, differs from that of the classical projection neurons, GCs. Notably, we demonstrate relatively lower activity-dependent increase in sustained feedback inhibitory synaptic inputs to SGCs when compared with GCs which would facilitate their persistent activity and preferential recruitment as part of memory ensembles. Since dentate GC activity levels during memory processing are heavily shaped by basal and feedback inhibition, the fundamental differences in basal and evoked sustained inhibition between SGCs and GCs characterized here provide a framework to reorganize current understanding of the dentate circuit processing.


Assuntos
Giro Denteado/fisiologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Animais , Potenciais Pós-Sinápticos Inibidores/fisiologia , Interneurônios/fisiologia , Camundongos , Parvalbuminas/metabolismo , Sinapses/fisiologia
2.
J Cell Sci ; 134(20)2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34515305

RESUMO

The advent of modern single-cell biology has revealed the striking molecular diversity of cell populations once thought to be more homogeneous. This newly appreciated complexity has made intersectional genetic approaches essential to understanding and probing cellular heterogeneity at the functional level. Here, we build on previous knowledge to develop a simple adeno-associated virus (AAV)-based approach to define specific subpopulations of cells by Boolean exclusion logic (AND NOT). This expression by Boolean exclusion (ExBoX) system encodes for a gene of interest that is turned on by a particular recombinase (Cre or FlpO) and turned off by another. ExBoX allows for the specific transcription of a gene of interest in cells expressing only the activating recombinase, but not in cells expressing both. We show the ability of the ExBoX system to tightly regulate expression of fluorescent reporters in vitro and in vivo, and further demonstrate the adaptability of the system by achieving expression of a variety of virally delivered coding sequences in the mouse brain. This simple strategy will expand the molecular toolkit available for cell- and time-specific gene expression in a variety of systems.


Assuntos
Neurônios , Recombinases , Animais , Expressão Gênica , Camundongos , Recombinases/genética
3.
Indian J Clin Biochem ; 37(3): 303-310, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35873616

RESUMO

Lead (Pb) is found in almost all phases in environment and biological systems. Pb stimulated oxidative stress is a state that involves the generation of free radicals beyond the permissible limits, which can deplete the antioxidant reserves and can result in oxidative stress, thus hampering the ability of the biological system to reverse the result. Exposure of rats to Pb (25 mg/kg body weight) for 8 weeks caused an increase in Pb levels in blood and brain. Activity of delta-aminolevulinic acid dehydratase (δ-ALAD) and antioxidant enzymes such as Superoxide dismutase (SOD) and Catalase (CAT) decreased in the blood of Pb-treated group with a concomitant increase in the level of lipid peroxidation (LPO) and no significant change in the level of reduced glutathione (GSH) level was found. Interestingly, co-treatment of Pb-treated rats with curcumin (30 mg/kg body weight) and quercetin (30 mg/kg body weight) for 8 weeks caused a significant decrease in Pb levels of blood and all brain regions versus those treated with Pb alone. A significant improvement in levels of MDA, δ-ALAD, SOD and CAT activities was observed in rats simultaneously treated with curcumin or Quercetin or both with lead. Therefore, the ameliorative impact of curcumin and Quercetin might be due to their antioxidant property hence were able to counter the oxidative stress generated by Pb. These results suggest that combination of curcumin and Quercetin could be utilized as a possible supplement with the relevant therapeutics in the suitable management of Pb toxicity.

4.
J Vasc Surg ; 71(2): 432-443.e4, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31171423

RESUMO

BACKGROUND: The aim of this study was to provide a nationwide, all-payer, real-world cost analysis of endovascular aortic aneurysm repair (EVAR) versus open aortic aneurysm repair (OAR) in patients with nonruptured abdominal aortic aneurysms (non-rAAA). METHODS: All non-rAAA patients registered between July 2009 and March 2015 in the Premier Healthcare Database were analyzed. The Student t-test and the χ2 test were used for continuous and categorical variables, respectively; median value comparisons were done with the Wilcoxon-Mann-Whitney rank-sum test. The in-hospital absolute mean total cost (sum of fixed cost and variable cost) and subcategories were analyzed after adjustment for inflation at July 2015. Fixed costs included all overhead costs while variables costs included in-hospital services including procedures, room and board, services provided by hospital staff, and pharmacy costs. Total cost was stratified based on admission type (emergency vs nonemergency), 75th percentile of length of hospital stay among individual procedures (expected vs extended stay), mortality, and complications. Student t-test and Fisher's analysis of variance were used for comparing mean cost. Year-wise comparison of mean cost was done with analysis of variance to look for a trend over time. RESULTS: Our study cohort included 38,809 non-rAAA patients (33,171 EVAR and 5638 OAR). The mean total cost of index admission was lower in EVAR in comparison with OAR ($32,052 vs $36,091; P < .001), with lower fixed costs ($11,309 vs $16,818; P < .001) and higher variable costs ($20,743 vs $19,272; P < .001). Cost of pharmacy, labor, operating room, room and board and other costs were significantly higher with OAR, whereas the supply cost was higher with EVAR. The expected hospital length of stay of patients who underwent EVAR was associated with a higher total cost ($27,271 vs $25,680; P < .001) and a higher variable cost ($18,186 vs $13,671; P < .001) than OAR patients. However, the extended hospital stay of patients who underwent EVAR had lower costs in all categories compared with the extended length of stay of those who underwent OAR. Mortality associated with EVAR was costlier than OAR associated mortality (mean $72,483 vs $59,804; P = .017). From 2009 to 2014, the mean total cost of EVAR increased significantly by 18.5% ($28,745 vs $34,049; P < .001) owing to a 7.8% increase in fixed costs ($10,931 vs $11,789; P < .001) and a 25.0% increase in variable costs ($17,804 vs $22,257; P < .001). The mean total cost OAR remained stable over time. CONCLUSIONS: Overall hospitalization costs associated with EVAR of non-rAAA was lower than the hospitalization cost of OAR. Interestingly, we found that, among patients who had an expected hospital length of stay, the hospitalization cost after OAR was significantly lower than after EVAR. The average hospitalization cost of OAR was stable during the 5 years study period, whereas the hospitalization cost of EVAR increased significantly over time. Further studies are required to identify reasons for increased costs associated with EVAR.


Assuntos
Aneurisma da Aorta Abdominal/economia , Aneurisma da Aorta Abdominal/cirurgia , Custos e Análise de Custo , Hospitalização/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Procedimentos Endovasculares/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Cirúrgicos Vasculares/economia , Procedimentos Cirúrgicos Vasculares/métodos
5.
J Neurosci Res ; 97(11): 1335-1344, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-29193309

RESUMO

Epilepsy, characterized by recurrent seizures and abnormal electrical activity in the brain, is one of the most prevalent brain disorders. Over two million people in the United States have been diagnosed with epilepsy and 3% of the general population will be diagnosed with it at some point in their lives. While most developmental epilepsies occur due to genetic predisposition, a class of "acquired" epilepsies results from a variety of brain insults. A leading etiological factor for epilepsy that is currently on the rise is traumatic brain injury (TBI), which accounts for up to 20% of all symptomatic epilepsies. Remarkably, the presence of an identified early insult that constitutes a risk for development of epilepsy provides a therapeutic window in which the pathological processes associated with brain injury can be manipulated to limit the subsequent development of recurrent seizure activity and epilepsy. Recent studies have revealed diverse pathologies, including enhanced excitability, activated immune signaling, cell death, and enhanced neurogenesis within a week after injury, suggesting a period of heightened adaptive and maladaptive plasticity. An integrated understanding of these processes and their cellular and molecular underpinnings could lead to novel targets to arrest epileptogenesis after trauma. This review attempts to highlight and relate the diverse early changes after trauma and their role in development of epilepsy and suggests potential strategies to limit neurological complications in the injured brain.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Encéfalo/fisiopatologia , Epilepsia/fisiopatologia , Animais , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/metabolismo , Epilepsia/etiologia , Epilepsia/metabolismo , Humanos , Neurogênese , Neurônios/fisiologia , Transdução de Sinais
6.
J Vasc Surg ; 68(1): 74-81, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29571623

RESUMO

OBJECTIVE: The majority of previous studies, including randomized controlled trials, have failed to provide sufficient evidence of superiority of endovascular aneurysm repair (EVAR) over open aortic repair (OAR) of ruptured abdominal aortic aneurysm (rAAA) while comparing mortality and complications. This is in part due to small study size, patient selection bias, scarce adjustment for essential variables, single insurance type, or selection of only older patients. This study aimed to provide real-world, contemporary, comprehensive, and robust evidence on mortality of EVAR vs OAR of rAAA. METHODS: A retrospective observational cohort study was performed of rAAA patients registered in the Premier Healthcare Database between July 2009 and March 2015. A multivariate logistic regression model was operated to estimate the association between procedure types (OAR vs EVAR) and in-hospital mortality. The final model was adjusted for demographics (age, sex, race, marital status, and geographic region), hospital characteristics (urban or rural, teaching or not), and potential confounders (hypertension, diabetes, hypercholesterolemia, obesity, ischemic heart disease, chronic kidney disease, symptoms of critical limb ischemia, chronic obstructive pulmonary disease, smoking, and alcoholism). Furthermore, coarsened exact matching was applied to substantiate the result in the matched cohort. RESULTS: There were a total of 3164 patients with rAAA (1550 [49.0%] OAR and 1614 [51.0%] EVAR). Mortality was 23.79% in the EVAR group compared with 36.26% in the OAR group (P < .001). The adjusted odds ratios of mortality (1.91; 95% confidence interval [CI], 1.62-2.25; P < .001), cardiac complication (1.54; 95% CI, 1.22-1.96; P < .001), pulmonary failure (1.90; 95% CI, 1.60-2.24; P < .001), renal failure (1.90; 95% CI, 1.61-2.23; P < .001), and bowel ischemia (2.40; 95% CI, 1.70-3.35; P < .001) were significantly higher after OAR compared with EVAR. We further applied coarsened exact matching, which followed the same pattern of mortality (odds ratio, 1.68; 95% CI 1.41-1.99; P < .001) and all major complications. CONCLUSIONS: Although the choice of repair of rAAA is highly dependent on the experience of the operating team and the anatomic suitability of the patient, this contemporary analysis of a large cohort of rAAA showed significantly higher adjusted risk of mortality in OAR compared with EVAR and substantially higher complications.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Distribuição de Qui-Quadrado , Comorbidade , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Medicina Baseada em Evidências , Feminino , Mortalidade Hospitalar , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
bioRxiv ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38798373

RESUMO

Circuit influences on the midbrain dopamine system are crucial to adaptive behavior and cognition. Recent developments in the study of neuropeptide systems have enabled high-resolution investigations of the intersection of neuromodulatory signals with basal ganglia circuitry, identifying the nociceptin/orphanin FQ (N/OFQ) endogenous opioid peptide system as a prospective regulator of striatal dopamine signaling. Using a prepronociceptin-Cre reporter mouse line, we characterized highly selective striosomal patterning of Pnoc mRNA expression in mouse dorsal striatum, reflecting early developmental expression of Pnoc . In the ventral striatum, Pnoc expression was was clustered across the nucleus accumbens core and medial shell, including in adult striatum. We found that Pnoc tdTomato reporter cells largely comprise a population of dopamine receptor D1 ( Drd1 ) expressing medium spiny projection neurons localized in dorsal striosomes, known to be unique among striatal projections neurons for their direct innervation of midbrain dopamine neurons. These findings provide new understanding of the intersection of the N/OFQ system among basal ganglia circuits with particular implications for developmental regulation or wiring of striatal-nigral circuits.

9.
J Neurosci ; 32(7): 2523-37, 2012 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-22396425

RESUMO

Brain injury is an etiological factor for temporal lobe epilepsy and can lead to memory and cognitive impairments. A recently characterized excitatory neuronal class in the dentate molecular layer, semilunar granule cell (SGC), has been proposed to regulate dentate network activity patterns and working memory formation. Although SGCs, like granule cells, project to CA3, their typical sustained firing and associational axon collaterals suggest that they are functionally distinct from granule cells. We find that brain injury results in an enhancement of SGC excitability associated with an increase in input resistance 1 week after trauma. In addition to prolonging miniature and spontaneous IPSC interevent intervals, brain injury significantly reduces the amplitude of tonic GABA currents in SGCs. The postinjury decrease in SGC tonic GABA currents is in direct contrast to the increase observed in granule cells after trauma. Although our observation that SGCs express Prox1 indicates a shared lineage with granule cells, data from control rats show that SGC tonic GABA currents are larger and sIPSC interevent intervals shorter than in granule cells, demonstrating inherent differences in inhibition between these cell types. GABA(A) receptor antagonists selectively augmented SGC input resistance in controls but not in head-injured rats. Moreover, post-traumatic differences in SGC firing were abolished in GABA(A) receptor blockers. Our data show that cell-type-specific post-traumatic decreases in tonic GABA currents boost SGC excitability after brain injury. Hyperexcitable SGCs could augment dentate throughput to CA3 and contribute substantively to the enhanced risk for epilepsy and memory dysfunction after traumatic brain injury.


Assuntos
Lesões Encefálicas/fisiopatologia , Giro Denteado/citologia , Giro Denteado/fisiologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Animais , Lesões Encefálicas/patologia , Regulação para Baixo/fisiologia , Masculino , Ratos , Ratos Wistar , Regulação para Cima/fisiologia
10.
Cancer Control ; 20(2): 117-29, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23571702

RESUMO

BACKGROUND: Barrett's esophagus (BE) is the most important identifiable risk factor for the progression to esophageal adenocarcinoma. METHODS: This article reviews the current endoscopic therapies for BE with high-grade dysplasia and intramucosal cancer and briefly discusses the endoscopic palliation of advanced esophageal cancer. RESULTS: The diagnosis of low-grade or high-grade dysplasia (HGD) is based on several cytologic criteria that suggest neoplastic transformation of the columnar epithelium. HGD and carcinoma in situ are regarded as equivalent. The presence of dysplasia, particularly HGD, is also a risk factor for synchronous and metachronous adenocarcinoma. Dysplasia is a marker of adenocarcinoma and also has been shown to be the preinvasive lesion. Esophagectomy has been the conventional treatment for T1 esophageal cancer and, although debated, is an appropriate option in some patients with HGD due to the presence of occult cancer in over one-third of patients. CONCLUSIONS: Endoscopic ablative modalities (eg, photodynamic therapy and cryoablation) and endoscopic resection techniques (eg, endoscopic mucosal resection) have demonstrated promising results. The significant morbidity and mortality of esophagectomy makes endoscopic treatment an attractive potential option.


Assuntos
Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagoscopia/métodos , Esôfago/cirurgia , Esôfago de Barrett/diagnóstico , Neoplasias Esofágicas/diagnóstico , Esôfago/patologia , Humanos , Cuidados Paliativos/métodos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/cirurgia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Indian J Pathol Microbiol ; 66(3): 511-516, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37530331

RESUMO

Background: The Fine needle aspiration cytology (FNAC) is considered as a valuable and distinguished diagnostic test in the initial assessment of the patients presenting with a mass in the head and neck region or when a recurrence is suspected after previous treatment. Aims: This study was therefore designed to elucidate the efficacy of FNAC as an alternate diagnostic tool to histopathology in head and neck swellings and evaluation of staining efficacy of PAP and MGG stain over Haematoxylin and eosin (H and E) in routine cytopathological smears. Settings and Design: The study was conducted in the Department of Oral and Maxillofacial Pathology, where FNAC samples were collected from 150 patients with head and neck swellings. Materials and Methods: All the slides were stained with H and E, Papanicolaou (PAP), and May Grunewald Giemsa (MGG) stains. The cytopathological diagnosis was compared with histopathological diagnosis based on H and E stained sections obtained from paraffin-embedded formalin-fixed biopsy specimen of benign and malignant neoplasms. Statistical Analysis Used: The resulting data were analyzed using SPSS software version 19. Differences between the variables were analyzed using Pearson Chi-square test and Kruskal-Wallis test wherever applicable. Results: The FNAC as a diagnostic tool has sensitivity of 84.8%, 72.72%, and 78.78%, specificity of 62.5%, 75%, and 75%, and accuracy of 80.48%, 73.14%, and 78.04% in H and E, MGG, and PAP stain, respectively. PAP stain was the most efficient stain when all qualitative parameters are taken into consideration with maximum sensitivity and specificity for achieving definitive cytodiagnosis. Conclusions: The FNAC is an inexpensive and minimally invasive technique to diagnose different types of head and neck swellings and complement histopathological diagnosis.


Assuntos
Corantes , Patologia Bucal , Humanos , Coloração e Rotulagem , Pescoço , Técnicas Citológicas , Corantes Azur , Hematoxilina
12.
bioRxiv ; 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37873292

RESUMO

Axo-axonic cells (AACs) provide specialized inhibition to the axon initial segment (AIS) of excitatory neurons and can regulate network output and synchrony. Although hippocampal dentate AACs are structurally altered in epilepsy, physiological analyses of dentate AACs are lacking. We demonstrate that parvalbumin neurons in the dentate molecular layer express PTHLH, an AAC marker, and exhibit morphology characteristic of AACs. Dentate AACs show high-frequency, non-adapting firing but lack persistent firing in the absence of input and have higher rheobase than basket cells suggesting that AACs can respond reliably to network activity. Early after pilocarpine-induced status epilepticus (SE), dentate AACs receive fewer spontaneous excitatory and inhibitory synaptic inputs and have significantly lower maximum firing frequency. Paired recordings and spatially localized optogenetic stimulation revealed that SE reduced the amplitude of unitary synaptic inputs from AACs to granule cells without altering reliability, short-term plasticity, or AIS GABA reversal potential. These changes compromised AAC-dependent shunting of granule cell firing in a multicompartmental model. These early post-SE changes in AAC physiology would limit their ability to receive and respond to input, undermining a critical brake on the dentate throughput during epileptogenesis.

13.
Prog Neurobiol ; 231: 102542, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37898313

RESUMO

Axo-axonic cells (AACs) provide specialized inhibition to the axon initial segment (AIS) of excitatory neurons and can regulate network output and synchrony. Although hippocampal dentate AACs are structurally altered in epilepsy, physiological analyses of dentate AACs are lacking. We demonstrate that parvalbumin neurons in the dentate molecular layer express PTHLH, an AAC marker, and exhibit morphology characteristic of AACs. Dentate AACs show high-frequency, non-adapting firing but lack persistent firing in the absence of input and have higher rheobase than basket cells suggesting that AACs can respond reliably to network activity. Early after pilocarpine-induced status epilepticus (SE), dentate AACs receive fewer spontaneous excitatory and inhibitory synaptic inputs and have significantly lower maximum firing frequency. Paired recordings and spatially localized optogenetic stimulation revealed that SE reduced the amplitude of unitary synaptic inputs from AACs to granule cells without altering reliability, short-term plasticity, or AIS GABA reversal potential. These changes compromised AAC-dependent shunting of granule cell firing in a multicompartmental model. These early post-SE changes in AAC physiology would limit their ability to receive and respond to input, undermining a critical brake on the dentate throughput during epileptogenesis.


Assuntos
Giro Denteado , Estado Epiléptico , Humanos , Reprodutibilidade dos Testes , Neurônios/fisiologia , Axônios , Estado Epiléptico/induzido quimicamente
14.
Gastrointest Endosc ; 75(4): 705-11, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22440200

RESUMO

BACKGROUND: Per current guidelines, patients with a first-degree relative (FDR) with adenomas should get screened at age 40. Data on the prevalence of adenomas and advanced adenomas (AAs) in these patients are lacking. OBJECTIVE: To examine the prevalence of adenomas and AAs in 40- to 49-year-old individuals undergoing screening colonoscopy because of a family history (FH) of polyps and to compare these data with those of a control population of similar age. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary care academic medical center and Veterans Affairs medical center. PATIENTS: Study subjects included all 40- to 49-year-old asymptomatic individuals undergoing initial screening colonoscopy at our institution from January 1, 2006, to June 1, 2009, because of an FDR with polyps. The control population consisted of all 40- to 49-year-old individuals who underwent their first colonoscopy during the same period because of abdominal pain, diarrhea, or constipation without an FH of polyps or colorectal cancer. INTERVENTION: Colonoscopy. MAIN OUTCOME MEASUREMENTS: The prevalence of adenomas of any size, AAs, and risk factors associated with adenomas. RESULTS: The prevalence of adenomas was greater in the FH of polyps group (n = 176) compared with the control sample (n = 178) (26.7% vs 13.5%; P = .002) but was not statistically greater for AAs (5.7% vs 3.4%; P = .3). After adjusting for confounders, FH of a polyp was associated with an increased prevalence of adenomas (odds ratio 2.8 [95% CI, 1.4-5.5]). LIMITATIONS: Limited data on polyp histology in FDRs and limited sample size. CONCLUSIONS: Among 40- to 49-year-old patients undergoing screening colonoscopy because of an FDR with polyps, the prevalence of adenomas was greater than in a control population. Prospective research is needed to quantify the prevalence of AAs in this group and to determine whether these individuals should undergo screening colonoscopy at age 40.


Assuntos
Adenoma/epidemiologia , Adenoma/patologia , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Adenoma/genética , Adulto , Neoplasias do Colo/genética , Colonoscopia , Intervalos de Confiança , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Estudos Retrospectivos , Fatores de Risco
15.
Front Neurosci ; 16: 800733, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360164

RESUMO

Progressive physiological changes in the hippocampal dentate gyrus circuits following traumatic brain injury (TBI) contribute to temporal evolution of neurological sequelae. Although early posttraumatic changes in dentate synaptic and extrasynaptic GABA currents have been reported, and whether they evolve over time and remain distinct between the two projection neuron classes, granule cells and semilunar granule cells, have not been evaluated. We examined long-term changes in tonic GABA currents and spontaneous inhibitory postsynaptic currents (sIPSCs) and in dentate projection neurons 3 months after moderate concussive fluid percussion injury (FPI) in adolescent rats. Granule cell tonic GABA current amplitude remained elevated up to 1 month after FPI, but decreased to levels comparable with age-matched controls by 3 months postinjury. Granule cell sIPSC frequency, which we previously reported to be increased 1 week after FPI, remained higher than in age-matched controls at 1 month and was significantly reduced 3 months after FPI. In semilunar granule cells, tonic GABA current amplitude and sIPSC frequency were not different from controls 3 months after FPI, which contrast with decreases observed 1 week after injury. The switch in granule cell inhibitory inputs from early increase to subsequent decrease could contribute to the delayed emergence of cognitive deficits and seizure susceptibility after brain injury.

16.
BMJ Open ; 12(10): e052336, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207036

RESUMO

INTRODUCTION: Mobile Vaani was implemented as a pilot programme across six blocks of Nalanda district in Bihar state, India to increase knowledge of rural women who were members of self-help groups on proper nutrition for pregnant or lactating mothers and infants, family planning and diarrhoea management. Conveners of self-help group meetings, community mobilisers, introduced women to the intervention by giving them access to interactive voice response informational and motivational content. A mixed methods outcome and embedded process evaluation was commissioned to assess the reach and impact of Mobile Vaani. METHODS: The outcome evaluation, conducted from January 2017 to November 2018, used a quasi-experimental pre-post design with a sample of 4800 married women aged 15-49 from self-help group households, who had a live birth in the past 24 months. Surveys with community mobilisers followed by meeting observations (n=116), in-depth interviews (n=180) with self-help group members and secondary analyses of system generated data were conducted to assess exposure and perceptions of the intervention. RESULTS: From the outcome evaluation, 23% of women interviewed had heard about Mobile Vaani. Women in the intervention arm had significantly higher knowledge than women in the comparison arm for two of seven focus outcomes: knowledge of how to make child's food nutrient and energy dense (treatment-on-treated: 18.8% (95% CI 0.4% to 37.2%, p<0.045)) and awareness of at least two modern spacing family planning methods (treatment-on-treated: 17.6% (95% CI 4.7% to 30.5%, p<0.008)). Women with any awareness of Mobile Vaani were happy with the programme and appreciated the ability to call in and listen to the content. CONCLUSION: Low population awareness and programme exposure are underpinned by broader population level barriers to mobile phone access and use among women and missed opportunities by the programme to improve targeting and programme promotion. Further research is needed to assess programmatic linkages with changes in health practices.


Assuntos
Lactação , Telemedicina , Criança , Feminino , Humanos , Índia , Lactente , Mães , Gravidez , População Rural
17.
Ambio ; 51(3): 531-545, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34155609

RESUMO

As largely documented in the literature, the stark restrictions enforced worldwide in 2020 to curb the COVID-19 pandemic also curtailed the production of air pollutants to some extent. This study investigates the perception of the air pollution as assessed by individuals located in ten countries: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the USA. The perceptions towards air quality were evaluated by employing an online survey administered in May 2020. Participants (N = 9394) in the ten countries expressed their opinions according to a Likert-scale response. A reduction in pollutant concentration was clearly perceived, albeit to a different extent, by all populations. The survey participants located in India and Italy perceived the largest drop in the air pollution concentration; conversely, the smallest variation was perceived among Chinese and Norwegian respondents. Among all the demographic indicators considered, only gender proved to be statistically significant.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Humanos , Pandemias , Material Particulado/análise , Percepção , SARS-CoV-2
18.
Gastrointest Endosc ; 74(1): 110-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21514930

RESUMO

BACKGROUND: Per current guidelines, patients with a first-degree relative (FDR) with colorectal cancer (CRC) should get screened at least at age 40. Data about the prevalence of adenomas and advanced adenomas (AAs) in these patients are lacking. OBJECTIVE: To examine the prevalence of adenomas and AAs in 40- to 49-year-old individuals undergoing screening colonoscopy for family history of CRC. DESIGN: Retrospective chart review. PATIENTS: Asymptomatic patients 40 to 49 years of age undergoing their first screening colonoscopy at the University of Michigan during the period 1999 to 2009 because of an FDR with CRC. MAIN OUTCOME MEASUREMENTS: Prevalence of adenomas (any size), AAs, and risk factors associated with adenomas. RESULTS: Among 640 study patients, the prevalence of adenomas (any size) was 15.4% and 3.3% for AAs. Adenoma prevalence was lower if the FDR with CRC was younger than 60 years of age versus an FDR with CRC older than 60 years of age (12.4% vs 19%, P = .034). Male sex (odds ratio 2.6; 95% CI, 1.06-4.4) and advancing age (odds ratio 1.16; 95% CI, 1.03-1.31) were associated with adenomas. LIMITATIONS: Limited data on risk factor exposure and insufficient sample size to assess risk factors for AAs. CONCLUSIONS: Among 40- to 49-year-old patients undergoing screening colonoscopy because of an FDR with CRC, the prevalence of adenomas and AAs is low. Further research should determine whether these individuals have a higher prevalence of adenomas compared with average-risk individuals.


Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Adenoma/diagnóstico , Adulto , Colonoscopia , Neoplasias Colorretais/diagnóstico , Família , Feminino , Humanos , Masculino , Programas de Rastreamento , Michigan , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco
19.
Cureus ; 13(8): e16813, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34522473

RESUMO

We describe the presentation and management of a three-year-old child with a history of pica, vitamin D deficiency, and sickle cell disease, who was admitted for pyelonephritis, and found to have elevated blood lead level (BLL) of 103.7 µg/dL, and who subsequently developed altered mental status and syndrome of inappropriate antidiuretic hormone secretion (SIADH). In consultation with Medical Toxicology, the patient was chelated with calcium disodium edetate (EDTA) and British Anti Lewisite (BAL). The patient's hyponatremia was managed with hypertonic saline infusion. The patient's encephalopathy improved throughout her hospital course, and she was discharged on hospital day 8. Following five days of EDTA and three days of BAL injections, her repeat BLL was 15.3 µg/dL. SIADH has been associated with severe lead poisoning and may be more likely to occur in high risk patients such as individuals with sickle cell anemia, particularly where medications are used that may cause iatrogenic hyponatremia.

20.
Radiol Case Rep ; 16(3): 661-663, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33488894

RESUMO

Cholelithiasis is a common gastrointestinal pathology that can lead to rare complications including cholecystoduodenal fistulas and GI hemorrhage. Diagnosing cholelithiasis and cholecystoduodenal fistulas in the emergency department (ED) using computed tomography (CT) imaging despite nonspecific and variable symptoms is critical in determining management strategies for medically complex patients. An 87-year-old medically complex female presented to the ED in hemorrhagic shock after several episodes of hematemesis, hematochezia, and other nonspecific gastrointestinal symptoms. A CT of the abdomen/pelvis was performed revealing cholecystitis with a large 6-cm stone; additionally, a biliary enteric fistula was noted with blood products in the gallbladder. This case highlights the importance of CT imaging in the setting of gastrointestinal bleeding with cholelithiasis and biliary enteric fistula diagnosis, and discusses potential management strategies of these diagnoses in medically complex patients.

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