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1.
Head Neck ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39104194

RESUMO

BACKGROUND: Hypocalcemia is the most common postoperative complication of total thyroidectomy. Near-infrared autofluorescence (NIRAF) technology is a surgical adjunct that has been increasingly utilized with the aim of preventing postoperative hypocalcemia, but its clinical benefits have not yet been firmly established. The aim of this study was to assess the clinical benefit of utilizing NIRAF technology in patients undergoing total thyroidectomy. METHODS: A systematic review and meta-analysis of randomized clinical trials was performed according to PRISMA guidelines. RESULTS: Seven randomized clinical trials with 1437 patients (318 males, 22.13%) undergoing total thyroidectomy were included for analysis. Risk of postoperative hypocalcemia was reduced in the NIRAF arm (RR, 0.65; 95%CI, 0.50-0.84). Use of NIRAF was also associated with a reduction in the risk of permanent parathyroid dysfunction (RR, 0.46; 95%CI, 0.22-0.95) and inadvertent parathyroid gland resection (RR, 0.40; 95%CI, 0.26-0.60). CONCLUSIONS: We present a systematic review and meta-analysis of randomized clinical trials examining the impact of NIRAF technology on preservation of parathyroid function. Our results suggest that use of camera-based NIRAF technology reduces the risk of postoperative hypocalcemia, permanent parathyroid dysfunction, and inadvertent parathyroid gland resection.

2.
bioRxiv ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38979173

RESUMO

Sensitization of spinal nociceptive circuits plays a crucial role in neuropathic pain. This sensitization depends on new gene expression that is primarily regulated via transcriptional and translational control mechanisms. The relative roles of these mechanisms in regulating gene expression in the clinically relevant chronic phase of neuropathic pain are not well understood. Here, we show that changes in gene expression in the spinal cord during the chronic phase of neuropathic pain are substantially regulated at the translational level. Downregulating spinal translation at the chronic phase alleviated pain hypersensitivity. Cell-type-specific profiling revealed that spinal inhibitory neurons exhibited greater changes in translation after peripheral nerve injury compared to excitatory neurons. Notably, increasing translation selectively in all inhibitory neurons or parvalbumin-positive (PV+) interneurons, but not excitatory neurons, promoted mechanical pain hypersensitivity. Furthermore, increasing translation in PV+ neurons decreased their intrinsic excitability and spiking activity, whereas reducing translation in spinal PV+ neurons prevented the nerve injury-induced decrease in excitability. Thus, translational control mechanisms in the spinal cord, particularly in inhibitory neurons, play a role in mediating neuropathic pain hypersensitivity.

3.
Toxicol Sci ; 200(2): 241-264, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38796678

RESUMO

Addressing human anatomical and physiological variability is a crucial component of human health risk assessment of chemicals. Experts have recommended probabilistic chemical risk assessment paradigms in which distributional adjustment factors are used to account for various sources of uncertainty and variability, including variability in the pharmacokinetic behavior of a given substance in different humans. In practice, convenient assumptions about the distribution forms of adjustment factors and human equivalent doses (HEDs) are often used. Parameters such as tissue volumes and blood flows are likewise often assumed to be lognormally or normally distributed without evaluating empirical data for consistency with these forms. In this work, we performed dosimetric extrapolations using physiologically based pharmacokinetic (PBPK) models for dichloromethane (DCM) and chloroform that incorporate uncertainty and variability to determine if the HEDs associated with such extrapolations are approximately lognormal and how they depend on the underlying distribution shapes chosen to represent model parameters. We accounted for uncertainty and variability in PBPK model parameters by randomly drawing their values from a variety of distribution types. We then performed reverse dosimetry to calculate HEDs based on animal points of departure for each set of sampled parameters. Corresponding samples of HEDs were tested to determine the impact of input parameter distributions on their central tendencies, extreme percentiles, and degree of conformance to lognormality. This work demonstrates that the measurable attributes of human variability should be considered more carefully and that generalized assumptions about parameter distribution shapes may lead to inaccurate estimates of extreme percentiles of HEDs.


Assuntos
Modelos Biológicos , Humanos , Animais , Medição de Risco , Clorofórmio/farmacocinética , Incerteza , Distribuição Tecidual , Relação Dose-Resposta a Droga
4.
Cureus ; 16(3): e56582, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646287

RESUMO

Multiple complicated concurrent hernias with obturator hernia and paraesophageal hernia unusually occur in clinical settings. The obturator hernias belong to a rare pelvic hernia that accounts for a minority of all abdominal hernias. Besides, paraesophageal hernias occur commonly in elderly female patients. Clinical manifestations of these hernias are usually unspecific and the diagnosis is based on computed tomography (CT). In this paper, we presented a case of multiple complicated hernias in an 81-year-old woman. She was admitted to our hospital due to intestinal obstruction that was caused by a simultaneous obturator and paraesophageal hernia. She was successfully treated by laparoscopic hernia repair. Postoperative progression was favorable. She was then discharged from the hospital after four hospital days.

5.
Life (Basel) ; 14(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38672795

RESUMO

During the last two decades, several cases of venous thrombosis (VTE) after a prolonged period at a computer have been described, denominated as "eThrombosis". Video gaming on a computer has become very popular and can be a social activity where several players gather to play against each other or in a virtual environment for several days ("LAN (i.e., Local Area Network) parties") where the participants are sedentary and consuming calorie-rich food items. The aim of this study was to investigate potential coagulation activation during a 42 h LAN party. Nine male gamers volunteered for the LAN party. Citrated blood was sampled before and every 6 h, and plasma was analyzed for thrombin generation, thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and D-dimer. Thrombin generation increased slightly but not significantly during the LAN party, whereas the coagulation activation markers were unchanged. These results do not indicate that the coagulation system is activated significantly during 42 h of gaming with minimal physical activity. Although increased activity cannot be excluded, it does not directly indicate a risk of VTE in general.

6.
Antimicrob Resist Infect Control ; 13(1): 12, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273403

RESUMO

BACKGROUND: Vietnam is among 11 countries in the Western Pacific region that has developed a National Action Plan for Antimicrobial Resistance (NAPCA). METHODS: This scoping review characterises health system barriers to the implementation of the Vietnam NAPCA, with reference to the WHO Health Systems Framework. RESULTS: Over 7 years, between 2013 and 2020, the Ministry of Health (MOH) of Vietnam has been implementing activities to achieve the six NAPCA objectives. They include revision of regulations needed for antimicrobial resistance (AMR) prevention programs; formation and operation of national management bodies; improvement of antimicrobial stewardship (AMS) in hospitals; maintenance of surveillance systems for AMR; provision of trainings on AMR and antibiotics use to doctors and pharmacists; and organization of nation-wide educational campaigns. Limited cooperation between MOH management bodies, shortages of human resource at all health system levels, a low degree of agreement between national and hospital guidelines on antibiotic use, low capability in the domestic supply of standardised drugs, and unequal training opportunities for lower-level health professionals present ongoing challenges. Actions suggested for the next period of the NAPCA include a final review of what has been achieved by the plan so far and evaluating the effectiveness of the different components of the plan. Different options on how to improve coordination across sectors in the development of a new NAPCA should be put forward. CONCLUSIONS: The 6-year implementation of the Vietnam NAPCA has yielded valuable lessons for AMS in Vietnam, guiding the development of future national plans, with a central focus on scaling up AMS in hospitals and promoting community AMS programs to combat AMR.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Humanos , Antibacterianos/uso terapêutico , Vietnã , Pessoal de Saúde , Farmacêuticos
7.
Environ Pollut ; 343: 123138, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38097160

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) associated with indoor PM pose a high risk to human health because of their toxicity. A total of 160 daily samples of indoor PM2.5 and PM0.1 were collected in Hanoi and analysed for 15 PAHs. In general, the concentrations of carcinogenic PAHs (car-PAHs) accounted for 21% ± 2%, 19.1% ± 2%, and 26% ± 3% of the concentrations of 15 PAHs in PM2.5, PM0.1-2.5, and PM0.1, respectively. Higher percentages of car-PAHs were found in smaller fractions (PM0.1), which can be easily deposited deep in the pulmonary regions of the human respiratory tract. The concentrations of 15 PAHs were higher in winter than in summer. The most abundant PAH species were naphthalene and phenanthrene, accounting for 11%-21% and 19%-23%, respectively. The PAH content in PM0.1 was almost twice as high as those in PM2.5 and PM0.1-2.5. Principal component analysis found that vehicle emissions and the combustion of biomass and coal were the main outdoor sources of PAHs, whereas indoor sources included cooking activities, the combustion of incense, scented candles, and domestic uses in houses. According to the results, 60%-90% of the PM0.1-bound BaP(eq) was deposited in the alveoli region, whereas 63%-75% of the PM2.5-bound BaP(eq) was deposited in head airways (HA), implying that most of the particles deposited in the HA region were PM0.1-2.5. The contributions of dibenz[a,h]anthracene and benzo[a]pyrene were dominant and contributed from 36% to 51% and 31%-50%, respectively, to the carcinogenic potential, whereas benzo[a]pyrene contributed from 30% to 49% to the mutagenic potential for both size fractions. The incremental lifetime cancer risk, simulated by Monte Carlo simulation, was within the limits set by the US EPA, indicating an acceptable risk for the occupants. These results provide an additional scientific basis for protecting human health from exposure to indoor PAHs.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Material Particulado/análise , Poluentes Atmosféricos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental , Benzo(a)pireno/análise , Medição de Risco , China
8.
Acta Neuropathol Commun ; 11(1): 201, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110990

RESUMO

Autosomal dominant pathogenic mutations in Leucine-rich repeat kinase 2 (LRRK2) cause Parkinson's disease (PD). The most common mutation, G2019S-LRRK2, increases the kinase activity of LRRK2 causing hyper-phosphorylation of its substrates. One of these substrates, Rab10, is phosphorylated at a conserved Thr73 residue (pRab10), and is one of the most abundant LRRK2 Rab GTPases expressed in various tissues. The involvement of Rab10 in neurodegenerative disease, including both PD and Alzheimer's disease makes pinpointing the cellular and subcellular localization of Rab10 and pRab10 in the brain an important step in understanding its functional role, and how post-translational modifications could impact function. To establish the specificity of antibodies to the phosphorylated form of Rab10 (pRab10), Rab10 specific antisense oligonucleotides were intraventricularly injected into the brains of mice. Further, Rab10 knock out induced neurons, differentiated from human induced pluripotent stem cells were used to test the pRab10 antibody specificity. To amplify the weak immunofluorescence signal of pRab10, tyramide signal amplification was utilized. Rab10 and pRab10 were expressed in the cortex, striatum and the substantia nigra pars compacta. Immunofluorescence for pRab10 was increased in G2019S-LRRK2 knockin mice. Neurons, astrocytes, microglia and oligodendrocytes all showed Rab10 and pRab10 expression. While Rab10 colocalized with endoplasmic reticulum, lysosome and trans-Golgi network markers, pRab10 did not localize to these organelles. However, pRab10, did overlap with markers of the presynaptic terminal in both mouse and human cortex, including α-synuclein. Results from this study suggest Rab10 and pRab10 are expressed in all brain areas and cell types tested in this study, but pRab10 is enriched at the presynaptic terminal. As Rab10 is a LRRK2 kinase substrate, increased kinase activity of G2019S-LRRK2 in PD may affect Rab10 mediated membrane trafficking at the presynaptic terminal in neurons in disease.


Assuntos
Células-Tronco Pluripotentes Induzidas , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Camundongos , Animais , Células-Tronco Pluripotentes Induzidas/metabolismo , Fosforilação , Doença de Parkinson/genética , Mutação , Encéfalo/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
9.
Chronic Illn ; : 17423953231209377, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37960844

RESUMO

OBJECTIVES: While most individuals infected with COVID-19 recover completely within a few weeks, some continue to experience lingering symptoms. This study was conducted to identify and describe the clinical and subclinical manifestations of adult patients from the long-term effects of COVID-19. METHODS: The study analyzed 205 medical records of inpatients (age ≥ 16 years, ≥ 4 weeks post-COVID-19 recovery, and a negative SARS-CoV-2 status at enrollment) at Thong Nhat Hospital, Vietnam, from 6 September 2021 to 26 August 2022, using R language software. RESULTS: The majority of patients hospitalized with long COVID-19 symptoms (92.68%) had normal consciousness. The most common symptoms on admission were fatigue (59.02%), dyspnea (52.68%), and cough (42.93%). In total, 80% of patients observed respiratory symptoms, primarily dyspnea, while 42.44% reported neurological symptoms, with sleep disturbance being the most common. Noticeably, 42.93% of patients experienced respiratory failure in the post-COVID-19 period, resembling acute respiratory distress syndrome. DISCUSSION: These findings provide crucial insights into the epidemiology, clinical, and subclinical aspects of post-COVID-19 conditions, shedding light on the prevalence of common symptoms and the demographic distribution of affected patients. Understanding these manifestations is vital for patient well-being, improved clinical practice, and targeted healthcare planning, potentially leading to better patient care, management, and future interventions.

10.
Biosensors (Basel) ; 13(8)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37622895

RESUMO

Alzheimer's disease has taken the spotlight as a neurodegenerative disease which has caused crucial issues to both society and the economy. Specifically, aging populations in developed countries face an increasingly serious problem due to the increasing budget for patient care and an inadequate labor force, and therefore a solution is urgently needed. Recently, diverse techniques for the detection of Alzheimer's biomarkers have been researched and developed to support early diagnosis and treatment. Among them, electrochemical biosensors and electrode modification proved their effectiveness in the detection of the Aß biomarker at appropriately low concentrations for practice and point-of-care application. This review discusses the production and detection ability of amyloid beta, an Alzheimer's biomarker, by electrochemical biosensors with SAM support for antibody conjugation. In addition, future perspectives on SAM for the improvement of electrochemical biosensors are also proposed and discussed.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Anticorpos , Biomarcadores
11.
Anal Chim Acta ; 1273: 341535, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37423666

RESUMO

Plasma phosphorylated-tau threonine 181 (p-tau181) is a promising biomarker for predicting Alzheimer's disease (AD) and mild cognitive impairment (MCI), which is the symptomatic pre-dementia stage of AD. To date, there are limitations in the current diagnosis and classification of the two stages of MCI and AD in clinical practice remain a dilemma. In this study, we aimed to discriminate and diagnose patients with MCI, AD, and healthy participants based on the accurate, label-free, and ultrasensitive detection of p-tau181 levels in human clinical plasma samples using our developed electrochemical impedance-based biosensor, which allows to detect p-tau181 at a very low concentration of 0.92 fg mL-1. Human plasma samples were collected from 20 patients with AD, 20 patients with MCI, and 20 individuals with healthy control. The change in charge-transfer resistance of the developed impedance-based biosensor caused by capturing p-tau181 in plasma samples was recorded to evaluate the determination of plasma p-tau181 levels in human clinical samples for discrimination and diagnosis of AD, MCI, and healthy control individuals, respectively. Receiver operating characteristic (ROC) curve, a standard analysis to judge the clinically diagnostic capability of our biosensor platform based on the estimated levels of plasma p-tau181, resulted a sensitivity of 95%, a specificity of 85%, the area under the ROC curve (AUC) value of 0.94 of the accuracy for discriminating AD patients from healthy controls; a sensitivity of 70%, a specificity of 70%, the AUC of 0.75 to discriminate MCI patients from healthy controls. Statistical analysis (one-way analysis of variance (ANOVA)) was used to compare the estimated plasma p-tau181 levels in clinical samples, indicated significantly higher for AD patients with healthy controls (***p ≤ 0.001), AD with MCI patients (***p ≤ 0.001), and MCI patients with healthy controls (*p ≤ 0.05), respectively. In addition, we compared our sensor to the global cognitive function scales and discovered that it performed noticeably improvement in diagnosing the stages of AD. These results demonstrated the good application of our developed electrochemical impedance-based biosensor in the identification of clinical disease stages. Moreover, in this study, a small dissociation constant (KD) of 0.533 pM was first determined to evaluate the high binding affinity between the p-tau181 biomarker and its antibody, providing a reference parameter for future studies of the p-tau181 biomarker and AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Proteínas tau , Impedância Elétrica , Peptídeos beta-Amiloides , Disfunção Cognitiva/diagnóstico , Biomarcadores
12.
Nucleic Acids Res ; 51(14): 7109-7124, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37188501

RESUMO

Antisense oligonucleotides (ASOs) dosed into cerebrospinal fluid (CSF) distribute broadly throughout the central nervous system (CNS). By modulating RNA, they hold the promise of targeting root molecular causes of disease and hold potential to treat myriad CNS disorders. Realization of this potential requires that ASOs must be active in the disease-relevant cells, and ideally, that monitorable biomarkers also reflect ASO activity in these cells. The biodistribution and activity of such centrally delivered ASOs have been deeply characterized in rodent and non-human primate (NHP) models, but usually only in bulk tissue, limiting our understanding of the distribution of ASO activity across individual cells and across diverse CNS cell types. Moreover, in human clinical trials, target engagement is usually monitorable only in a single compartment, CSF. We sought a deeper understanding of how individual cells and cell types contribute to bulk tissue signal in the CNS, and how these are linked to CSF biomarker outcomes. We employed single nucleus transcriptomics on tissue from mice treated with RNase H1 ASOs against Prnp and Malat1 and NHPs treated with an ASO against PRNP. Pharmacologic activity was observed in every cell type, though sometimes with substantial differences in magnitude. Single cell RNA count distributions implied target RNA suppression in every single sequenced cell, rather than intense knockdown in only some cells. Duration of action up to 12 weeks post-dose differed across cell types, being shorter in microglia than in neurons. Suppression in neurons was generally similar to, or more robust than, the bulk tissue. In macaques, PrP in CSF was lowered 40% in conjunction with PRNP knockdown across all cell types including neurons, arguing that a CSF biomarker readout is likely to reflect ASO pharmacodynamic effect in disease-relevant cells in a neuronal disorder. Our results provide a reference dataset for ASO activity distribution in the CNS and establish single nucleus sequencing as a method for evaluating cell type specificity of oligonucleotide therapeutics and other modalities.


Antisense oligonucleotide (ASO) drugs are a type of chemically modified DNA that can be injected into cerebrospinal fluid in order to enter brain cells and reduce the amount of RNA from a specific gene. The brain is a complex mixture of hundreds of billions of cells. When an ASO lowers a target gene's RNA by 50%, is that a 50% reduction in 100% of cells, or a 100% reduction in 50% of cells? Are the many different cell types of the brain affected equally? This new study uses single cell RNA sequencing to answer these questions, finding that ASOs are broadly active across cell types and individual cells, and linking reduction of target protein in cerebrospinal fluid to disease-relevant cells.


Assuntos
Encéfalo , Oligonucleotídeos Antissenso , Animais , Camundongos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Oligonucleotídeos/metabolismo , Oligonucleotídeos Antissenso/administração & dosagem , Oligonucleotídeos Antissenso/análise , RNA/metabolismo , Distribuição Tecidual , Fatores de Transcrição/metabolismo , Líquido Cefalorraquidiano/química , Doenças do Sistema Nervoso Central/terapia
13.
Methods Mol Biol ; 2667: 139-158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37145282

RESUMO

Coccidioidomycosis, caused by the dimorphic pathogens Coccidioides posadasii and C. immitis, is a fungal disease endemic to the southwestern United States, Mexico, and some regions of Central and South America. The mouse is the primary model for studying pathology and immunology of disease. Mice in general are extremely susceptible to Coccidioides spp., which creates challenges in studying the adaptive immune responses that are required for host control of coccidioidomycosis. Here, we describe how to infect mice to model asymptomatic infection with controlled, chronic granulomas and a slowly progressive but ultimately fatal infection that has kinetics more similar to the human disease.


Assuntos
Coccidioidomicose , Humanos , Animais , Camundongos , Coccidioides , América do Sul/epidemiologia , México
14.
Micromachines (Basel) ; 14(5)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37241556

RESUMO

Advancing low-cost and user-friendly innovations to benefit public health is an important task of scientific and engineering research. According to the World Health Organization (WHO), electrochemical sensors are being developed for low-cost SARS-CoV-2 diagnosis, particularly in resource-limited settings. Nanostructures with sizes ranging from 10 nm to a few micrometers could deliver optimum electrochemical behavior (e.g., quick response, compact size, sensitivity and selectivity, and portability), providing an excellent alternative to the existing techniques. Therefore, nanostructures, such as metal, 1D, and 2D materials, have been successfully applied in in vitro and in vivo detection of a wide range of infectious diseases, particularly SARS-CoV-2. Electrochemical detection methods reduce the cost of electrodes, provide analytical ability to detect targets with a wide variety of nanomaterials, and are an essential strategy in biomarker sensing as they can rapidly, sensitively, and selectively detect SARS-CoV-2. The current studies in this area provide fundamental knowledge of electrochemical techniques for future applications.

15.
bioRxiv ; 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36824749

RESUMO

Antisense oligonucleotides (ASOs) dosed into cerebrospinal fluid (CSF) distribute broadly throughout the brain and hold the promise of treating myriad brain diseases by modulating RNA. CNS tissue is not routinely biopsied in living individuals, leading to reliance on CSF biomarkers to inform on drug target engagement. Animal models can link CSF biomarkers to brain parenchyma, but our understanding of how individual cells contribute to bulk tissue signal is limited. Here we employed single nucleus transcriptomics on tissue from mice treated with RNase H1 ASOs against Prnp and Malat1 and macaques treated with an ASO against PRNP . Activity was observed in every cell type, though sometimes with substantial differences in magnitude. Single cell RNA count distributions implied target suppression in every single sequenced cell, rather than intense knockdown in only some cells. Duration of action up to 12 weeks post-dose differed across cell types, being shorter in microglia than in neurons. Suppression in neurons was generally similar to, or more robust than, the bulk tissue. In macaques, PrP in CSF was lowered 40% in conjunction with PRNP knockdown across all cell types including neurons, arguing that a CSF biomarker readout is likely to reflect disease-relevant cells in a neuronal disorder.

16.
Dev Cell ; 58(3): 174-191.e8, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36706755

RESUMO

The blood barriers of the nervous system protect neural environments but can hinder therapeutic accessibility. The blood-brain barrier (BBB) is well characterized, consisting of endothelial cells with specialized tight junctions and low levels of transcytosis, properties conferred by contacting pericytes and astrocytes. In contrast, the blood-nerve barrier (BNB) of the peripheral nervous system is poorly defined. Here, we characterize the structure of the mammalian BNB, identify the processes that confer barrier function, and demonstrate how the barrier can be opened in response to injury. The homeostatic BNB is leakier than the BBB, which we show is due to higher levels of transcytosis. However, the barrier is reinforced by macrophages that specifically engulf leaked materials, identifying a role for resident macrophages as an important component of the BNB. Finally, we demonstrate the exploitation of these processes to effectively deliver RNA-targeting therapeutics to peripheral nerves, indicating new treatment approaches for nervous system pathologies.


Assuntos
Barreira Hematoneural , Células Endoteliais , Animais , Barreira Hematoneural/fisiologia , Células Endoteliais/fisiologia , Barreira Hematoencefálica/fisiologia , Macrófagos , Pericitos/fisiologia , Mamíferos
17.
Sci Total Environ ; 857(Pt 3): 159537, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36270373

RESUMO

PM2.5 pollution is a serious problem in Vietnam and around the world, having bad impacts on human health, animals and environment. Regular monitoring at a large scale is important to assess the status of air pollution, develop solutions and evaluate the effectiveness of policy implementation. However, air quality monitoring stations in Vietnam are limited. In this article, we propose an approach to estimate daily PM2.5 concentration from 2012 to 2020 over the Vietnamese territory, which is strongly affected by cloudy conditions, using a modern statistical model named Mixed Effect Model (MEM) on a dataset consisting of ground PM2.5 measurements, integrated satellite Aerosol Optical Depth (AOD), meteorological and land use maps. The result of this approach is the first long-term, full coverage and high quality PM2.5 dataset of Vietnam. The daily mean PM2.5 maps have high validation results in comparison with ground PM2.5 measurement (Pearson r of 0.87, R2 of 0.75, RMSE of 11.76 µg/m3, and MRE of 36.57 % on a total of 13,886 data samples). The aggregated monthly and annual average maps from 2012 to 2020 in Vietnam have outstanding quality when compared with another global PM2.5 product. The PM2.5 concentration maps has shown spatial distribution and seasonal variations of PM2.5 concentration in Vietnam in a long period from 2012 to 2020 and has been used in other studies and applications in the environment and public health at the national scale, which has not been possible before because of the lack of monitoring stations and an appropriate PM2.5 modeling approach.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Material Particulado/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Vietnã , Poluição do Ar/análise , Aerossóis/análise
18.
Surgery ; 173(1): 132-137, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36511281

RESUMO

BACKGROUND: The usefulness of incorporating near-infrared autofluorescence into the surgical workflow of endocrine surgeons is unclear. Our aim was to develop a prospective registry and gather expert opinion on appropriate use of this technology. METHODS: This was a prospective multicenter collaborative study of patients undergoing thyroidectomy and parathyroidectomy at 7 academic centers. A questionnaire was disseminated among 24 participating surgeons. RESULTS: Overall, 827 thyroidectomy and parathyroidectomy procedures were entered into registry: 42% of surgeons found near-infrared autofluorescence useful in identifying parathyroid glands before they became apparent; 67% correlated near-infrared autofluorescence pattern to normal and abnormal glands; 38% of surgeons used near-infrared autofluorescence, rather than frozen section, to confirm parathyroid tissue; and 87% and 78% of surgeons reported near-infrared autofluorescence did not improve the success rate after parathyroidectomy or the ability to find ectopic glands, respectively. During thyroidectomy, 66% of surgeons routinely used near-infrared autofluorescence to rule out inadvertent parathyroidectomy. However, only 36% and 45% felt near-infrared autofluorescence decreased inadvertent parathyroidectomy rates and improved ability to preserve parathyroid glands during central neck dissections, respectively. CONCLUSION: This survey study identified areas of greatest potential use for near-infrared autofluorescence, which can form the basis of future objective trials to document the usefulness of this technology.


Assuntos
Glândulas Paratireoides , Glândula Tireoide , Humanos , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/cirurgia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/cirurgia , Imagem Óptica/métodos , Paratireoidectomia/métodos , Tireoidectomia/métodos
19.
Cureus ; 15(12): e51098, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38274935

RESUMO

Introduction Heart failure is currently a global health issue, imposing a burden on disease prevalence and mortality rates for patients, while simultaneously impacting the quality of life for affected individuals. Data on assessing the health-related quality of life (HRQoL) of patients with chronic heart failure in developing countries, including Vietnam, is still limited. This study was conducted with the aim of describing the quality of life of patients with chronic heart failure in Vietnam. Methods This cross-sectional investigation enrolled 140 chronic heart failure outpatients, utilizing a convenience sample at Hai Duong Province Hospital, Vietnam, spanning from December 2021 to April 2022. Essential patient variables encompassing age, gender, and heart failure duration were gathered. Surveying of patients took place at the outpatient clinic during chronic heart failure follow-up visits using the 36-Item Short Form Health Survey (SF-36) questionnaire. The SF-36 comprises eight dimensions: (1) Physical functioning, (2) Role limitations due to physical health, (3) Bodily pain, (4) General health perceptions, (5) Vitality, (6) Social role functioning, (7) Role limitations due to emotional health, and (8) Mental health. Component analysis of the SF-36 revealed two distinct concepts: a physical component summary (PCS) reflecting the physical aspect and a mental component summary (MCS) reflecting the mental aspect. Results The research involved 140 participants diagnosed with chronic heart failure, having a median age of 59 years (interquartile range (IQR): 52-63). Among them, 61.4% were male, and 50% exhibited reduced left ventricular ejection fraction (LVEF) (≤ 40%). The role limitations due to the physical health domain indicated the lowest score, registering a median value of 0 (IQR 0-25). Domains with median scores below the 25-point threshold encompassed role limitations due to physical health (0 points). Those with scores ranging from 25 to 49 points constituted general health perceptions (25 points), role limitations due to emotional health (33.3 points), vitality (45 points), and mental health (48 points). Bodily pain and social role functioning achieved median scores at a moderate level (50-74 points), scoring 62 and 62.5 points, respectively. The overall HRQoL score on the SF-36 scale was 45.2 (IQR: 32.1-58.7) points. Median scores for the PCS and MCS were 44.3 (IQR: 30.5-52) and 47.0 (IQR: 32.6-65.4), respectively. No statistically significant differences in PCS and MCS scores were observed when subgroup analysis was performed based on variables like age, gender, or LVEF. However, in the vitality domain, female patients exhibited a significantly lower median score than male patients (p-value = 0.046). In the physical functioning domain, individuals aged ≥ 60 had lower median scores than those aged < 60 years (p = 0.022). Additionally, the group with LVEF ≤ 40% had lower median scores compared to the group with LVEF > 40% (p = 0.038) in role limitations due to emotional health domain. Conclusion In Vietnam, the HRQoL in the outpatient population with chronic heart failure was notably low when assessed using the SF-36 questionnaire. Large-scale, multicenter studies are needed to provide stronger, more conclusive evidence.

20.
AIDS Res Ther ; 19(1): 63, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517849

RESUMO

BACKGROUND: Stigma around human immunodeficiency virus (HIV), injection drug use (IDU), and mental health disorders can be co-occurring and have different impacts on the well-being of people living with HIV (PWH) who use drugs and have mental health disorders. This stigma can come from society, health professionals, and internalized stigma. A person who has more than one health condition can experience overlapping health-related stigma and levels of stigma which can prevent them from receiving necessary support and healthcare, serving to intensify their experience with stigma. This study investigates HIV, drug use, and mental health stigmas in three dimensions (social, internalized, and professional) around PWH on methadone maintenance treatment (MMT) who have common mental disorders (CMDs) including depression, anxiety, and stress-related disorders in Hanoi, Vietnam.Please check and confirm whether corresponding author's email id is correctly identified.The cooresponding author's email is correct METHODS: We conducted semi-structured, in-depth interviews (IDIs) (n = 21) and two focus group discussions (FGDs) (n = 10) with PWH receiving MMT who have CMD symptoms, their family members, clinic health care providers, and clinic directors. We applied thematic analysis using NVIVO software version 12.0, with themes based on IDI and FGD guides and emergent themes from interview transcripts. RESULTS: The study found evidence of different stigmas towards HIV, IDU, and CMDs from the community, family, health care providers, and participants themselves. Community and family members were physically and emotionally distant from patients due to societal stigma around illicit drug use and fears of acquiring HIV. Participants often conflated stigmas around drug use and HIV, referring to these stigmas interchangeably. The internalized stigma around having HIV and injecting drugs made PWH on MMT hesitant to seek support for CMDs. These stigmas compounded to negatively impact participants' health. CONCLUSIONS: Strategies to reduce stigma affecting PWH on MMT should concurrently address stigmas around HIV, drug addiction, and mental health. Future studies could explore approaches to address internalized stigma to improve self-esteem, mental health, and capacities to cope with stigma for PWH on MMT. TRIAL REGISTRATION: NCT04790201, available at clinicaltrials.gov.


Assuntos
Infecções por HIV , Transtornos Mentais , Metadona , Estigma Social , Humanos , Infecções por HIV/psicologia , Transtornos Mentais/psicologia , Metadona/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/psicologia , Vietnã/epidemiologia , Pesquisa Qualitativa
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