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Preterm birth is a serious pregnancy complication that affects neonatal mortality, morbidity, and long-term neurological prognosis. Predicting spontaneous preterm delivery (PTD) is important for its management. While excluding the risk of PTD is important, identifying women at high risk of PTD is imperative for medical intervention. Currently used PTD prediction parameters in clinical practice have shown high negative predictive values, but low positive predictive values. We focused on sulfated and sialylated glycocalyx changes in the uterus and vagina prior to the onset of parturition and explored the potential of electrophysiological detection of these changes as a PTD prediction parameter with a high positive predictive value. In vivo local vaginal bioelectrical impedance (VZ) was measured using two different mouse PTD models. PTD was induced in ICR mice through the subcutaneous injection of mifepristone or local intrauterine injection of lipopolysaccharide (LPS). The PTD rates were 100% and 60% post-administration of mifepristone (16-20 h, n = 4) and LPS (12-24 h, n = 20), respectively. The local VZ values (15 and 10 h after mifepristone or LPS treatment, respectively) were significantly lower in the PTD group than in the non-PTD group. Receiver operator characteristic (ROC) curve analysis of VZ at 125 kHz as a predictor of PTD showed an area under the ROC curve of 1.00 and 0.77 and positive predictive values of 1.00 and 0.86, for the mifepristone and LPS models, respectively, suggesting that local VZ value can predict PTD. Histological examination of the LPS-treated model 6 h post-treatment revealed increased expression of sulfomucins and/or sulfated proteoglycans and sialomucins in the cervical epithelium, cervical stroma and vaginal stroma. In conclusion, local VZ values can determine sulfated and sialylated glycocalyx alterations within the uterus and vagina and might be a useful PTD prediction parameter.
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Impedância Elétrica , Camundongos Endogâmicos ICR , Nascimento Prematuro , Vagina , Animais , Feminino , Vagina/metabolismo , Vagina/efeitos dos fármacos , Vagina/patologia , Gravidez , Camundongos , Nascimento Prematuro/metabolismo , Nascimento Prematuro/diagnóstico , Mifepristona/farmacologia , Útero/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/toxicidade , Valor Preditivo dos Testes , Curva ROC , Modelos Animais de DoençasRESUMO
OBJECTIVE: To conduct an Australian community-led survey of adults with type 1 diabetes (T1D), identifying priorities for, and barriers to, optimal use of advanced glucose management technologies. RESEARCH DESIGN AND METHODS: A 30-question online survey of current or past users of insulin pump therapy (IPT), real-time continuous glucose monitoring (RT-CGM), or intermittently scanned CGM (isCGM) explored perceptions regarding device design, access, education, outcomes, and support. RESULTS: Between November 2021 and January 2022, surveys were completed by 3,380 participants (age [mean ± SD] 45 ± 16 years; 62% female; 20 ± 14 years diabetes), with 55%, 82%, and 55% reporting experience with IPT, RT-CGM, and isCGM, respectively. Overall, most considered diabetes technology '(extremely) important' for maintaining target glucose levels (98%) and reducing hypoglycaemia severity and frequency (93%). For most, technology contributed positively to emotional well-being (IPT 89%; RT-CGM 91%; isCGM 87%), which was associated with device effectiveness in maintaining glucose in range, comfort, and convenience. Barriers included affordability (IPT 68%; RT-CGM 81%; isCGM 69%) and insufficient information for informed choices about device suitability (IPT 39%; RT-CGM 41%; isCGM 36%). CONCLUSIONS: Technology is perceived by adults with T1D as important for managing glycaemia and emotional well-being. Modifiable barriers to use include affordability, and information regarding device suitability.
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Diabetes Mellitus Tipo 1 , Insulinas , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Masculino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Glicemia , Automonitorização da Glicemia , Austrália/epidemiologia , Poder Psicológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
Endotheliochorial cat (Felis catus) and lion (Panthera leo) term placentae and one 6 week placenta (term 60-63 days) from a dog (Canis familiaris) were stained with a panel of 24 lectins to compare glycosylation at the feto-maternal interface. Glycan expression in lion and cat placentae was very similar apart from the occurrence of terminal α-galactose in the lion trophoblast. The dog differed in several respects, particularly in the trophoblast, consistent with species-specific glycotypes differing according to the degree of their evolutionary divergence. The data suggest that evolutionary effects on the glycotype are most readily observed in trophoblast.
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Canidae , Leões , Gatos , Animais , Feminino , Gravidez , Cães , Placenta , Glicosilação , TrofoblastosRESUMO
INTRODUCTION: Placental glycosylation has been examined on eight feline placentae ranging from approximately 15 to 60 days post-conception as little is known about changes in glycan distribution in this species. METHODS: Specimens were resin embedded and lectin histochemistry was applied to semi-thin sections using a panel of 24 lectins and an avidin-biotin revealing system. RESULTS: Abundant tri-tetraantennary complex N-glycan and α-galactosyl residues found in the syncytium in early pregnancy were greatly reduced in mid-pregnancy, though retained at the invasion front in the syncytium (N-glycan) or cytotrophoblast layer (αGal). Some other glycans were also uniquely present in invading cells. Abundant polylactosamine was found in the infolding basal lamina of syncytiotrophoblast and the apical villous cytotrophoblast membrane. Syncytial secretory granules often clustered near the apical membrane abutting maternal vessels. Decidual cells selectively expressed ß-galactosyl residues throughout pregnancy and highly branched N-glycan levels increased over time. DISCUSSION: Glycan distribution changes significantly over pregnancy, probably relating to the development of transport and invasive properties of trophoblast which in the endotheliochorial placenta reaches the level of the maternal vessels. Highly branched complex N-glycans, often associated with invasive cells, N-Acetylgalactosamine and terminal α-galactosyl residues are present at the invasion front abutting the junctional zone of the endometrium. Abundant polylactosamine on the syncytiotrophoblast basal lamina may reflect the presence of specialised adhesive interactions, while clustering of glycosylated granules apically is probably associated with secretion and absorption of material via maternal vasculature. It is suggested that lamellar and invasive cytotrophoblast represent distinct differentiation pathways. 246 words.
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Placenta , Trofoblastos , Gravidez , Animais , Gatos , Feminino , Trofoblastos/metabolismo , Placenta/metabolismo , Placentação , Lectinas/análise , Polissacarídeos/metabolismo , Diferenciação CelularRESUMO
Placental hormones orchestrate maternal metabolic adaptations to support pregnancy. We hypothesized that placental ER stress, which characterizes early-onset pre-eclampsia (ePE), compromises glycosylation, reducing hormone bioactivity and these maladaptations predispose the mother to metabolic disease in later life. We demonstrate ER stress reduces the complexity and sialylation of trophoblast protein N-glycosylation, while aberrant glycosylation of vascular endothelial growth factor reduced its bioactivity. ER stress alters the expression of 66 of the 146 genes annotated with "protein glycosylation" and reduces the expression of sialyltransferases. Using mouse placental explants, we show ER stress promotes the secretion of mis-glycosylated glycoproteins. Pregnant mice carrying placentas with junctional zone-specific ER stress have reduced blood glucose, anomalous hepatic glucose metabolism, increased cellular stress and elevated DNA methyltransferase 3A. Using pregnancy-specific glycoproteins as a readout, we also demonstrate aberrant glycosylation of placental proteins in women with ePE, thus providing a mechanistic link between ePE and subsequent maternal metabolic disorders.
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BACKGROUND: Recent trends in neonatal intensive care unit design have been directed toward reducing negative stimuli and creating a more developmentally appropriate environment for infants who require intensive care. These efforts have included reconfiguring units to provide private rooms for infants. PURPOSE: The purpose of this integrative review was to synthesize and critically analyze negative outcomes for patients, families, and staff who have been identified in the literature related to single-family room (SFR) care in the neonatal intensive care unit. METHODS/SEARCH STRATEGY: The electronic databases of CINAHL, ProQuest Nursing & Allied Health, and PubMed databases were utilized. Inclusion criteria were research studies in English, conducted from 2011 to 2021, in which the focus of the study was related to unit design (SFRs). Based on the inclusion criteria, our search yielded 202 articles, with an additional 2 articles found through reference list searches. After screening, 44 articles met our full inclusion/exclusion criteria. These studies were examined for outcomes related to SFR unit design. FINDINGS/RESULTS: Our findings revealed both positive and negative outcomes related to SFR unit design when compared with traditional open bay units. These outcomes were grouped into 4 domains: Environmental Outcomes, Infant Outcomes, Parent Outcomes, and Staff Outcomes. IMPLICATIONS FOR PRACTICE AND RESEARCH: Although SFR neonatal intensive care unit design improves some outcomes for infants, families, and staff, some unexpected outcomes have been identified. Although these do not negate the positive outcomes, they should be recognized so that steps can be taken to address potential issues and prevent undesired outcomes.
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Arquitetura Hospitalar , Unidades de Terapia Intensiva Neonatal , Recém-Nascido , Lactente , Humanos , Pais , Cuidados Críticos , Quartos de PacientesRESUMO
Many health professional students have insufficient general knowledge about individuals with neurodevelopmental disabilities. Students lack the expertise required to work with this population and their families. Interprofessional practice education (IPE) programs, designed for working with individuals with specialized needs and their families, are needed to improve overall care provided. An IPE program related to neurodevelopmental disabilities for health professional students was implemented focusing on applied learning and community engagement to develop competencies for students related to neurodevelopmental disabilities at a state university in the U.S. The purpose of this research was to describe the development and implementation of an IPE program and to examine the effectiveness of the IPE program aimed at developing identified competencies and increase awareness related to care of individuals with ND for health professional students. The findings suggest the IPE program enhanced health professional students' perceived competencies to identify and provide culturally sensitive and family-centered care for individuals with neurodevelopmental disabilities and their families. This experience also provided an opportunity for personal/professional growth and increased awareness of the unique needs of these individuals with neurodevelopmental disabilities and their families.
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Pessoal de Saúde , Relações Interprofissionais , Humanos , Projetos Piloto , Pessoal de Saúde/educação , Estudantes , CurrículoRESUMO
Haberland syndrome or encephalocraniocutaneous lipomatosis (ECCL) is a rare, congenital syndrome characterized by lipomas and noncancerous tumors of the scalp, skin, and eyes, in addition to intellectual disability, early onset seizures, and ectomesodermal dysgenesis. The diagnosis of ECCL is classically made by clinical presentation, imaging, and histopathological findings, but due to the spectrum of clinical presentation and symptom severity, diagnosis is often delayed until adolescence or adulthood. Here we present a newborn male infant, one of the earliest case diagnoses to our knowledge, with a unique constellation of physical exam and neuroimaging findings consistent with this diagnosis. We aim to address important neonatal findings to aid in early detection and diagnosis of this unique disease, which is thought to improve clinical outcomes and patient quality of life.
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PURPOSE: To demonstrate the diagnostic performance of rapid SARS-CoV-2 RT-LAMP assays, comparing the performance of genomic versus sub-genomic sequence target with subsequent application in an asymptomatic screening population. METHODS: RT-LAMP diagnostic specificity (DSe) and sensitivity (DSe) was determined using 114 RT-PCR clinically positive and 88 RT-PCR clinically negative swab samples processed through the diagnostic RT-PCR service within the University Hospitals of Leicester NHS Trust. A swab-based RT-LAMP SARS-CoV-2 screening programme was subsequently made available to all staff and students at the University of Leicester (Autumn 2020), implemented to ISO 15189:2012 standards using NHS IT infrastructure and supported by University Hospital Leicester via confirmatory NHS diagnostic laboratory testing of RT-LAMP 'positive' samples. RESULTS: Validation samples reporting a Ct < 20 were detected at 100% DSe and DSp, reducing to 95% DSe (100% DSp) for all samples reporting a Ct < 30 (both genomic dual sub-genomic assays). Advisory screening identified nine positive cases in 1680 symptom free individuals (equivalent to 540 cases per 100,000) with results reported back to participants and feed into national statistics within 48 hours. CONCLUSION: This work demonstrates the utility of a rapid RT-LAMP assay for collapsing transmission of SARS-CoV-2 in an asymptomatic screening population.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/epidemiologia , Humanos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/genética , SARS-CoV-2/genética , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Little is known about the glycosylation of placental villi and areolae of cetaceans. Term tissue from the delivered placenta of an Indo-Pacific Bottlenose Dolphin (Tursiops aduncus) was examined using lectin histochemistry to compare trophoblast glycosylation in these two locations. METHODS: Placental blocks fixed in 10% formalin were resin-embedded before semithin sections were stained with 24 biotinylated lectins and an avidin-biotin revealing system. RESULTS: Areolar trophoblast was composed of large, bulbous cells packed with numerous granules compared to the smaller, cuboidal cells clothing the chorionic villi, which had a sparser, mainly subapical granule population. Both were richly glycosylated; generally areolar cells were more heavily stained apart from poor binding to some N-acetylgalactosamine and N-acetylglucosamine termini. Most striking was the distribution of α1,2-linked fucosyl residues, weakly expressed in villous trophoblast but intensely stained in some areolar cells, also terminal sialic acids. Some lectins bound in a variable fashion. Staining of terminal α-d-mannose, which locates mainly to lysosomes, was heavy in areolar cells compared to scattered irregular foci in villous cells. DISCUSSION AND CONCLUSION: The many intracellular inclusions reflect ongoing lysosomal breakdown of histotroph in areolar cells which often show heterogeneous glycosylation staining unlike the uniformly stained villous cells, possibly reflecting partial breakdown of ingested sialoglycoprotein, cell turnover or regional variation in uptake of histotroph. Our results indicate that Dolphin areolae are functionally distinct from villous trophoblast, performing absorptive and phagocytic functions similar to other Artiodactyla.
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Golfinho Nariz-de-Garrafa , Placenta , Animais , Golfinho Nariz-de-Garrafa/metabolismo , Feminino , Glicosilação , Lectinas/metabolismo , Placenta/metabolismo , Gravidez , Trofoblastos/metabolismoRESUMO
As more is understood about the hereditary nature of disease risk, the utility of genetic testing within cardiovascular medicine is increasingly being explored. Although testing may afford more personalized risk stratification, there is a paucity of information regarding patient knowledge, attitudes, and beliefs toward genetic testing among cardiology patients. Participants (n = 530) recruited primarily from a cardiology clinic filled out a 41-item written questionnaire assessing knowledge, beliefs, and attitudes toward genetic testing, motivators and detractors for considering genetic testing, and perceived likelihood for behavior change after hypothetical genetic testing risk stratification. Path analysis was used to test the hypothetical models predicting the likelihood of getting a genetic test and making behavior changes following genetic testing. The patient population was late-middle-aged (59.0 ± 14.5 years), majority women (61.5%), and about half reported having a bachelor's degree. 58.1% of participants self-identified as White, 25.7% as African American or Black, 6.8% as Spanish, Latino, or Hispanic, 3.0% as Asian or Pacific Islander, and 0.5% as Native American. Gender (being a woman) and more years of education were related to greater knowledge about genetic testing. Racial identity and years of education were related to beliefs about genetic testing. Beliefs, but not knowledge, were related to more positive attitudes and a higher likelihood of pursuing genetic testing. Positive attitudes were related to greater perceived personal control (PPC). Furthermore, attitudes and PPC were related to higher likelihood of lifestyle change after genetic testing. These results highlight the need to integrate the experiences of racialized communities into education/counseling efforts. Most educational counseling efforts lack a nuanced discussion of social determinants of health or beliefs. In addition to factual information, educational counseling must also address people's beliefs, concerns, and the intersecting experiences and identities, which shape patients' relationships with the evolving landscape of healthcare and personalized medicine.
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Atitude , Cardiologia , Negro ou Afro-Americano , Instituições de Assistência Ambulatorial , Feminino , Testes Genéticos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
CASE PRESENTATION: A 73-year-old frail woman presented with 3 months of progressively worsening exertional dyspnea, mild cough with white mucus, voice changes, and few episodes of dysphagia. She denied weight loss, night sweats, chest pain, or hemoptysis. Medical history was significant for hypertension, remote 30 years of tobacco use, and regular alcohol use. She had neither asbestos nor occupational exposure. She had no family history of malignancy.
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Dispneia , Tórax , Idoso , Dor no Peito , Tosse/diagnóstico , Tosse/etiologia , Diagnóstico Diferencial , Dispneia/diagnóstico , Dispneia/etiologia , Feminino , HumanosRESUMO
Prolonged pregnancy describes a pregnancy that progresses beyond 42 weeks' gestation (294 days). In humans, prolonged pregnancy is associated with increasing perinatal mortality, neonatal compromise and birth by Caesarean section. The underpinning reasons behind these increased risks are unknown; one potential explanation is reduced placental function due to ageing processes. This review describes the structural and functional changes seen in prolonged pregnancy in humans and in animal models. Prolonged pregnancies are associated with reduced placental growth, leading to an increase in fetal to placental weight ratio. Microscopic changes include aggregation of syncytiotrophoblast nuclei, reduced villous vascularity with a concomitant impairment of trophoblast transport processes (reduced pinocytosis); this is associated with increased evidence of oxidative stress, with downstream consequences including cellular senescence, autophagy and apoptosis; importantly many of these changes are similar to fetal growth restriction and pre-eclampsia. Thus, we argue that these observations provide evidence of ageing within the placenta, which may initially be adaptive but can become pathological leading to a reduction in placental function. This provides a biological basis for the increased risk of adverse outcomes observed in prolonged pregnancies. Greater insight into the effects and risks of placental ageing may be useful to guide clinicians on the management of prolonged pregnancies.
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Pré-Eclâmpsia , Gravidez Prolongada , Animais , Cesárea/efeitos adversos , Feminino , Retardo do Crescimento Fetal/patologia , Humanos , Placenta/patologia , Pré-Eclâmpsia/patologia , Gravidez , Gravidez Prolongada/patologiaRESUMO
BACKGROUND: Frozen section is a standard of care procedure during thoracic surgery when an immediate diagnosis is needed. An alternative procedure is intraoperative cytology. Video-assisted thoracic surgery is currently widely used for thoracic surgical procedures. The aim of this study was to assess intraoperative cytology together with frozen section for accuracy, turnaround time, and total response time during video-assisted thoracic surgery. METHODS: We included patients having video-assisted thoracic surgery between August 2018 and February 2019 at our institution. A cytopathologist and a surgical pathologist independently performed intraoperative cytology and frozen sections, respectively. Final histologic diagnosis was the reference standard. Intraoperative cytology, frozen section turnaround, and total response times were analyzed. RESULTS: A total of 52 specimens from 27 patients were included. The intraoperative cytology correlated with final histology in 98% of cases. Frozen section correlated with final histology in 100% of cases. Intraoperative cytology turnaround and total response times were equal (mean, 4.35 minutes; range, 2-15 minutes). Mean frozen section turnaround and response times were 26.2 minutes (range, 9-61 minutes) and 36.7 minutes (range, 16-90 minutes), respectively. We found a statistically significant difference between intraoperative cytology and frozen section turnaround time and total response times (P < .001). CONCLUSIONS: This study highlights that intraoperative cytology could be as accurate as frozen section and considerably faster during video-assisted thoracic surgery (P < .001). Total response time could potentially be used as a quality metric for video-assisted thoracic surgery.
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Citodiagnóstico/tendências , Melhoria de Qualidade , Neoplasias Torácicas/diagnóstico , Cirurgia Torácica Vídeoassistida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Neoplasias Torácicas/cirurgiaRESUMO
Leveraging elements of game design and theories of human motivation, gamification provides a variety of techniques to engage learners in novel ways. Our Clinical and Translational Science Award created the software platform (Kaizen-Education©) to deliver gamified educational content in 2012. Here, we explore two novel use cases of this platform to provide practical insights for leveraging these methods in educational settings: (1) national training in rigor, reproducibility, and transparency and (2) attainment of learner competency (n = 7) as a gauge of curricular effectiveness across Master of Public Health degree tracks (n = 5). Data were captured in real time during player interaction with Kaizen-Education© to provide descriptive analyses of player engagement in both implementation examples. We then assessed item analysis to assess knowledge gain and competency attainment. We have just begun to leverage the potential for gamification to engage learners, enhance knowledge acquisition, and document completion of training, across various learning environments. We encourage a systematic approach to gamification applying insights from self-determination theory to learners and learning environments, a methodical approach to game design and rigorous analysis after implementation to generate evidence-based insights to maximize educational return for time invested.
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Traumatic Brain Injury (TBI) is a highly prevalent and serious public health concern. Most cases of TBI are mild in nature, yet some individuals may develop following-up persistent disability. The pathophysiologic causes for those with persistent postconcussive symptoms are most likely multifactorial and the underlying mechanism is not well understood, although it is clear that sleep disturbances feature prominently in those with persistent disability. The sleep electroencephalogram (EEG) provides a direct window into neuronal activity during an otherwise highly stereotyped behavioral state, and represents a promising quantitative measure for TBI diagnosis and prognosis. With the ever-evolving domain of machine learning, deep convolutional neural networks, and the development of better architectures, these approaches hold promise to solve some of the long entrenched challenges of personalized medicine for uses in recommendation systems and/or in health monitoring systems. In particular, advanced EEG analysis to identify putative EEG biomarkers of neurological disease could be highly relevant in the prognostication of mild TBI, an otherwise heterogeneous disorder with a wide range of affected phenotypes and disability levels. In this work, we investigate the use of various machine learning techniques and deep neural network architectures on a cohort of human subjects with sleep EEG recordings from overnight, in-lab, diagnostic polysomnography (PSG). An optimal scheme is explored for the classification of TBI versus non-TBI control subjects. The results were promising with an accuracy of â¼95% in random sampling arrangement and â¼70% in independent validation arrangement when appropriate parameters were used using a small number of subjects (10 mTBI subjects and 9 age- and sex-matched controls). We are thus confident that, with additional data and further studies, we would be able to build a generalized model to detect TBI accurately, not only via attended, in-lab PSG recordings, but also in practical scenarios such as EEG data obtained from simple wearables in daily life.
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Concussão Encefálica , Aprendizado Profundo , Eletroencefalografia , Humanos , Aprendizado de Máquina , SonoRESUMO
GABA (Gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the central nervous system of mammals. It is known to be related with various neurological disorders. GABA plays a crucial role in normal neuronal activity, information processing and plasticity, and neuronal network synchronization. To date, microdialysis has been widely used to monitor the level of GABA but the temporal and spatial resolution is limited. Besides, electrochemical sensors for neurotransmitter measurement, having high temporal and spatial resolution, overcome this problem. Here, using a cost-effective method of electrodeposition of platinum black (Pt-black), a highly sensitive, GABA specific, amperometric electrochemical sensor is fabricated. Nanostructured Pt-black increases the active surface area of the electrode contributing to higher sensitivity. Along with that, a self-referencing site and an exclusion layer are integrated to increase the selectivity and the signal-to-noise ratio (SNR) of the biosensor. This provides a prototype for a highly sensitive GABA sensor that could later be used to study various neurological disorders related to GABA concentrations.Clinical Relevance- This electrochemical sensor allows real-time monitoring of major inhibitory neurotransmitter (GABA) with high sensitivity which can be used for studying various neurological disorders.