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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(3): 491-496, 2024 Mar 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38970524

RESUMO

X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy. In February 2021, a male neonate was admitted to the West China Second University Hospital, Sichuan University, with clinical manifestations of hypotonia, accompanied by distinctive facial features, and requiring continuous ventilatory support. He was born prematurely at 36+2 weeks gestation and developed respiratory distress postnatally, followed by difficulty in weaning from mechanical ventilation. Additional clinical features included hypotonia of the limbs, swallowing dysfunction, and specific facial characteristics (elongated limbs, narrow face, high-arched palate, wrist drop, empty scrotum, elongated fingers/toes). Genetic testing confirmed the diagnosis of XLMTM. Whole-exome sequencing analysis of the family revealed no mutations in the father, paternal grandfather, or paternal grandmother, while the mother had a heterozygous mutation. The pathogenic mutation was identified as MTM1 gene (OMIM: 300415), chromosome position chrX-150649714, with a nucleotide change of c.868-2A>C. The patient exhibited typical facial features. Genetic testing is crucial for accurate diagnosis of XLMTM in infants presenting with abnormal muscle tone and distinctive facial features.


Assuntos
Mutação , Miopatias Congênitas Estruturais , Proteínas Tirosina Fosfatases não Receptoras , Humanos , Miopatias Congênitas Estruturais/genética , Miopatias Congênitas Estruturais/diagnóstico , Masculino , Recém-Nascido , Proteínas Tirosina Fosfatases não Receptoras/genética , Sequenciamento do Exoma , Testes Genéticos , Hipotonia Muscular/genética
2.
Front Cell Infect Microbiol ; 14: 1399782, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39027137

RESUMO

Background: Accurate detection of influenza virus in clinical samples requires correct execution of all aspects of the detection test. If the viral load in a sample is below the detection limit, a false negative result may be obtained. To overcome this issue, we developed a modified transport medium (MTM) for clinical sample transportation to increase viral detection sensitivity. Method: We first validated the MTM using laboratory-stocked influenza A viruses (IAVs: H1N1, H3N2, H7N3, H9N2) and influenza B viruses (IBVs: Yamagata, Victoria). We also tested clinical samples. A total of 110 patients were enrolled and a pair of samples were collected to determine the sensitivity of real-time polymerase chain reaction (RT-PCR) following MTM treatment. Result: After 24 h culturing in MTM, the viral loads were increased, represented by a 10-fold increase in detection sensitivity for H1N1, H9N2, and IBVs, a 100-fold increase for H3N2, and a 1,000-fold increase for H7N3. We further tested the effects of MTM on 19 IAV and 11 IBV stored clinical samples. The RT-PCR results showed that the positive detection rate of IAV samples increased from 63.16% (12/19) without MTM culturing to 78.95% (15/19) after 48 h culturing, and finally 89.47% (17/19) after 72 h culturing. MTM treatment of IBV clinical samples also increased the positive detection rate from 36.36% (4/11, 0 h) to 63.64% (7/11, 48 h) to 72.73% (8/11, 72 h). For clinical samples detected by RT-PCR, MTM outperformed other transport mediums in terms of viral detection rate (11.81% increase, P=0.007). Conclusion: Our results demonstrated that the use of MTM for clinical applications can increase detection sensitivity, thus facilitating the accurate diagnosis of influenza infection.


Assuntos
Vírus da Influenza A , Vírus da Influenza B , Influenza Humana , Sensibilidade e Especificidade , Manejo de Espécimes , Carga Viral , Humanos , Influenza Humana/diagnóstico , Influenza Humana/virologia , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/genética , Vírus da Influenza B/isolamento & purificação , Vírus da Influenza B/genética , Manejo de Espécimes/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Meios de Cultura/química , Pessoa de Meia-Idade , Feminino , Adulto , Masculino
3.
Health Sci Rep ; 7(6): e2122, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38831778

RESUMO

Introduction: Between 2000 and 2015, significant gains were recorded in reducing the global burden of malaria due to enhanced global collaboration and increased funding. However, progress has stagnated post-2015, and the COVID-19 pandemic seems to have reversed some of these gains, necessitating a critical reevaluation of interventions. This paper aims to analyze the setbacks and offer recommendations for advancement in malaria control and prevention in sub-Saharan Africa. Methods: We conducted searches on Google Scholar, PubMed, and relevant organization websites to identify relevant studies on malaria control and prevention and associated challenges in sub-Saharan Africa from 2015 to the present. Additionally, studies on individual sub-Saharan African countries were reviewed to ensure comprehensiveness. Data from selected studies were extracted and analyzed using a narrative synthesis approach to offer a concise overview of the evidence. Findings: We observe that the halt in progress of malaria control in sub-Saharan Africa has deep roots in socioeconomic, political, and environmental factors. These challenges are exacerbated by the population explosion in the region, low coverage of interventions due to funding deficits and incessant crises, and the degradation of the efficacy of existing malaria commodities. Conclusion: Sub-Saharan Africa is at a crossroads in its fight against malaria. Promising new frontiers such as malaria vaccines, preventive monoclonal antibodies, new-generation insecticide-treated nets, and potentially artificial intelligence-driven technologies offer hope in advancing malaria control and prevention in the region. Through commitment and collaboration, leveraging these opportunities can help surmount challenges and ultimately eliminate malaria in sub-Saharan Africa.

4.
Proc Natl Acad Sci U S A ; 121(23): e2217971121, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38805272

RESUMO

Myogenesis is a multistep process that requires a spatiotemporal regulation of cell events resulting finally in myoblast fusion into multinucleated myotubes. Most major insights into the mechanisms underlying fusion seem to be conserved from insects to mammals and include the formation of podosome-like protrusions (PLPs) that exert a driving force toward the founder cell. However, the machinery that governs this process remains poorly understood. In this study, we demonstrate that MTM1 is the main enzyme responsible for the production of phosphatidylinositol 5-phosphate, which in turn fuels PI5P 4-kinase α to produce a minor and functional pool of phosphatidylinositol 4,5-bisphosphate that concentrates in PLPs containing the scaffolding protein Tks5, Dynamin-2, and the fusogenic protein Myomaker. Collectively, our data reveal a functional crosstalk between a PI-phosphatase and a PI-kinase in the regulation of PLP formation.


Assuntos
Fusão Celular , Mioblastos , Fosfatos de Fosfatidilinositol , Podossomos , Animais , Fosfatos de Fosfatidilinositol/metabolismo , Camundongos , Mioblastos/metabolismo , Mioblastos/citologia , Podossomos/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/genética , Desenvolvimento Muscular/fisiologia
5.
Molecules ; 29(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38792136

RESUMO

Cu/SAPO-34 synthesized via a one-pot method with relatively low silicon content and copper loading at around 2 wt.% facilitated continuous oxidation of methane to methanol with a methanol space time yield of 504 µmolCH3OH/gcat/h. Remarkably, the methanol yield exceeded 1800 mmolCH3OH/molCu/h at 623 K. Typically, the presence of trace oxygen in the system was the key to maintaining the high selectivity to methanol. Characterization results from a series of techniques, including XRD, SEM, TEM, H2-TPR, NH3-TPD, UV-vis, and FTIR, indicated that Cu2+ existed in the position where it moves from hexagonal rings to elliptical cages as the active center.

7.
Intern Med ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631855

RESUMO

X-linked myotubular myopathy (XLMTM) is a rare genetic disorder caused by X-linked mutations in the MTM1 gene. Although heterozygous females are typically asymptomatic, affected cases have recently been reported. We herein report a case of XLMTM manifesting carrier of the pathogenic c.206dupG mutation in MTM1 with uncommon extramuscular symptoms. She developed gaze nystagmus and cognitive impairment in addition to muscle weakness. Electrophysiological studies and brain magnetic resonance imaging indicated the involvement of the central and peripheral nervous systems. XLMTM manifesting carriers may have a wider spectrum of clinical phenotypes than currently assumed. Appropriate follow-up of extramuscular and conventional muscular manifestations is important in such cases.

8.
Front Public Health ; 12: 1327442, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38282759

RESUMO

Introduction: Theoretical models of health behavior are important guides for disease prevention and detection, treatment and rehabilitation, and promotion and maintenance of physical and mental health, but there are no intervention studies related to differentiated thyroid cancer (DTC) that use theoretical models of health as a guide. In this study, we used a microblogging platform as an intervention vehicle and mobile patient-doctor interactive health education as a means of intervention, with the aim of improving the health behaviors of DTC patients as well as the corresponding clinical outcomes. Methods: This research project is a quantitative methodological study, and the trial will be a single-blind, single-center randomized controlled trial conducted at the Fourth Hospital of Harbin Medical University in Harbin, Heilongjiang Province. The study subjects are patients over 18 years of age with differentiated thyroid cancer who were given radioactive iodine-131 therapy as well as endocrine therapy after radical surgery for thyroid cancer. The intervention group will receive MTM-mhealth, and the realization of health education will rely on the smart terminal WeChat platform. Routine discharge education will be given to the control group at discharge. The primary outcome will be change in thyroid-stimulating hormone (TSH) from baseline and at 3 and 6 months of follow-up, and secondary outcomes will include change in self-management behavior, social cognitive and psychological, and metabolic control. Discussion: This study will explore a feasible mHealth intervention program applied to a population of DTC patients using the Multi-theory model of health behavior change (MTM) as a guide, with the aim of evaluating the MTM-based intervention program for clinical outcome improvement in DTC patients, as well as determining the effectiveness of the MTM-based intervention program in improving self-management skills in DTC patients. The results of this study will indicate the feasibility as well as the effectiveness of the application of health theoretical modeling combined with mHealth applications in disease prognostic health management models, and provide policy recommendations and technological translations for the development of mobility-based health management applications in the field of health management.


Assuntos
Autogestão , Telemedicina , Neoplasias da Glândula Tireoide , Adulto , Humanos , Comportamentos Relacionados com a Saúde , Radioisótopos do Iodo/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Telemedicina/métodos , Neoplasias da Glândula Tireoide/tratamento farmacológico
9.
Hosp Pharm ; 59(1): 94-101, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38223865

RESUMO

Background: COVID-19 infection is associated with a high risk of venous thromboembolism (VTE) events. VTE prophylaxis reduces the risk of these events. The optimal dose of VTE prophylaxis however remains uncertain. Objectives: To compare the incidence of VTE in patients treated with either standard dose VTE versus intermediate dose VTE prophylaxis. Methods: In this retrospective cohort study, we analyzed data from 1786 adult patients admitted into the hospital with polymerase chain reaction confirmed COVID-19 infection between April 2020 to September 2021. For analysis, patients were divided into 2 cohorts: either standard dose prophylaxis treatment group (patients who received either unfractionated heparin 5000units 3 times a day or enoxaparin 30-40 mg daily subcutaneously) or intermediate dose VTE prophylaxis group (patients received either unfractionated heparin 7500 units 3 times daily or enoxaparin 30-40 mg twice a day subcutaneously). The primary outcome was incidence of VTE events described as either deep vein thrombosis (DVT) or pulmonary embolism (PE). Secondary outcome was bleeding events. Results: During the study period, 398 (22%) patients were primarily treated with standard dose VTE prophylaxis, whereas 1388 (78%) patients were treated with intermediate dose VTE prophylaxis. There was a significantly higher incidence of venous thromboembolism events noted in the standard dose prophylaxis treatment group when compared with the intermediate dose prophylaxis group (25/398 (6.3%) vs 35/1388 (2.5%) P < .001, [Odds Ratio 2.6197, 95% confidence interval = 1.5482-4.4327]). Multivariable-adjusted logistic regression, adjusting for age, obesity, and smoking, with the intermediate dose prophylaxis treatment group as the referent category revealed higher odds for incident venous thromboembolism events in the standard dose prophylaxis group. There was no statistically significant difference in bleeding events between the 2 treatment groups (9 (2.3%) for standard dose prophylaxis group vs 46 (3.3%) for intermediate dose prophylaxis group P = .26). Conclusions: Among patients hospitalized with COVID-19 infection, patients receiving intermediate dose VTE prophylaxis experienced lower incident rates of venous thromboembolism events compared to those receiving standard dose VTE prophylaxis without a statistically significant increase in the risk of bleeding events.

10.
J Food Prot ; 87(2): 100214, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38182093

RESUMO

Validated alternative test methodologies may be used in place of culture-based methods recommended for environmental monitoring programs (EMPs) for Listeria in food production facilities. In order to help guide decisions on which testing method to use to simplify Listeria EMP implementation in food production facilities, alternative methods were compared to the culture-based method in actual EMPs for Listeria. Seventy-two samples collected from two facilities of souzai production businesses that use meat and meat products as ingredients, one facility of processed meat product production business, and one facility of processed meat product and souzai production business were applied to EMPs for Listeria using the culture-based method, 3MTM Molecular Detection System (MDS), and InSite L. mono Glo (InSite). The kappa coefficient in MDS was 0.65 for Listeria monocytogenes and 0.74 for Listeria spp., both of which were deemed substantial compared with the culture-based method. The kappa coefficient in InSite was -0.01 for L. monocytogenes and 0.50 for Listeria spp., which indicated poor and moderate reproducibility, respectively. When the medium of InSite was smeared on agar medium, 7 of the 19 samples tested positive only for Listeria spp. (negative for L. monocytogenes) but L. monocytogenes was cultured, indicating that the sensitivity of detecting L. monocytogenes via fluorescence may be low. MDS was considered a useful alternative for both L. monocytogenes and Listeria spp. as targets, and InSite was not possible as a substitute for detecting L. monocytogenes; however, it is considered a helpful alternative method for detecting Listeria spp. EMPs for Listeria often target Listeria spp. as an indicator of L. monocytogenes. The alternative methods studied in this study are rapid, simple, and useful in EMPs for Listeria. However, the data in this study were a comparatively small sample set and impacted by variability, so more robust comparisons are desirable in the future.


Assuntos
Listeria monocytogenes , Listeria , Microbiologia de Alimentos , Reprodutibilidade dos Testes , Monitoramento Ambiental , Contaminação de Alimentos/análise
11.
Ultrasound Med Biol ; 50(4): 617-626, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38281888

RESUMO

OBJECTIVE: To investigate the diagnostic and prognostic value of contrast-enhanced ultrasound (CEUS) and clinical indicators of the vessels encapsulating tumor clusters (VETC) pattern and macrotrabecular-massive subtype in hepatocellular carcinoma (MTM-HCC). METHODS: This retrospective study included patients who underwent preoperative CEUS and hepatectomy for HCC between August 2018 and August 2021. Multivariable logistic regression was performed to select independent correlated factors of VETC-HCC and MTM-HCC to develop nomogram models. The association between model outcomes and early postoperative HCC recurrence was assessed using Kaplan-Meier curve and Cox regression analysis. RESULTS: The training cohort included 182 patients (54.3 ± 11.3 years, 168 males) and the validation cohort included 91 patients (54.8 ± 10.6 years, 81 males). Multivariate logistic regression analysis revealed that α-fetoprotein (AFP) levels (odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.49-3.42, p < 0.001), intratumoral nonenhancement (OR: 2.40, 95% CI: 1.02-5.64, p = 0.044), and the perfusion pattern in the CEUS arterial phase (OR: 2.27, 95% CI: 1.05-4.91, p = 0.038) were independent predictors of VETC-HCC. Besides, the former two were also independently associated with MTM-HCC (AFP level: OR: 2.36, 95% CI: 1.36-4.09, p = 0.002; intratumoral nonenhancement: OR: 3.72, 95% CI: 1.02-13.56, p = 0.046). Nomogram models were constructed based on the aforementioned indicators. Kaplan-Meier curve analysis indicated that predicted VETC-HCC or MTM-HCC exhibited higher rates of early recurrence (log-rank p < 0.001 and p = 0.002, respectively). Cox regression analysis showed that a high risk of VETC-HCC was independently correlated with early recurrence (p = 0.011). CONCLUSION: CEUS combined with AFP levels can predict VETC-HCC/MTM-HCC and prognosis preoperatively.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Carcinoma Hepatocelular/patologia , Prognóstico , alfa-Fetoproteínas , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Biomarcadores
12.
J Biochem ; 175(2): 125-131, 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-37848047

RESUMO

A transverse-tubule (T-tubule) is an invagination of the plasma membrane penetrating deep into muscle cells. An extensive membrane network of T-tubules is crucial for rapid and synchronized signal transmission from the cell surface to the entire sarcoplasmic reticulum for Ca2+ release, leading to muscle contraction. T-tubules are also indispensable for the formation and positioning of other muscle organelles. Their structure and physiological roles are relatively well established; however, the mechanisms shaping T-tubules require further elucidation. Centronuclear myopathy (CNM), an inherited muscular disorder, accompanies structural defects in T-tubules. Membrane traffic-related genes, including MTM1 (Myotubularin 1), DNM2 (Dynamin 2), and BIN1 (Bridging Integrator-1), were identified as causative genes of CNM. In addition, causative genes for other muscle diseases are also reported to be involved in the formation and maintenance of T-tubules. This review summarizes current knowledge on the mechanisms of how T-tubule formation and maintenance is regulated.


Assuntos
Miopatias Congênitas Estruturais , Humanos , Citosol , Miopatias Congênitas Estruturais/genética , Contração Muscular , Membrana Celular , Músculos , Músculo Esquelético
13.
Genes (Basel) ; 14(12)2023 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-38136996

RESUMO

BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy resulting from dysfunction of the protein myotubularin encoded by the MTM1 gene. XLMTM has a high neonatal and infantile mortality rate due to a severe myopathic phenotype and respiratory failure. However, in a minority of XLMTM cases, patients present with milder phenotypes and achieve ambulation and adulthood. Notable facial dysmorphia is also present. METHODS: We investigated the genotype-phenotype correlations in newly diagnosed XLMTM patients in a patients' cohort (previously published data plus three novel variants, n = 414). Based on the facial gestalt difference between XLMTM patients and unaffected controls, we investigated the use of the Face2Gene application. RESULTS: Significant associations between severe phenotype and truncating variants (p < 0.001), frameshift variants (p < 0.001), nonsense variants (p = 0.006), and in/del variants (p = 0.036) were present. Missense variants were significantly associated with the mild and moderate phenotype (p < 0.001). The Face2Gene application showed a significant difference between XLMTM patients and unaffected controls (p = 0.001). CONCLUSIONS: Using genotype-phenotype correlations could predict the disease course in most XLMTM patients, but still with limitations. The Face2Gene application seems to be a practical, non-invasive diagnostic approach in XLMTM using the correct algorithm.


Assuntos
Mutação de Sentido Incorreto , Miopatias Congênitas Estruturais , Recém-Nascido , Humanos , Prognóstico , Fenótipo , Miopatias Congênitas Estruturais/diagnóstico , Miopatias Congênitas Estruturais/genética , Estudos de Associação Genética
14.
Vaccines (Basel) ; 11(9)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37766165

RESUMO

BACKGROUND: In developing countries, access to information, awareness, and availability of COVID-19 vaccines are key challenges. Somalia launched the COVID-19 vaccination in March 2021; however, the uptake of the vaccination is slow, which creates fear of further loss of life in the country unless intentional and organized campaigning and efforts are made to improve both the availability of the vaccine and its acceptance by the community. This study aimed to understand the current level of awareness, accessibility, trust, and hesitancy toward the COVID-19 vaccine among women in Somalia. METHODS: To assess COVID-19 vaccine uptake, acceptance, community awareness, and hesitancy rates in Somalia, we carried out a cross-sectional mixed methods study in three regions of Somalia that were selected randomly out of the 18 regions of Somalia. A multi-theory model (MTM) was developed to identify correlated factors associated with the hesitancy or non-hesitancy toward COVID-19 vaccination among women of all ages (18 years and above). RESULTS: A total of 999 eligible women (333 in each district) of 18-98 years old were interviewed in March 2022. About two-thirds (63.76%) of participants reported hesitancy about receiving the COVID-19 vaccine. The theory model initiation construct indicated that behavioral confidence in the vaccine (b = 0.476, p < 0.001), participatory dialogue (at b = 0.136, p < 0.004), and changes in the physical environment (b = 0.248, p = 0.015) were significantly associated with COVID-19 vaccine acceptance among women who were not hesitant to take the vaccine. CONCLUSIONS: The availability of COVID-19 vaccines may not translate into their uptake. The decision to get the vaccine was determined by multiple factors, including the perceived value of the vaccination, previous experience with the vaccine, perceived risk of infection, accessibility and affordability, and trust in the vaccine itself. Public health education programming and messaging must be developed to encourage vaccine uptake among women with varying levels of vaccine hesitancy.

15.
J Pediatr Genet ; 12(3): 258-262, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37575650

RESUMO

X-linked myotubular myopathy (XLMTM), a centronuclear congenital myopathy secondary to pathogenic variants in the MTM1 gene encoding myotubularin, is typically recognized for its classic and severe phenotype which includes neonatal hypotonia, severe muscle weakness, long-term ventilator dependence, markedly delayed gross motor milestones with inability to independently ambulate, and a high neonatal and childhood mortality. However, milder congenital forms of the condition and other phenotypes are recognized. We describe a 6-year-old boy with a mild XLMTM phenotype with independent gait and no respiratory insufficiency even in the neonatal period. The child has a hemizygous novel splice site variant in the MTM1 gene (c.232-25A > T) whose pathogenicity was confirmed by cDNA studies (exon 5 skipping) and muscle biopsy findings. We also compared the phenotype of our patient with the few reported cases that presented a mild XLMTM phenotype and no respiratory distress at birth, and discussed the potential mechanisms underlying this phenotype such as the presence of residual expression of the normal myotubularin transcript.

16.
Environ Monit Assess ; 195(9): 1107, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37642821

RESUMO

The study reported herein presents the methane generation potential from municipal solid waste (MSW) generated in Kanpur city using four established methods, namely: the IPCC Default Method (DM), EPER Germany, The IPCC First Order Decay (FOD) method, and the Modified Triangular Method (MTM). Results revealed that the average maximum and minimum emissions with respect to total MSW generated and considered over the study period were obtained in the IPCC Default Method (19.17Gg/year) and the MTM (1.00Gg/year), respectively. Furthermore, the sensitivity analysis carried out revealed that the MTM method is the least uncertain method in predicting the methane emissions. Energy generation using the Yedla method and the Stoichiometric method was also carried out, highlighting the potential for energy recovery using methane emissions. The total energy generation potential using the Yedla method over the entire study period was determined to be 924 TJ, with an increased potential of 30% between the periods of 2022 to 2031. According to the study, there exists significant potential for effectively managing the greenhouse gas emissions from open dumpsite by harnessing the methane produced and using it for energy generation.


Assuntos
Monitoramento Ambiental , Resíduos Sólidos , Índia , Alemanha , Metano
17.
Pathogens ; 12(8)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37623932

RESUMO

The ability of Mycobacterium bovis (M. bovis) to survive in bovine milk has emerged as a serious public health concern. The first objective of this study was to evaluate the diagnostic utility of IS1081-targeted real-time PCR for the detection of M. bovis DNA in different fractions of bovine milk. In a model study, bovine milk samples were spiked with serially diluted M. bovis BCG to investigate the detection limit of M. bovis DNA in whole milk and milk fractions (cream, pellet, and pellet + cream combined) using IS1081 real-time PCR. The assay was then used to detect M. bovis DNA in whole milk and milk fractions from naturally infected animals. The results showed that the IS1081 real-time PCR was more sensitive when detecting M. bovis DNA in the cream layer alone and cream + pellet combined compared to whole milk or the pellet alone. While PCR-based diagnostic assays for the detection of M. bovis in milk samples provide a quicker diagnostic tool for bovine tuberculosis, safe processing, and handling of M. bovis-infected milk samples remain a challenge and pose a human health risk. PrimeStore Molecular Transport Medium (MTM) has been shown to rapidly inactivate infected specimens while preserving nucleic acid for subsequent Molecular analysis. Therefore, the secondary objective of this study was to evaluate the ability of MTM to inactivate M. bovis BCG in spiked milk samples as well as its ability to preserve BCG DNA for the PCR assay. The results showed that MTM can successfully inactivate BCG alone or in spiked milk samples while preserving DNA for the PCR assay. The CT values of M. bovis BCG alone and spiked milk samples aliquoted in MTM and without MTM were similar at various dilutions. Taken together, our results indicate that using DNA extracted from the milk cream fraction alone or combined milk cream and pellet improved the recovery rate of M. bovis DNA in bovine milk samples. MTM has the potential to provide a safe and rapid sample processing tool for M. bovis inactivation in milk samples and preserve DNA for molecular diagnostics.

18.
Protein Sci ; 32(8): e4731, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37462942

RESUMO

The mTORC1 signaling pathway regulates cell growth and metabolism in a variety of organisms from yeast to human, and inhibition of the mTORC1 pathway has the prospect to treat cancer or achieve longevity. The tuberous sclerosis protein complex (TSCC) is a master negative regulator of the mTORC1 signaling pathway through hydrolyzing the GTP loaded on the small GTPase Rheb, which is a key activator of mTOR. However, the large size (~700 kDa) and complex structural organization of TSCC render it vulnerable to degradation and inactivation, thus limiting its potential application. In this work, based on thorough analysis and understanding of the structural mechanism of how the stabilization domain of TSC2 secures the association of TSC2-GAP with Rheb and thus enhances its GAP activity, we designed two proteins, namely SSG-MTM (short stabilization domain and GAP domain-membrane targeting motif) and SSG-TSC1N, which were able to function like TSCC to negatively regulate Rheb and mTORC1, but with much-reduced sizes (~1/15 and ~ 1/9 of the size of TSCC, respectively). Biochemical and cell biological assays demonstrated that these designed proteins indeed could promote the GTPase activity of Rheb to hydrolyze GTP, inhibit the kinase activity of mTORC1, and prevent mTORC1 from down-regulating catabolism and autophagy.


Assuntos
Alvo Mecanístico do Complexo 1 de Rapamicina , Neuropeptídeos , Proteína 2 do Complexo Esclerose Tuberosa , Esclerose Tuberosa , Humanos , Guanosina Trifosfato , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Complexos Multiproteicos/metabolismo , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Proteína Enriquecida em Homólogo de Ras do Encéfalo/genética , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Esclerose Tuberosa/genética , Esclerose Tuberosa/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo , Proteínas Supressoras de Tumor
19.
Med Phys ; 50(9): 5398-5409, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37490302

RESUMO

BACKGROUND: Myopic traction maculopathy (MTM) are retinal disorder caused by traction force on the macula, which can lead to varying degrees of vision loss in eyes with high myopia. Optical coherence tomography (OCT) is an effective imaging technique for diagnosing, detecting and classifying retinopathy. MTM has been classified into different patterns by OCT, corresponding to different clinical strategies. PURPOSE: We aimed to engineer a deep learning model that can automatically identify MTM in highly myopic (HM) eyes using OCT images. METHODS: A five-class classification model was developed using 2837 OCT images from 958 HM patients. We adopted a ResNet-34 architecture to train the model to identify MTM: no MTM (class 0), extra-foveal maculoschisis (class 1), inner lamellar macular hole (class 2), outer foveoschisis (class 3), and discontinuity or detachment of foveal outer hyperreflective layers (class 4). An independent test set of 604 images from 173 HM patients was used to evaluate the model's performance. Classification performance was assessed according to the area under the curve (AUC), accuracy, sensitivity, specificity. RESULTS: Our model exhibited a high training performance for classification (F1-score of 0.953; AUCs of 0.961 to 0.998). In test set, it achieved sensitivities (91.67%-97.78 %) and specificities (98.33%-99.17%) as good as, or better than, those of experienced clinicians. Heatmaps were generated to provide visual explanations. CONCLUSIONS: We established a deep learning model for MTM classification using OCT images. This model performed equally well or better than retinal specialists and is suitable for large-scale screening and identifying MTM in HM eyes.


Assuntos
Degeneração Macular , Miopia Degenerativa , Humanos , Miopia Degenerativa/diagnóstico , Tomografia de Coerência Óptica/métodos , Tração , Acuidade Visual , Degeneração Macular/diagnóstico por imagem , Estudos Retrospectivos
20.
Sensors (Basel) ; 23(13)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37447721

RESUMO

In this work, a highly miniaturized microstrip antenna array based on two elements is proposed for multiple inputs multiple outputs (MIMO) application systems at sub-6 GHz frequency bands. The antenna is structured from a meander line in conjugate with an interdigital capacitor when excited through the monopole basic antenna. The proposed antenna elements are separated with a Minkowski factor-shaped metamaterial (MTM) column to achieve a separation distance (D) of 0.08λ at 3 GHz when printed on an FR-4 substrate. Later on, the antenna performance in terms of bandwidth and gain is controlled using a photonic process based on optical active switches based on light-dependent resistances (LDR). Therefore, the reconfiguration complexity with such a technique can be eliminated significantly without the need for a biasing circuit. The antenna design was conducted through several parametric studies to arrive at the optimal design that realizes the frequency bandwidth between 3 and 5.5 GHz with a maximum gain of about 4.5 dBi when all LDR terminals are off. For a wireless channel performance study-based massive MIMO environment, the proposed antenna is suitable to be configured in arrays of 64 × 64 elements. From this study, it was found the maximum bit error rate (BER) does not exceed 0.15 with a channel capacity (CC) of 2 Gbps. For validation, the antenna was fabricated based on two elements and tested experimentally. Finally, it was revealed that the measured results agree very well with simulations after comparing the theoretical calculations with the measured data.


Assuntos
Fótons , Tecnologia
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