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BACKGROUND: Housing instability in the United States is a critical social determinant of health, influencing health outcomes and health care utilization. This scoping review aimed to analyze literature on US health system screening and response programs addressing housing instability, highlighting methodologies, geographic and demographic variations, and policy implications. METHODS: Adhering to PRISMA-ScR guidelines, the review included studies focusing on US health systems that screen and refer for housing instability. Major scholarly databases, including PubMed and Scopus, were queried. Screening and response program characteristics, methodologies, and outcomes were characterized. RESULTS: Thirty studies published between 2003 and 2023 were included in this study. Included studies were primarily cross-sectional (26.7%) or quality improvement (20.0%), among 9 other designs. Screening programs were predominantly implemented in academic hospital systems (46.7%) and in the Northeast (63.3%). Of the 25 adult population studies, 68.0% were in outpatient settings, and of the 23 studies providing detailed information on their process, 52.2% used electronic health record entry. Of the 22 studies that describe their screening tool, 15 used institution-specific tools, and only 4 of the remaining 7 studies used identical tools. Of the 20 studies that described their response to positive screenings, 13 provided patients with a paper or electronic referral to a collaborating community partner, while only 6 aided the patient in connecting with community resources. CONCLUSION: This study found significant variability in screening and response programs for housing instability among US health care providers. A lack of standardized definitions and methodologies hampers effective comparison and implementation of these programs. Future research should focus on standardizing screening methods and measurement of interventions and outcomes to address housing instability.
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INTRODUCTION: This study evaluated the psychometric properties of the Subjective Memory Complaints Questionnaire (SMCQ) in a non-Hispanic White (NHW) and Mexican American (MA) sample from Texas in the USA. METHODS: Data were obtained from the Health and Aging Brain Study - Health Disparities (HABS-HD; N = 1,691, age = 66.5 ± 8.7, education = 12.4 ± 4.8, 60.6% female, 33.2% MA Spanish speaking). Unidimensionality of the SMCQ was evaluated with confirmatory factor analysis. Differential item functioning (DIF) of the SMCQ was assessed across age, sex, education, and ethnicity/language using item response theory/logistic ordinal regression. Associations of the SMCQ in relation to cognitive status, Alzheimer's disease (AD) blood-based biomarkers, and psychological distress were examined. RESULTS: The SMCQ showed excellent fit in a single-factor model (CFI = 0.97, TLI = 0.97, RMSEA [95% CI] = 0.05 [0.04, 0.05], SRMR = 0.07). Significant item-level DIF was detected by education level and ethnicity/language, but not by age or sex; when detected, DIF was not salient (i.e., adverse). The SMCQ was associated with greater psychological distress, worse Clinical Dementia Rating scores, and greater disease burden as measured by total tau and neurofilament light. CONCLUSIONS: Practically negligible item-level bias was identified across education and ethnicity/language. Detected DIF can be described as benign, indicating that some items manifested differently between groups but had minimal impact on measurement properties. These results demonstrate that the SMCQ performs appropriately across demographic variables. Our findings also provide support for the associations of SMCQ scores with self-reported mood, cognitive status, and AD blood-based biomarkers.
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Purpose: Immunizations have long been pivotal in preventing diseases like HZ (herpes zoster), caused by VZV (varicella zoster virus). This study aims to evaluate the efficacy and safety of the RZV (recombinant zoster vaccine) compared to the ZVL (zoster vaccine live) and to report rare adverse events following RZV administration. Observation: Herein, we report an unusual case of a 59-year-old man who developed a V1-limited rash with a positive HZ PCR (polymerase chain reaction) test following administration of RZV in the United States. Conclusion: The development of RZV has significantly improved the prevention of HZ compared to ZVL. Nevertheless, rare adverse events, such as dermatomal reactions, underscore the importance of ongoing monitoring and research into the immunomodulatory effects of RZV. Physicians should continue to administer the RZV to patients but be cognizant that reactivation may rarely subsequently occur. Case Presentation: The patient with a history of benign prostatic hyperplasia was treated at an outside hospital two days after receiving the RZV complaining of paresthesia and a rash on his nasolacrimal area and forehead. The patient presented to the ED (emergency department), 9 days post-vaccination due to persistence of his symptoms despite use of amoxicillin, valacyclovir, and an unidentified eye drop. The dose of valacyclovir was increased, and he completed 1 g TID (three times a day) PO (per orally) for 10 days with subsequent resolution of symptoms. A positive PCR test confirmed the diagnosis of HZ. Topical mupirocin ointment was initiated and the patient was referred for ophthalmologic evaluation.
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Activity-dependent protein synthesis is crucial for long-lasting forms of synaptic plasticity. However, our understanding of translational mechanisms controlling GABAergic synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABAARs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the mechanisms controlling plasticity-induced gephyrin translation remain unknown. We identify miR153 as a novel regulator of Gphn mRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting inhibitory synaptic structure and function. iLTP induction downregulates miR153, reversing its translational suppression of Gphn mRNA and promoting de novo gephyrin protein synthesis and synaptic clustering during iLTP. Finally, we find that reduced miR153 expression during iLTP is driven by an excitation-transcription coupling pathway involving calcineurin, NFAT and HDACs, which also controls the miRNA-dependent upregulation of GABAARs. Together, we delineate a miRNA-dependent post-transcriptional mechanism that controls the expression of the key synaptic scaffold, gephyrin, and may converge with parallel miRNA pathways to coordinate gene upregulation to maintain inhibitory synaptic plasticity.
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Cognitive deficits in people with bipolar disorder (BD) may be the result of the illness or its treatment, but they could also reflect genetic risk factors shared between BD and cognition. We investigated this question using empirical genetic relationships within a sample of patients with BD and their unaffected relatives. Participants with bipolar I, II, or schizoaffective disorder ("narrow" BD, n = 69), related mood disorders ("broad" BD, n = 135), and their clinically unaffected relatives (n = 227) completed five cognitive tests. General cognitive function (g) was quantified via principal components analysis (PCA). Heritability and genetic correlations were estimated with SOLAR-Eclipse. Participants with "narrow" or "broad" diagnoses showed deficits in g, although affect recognition was unimpaired. Cognitive performance was significantly heritable (h2 = 0.322 for g, p < 0.005). Coheritability between psychopathology and g was small (0.0184 for narrow and 0.0327 for broad) and healthy relatives of those with BD were cognitively unimpaired. In this family sample, cognitive deficits were present in participants with BD but were not explained by substantial overlaps in genetic determinants of mood and cognition. These findings support the view that cognitive deficits in BD are largely the result of the illness or its treatment.
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Purpose: To describe the presentation of lacrimal gland secretions mimicking a positive Seidel test following combined complex cataract surgery and endocyclophotocoagulation (ECP). Observation: The patient presented with a posterior subcapsular cataract (PSC) most likely secondary to chronic steroid use for a history of chemical burns from a firework injury in 2019. This injury resulted in symblepharon formation and limbal stem cell deficiency. He also developed glaucoma secondary to steroid response and angle structure damage. On postoperative day 1 (POD 1) after combined cataract surgery and ECP, the patient's paracentesis was Seidel positive and aqueous suppression was started. On postoperative week 1 (POW 1), the paracentesis was Seidel negative; however, it was noted at this visit that there were 3 pinpoint areas in the superotemporal conjunctiva that were Seidel positive. Digital pressure did not worsen the leak. Ultrasound biomicroscopy (UBM) was performed at POW 2.5 and showed lacrimal gland ducts in the superotemporal conjunctiva. Given this, it is likely that the "Seidel positive" finding was not due to aqueous humor leakage, but secretions from lacrimal gland tissue that may have been dragged more anteriorly due to conjunctiva scarring, thus producing a false positive Seidel sign. Conclusion & importance: This case highlights a false positive Seidel sign in the context of an eye with a complex ocular history and recent surgery. Clinicians should recognize that a false positive Seidel sign is possible if normal lacrimal gland anatomy has been disturbed.
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Excitotoxicity and the concurrent loss of inhibition are well-defined mechanisms driving acute elevation in excitatory/inhibitory (E/I) balance and neuronal cell death following an ischemic insult to the brain. Despite the high prevalence of long-term disability in survivors of global cerebral ischemia (GCI) as a consequence of cardiac arrest, it remains unclear whether E/I imbalance persists beyond the acute phase and negatively affects functional recovery. We previously demonstrated sustained impairment of long-term potentiation (LTP) in hippocampal CA1 neurons correlating with deficits in learning and memory tasks in a murine model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Here, we use CA/CPR and an in vitro ischemia model to elucidate mechanisms by which E/I imbalance contributes to ongoing hippocampal dysfunction in male mice. We reveal increased postsynaptic GABAA receptor (GABAAR) clustering and function in the CA1 region of the hippocampus that reduces the E/I ratio. Importantly, reduced GABAAR clustering observed in the first 24â h rebounds to an elevation of GABAergic clustering by 3â d postischemia. This increase in GABAergic inhibition required activation of the Ca2+-permeable ion channel transient receptor potential melastatin-2 (TRPM2), previously implicated in persistent LTP and memory deficits following CA/CPR. Furthermore, we find Ca2+-signaling, likely downstream of TRPM2 activation, upregulates Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, thereby driving the elevation of postsynaptic inhibitory function. Thus, we propose a novel mechanism by which inhibitory synaptic strength is upregulated in the context of ischemia and identify TRPM2 and CaMKII as potential pharmacological targets to restore perturbed synaptic plasticity and ameliorate cognitive function.
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Transdução de Sinais , Canais de Cátion TRPM , Animais , Masculino , Camundongos , Isquemia Encefálica/metabolismo , Região CA1 Hipocampal/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Neurônios GABAérgicos/metabolismo , Parada Cardíaca/complicações , Parada Cardíaca/metabolismo , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL , Inibição Neural/fisiologia , Receptores de GABA-A/metabolismo , Canais de Cátion TRPM/metabolismoRESUMO
BACKGROUND: Apathy was identified as a feature of HIV early in the epidemic; however, there are no systematic reviews of the diverse literature on the sociodemographic and clinical correlates of apathy in HIV disease. METHODS: The current study adopted a hybrid systematic-narrative review methodology in which we used PRISMA guidelines to identify, summarize, and critique peer-reviewed, empirical studies of apathy in HIV disease in the era of combination antiretroviral therapy. RESULTS: A total of 34 studies of apathy in persons living with HIV (PLWH) were identified. Findings across these studies showed that apathy was reliably related to the structure of grey and white matter pathways commonly implicated in apathy, poorer everyday functioning, education, and other neuropsychiatric symptoms (e.g., depression). Apathy was not reliably associated with age, sex, race/ethnicity, cognition, and clinical markers of HIV disease. LIMITATIONS: The current review does not provide rigorous quantitative estimates of clinical correlates of apathy, and the exclusion criteria of non-English and non-peer reviewed publications introduces risk of bias and Type I error. CONCLUSIONS: Apathy occurs at higher rates in PLWH and is linked to neuroanatomical differences, as well as negative outcomes for everyday functions, aspects of neurocognition, and neuropsychiatric symptoms. As such, apathy is an important component to consider in the clinical assessment, diagnosis, and management of neurocognitive disorders in PLWH. Future work is needed to replicate existing findings with larger sample sizes and longitudinal designs, examine apathy as a multi-dimensional construct, and develop evidence-based treatments for apathy in PLWH.
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Apatia , Infecções por HIV , Humanos , Infecções por HIV/psicologia , Infecções por HIV/tratamento farmacológicoRESUMO
OBJECTIVES: The primary aim was to evaluate apathy assessment measures in relation to cognitive impairment among Hispanic/Latin Americans. METHODS: A systematic review on the relationship between apathy and cognitive impairment among Hispanic/Latin Americans across normal aging and neurocognitive disorders was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and using APA PsycInfo, Embase, and PubMed databases. Inclusion criteria required (1) a sample of English or Spanish-speaking adults ages 18 years and older, (2) with measures of apathy, (3) assessment of cognitive functioning or diagnosis of neurocognitive disorder, (4) with at least 18.5% Hispanic/Latin American represented in the sample. RESULTS: Only 14 papers met criteria to be included in this review. Of the 12 cross-sectional studies, 9 demonstrated significant associations between increased apathy and cognitive impairment, 1 demonstrated a descriptive difference between apathy and cognitive status (ie, no hypothesis test conducted), while 2 demonstrated null effects. These cross-sectional studies consisted of community and clinic samples of participants across North and South America. Two longitudinal studies conducted in North America demonstrated non-significant associations of apathy with cognitive status. CONCLUSIONS: The Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) apathy subscales were the most used measures for apathy in this review (85.7% of included studies). However, validity evidence from a review of apathy measures has warranted caution against the use of the NPI outside the context of screening for apathy. This potential measurement bias with Hispanic/Latin Americans apathy research limits conclusions drawn from the present review.
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Apatia , Disfunção Cognitiva , Humanos , Estudos Transversais , Disfunção Cognitiva/psicologia , Transtornos Neurocognitivos , Hispânico ou LatinoRESUMO
Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inadequate animal models for human psychiatric conditions. Human-derived induced pluripotent stem cells (iPSCs) provide a renewable cellular reagent that can be differentiated into living, disease-relevant cells and 3D brain organoids carrying the full complement of genetic variants present in the donor germline. Experimental studies of iPSC-derived cells allow functional characterization of risk alleles, establishment of causal relationships between genes and neurobiology, and screening for novel therapeutics. Here we report the creation and availability of an iPSC resource comprising clinical, genomic, and cellular data obtained from genetically isolated families with BD and related conditions. Results from the first 324 study participants, 61 of whom have validated pluripotent clones, show enrichment of rare single nucleotide variants and CNVs overlapping many known risk genes and pathogenic CNVs. This growing iPSC resource is available to scientists pursuing functional genomic studies of BD and related conditions.
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Transtorno Depressivo Maior , Células-Tronco Pluripotentes Induzidas , Transtornos Psicóticos , Esquizofrenia , Animais , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Transtornos Psicóticos/metabolismo , Esquizofrenia/genética , Esquizofrenia/metabolismo , Genômica , Estudo de Associação Genômica AmplaRESUMO
Synaptic inhibition is critical for controlling neuronal excitability and function. During global cerebral ischemia (GCI), inhibitory synapses are rapidly eliminated, causing hyper-excitability which contributes to cell-death and the pathophysiology of disease. Sequential disassembly of inhibitory synapses begins within minutes of ischemia onset: GABAARs are rapidly trafficked away from the synapse, the gephyrin scaffold is removed, followed by loss of the presynaptic terminal. GABAARs are endocytosed during GCI, but how this process accompanies synapse disassembly remains unclear. Here, we define the precise trafficking itinerary of GABAARs during the initial stages of GCI, placing them in the context of rapid synapse elimination. Ischemia-induced GABAAR internalization quickly follows their initial dispersal from the synapse, and is controlled by PP1α signaling. During reperfusion injury, GABAARs are then trafficked to lysosomes for degradation, leading to permanent removal of synaptic GABAARs and contributing to the profound reduction in synaptic inhibition observed hours following ischemia onset.
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Using data from Vietnamese-origin older immigrants/refugees in the Houston, Texas area, we assessed their overall health, chronic conditions, disability, depressive symptoms, and cognitive impairment, and examined the association between their chronic conditions and disability by comorbidity clusters. The mean age of the sample was 76 years old. The majority were married in fair/poor health with several chronic conditions and disabilities and lived with families in low-income households. Hypertension and arthritis were the most common health conditions, but cognitive impairment had the most significant impact on their disability. They experienced similar health conditions to other older Americans but had higher rates of depressive symptoms and cognitive impairment possibly due to cultural factors that may have delayed mental health treatment. Culturally and linguistically tailored services created by policymakers, healthcare professionals, and local social service agencies are recommended for the well-being of immigrants/refugees who migrated to the U.S. for a better life.
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Reactive oxygen species (ROS) are a heterogeneous group of highly reactive ions and molecules derived from molecular oxygen (O2) which can cause DNA damage and lead to skin cancer. NADPH oxidase 1 (Nox1) is a major producer of ROS in the skin upon exposure to ultraviolet light. Functionally, Nox1 forms a holoenzyme complex that generates two superoxide molecules and reduces NADPH. The signaling activation occurs when the organizer subunit Noxo1 translocates to the plasma membrane bringing a cytochrome p450, through interaction with Cyba. We propose to design inhibitors that prevent Cyba-Noxo1 binding as a topical application to reduce UV-generated ROS in human skin cells. Design started from an apocynin backbone structure to generate a small molecule to serve as an anchor point. The initial compound was then modified by addition of a polyethylene glycol linked biotin. Both inhibitors were found to be non-toxic in human keratinocyte cells. Further in vitro experiments using isothermal calorimetric binding quantification showed the modified biotinylated compound bound Noxo1 peptide with a KD of 2 nM. Both using isothermal calorimetric binding and MALDI (TOF) MS showed that binding of a Cyba peptide to Noxo1 was blocked. In vivo experiments were performed using donated skin explants with topical application of the two inhibitors. Experiments show that ultraviolet light exposure of with the lead compound was able to reduce the amount of cyclobutene pyrimidine dimers in DNA, a molecule known to lead to carcinogenesis. Further synthesis showed that the polyethylene glycol but not the biotin was essential for inhibition.
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Biotina , NADPH Oxidases , Humanos , Espécies Reativas de Oxigênio/metabolismo , Biotina/metabolismo , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Superóxidos/metabolismo , NADPH Oxidase 1/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
Activity-dependent protein synthesis is crucial for many long-lasting forms of synaptic plasticity. However, our understanding of the translational mechanisms controlling inhibitory synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABAARs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the precise mechanisms controlling gephyrin translation during this process remain unknown. Here, we identify miR153 as a novel regulator of Gphn mRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting GABAergic synaptic structure and function. We find that iLTP induction downregulates miR153, reversing its translational suppression of Gphn mRNA and allowing for increased de novo gephyrin protein synthesis and synaptic clustering during iLTP. Finally, we find that reduced miR153 expression during iLTP is driven by an excitation-transcription coupling pathway involving calcineurin, NFAT and HDACs, which also controls the miRNA-dependent upregulation of GABAARs. Overall, this work delineates a miRNA-dependent post-transcriptional mechanism that controls the expression of the key synaptic scaffold, gephyrin, and may converge with parallel miRNA pathways to coordinate gene upregulation to maintain inhibitory synaptic plasticity.
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Microbial experimental systems provide a platform to observe how networks of groups emerge to impact plant development. We applied selection pressure for microbiome enhancement of Brassica rapa biomass to examine adaptive bacterial group dynamics under soil nitrogen limitation. In the 9th and final generation of the experiment, selection pressure enhanced B. rapa seed yield and nitrogen use efficiency compared to our control treatment, with no effect between the random selection and control treatments. Aboveground biomass increased for both the high biomass selection and random selection plants. Soil bacterial diversity declined under high B. rapa biomass selection, suggesting a possible ecological filtering mechanism to remove bacterial taxa. Distinct sub-groups of interactions emerged among bacterial phyla such as Proteobacteria and Bacteroidetes in response to selection. Extended Local Similarity Analysis and NetShift indicated greater connectivity of the bacterial community, with more edges, shorter path lengths, and altered modularity through the course of selection for enhanced plant biomass. In contrast, bacterial communities under random selection and no selection showed less complex interaction profiles of bacterial taxa. These results suggest that group-level bacterial interactions could be modified to collectively shift microbiome functions impacting the growth of the host plant under soil nitrogen limitation.
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Brassica rapa , Microbiota , Bactérias/genética , Brassica rapa/microbiologia , Nitrogênio , Plantas , Rizosfera , Sementes , Solo , Microbiologia do SoloRESUMO
BACKGROUND: Skepticism among the public surrounding the COVID-19 vaccine is still prevalent despite vaccine-positive communication and many Americans having already received the vaccine. Side effects of the vaccine, as well as its expeditious research and development, are among the top concerns among those hesitant to receive the coronavirus vaccine. Moreover, there is additional concern regarding the association between comorbidities and severity of illness due to the coronavirus pandemic. OBJECTIVE: We aimed to describe the pandemic- and vaccine-related concerns of South Texas residents who attended the UT Health San Antonio School of Nursing's vaccine clinic with the goal of better understanding vaccine-related misconceptions and hesitancy for subsequent vaccination campaigns and boosters. METHODS: An electronic survey accessible via a QR code on printed flyers was distributed throughout the waiting areas and post-vaccine observation rooms within the COVID-19 vaccine clinic at UT Health San Antonio School of Nursing from April 5 to 16, 2021. The survey contained a primary open-ended question designed to obtain information on concerns of the clinic attendees regarding the COVID-19 pandemic and COVID-19 vaccine. A thematic analysis was performed on the qualitative data to identify major themes to better understand concerns of vaccine clinic visitors. RESULTS: During the 11-day period, 510 attendees received vaccinations through the vaccination clinic and completed the survey. Five areas of concern were identified by the 277 attendees: immunity, future vaccinations, vaccine symptoms and safety, protocol post-vaccination, and child vaccinations. Post-hoc sentiment analysis showed that responses were generally neutral or negative. CONCLUSION: This study provides a perspective regarding questions and concerns of South Texas residents regarding the COVID-19 pandemic, the vaccine, and their general health status within a vaccinated population. Vaccine recipients were found to still have questions even after receiving the vaccine, suggesting that eliminating uncertainty surrounding the COVID-19 vaccine is not necessary to motivate individuals to receive the vaccine. Instead, addressing concerns through public health messaging could be a useful strategy to address vaccine-related concerns and increase subsequent vaccine uptake in future vaccination campaigns and boosters.
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COVID-19 , Vacinas contra Influenza , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Criança , Humanos , Pandemias , Estados Unidos , VacinaçãoRESUMO
We translated the Medication Management Ability Assessment (MMAA) from English to Spanish for use via tele-assessment and examined its reliability and validity. Following International Test Commission Guidelines for Translating and Adapting Tests, we used translation/back-translation and a small focus group (n = 6) to adapt a Spanish version of the MMAA. Eighty-six Spanish-speaking adults completed the adapted MMAA via tele-assessment at baseline and at a two-week follow-up visit. Participants also completed several self-report and performance-based cognitive and functional measures. The internal consistency of the MMAA was excellent (standardized Cronbach's α = 0.90). Performance-based functional assessments (PBFAs) and objective cognition were positively associated with the MMAA at small to medium effect sizes. Self-report measures of daily function and cognition, measures of health literacy, and estimates of premorbid intellectual functioning were not significantly associated with MMAA performance. The test-retest reliability of the MMAA was good (CCC = 0.73, 95% CI [0.62, 0.81]; rs = 0.37, p < 0.001) and demonstrated a small practice effect (Cohen's d = 0.36, p = 0.001). Preliminary evidence for the construct validity of a Spanish-language MMAA administered via tele-assessment further expands the potential clinical utility of PBFAs in culturally diverse, Spanish-speaking populations.
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GABAergic synaptic inhibition controls neuronal firing, excitability, and synaptic plasticity to regulate neuronal circuits. Following an acute excitotoxic insult, inhibitory synapses are eliminated, reducing synaptic inhibition, elevating circuit excitability, and contributing to the pathophysiology of brain injuries. However, mechanisms that drive inhibitory synapse disassembly and elimination are undefined. We find that inhibitory synapses are disassembled in a sequential manner following excitotoxicity: GABAARs undergo rapid nanoscale rearrangement and are dispersed from the synapse along with presynaptic active zone components, followed by the gradual removal of the gephyrin scaffold, prior to complete elimination of the presynaptic terminal. GABAAR nanoscale reorganization and synaptic declustering depends on calcineurin signaling, whereas disassembly of gephyrin relies on calpain activation, and blockade of both enzymes preserves inhibitory synapses after excitotoxic insult. Thus, inhibitory synapse disassembly occurs rapidly, with nanoscale precision, in a stepwise manner and most likely represents a critical step in the progression of hyperexcitability following excitotoxicity.
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Lesões Encefálicas/fisiopatologia , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Terminações Pré-Sinápticas/metabolismo , Receptores de GABA-A/metabolismo , Sinapses/metabolismo , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
BACKGROUND: Assessing depression symptoms in Hispanic/Latin American (H/Ls) older adults, a group at high risk for depression, is nuanced due to the influence of cultural characteristics in symptom expression and manifestation. Little is known about the psychometric properties of available measures when used with this population. METHODS: We conducted a two-stage systematic review of available depression assessment tools. We first identified self-report measures designed for use with adults. We then identified studies where at least one of such measures was used with older H/Ls that reported psychometric properties for the measure(s) used. RESULTS: Only 3 measures were identified for use with older H/Ls: the BDI, GDS, and CES-D. However, few data were found to support the validity of the BDI, and the CES-D was not consistently valid across cultural groups. The GDS was found appropriate, though its performance varied based on race/ethnicity, nationality, and cutoff scores. The CES-D and GDS also demonstrated varying psychometric properties based on study setting (research versus clinical) and target population (inpatient psychiatric patients versus community-dwelling individuals). LIMITATIONS: The number of articles that met criteria for inclusion in our review was small, and there was variation among samples of the few studies included. CONCLUSIONS: Currently available self-report depression screening measures have acceptable applicability among older H/Ls, but their utility may vary based on their intended use. Modified cutoff scores may be beneficial in maximizing the utility of these measures when given to diverse older adults.