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1.
J Exerc Sci Fit ; 22(4): 329-340, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38993983

RESUMO

Objective: This study aims to examine the comparative effects of 75 min of volume-matched once-weekly and thrice-weekly high-intensity interval training (HIIT) on body adiposity in adults with central obesity. Methods: This assessor-blinded, three-arm, randomized controlled trial will recruit 315 physically inactive adults with central obesity (aged ≥18 years, body mass index ≥23, waist circumference ≥90 cm for men and ≥80 cm for women). Participants will be randomly allocated to the once-weekly HIIT, thrice-weekly HIIT or usual care control group. Participants in the HIIT groups will receive weekly exercise training sessions for 16 weeks, prescribed either once or three times weekly. Each HIIT session will consist of a supervised program of four 4-min high-intensity intervals at 85%-95% peak heart rate (HRpeak) interspersed with 3-min active recovery intervals at 50%-70% HRpeak. Participants in the once-weekly HIIT group will perform the 25-min HIIT bout three times with a break between each 25-min HIIT bout. The usual care control group will receive bi-weekly health education classes. The outcome assessments will be conducted at baseline, 16 weeks (post-intervention) and 32 weeks (follow-up). The primary outcome will be total body adiposity assessed by dual-energy X-ray absorptiometry (DXA). The secondary outcome measures will include markers of cardiovascular and metabolic health (body composition, cardiorespiratory fitness, blood pressure, and blood lipids), mental health, cognitive performance, health-related quality of life, sleep quality, habitual physical activity, diet, medication, adverse events and adherence to the intervention. Impact of the project: The findings from this study are expected to consolidate the therapeutic efficacy of HIIT for the management of central obesity and inform the comparative compliance, feasibility and suitability of once-weekly and thrice-weekly HIIT as exercise strategies to manage obesity. In particular, the present study is expected to provide a novel perspective on the utility of low-frequency HIIT (i.e., once-weekly) as an effective and sustainable exercise strategy to tackle the obesity pandemic. The anticipated findings will hold substantial translational value by informing public health policies and enhancing exercise compliance in the physically inactive obese population. Trial registration: ClinicalTrials.gov (NCT04887454).

2.
Asia Pac Allergy ; 14(2): 84-89, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38827262

RESUMO

Chemoimmunotherapy is an effective therapy for an individual with nonsmall-cell lung cancer (NSCLC) without anaplastic lymphoma kinase or epidermal growth factor receptor mutations. However, it can also be related to adverse cutaneous reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with high morbidities and mortality rates. We present a case of a 65-year-old male with NSCLC who underwent first-line chemotherapy with paclitaxel, carboplatin, and pembrolizumab, which was later followed by a second cycle of the same therapies. The patient developed a fever and rash 12 days after the second cycle. Pembrolizumab was strongly suspected as the culprit medication because cutaneous reactions to this drug have been frequently reported and threw other medications used as less likely candidates. This is the first case reported in Vietnam of SJS/TEN related to pembrolizumab and contributes to our knowledge of severe skin reactions associated with immune checkpoint inhibitors.

3.
Biochem J ; 481(14): 945-955, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38899489

RESUMO

The PDZ (Postsynaptic density protein-95[PSD-95]/Discs-large) domain, prevalent as a recognition module, has attracted significant attention given its ability to specifically recognize ligands with consensus motifs (also termed PDZ binding motifs [PBMs]). PBMs typically bear a C-terminal carboxylate as a recognition handle and have been extensively characterized, whilst internal ligands are less well known. Here we characterize a short linear motif (SLiM) - EESTSFQGP - as an internal PBM based on its strong binding affinity towards the SHANK1 PDZ domain (SHANK1656-762 hereafter referred to as SHANK1). Using the acetylated analogue Ac-EESTSFQGP-CONH2 as a competitor for the interaction of SHANK1 with FAM-Ahx-EESTSFQGP-CONH2 or a typical fluorophore-labelled C-terminal PBM - GKAP - FITC-Ahx-EAQTRL-COOH - the internal SLiM was demonstrated to show comparable low-micromolar IC50 by competition fluorescent anisotropy. To gain further insight into the internal ligand interaction at the molecular level, we obtained the X-ray co-crystal structure of the Ac-EESTSFQGP-CONH2/SHANK1 complex and compared this to the Ac-EAQTRL-COOH/SHANK1 complex. The crystallographic studies reveal that the SHANK1 backbones for the two interactions overlap significantly. The main structural differences were shown to result from the flexible loops which reorganize to accommodate the two PBMs with distinct lengths and terminal groups. In addition, the two C-terminal residues Gly and Pro in Ac-EESTSFQGP-CONH2 were shown not to participate in interaction with the target protein, implying further truncation and structural modification using peptidomimetic approaches on this sequence may be feasible. Taken together, the SLiM Ac-EESTSFQGP-CONH2 holds potential as an internal ligand for targeting SHANK1.


Assuntos
Proteínas do Tecido Nervoso , Domínios PDZ , Ligação Proteica , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Cristalografia por Raios X , Humanos , Ligantes , Animais , Sequência de Aminoácidos , Motivos de Aminoácidos , Sítios de Ligação
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 666-674, 2024 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-38708499

RESUMO

OBJECTIVE: To investigate the changes of mitochondrial respiratory function during myocardial fibrosis in mice with myocardial infarction (MI) and its correlation with the increase of glycolytic flux. METHODS: Forty C57BL/6N mice were randomized into two equal groups to receive sham operation or ligation of the left anterior descending coronary artery to induce acute MI. At 28 days after the operation, 5 mice from each group were euthanized and left ventricular tissue samples were collected for transcriptomic sequencing. FPKM method was used to calculate gene expression levels to identify the differentially expressed genes (DEGs) in MI mice, which were analyzed using GO and KEGG databases to determine the pathways affecting the disease process. Heat maps were drawn to show the differential expressions of the pathways and the related genes in the enrichment analysis. In primary cultures of neonatal mouse cardiac fibroblasts (CFs), the changes in mitochondrial respiration and glycolysis levels in response to treatment with the pro-fibrotic agonist TGF-ß1 were analyzed using Seahorse experiment. RESULTS: The mouse models of MI showed significantly increased diastolic and systolic left ventricular diameter (P < 0.05) and decreased left ventricular ejection fraction (P < 0.0001). A total of 124 up-regulated and 106 down-regulated DEGs were identified in the myocardial tissues of MI mice, and GO and KEGG enrichment analysis showed that these DEGs were significantly enriched in fatty acid metabolism, organelles and other metabolic pathways and in the mitochondria. Heat maps revealed fatty acid beta oxidation, mitochondrial dysfunction and increased glycolysis levels in MI mice. In the primary culture of CFs, treatment with TGF-ß1 significantly reduced the basal and maximum respiratory levels and increased the basal and maximum glycolysis levels (P < 0.0001). CONCLUSION: During myocardial fibrosis, energy metabolism remodeling occurs in the CFs, manifested by lowered mitochondrial function and increased energy generation through glycolysis.


Assuntos
Metabolismo Energético , Fibrose , Camundongos Endogâmicos C57BL , Infarto do Miocárdio , Animais , Camundongos , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Miocárdio/metabolismo , Miocárdio/patologia , Modelos Animais de Doenças , Mitocôndrias/metabolismo , Glicólise , Perfilação da Expressão Gênica , Transcriptoma , Fibroblastos/metabolismo , Masculino , Fator de Crescimento Transformador beta1/metabolismo
5.
ACS Phys Chem Au ; 4(2): 180-190, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38560756

RESUMO

Base pairing complementarity is central to DNA function. G·C and A·T pair specificity is thought to originate from the different number of hydrogen bonds the pairs make. Quantifying how many hydrogen bonds exist can be difficult because water molecules in the surrounding can make up for or disrupt direct hydrogen bonds, and the hydration structures around A·T and G·C pairs on duplex DNA are distinct. Large-scale computer simulations have been used here to create a detailed map for the hydration structure on A·T and G·C base pairs in water. The contributions of specific hydration waters to the free energy of each of the hydrogen bonds in the A·T and G·C pairs were computed. Using the equilibrium fractions of hydrated versus unhydrated states from the hydration profiles, the impact of specific bound waters on each hydrogen bond can be uniquely quantified using a thermodynamic construction. The findings suggest that hydration water in the minor groove of an A·T pair can provide up to about 2 kcal/mol of free energy advantage, effectively making up for the missing third hydrogen bond in the A·T pair compared to G·C, rendering the intrinsic thermodynamic stability of the A·T pair almost synonymous with G·C.

6.
Nat Commun ; 15(1): 669, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253620

RESUMO

The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1, reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.


Assuntos
Adenosina , Infecções por Helicobacter , Helicobacter pylori , Receptores Depuradores Classe E , Animais , Humanos , Camundongos , Adenosina/análogos & derivados , Catalase/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , RNA Mensageiro/genética , Receptores Depuradores Classe E/genética
7.
Biotechnol Bioeng ; 121(3): 823-834, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38151894

RESUMO

This review covers currently available cardiac implantable electronic devices (CIEDs) as well as updated progress in real-time monitoring techniques for CIEDs. A variety of implantable and wearable devices that can diagnose and monitor patients with cardiovascular diseases are summarized, and various working mechanisms and principles of monitoring techniques for Telehealth and mHealth are discussed. In addition, future research directions are presented based on the rapidly evolving research landscape including Artificial Intelligence (AI).


Assuntos
Doenças Cardiovasculares , Desfibriladores Implantáveis , Marca-Passo Artificial , Telemedicina , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Inteligência Artificial
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(11): 1919-1925, 2023 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-38081610

RESUMO

OBJECTIVE: To investigate the learning curve and clinical efficacy of aortic dissection and non-dissection aortic surgeries through upper hemisternotomy. METHODS: We retrospectively analyzed the perioperative data of aortic dissection and non-dissection surgeries through upper hemisternotomy performed by the same surgical team. Based on cardiopulmonary bypass time and aortic cross-clamping time, the learning curves were plotted using cumulative (CUSUM) analysis and the fitting curve, and the learning process was divided into the improvement period and proficiency period. We compared the perioperative parameters in the two stages, and verified whether the critical point was the number of operations required to overcome the learning curve. The safety and short-term efficacy of the aortic surgeries were analyzed after achieving proficiency. RESULTS: A total of 107 patients were analyzed, including 47 undergoing aortic dissection (ascending aorta replacement + arch replacement + descending aorta stent implantation and/or aortic root treatment) and 60 undergoing non-dissection surgeries (artery root surgery and/or ascending aorta replacement). The optimal fitting equation was y=-0.019x3+0.251x2+28.852x-6.076 (R2=0.918, P < 0.05) for CPB time and y=-0.015x3-0.093x2+34.799x-27.316 (R2=0.92, P < 0.05) for aortic cross-clamping time. In the dissection group, with 27 cases as the boundary, the perioperative parameters were significantly better in the proficiency stage than in the improvement stage, and the critical point was the number of surgeries needed to overcome the learning curve. The best fitting equation was y=0.013x3-1.826x2 + 62.353x+193.189 (R2=0.906, P < 0.05) for CPB time and y= 0.009x3-1.416x2+49.389x+177.335 (R2=0.90, P < 0.05) for aortic cross-clamping time. In the non-dissecting aorta group, where 22 cases served as the boundary, the perioperative parameters were also better in the proficiency period than in the improvement period. CONCLUSION: Both aortic dissection and non-dissection surgeries through upper hemisternotomy are safe and can significantly improve the short-term postoperative efficacy after achieving proficiency, but the latter approach has a shorter learning curve.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Humanos , Curva de Aprendizado , Estudos Retrospectivos , Dissecção Aórtica/cirurgia , Aorta/cirurgia , Resultado do Tratamento , Aneurisma da Aorta Torácica/cirurgia
9.
Cell Rep ; 42(10): 113184, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37776520

RESUMO

Kinases are important therapeutic targets, and their inhibitors are classified according to their mechanism of action, which range from blocking ATP binding to covalent inhibition. Here, a mechanism of inhibition is highlighted by capturing p21-activated kinase 5 (PAK5) in an intermediate state of activation using an Affimer reagent that binds in the P+1 pocket. PAK5 was identified from a non-hypothesis-driven high-content imaging RNAi screen in urothelial cancer cells. Silencing of PAK5 resulted in reduced cell number, G1/S arrest, and enlargement of cells, suggesting it to be important in urothelial cancer cell line survival and proliferation. Affimer reagents were isolated to identify mechanisms of inhibition. The Affimer PAK5-Af17 recapitulated the phenotype seen with siRNA. Co-crystallization revealed that PAK5-Af17 bound in the P+1 pocket of PAK5, locking the kinase into a partial activation state. This mechanism of inhibition indicates that another class of kinase inhibitors is possible.


Assuntos
Neoplasias , Quinases Ativadas por p21 , Humanos , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo , Fosforilação , Ligação Proteica
10.
Ophthalmol Ther ; 12(5): 2281-2293, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37458978

RESUMO

OBJECTIVE: The objective of this scoping review is to understand the extent and type of evidence in relation to telemedicine imaging devices for cornea and external segment conditions. INTRODUCTION: The coronavirus pandemic has emphasized the benefits of telemedicine in diagnosing and managing ocular diseases. With the rapid advancement of technology in slit lamp biomicroscopes, smartphones and other ocular surface imaging modalities, telemedicine applications for cornea and external diseases have become an active area of research. INCLUSION CRITERIA: For studies to be included, they had to discuss the concept of imaging devices for cornea and external diseases in the context of telemedicine. There was no restriction on the studied population or participants. METHODS: A scoping review was conducted according to an a priori protocol. Documents written in English were identified from the PubMed and Embase databases and searches. Anterior segment imaging devices were then classified into different categories. RESULTS: Anterior segment imaging devices identified in this review included 19 slit lamp-based devices, 17 smartphone-based devices and 15 other devices. These tools can detect a wide variety of cornea and external diseases (e.g., pterygium, conjunctivitis, corneal opacity, corneal ulcer, and blepharitis). Fewer than half of the devices (24/51) were assessed for diagnostic performance. Their diagnostic accuracy varied greatly from condition to condition and from device to device. The inter-rater reliability of different photo-graders assessing images was assessed in only a few studies. CONCLUSIONS: Anterior segment imaging devices are promising tools for remote diagnosis and management of patients with cornea and external disease. However, there are significant gaps in the literature regarding the diagnostic accuracy and inter-rater reliability of several devices. Future research with rigorous methods is required to validate the use of these devices in telemedicine settings.

11.
Blood Coagul Fibrinolysis ; 34(6): 403-407, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37395200

RESUMO

The goal of this study was to describe hematologic and coagulation laboratory parameters and identify if these laboratory studies could predict blood loss in a cohort of pediatric patients undergoing complex cranial vault reconstruction (CCVR) for repair of craniosynostosis. We reviewed records from 95 pediatric CCVR patients between 2015 and 2019. Primary outcome measures were hematologic and coagulation laboratory parameters. Secondary outcome measures were intraoperative and postoperative calculated blood loss (CBL). Preoperative laboratory values were within normal limits and did not predict outcomes. Intraoperative platelet count and fibrinogen predicted CBL but without clinically relevant thrombocytopenia or hypofibrinogenemia. Intraoperative prothrombin time (PT) and partial thromboplastin time (PTT) predicted perioperative CBL, possibly reflecting surgically induced coagulopathy. Postoperative laboratory values did not predict postoperative blood loss. We found that standard hematologic and coagulation laboratory parameters predicted intraoperative and postoperative blood loss but provided limited mechanistic information to improve our understanding of coagulopathy in craniofacial surgery.


Assuntos
Transtornos da Coagulação Sanguínea , Perda Sanguínea Cirúrgica , Humanos , Criança , Transfusão de Sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Testes de Coagulação Sanguínea , Hemorragia Pós-Operatória
12.
Int J Ther Massage Bodywork ; 16(2): 29-38, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37265536

RESUMO

Background: Myofascial pain syndrome (MPS) is the most common diagnosis in patient presenting with chronic non-specific neck pain. It affects people's work performance, productivity, and quality of life. To date, there is little research evaluating the effectiveness of non-invasive techniques, such as ISBT-Bowen Therapy in managing neck MPS. Objectives: To investigate the effectiveness of Bowen therapy in managing myofascial pain syndrome with symptoms lasting for more than six weeks. The study will also examine the long-term effect of ISBT-Bowen Therapy on functional enhancement, quality of life, and physical and mental well-being. Methods: This is a prospective, single-blinded randomized controlled trial (RCT). A total of 90 myofascial neck pain patients were recruited and randomized to receive 8 sessions of ISBT-Bowen Therapy over a 12-week period (n = 45) or to continue their usual conventional treatment (n = 45). Pressure pain threshold (PPT), cervical range of motion (CROM), numerical rating pain scores, Neck Disability Index (NDI), SF-12 Health Survey (SF-12) Version 2, Generalized Anxiety Disorder 7-item (GAD7), and Patient Health Questionnaire (PHQ9) were measured at baseline, 12 weeks, and 24 weeks after baseline. Results: When compared with the control group, PPT significantly increased after ISBT-Bowen Therapy at 12 and 24 weeks. CROM on flexion, lateral flexion, and rotation were greatly improved at 12 weeks after Bowen therapy, and maintained at 24 weeks, except left lateral flexion. NDI, GAD7, and PHQ9 were all reduced after Bowen Therapy at both 12 and 24 weeks. Both Physical and Mental Component Summary scores of SF-12 were improved after Bowen therapy at 12 and 24 weeks. Conclusions: This study confirmed the efficacy of ISBT-Bowen Therapy for patients with MPS. It alleviates pain, improves functional outcomes, enhances quality of life, and relieves mood symptoms.

13.
J Prev Alzheimers Dis ; 10(3): 443-452, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37357284

RESUMO

OBJECTIVE: The brain-kidney axis was proposed to emphasize roles of kidney functioning in modulating neurodegeneration. We aimed to evaluate the associations of renal diseases and blood markers with risk of dementia or cognitive decline among non-demented adults. METHODS: The PubMed, EMBASE, and Cochrane library were searched until February 1st, 2022, to include longitudinal studies. Multivariate adjusted effects were pooled by random-effects models. The robust error meta-regression models were used for dose-response analyses. The credibility of meta-analyses was graded and an innovative index (Sdifference) was developed to evaluate the evidence tendency. RESULTS: A total of 41 longitudinal studies (6,480,136 participants, mean age range: 58.5-83.5 years) were included, of which 33 were for meta-analyses. Though with low level of evidence, five indicators of kidney were associated with increased risk of dementia or cognitive decline, including acute kidney injury (hazard ratio [HR] = 2.24, p = 0.0001), chronic kidney disease (HR = 1.29, p = 0.0001), higher serum creatinine (HR = 1.35, p = 0.0001), higher urine albumin creatine ratio (UACR, HR = 1.23, p = 0.0001), and lower estimated glomerular filtration rate (eGFR, HR = 1.18, p = 0.0001). A linear relationship was revealed for eGFR (p = 0.0217) or UACR (p = 0.0006). Heterogeneity is a main concern to jeopardize the evidence robustness, especially for eGFR (Sdifference = 0.05). CONCLUSION: Some renal indicators were associated with a higher risk of dementia, though the evidence base warrants further strengthening. Renal function management might serve as a promising target for dementia prediction and prevention.


Assuntos
Disfunção Cognitiva , Demência , Insuficiência Renal Crônica , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Rim/fisiologia , Disfunção Cognitiva/complicações , Encéfalo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/psicologia , Demência/complicações
14.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(3): 450-455, 2023 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-37291920

RESUMO

OBJECTIVE: To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests. METHODS: In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years. RESULTS: In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect. CONCLUSION: Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.


Assuntos
Diabetes Mellitus Tipo 2 , Autogestão , Humanos , Diabetes Mellitus Tipo 2/terapia , Autoeficácia , Automonitorização da Glicemia , Glicemia , Autocuidado
15.
Bioeng Transl Med ; 8(3): e10495, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37206238

RESUMO

Macro-encapsulation systems for delivery of cellular therapeutics in diabetes treatment offer major advantages such as device retrievability and high cell packing density. However, microtissue aggregation and absence of vasculature have been implicated in the inadequate transfer of nutrients and oxygen to the transplanted cellular grafts. Herein, we develop a hydrogel-based macrodevice to encapsulate therapeutic microtissues positioned in homogeneous spatial distribution to mitigate their aggregation while concurrently supporting an organized intra-device network of vascular-inductive cells. Termed Waffle-inspired Interlocking Macro-encapsulation (WIM) device, this platform comprises two modules with complementary topography features that fit together in a lock-and-key configuration. The waffle-inspired grid-like micropattern of the "lock" component effectively entraps insulin-secreting microtissues in controlled locations while the interlocking design places them in a co-planar spatial arrangement with close proximity to vascular-inductive cells. The WIM device co-laden with INS-1E microtissues and human umbilical vascular endothelial cells (HUVECs) maintains desirable cellular viability in vitro with the encapsulated microtissues retaining their glucose-responsive insulin secretion while embedded HUVECs express pro-angiogenic markers. Furthermore, a subcutaneously implanted alginate-coated WIM device encapsulating primary rat islets achieves blood glucose control for 2 weeks in chemically induced diabetic mice. Overall, this macrodevice design lays foundation for a cell delivery platform, which has the potential to facilitate nutrients and oxygen transport to therapeutic grafts and thereby might lead to improved disease management outcome.

16.
J Immigr Minor Health ; 25(6): 1426-1462, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37009980

RESUMO

Refugees encounter numerous healthcare access barriers in host countries, leading to lower utilization rates and poorer health outcomes. In the US, social inequities and fragmented health systems may exacerbate these disparities. Understanding these factors is necessary to ensure equitable care of refugee populations. A systematic literature review of qualitative studies on US adult refugee healthcare access from January 2000 to June 2021 was performed in accordance with PRISMA. Studies were analyzed deductively and then inductively to incorporate previous findings in other resettlement countries and emergence of US-specific themes. 64 articles representing 16+ countries of origin emerged from the final analysis, yielding nine interrelated themes related to health literacy, cost of services, cultural beliefs, and social supports, among others. The main challenges to refugees' healthcare access emerge from the interactions of care fragmentation with adverse social determinants. Given diverse barriers, integrated care models are recommended in treating refugee populations.


Assuntos
Letramento em Saúde , Refugiados , Humanos , Adulto , Acessibilidade aos Serviços de Saúde , Pesquisa Qualitativa , Apoio Social
17.
Clin Neurol Neurosurg ; 226: 107629, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36822137

RESUMO

INTRODUCTION: Meningiomas have varying degrees of aggressive behavior. Some systemic hematologic makers are associated with malignancy, but their value in predicting aggressive meningioma behavior is not fully understood. OBJECTIVE: To evaluate the association between preoperative markers such as neutrophil-lymphocyte ratio (NLR), neutrophil-monocyte ratio (NMR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), and diagnostic and prognostic factors including WHO grade, proliferation index, presence of edema on preoperative MRI, and tumor recurrence. METHODS: A retrospective review of patients treated between 2000 and 2019 with a preoperative complete blood count (CBC) differential lab draw before intracranial meningioma resection was conducted. All preoperative steroid dosages were converted to dexamethasone equivalents. Primary outcomes included presence/absence of perilesional edema, WHO grade, Ki-67/MIB-index, and recurrence. Univariate and multivariable regression analyses were conducted. RESULTS: A total of 209 meningioma patients were included. Of these, 143 (68 %) were WHO grade I, 61 (29 %) grade II and 5 (2 %) were grade III. Recurrence was reported in 19 (9.1 %) tumors. No hematologic markers were associated with recurrence. In separate multivariable logistic analyses, no biomarkers were associated with perilesional edema or WHO grade. MLR was associated with higher MIB-index (p = 0.018, OR 6.57, 95 % CI 1.37-30.91). CONCLUSION: Most hematologic markers were not associated with meningioma invasiveness, grade, proliferative index, or aggressiveness. Preoperative MLR was associated with high proliferation index in patients undergoing surgery for intracranial meningioma. Higher MLR could be a surrogate for meningioma proliferation and has potential to be used as an adjunct for risk-stratifying meningiomas.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/cirurgia , Recidiva Local de Neoplasia/cirurgia , Linfócitos/patologia , Monócitos/patologia , Estudos Retrospectivos , Neoplasias Meníngeas/cirurgia , Prognóstico
18.
J Am Med Inform Assoc ; 30(1): 202-205, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36228129

RESUMO

Clinical informatics remains underappreciated among medical students in part due to a lack of integration into undergraduate medical education (UME). New developments in the study and practice of medicine are traditionally introduced via formal integration into undergraduate medical curricula. While this path has certain advantages, curricular changes are slow and may fail to showcase the breadth of clinical informatics activities. Less formal and more flexible approaches can circumvent these drawbacks. Interest groups (IGs), which are organized through the Association of American Medical College Careers in Medicine (CiM) program, exemplify the informal approach. CiM IGs are student-led groups that provide exposure to different specialty options, acting as an adjunct to the traditional medical curriculum. While the primary purpose of these groups is to assist students applying to residency programs, we took a novel approach of using an IG to increase student exposure to an area of medicine that had not yet been formally integrated at our institution. IGs provide unique advantages to formal integration into a curriculum as they can be more easily setup and can quickly respond to student interests. Furthermore, IGs can act synergistically with UME, acting as proving grounds for ideas that can lead to new courses. We believe that the lessons and takeaways from our experience can act as a guide for those interested in starting similar organizations at their own schools.


Assuntos
Educação de Graduação em Medicina , Informática Médica , Médicos , Humanos , Opinião Pública , Currículo , Informática Médica/educação
19.
J Neurosurg Sci ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36112122

RESUMO

BACKGROUND: Social media use in neurosurgery remains an understudied phenomenon. Our study aims to examine the global membership and engagement of the prominent Neurosurgery Cocktail Facebook group with over 25,000 neurosurgeons and trainees worldwide, specifically during the COVID-19 pandemic. METHODS: Neurosurgery Cocktail's numbers of members, posts, comments, and reactions were collected from December 2019 to November 2020. Anonymized aggregate data of members' characteristics, including age, sex, and country of origin in November 2020, were also obtained. The most engaging posts in November 2020 were categorized into topics by a majority consensus of 3 reviewers. RESULTS: The average number of members steadily increased from 21,266 in December 2019 to 25,218 in November 2020. In November 2020, 18.8% of members were women, and 71.3% were between 25-44 years old. With members from 100 countries, 77.9% are from low-and middle-income countries, with the highest representation from India, Egypt, and Brazil. After the COVID-19 pandemic declaration, daily engagement peaked in April 2020 with a daily average of 41.63 posts, 336.4 comments, and 1,914.6 reactions before returning to prepandemic levels. Among the 99 top posts in November 2020, the majority (56.5%) were classified as "interesting cases", with "education-related" as the second-most common topic (16.2%). CONCLUSIONS: Neurosurgery Cocktail has shown steady growth since its creation. The COVID-19 pandemic was correlated with a spike in activity without lasting impact. The group demonstrates social media's potential for knowledge exchange and promoting organic international collaborations.

20.
J Neurooncol ; 160(1): 33-40, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35921021

RESUMO

INTRODUCTION: Cystic meningiomas are rare, accounting for 2-7% of all intracranial meningiomas. Little is known regarding whether these meningiomas behave differently compared to solid meningiomas. We sought to study this relatively uncommon imaging appearance of meningioma and to evaluate its clinical significance. METHODS: A single-institution retrospective cohort study of surgically-treated meningioma patients between 2000 and 2019 was conducted. Cystic meningioma was defined as a tumor with an intratumoral or peritumoral cyst present on preoperative imaging. Demographics, preoperative imaging, histopathology characteristics, operative data, and surgical outcomes were reviewed. Imaging variables, histopathology and outcomes were reported for cystic meningiomas and compared with non-cystic meningiomas. Univariate/multivariable analyses were conducted. RESULTS: Of 737 total meningiomas treated surgically, 38 (5.2%) were cystic. Gross total resection (GTR) was achieved in 84.2% of cystic meningioma patients. Eighty-two percent of cystic meningiomas were WHO grade I (n = 31), 15.7% were grade II and 2.6% were grade III. Most cystic meningiomas had low Ki-67/MIB-1 proliferation index (n = 24, 63.2%). A total of 18.4% (n = 7) patients with cystic meningioma had recurrence compared to 12.2% (n = 80) of patients with non-cystic meningioma (p = 0.228). No significant difference in median time to recurrence was observed between cystic and non-cystic meningiomas (25.4, Q1:13.9, Q3:46.9 months vs. 13.4, Q1:8.6, Q3:35.5 months, p = 0.080). CONCLUSIONS: A small portion of intracranial meningiomas have cystic characteristics on imaging. Cystic meningiomas are frequently WHO grade I, have low proliferation index, and had similar outcomes compared to non-cystic meningioma. Cysts in meningioma may not be a surrogate to determine aggressive meningioma behavior.


Assuntos
Cistos , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Meningioma/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Estudos Retrospectivos , Cistos/patologia , Recidiva Local de Neoplasia/cirurgia
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