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1.
Exp Aging Res ; : 1-12, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38357913

RESUMO

The aim was to examine the diagnostic efficacy of hippocampal subregions volume and texture in differentiating amnestic mild cognitive impairment (MCI) from normal aging changes. Ninety MCI subjects and eighty-eight well-matched healthy controls (HCs) were selected. Twelve hippocampal subregions volume and texture features were extracted using Freesurfer and MaZda based on T1 weighted MRI. Then, two-sample t-test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were developed to select a subset of the original features. Support vector machine (SVM) was used to perform the classification task and the area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the diagnostic efficacy of the model. The volume features with high discriminative power were mainly located in the bilateral CA1 and CA4, while texture feature were gray-level non-uniformity, run length non-uniformity and fraction. Our model based on hippocampal subregions volume and texture features achieved better classification performance with an AUC of 0.90. The volume and texture of hippocampal subregions can be utilized for the diagnosis of MCI. Moreover, we found that the features that contributed most to the model were mainly textural features, followed by volume. These results may guide future studies using structural scans to classify patients with MCI.

2.
Geriatr Nurs ; 57: 31-44, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38503146

RESUMO

OBJECTIVE: To explore the effectiveness of virtual reality (VR) exergames on physical function, cognition and depression among older nursing home residents. METHODS: A systematic review and meta-analysis were conducted. The PubMed, Ovid, Embase, Cochrane, CINAHL, and Web of Science databases were searched for relevant studies from inception until June 1, 2023. The reviewers independently completed the study selection, data extraction and quality assessment. Subgroup analyses were conducted to explore the sources of between-study heterogeneity and to determine whether participant or intervention characteristics influenced effect sizes. RESULTS: Eighteen studies met the inclusion criteria and were selected for qualitative and quantitative synthesis. The overall methodological quality was relatively high, and the overall evidence grade was moderate. VR exergames had a large effect on physical function, including mobility [SMD=-0.66, P < 0.001], balance [SMD=0.95, P < 0.001], and lower limb strength [SMD=0.53, P = 0.0009]; and a moderate effect on cognition [SMD=0.48, P = 0.02] and depression [SMD=-0.72, P = 0.03]. Subgroup analyses revealed that a training frequency of 2 sessions per week and coordinating with physiotherapists yielded greater improvements in mobility (P = 0.009; P = 0.0001). VR exergames had especially beneficial effects on balance for physically fit participants (P = 0.03) and on cognition for participants with cognitive impairment (P = 0.01). Additionally, regarding the improvement of depression, commercial VR exergames were superior to self-made systems (P = 0.03). CONCLUSION: VR exergames can provide a positive impact on physical function, cognition and depression among older nursing home residents. The study also demonstrated the different benefits of exergames between participants who were physically fit and those with cognitive impairment, which is considered as an innovative, cost-efficient and sustainable approach. Specifically, commercial VR exergame programs with a frequency of 2 sessions per week and coordinating with physiotherapists may be the most appropriate and effective option.


Assuntos
Cognição , Depressão , Casas de Saúde , Realidade Virtual , Humanos , Depressão/terapia , Cognição/fisiologia , Idoso , Jogos de Vídeo , Terapia por Exercício/métodos , Desempenho Físico Funcional
3.
Kidney Blood Press Res ; 47(9): 545-555, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35878597

RESUMO

BACKGROUND: Currently, the interaction between proton pump inhibitors (PPIs) and their effects on hemodialysis (HD) patients has not been clarified. OBJECTIVES: Here, we aimed to explore the association between PPIs and adverse outcomes in HD patients. METHODS: A search was performed on the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to April 10, 2022. Studies examining the association (odds ratio [OR]) between PPIs and side effects were identified. The study followed guidelines prescribed in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and was registered with PROSPERO (CRD42021291177). RESULTS: A total of 12 studies comprising 4,227,497 HD patients with PPIs were identified. Results showed that PPI use was associated with an increased risk of bone fracture and hip fracture in the HD patients (pooled OR = 1.29, 95% CI = 1.21-1.37, p < 0.00001, I2 = 0%; pooled OR = 1.37, 95% CI = 1.12-1.67, p = 0.002, I2 = 82%). Besides, HD patients who received PPIs were more likely to develop hypomagnesemia compared with those who did not receive PPIs (pooled OR = 2.79, 95% CI = 1.95-4.00, p < 0.00001, I2 = 0%). In addition, PPIs use was linked to abdominal aortic calcification and all-cause mortality (pooled OR = 2.03, 95% CI = 1.28-3.24, p = 0.003, I2 = 0%) (pooled OR = 1.44, 95% CI = 1.17-1.78, p = 0.0006, I2 = 0%). CONCLUSIONS: Taken together, the present results demonstrate that PPIs use in HD patients is independently associated with adverse reactions such as hip fracture, hypomagnesemia, abdominal aortic calcification, and all-cause mortality. Thus, the use of PPIs in HD patients should be carefully evaluated and optimized.


Assuntos
Inibidores da Bomba de Prótons , Diálise Renal , Humanos , Doença Iatrogênica , Magnésio , Razão de Chances , Inibidores da Bomba de Prótons/efeitos adversos , Diálise Renal/efeitos adversos
4.
Kidney Blood Press Res ; 47(11): 643-653, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36116428

RESUMO

BACKGROUND: Risk factors like female sex, fistula location, hypertension, albumin, diabetes, arteriovenous graft (AVG), age, and other factors are related to arteriovenous fistula thrombus (AVFT), but the consistency and magnitude of their associations have not been confirmed by meta-analysis. OBJECTIVES: The purpose of this study was to provide a comprehensive and up-to-date synthesis of evidence on the association between potential risk factors and AVFT. METHODS: In this systematic review and meta-analysis, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for articles published up to April 20th, 2022, and cohort, cross-sectional, and case-control studies examining the association (odds ratio [OR]) between potential risk factors and AVFT were identified. The other inclusion criteria were sufficient data for analysis and nonoverlapping datasets, excluding reviews, meta-analyses, and articles with overlapping datasets. Extracted variables included first author, publication year, study type, sample size, percentage of women, vascular access type, risk or protective factors, and measure of association (adjusted estimates of effect of all risk factors). The study protocol is registered at PROSPERO (CRD42020201884) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Among the 27 identified studies, data from 24 cohort, 2 case-control, and 1 cross-sectional study were included in this review. When compared to non-AVFT, our data showed that the significant risk factors were AVG (pooled OR = 6.28, 95% CI = 1.79-22.02, p = 0.004, I2 = 87%), age (pooled OR = 1.06, 95% CI = 1.00-1.13, p = 0.05, I2 = 98%), female sex (pooled OR = 2.62, 95% CI = 2.56-2.69, p < 0.00001, I2 = 0%), C-reactive protein (pooled OR = 1.18, 95% CI = 1.08-1.30, p = 0.0005, I2 = 90%), fistula site (distal) (pooled OR = 3.64, 95% CI = 1.74-7.62, p = 0.0006, I2 = 47%), hypertension (pooled OR = 1.21, 95% CI = 1.00-1.47, p = 0.05, I2 = 46%), CD34+KDR+ cell (pooled OR = 1.85, 95% CI = 1.33-2.57, p = 0.0002, I2 = 0%), and eprex use (pooled OR = 5.36, 95% CI = 1.82-15.77, p = 0.002, I2 = 0%). CONCLUSIONS: The meta-analysis suggests that AVG, age, female sex, CRP level, fistula site (distal), hypertension, CD34+KDR+ cell, and the use of eprex are independent risk factors for AVFT. Therefore, clinical medical staff should treat these risk factors carefully, identify them early, and prevent them early to reduce the occurrence of AVFT.


Assuntos
Fístula Arteriovenosa , Hipertensão , Trombose , Feminino , Humanos , Estudos Transversais , Epoetina alfa , Fatores de Risco , Trombose/etiologia , Masculino
5.
Am J Med Genet A ; 179(11): 2178-2189, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31479204

RESUMO

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype-phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Duplicação Cromossômica/genética , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Adulto , Variação Biológica da População , Aberrações Cromossômicas , Cromossomos Humanos Par 22/genética , Hibridização Genômica Comparativa , Feminino , Estudos de Associação Genética/métodos , Humanos , Lactente , Masculino , Fenótipo
6.
Eur Spine J ; 27(10): 2550-2564, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29923019

RESUMO

INTRODUCTION: Kyphoplasty has been widely used to treat vertebral compression fractures (VCFs). In standard procedure of kyphoplasty, two balloons were inserted into the vertebral body through bipedicular and inflated simultaneously, while using a single balloon two times is also a common method in clinic to lessen the financial burden of patients. However, the effect and safety of single balloon versus double balloon bipedicular kyphoplasty are still controversy. METHODS: In this systematic review and meta-analysis, eligible studies were identified through a comprehensive literature search of PubMed, Cochrane library EMBASE, Web of Science, Wanfang, CNKI, VIP and CBM until January 1, 2018. Results from individual studies were pooled using a random or fixed effects model. RESULTS: Seven articles were included in the systematic review and five studies were consisted in meta-analysis. We observed no significant difference between single balloon and double balloon bipedicular kyphoplasty in visual analog scale (VAS), angle (kyphotic angle and Cobb angle), consumption (operation time, cement volume and volume of bleeding), vertebral height (anterior height, medium height and posterior height) and complications (cement leakage and new VCFs), while the cost of single balloon bipedicular kyphoplasty is lower than that of double balloon bipedicular kyphoplasty. The results of our meta-analysis also demonstrated that single balloon can significantly improve the VAS, angle and vertebral height of patients suffering from VCFs. CONCLUSION: This systematic review and meta-analysis collectively concludes that single balloon bipedicular kyphoplasty is as effective as double balloon bipedicular kyphoplasty in improving clinical symptoms, deformity and complications of VCFs but not so expensive. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Fraturas por Compressão/cirurgia , Cifoplastia , Fraturas da Coluna Vertebral/cirurgia , Coluna Vertebral/cirurgia , Humanos , Cifoplastia/efeitos adversos , Cifoplastia/métodos , Cifoplastia/estatística & dados numéricos
7.
Med Sci Monit ; 23: 5907-5915, 2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29236682

RESUMO

BACKGROUND Percutaneous kyphoplasty (PKP) has been widely used to treat vertebral compression fractures (VCFs). Bilateral percutaneous punctures are always performed to access the fractured vertebrae. However, the procedure has expensive clinical costs, especially the cost for the device, which creates a heavy financial burden for patients. MATERIAL AND METHODS Data from 49 patients who have single-level non-neoplastic vertebral compression fracture (VCF) were collected for 12 months after treated by PKP, including 21 cases that used bilateral puncture with single balloon (S group) and 28 cases that used bilateral puncture with double balloon (D group). We assessed the clinical (visual analogue scale, VAS) and radiological (vertebral height and kyphotic angle, KA) outcomes. Cost data (gross medical cost, cost for the device and cost for drugs) were obtained from the medical bill of each patient. RESULTS Baseline patient variables were similar between the two groups except the compensation (S group

Assuntos
Fraturas por Compressão/cirurgia , Cifoplastia/métodos , Idoso , Povo Asiático , Cimentos Ósseos/uso terapêutico , China , Feminino , Humanos , Cifoplastia/economia , Cifose/cirurgia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Fraturas da Coluna Vertebral/cirurgia , Traumatismos da Coluna Vertebral/cirurgia , Coluna Vertebral/cirurgia , Resultado do Tratamento , Vertebroplastia/métodos
8.
Biol Pharm Bull ; 39(5): 815-22, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26902225

RESUMO

Psoralen is a major active component of Psoralea corylifolia. In the present study, we analyzed psoralen-induced changes in human breast cancer MCF-7/ADR cells and investigated the underlying mechanisms of the anticancer effect on MCF-7/ADR cells. We measured cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate the cytotoxicity and multidrug resistance (MDR) reversal activity of psoralen. The cell cycle distribution and apoptosis, accumulation and efflux of rhodamine123 (Rh123), and P-glycoprotein (P-gp) expression levels of MCF-7/ADR cells treated with psoralen were all detected by flow cytometry (FCM). We assessed P-gp ATPase activity by monitoring ATP consumption. We evaluated the activity of nuclear factor-kappaB (NF-κB) and the expression of E-cadherin, vimentin and α-smooth muscle actin (SMA) involved in regulating epithelial-mesenchymal transition (EMT). The results showed that psoralen inhibited the proliferation of MCF-7/ADR cells as shown by G0/G1 phase arrest rather than encouraging apoptosis. It was also observed that psoralen reversed MDR through inhibiting ATPase activity rather than reducing P-gp expression. Our results further showed that psoralen inhibited the migration abilities of MCF-7/ADR cells by repressing EMT possibly through inhibiting the activation of NF-κB. Our findings provided a systematic and detailed description of the anti-cancer effect of psoralen on MCF-7/ADR cells for the exploration of natural compounds as novel anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Ficusina/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Actinas/genética , Adenosina Trifosfatases/metabolismo , Antígenos CD , Caderinas/genética , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Células MCF-7 , NF-kappa B/metabolismo , Vimentina/genética
9.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(5): 1458-63, 2016 May.
Artigo em Zh | MEDLINE | ID: mdl-30001031

RESUMO

During the synthesis of crystal material, specific dopant can enhance the qualities and performance of crystals, while the types, concentrations and distributions of doping elements also have significant influence on the structures and properties of artificial crystals. Hence, it is very important to determine the concentrations of doping elements for further improving the crystal material formulas, crystal growth process, andits quality control. Currently, the analysis techniques for doping elements' characterization include atomic spectrometry, X-ray fluorescence spectrometry, inorganic mass spectrometry, electron probe microanalysis, etc. The principles, advantages and disadvantages of these techniques are discussed in this paper. Considering the specialties and scope of application, it is necessary to choose the suitable methods to improve the efficiency and accuracy. Meanwhile, the developing trends of analysis methods for doping elements are also prospected.

10.
Am J Med Genet A ; 167A(4): 791-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25820398

RESUMO

Persistent müllerian duct syndrome (PMD) with antimüllerian hormone (AMH) deficiency is usually associated with mutations or deletions of the AMH gene, although many cases have no identified gene association. We report on a genetic male with PMD and AMH deficiency associated with distal monosomy 10q. A term 3,230 g infant was born to a healthy 27-year-old. Fetal ultrasound had shown possible genital ambiguity. Postnatal exam showed a 0.5 cm phallus with basal meatus, normal scrotum with no palpable gonads, no vaginal orifice, and a rectal fistula with an imperforate anus. Voiding cystourethrogram with ultrasound, cystoscopy, and laparoscopy showed normal bladder, urethral orifice, distal vagina, cervix, and bilateral abdominal testis. At 24 hours of life, testosterone was within normal range with low AMH level. Chromosome microarray analysis showed 46, XY, del10(10q25.3q26.13) involving an 8.2 MB interstitial deletion. Whole exome sequencing identified a NOTCH2 variant (1p11.2). AMH sequencing revealed no abnormalities. Following multidisciplinary team and parent discussion, male gender was assigned. Testosterone treatment resulted in penile length of 1.5 cm. Bilateral orchiopexy and posterior sagittal anorectoplasty were performed at 11 months of age; rudimentary müllerian structures were identified. This observation suggests an association of 10qter elements with male differentiation including AMH expression and is similar to a patient with 46, XY, del(10q26.1) in which AMH levels were not reported. Regional candidate genes include FGFR2 (10q26.13). The possible contribution of a NOTCH2 variant cannot be excluded.


Assuntos
Deleção Cromossômica , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Hormônio Antimülleriano/deficiência , Cromossomos Humanos Par 10 , Transtorno 46,XY do Desenvolvimento Sexual/genética , Humanos , Lactente , Masculino , Ductos Paramesonéfricos/patologia
11.
Clin Chem Lab Med ; 52(6): 899-909, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24406287

RESUMO

BACKGROUND: Hyper-methylation of CpG dinucleotides in the promoter region of inhibitor of cyclin-dependent kinase 4A (INK4A) has been reported in 60%-80% of hepatocellular carcinoma (HCC). As INK4A promoter hypermethylation event occurs early in HCC progression, the quantification of INK4A promoter methylation in blood sample may represent a useful biomarker for non-invasive diagnosis and prediction of response to therapy. METHODS: We examined INK4A promoter methylation using circulating cell-free DNA (ccfDNA) in a total of 109 serum specimens, including 66 HCC and 43 benign chronic liver diseases. Methylation of the individual seven CpG sites was examined using pyrosequencing. RESULTS: Our results showed that there were significantly higher levels of methylated INK4A in HCC specimens than controls and that the seven CpG sites had different levels of methylation and might exist in different PCR amplicons. The area under receiver operating characteristic (ROC) curve was 0.82, with 65.3% sensitivity and 87.2% specificity at 5% (LOD), 39.0% sensitivity and 96.5% specificity at 7% LOD, and 20.3% sensitivity and 98.8% specificity at 10% LOD, respectively. CONCLUSIONS: Our results support additional studies incorporating INK4A methylation testing of ccfDNA to further validate the diagnostic, predictive, and prognostic characteristics of this biomarker in HCC patients. The knowledge of the existence of epi-alleles should help improve assay design to maximize detection.


Assuntos
Carcinoma Hepatocelular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , DNA/sangue , Neoplasias Hepáticas/genética , Regiões Promotoras Genéticas/genética , Análise de Sequência de DNA/métodos , Alelos , Sequência de Bases , Carcinoma Hepatocelular/sangue , Linhagem Celular Tumoral , Ilhas de CpG/genética , DNA/genética , Humanos , Neoplasias Hepáticas/sangue
12.
Lab Med ; 55(1): 103-105, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-37184333

RESUMO

Triploidy is a genetic occurrence in which the chromosome count is 3n = 69 with a double (2n) chromosomal contribution to the conceptus from one parent. Such pregnancies are usually nonviable and are estimated to account for approximately 1% of recognized conceptions and 10% of recognized miscarriages. Majority opinion is that fetal losses due to triploidies are caused by the presence of 2 copies of paternal chromosomes. In this study, we present a digynic monoandric triploid miscarriage from a 32-year-old G7P1051 at approximately 13 weeks gestation, in which 2 copies of the maternal chromosomes are present in the fetus. This unusual phenomenon is supported by nonmolar placental histology, chromosomal microarray, and short tandem repeat assays, with the latter 2 being discussed in detail. Furthermore, this study includes discussion of recurrent miscarriage, recurrent triploidy, and long-term clinical follow-up of the patient.


Assuntos
Aborto Habitual , Triploidia , Humanos , Gravidez , Feminino , Adulto , Placenta , Aborto Habitual/genética
13.
Clin Chim Acta ; 552: 117635, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37952813

RESUMO

BACKGROUND: Bisalbuminemia and bisalbuminuria are rarely encountered serum and urine albumin anomalies characterized by the presence of a bifid albumin band on serum/urine protein electrophoresis (SPE/UPE) and serum/urine immunofixation electrophoresis (SIFE/UIFE). They are usually detected incidentally while screening for monoclonal gammopathy with a cumulative frequency of 1:1,000---1:10,000. CASE REPORT: We report two cases of bisalbuminemia in two adult male diabetic patients. The first patient had a history of rheumatoid arthritis and strong clinical suspicion for Sjogren syndrome. The SPEP/UPEP and SIFE/UIFE in this patient showed combined bisalbuminemia and bisalbuminuria. While the second patient had chronic kidney disease due to nephrotic syndrome but showed bisalbuminemia alone. CONCLUSION: Bisalbuminemia and bisalbuminuria are rare findings with few case reports available in the English literature. These findings may occur secondary to inherited albumin variants or may be acquired. Diabetes mellitus is the medical condition most associated with acquired bisalbuminemia and bisalbuminuria. Although most cases of bisalbuminemia and bisalbuminuria are clinically insignificant, some albumin variants may have altered affinity for steroid hormones (e.g., thyroxine) and/or drugs which potentially could be clinically significant.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Síndrome Nefrótica , Adulto , Humanos , Masculino , Albuminas/análise , Eletroforese
14.
Lab Med ; 55(2): 245-248, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-37294932

RESUMO

BACKGROUND: Double trisomies are rare findings among products of conception and are often lethal to the developing embryo or fetus. METHODS: Here we describe a double trisomy case with symptoms of threatened miscarriage at 9 weeks gestation. Ultrasound revealed an anembryonic pregnancy. Pregnancy was terminated by dilation and curettage at gestational age 11 weeks and 6 days. Histologic examination and chromosome microarray were performed on a formalin-fixed product of conception (POC) sample to identify the cause of the anembryonic pregnancy. RESULTS: Chromosome microarray analysis revealed a female chromosome complement with double trisomies 10 and 20, arr(10,20)x3, consistent with a karyotype of 48,XX,+10,+20. CONCLUSION: To the best of our knowledge, this is the first reported case of double trisomy 10 and 20 in a POC. Due to nonspecific histopathological findings, chromosomal microarray is a powerful tool in identifying and differentiating chromosomal aneuploidies.


Assuntos
Aborto Espontâneo , Transtornos Cromossômicos , Gravidez , Feminino , Humanos , Lactente , Trissomia/diagnóstico , Trissomia/genética , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Aneuploidia , Cariotipagem , Aborto Espontâneo/genética , Aborto Espontâneo/patologia
15.
Lab Med ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527227

RESUMO

Non-small cell lung cancer (NSCLC) has been found to have recurrent genetic abnormalities, and novel therapies targeting these aberrations have improved patient survival. In this study, specimens from benign tissue, primary tumors, and brain metastases were obtained at autopsy from a 55-year-old White female patient diagnosed with NSCLC and were examined using next-generation sequencing (NGS) and chromosomal microarray assay (CMA). No genetic aberrations were noted in the benign tissue; however, NGS identified a mutation in the KRAS proto-oncogene, GTPase (KRAS): KRAS exon 2 p.G12D in primary and metastatic tumor specimens. We observed 7 DNA copy number aberrations (CNAs) in primary and metastatic tumor specimens; an additional 7 CNAs were exclusively detected in the metastatic tumor specimens. These DNA alterations may be genetic drivers in the pathogenesis of the tumor specimen from our patient and may serve as biomarkers for the classification and prognosis of NSCLC.

16.
Pathogens ; 13(3)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38535583

RESUMO

Alzheimer's Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (Aß42 and hyperphosphorylated tau). Controversies and challenges of the virus-AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion.

17.
J Carcinog ; 12: 5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23599687

RESUMO

INTRODUCTION AND HYPOTHESIS: Nuclear atypia with features of multi nuclei have been detected in human melanoma specimens. We found that the K type human endogenous retroviral element (HERV K) is expressed in such cells. Since cellular syncytia can form when cells are infected with retroviruses, we hypothesized that HERV K expressed in melanoma cells may contribute to the formation of multinuclear atypia cells in melanoma. EXPERIMENTS AND RESULTS: We specifically inhibited HERV K expression using RNA interference (RNAi) and monoclonal antibodies and observed dramatic reduction of intercellular fusion of cultured melanoma cells. Importantly, we identified loss of heterozygosity (LOH)of D19S433 in a cell clone that survived and proliferated after cell fusion. CONCLUSION: Our results support the notion that proteins encoded by HERV K can mediate intercellular fusion of melanoma cells, which may generate multinuclear cells and drive the evolution of genetic changes that provide growth and survival advantages.

18.
Cureus ; 15(3): e36668, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37102003

RESUMO

Thromboembolism is known to be a multifactorial event that is impacted by various genetic and environmental factors. The genetics society's recommended name for this variant is c.*97G>A (this is the nomenclature we need to use in the patient report). However, people have been using legacy names c.20210G>A or G20210A (so these are common names). One of the most common genetic variants associated with inherited thrombophilias, F2 c.20210G>A is acknowledged to be a weak but significant risk factor for thromboembolism. However, its clinical presentation has been described as phenotypically heterogeneous. We present two rare cases with homozygous F2 c.20210G>A variant, one of which also carries a heterozygous variant in coagulation factor V gene F5, c.1601G>A (p.Arg534Gln; commonly known as factor V Leiden). We described the clinical courses of these two cases and discussed F2 c.20210G>A and factor V Leiden as genetic risk factors in thromboembolism, the role of provoking factors, such as surgery and malignancy, and the management of such patients.

19.
Cureus ; 15(6): e40185, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37431359

RESUMO

Cystic fibrosis (CF) is a genetic disease that affects the lung, pancreas, and other organs caused by the presence of biallelic CF-causing variants in the cystic fibrosis conductance regular gene (CFTR). CFTR variants can also be found in CFTR-related disorders (CFTR-RD), which present milder symptoms. Increasing access to next-generation sequencing has demonstrated that both CF and CFTR-RD have a broader array of genotypes than formerly thought. Here we present three patients who carry the most common CFTR pathogenic variant - F508del - but express a wide array of phenotypes. These cases open discussion on the role of concurrent variants in CFTR, the importance of early diagnosis and treatment, and the contribution of lifestyle factors in CF and CFTR-RD presentation.

20.
J Hypertens ; 41(1): 159-170, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36453659

RESUMO

OBJECTIVES: High sodium intake is strongly associated with hypertension and obesity. This study aims to investigate the relationship between 24-h urinary sodium (a surrogate measure of sodium intake), ambulatory blood pressure parameters, left atrial function, and left atrioventricular coupling. Further, we intend to examine whether blood pressure and BMI might be mediators of the relationship between 24-h urinary sodium and subclinical cardiac function. METHODS: Our study had 398 participants, all of whom were subjected to 24-h urine collection, 24-h ambulatory blood pressure measurement, and cardiac magnetic resonance imaging. RESULTS: The average age of the participants was 55.70 ±â€Š11.30 years old. The mean urinary sodium of the participants was 172.01 ±â€Š80.24 mmol/24 h. After adjusting for age, sex, history of diabetes, smoking status, alcohol consumption, and use of diuretics, 24-h urinary sodium was correlated with multiple ambulatory blood pressure parameters, BMI, left atrial function, and the left atrioventricular coupling index (LACI) (P < 0.05). Mediation analysis showed that BMI explained 16% of the indirect effect of 24-h urinary sodium and left atrial function and 30% of the indirect effect of LACI. Independent of the mediator, 24-h urinary sodium had a significant direct effect on left atrial function and left atrioventricular coupling. CONCLUSIONS: Higher 24-h urinary sodium was associated with a greater BMI as well as poor left atrial function and left atrioventricular coupling, and the BMI mediated the relationship between 24-h urinary sodium and subclinical left cardiac function. Furthermore, and more importantly, 24-h urinary sodium may have directly affected the left atrial function and left atrioventricular coupling independent of intermediary factors.


Assuntos
Função do Átrio Esquerdo , Sódio na Dieta , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Monitorização Ambulatorial da Pressão Arterial , Radioisótopos de Sódio , China
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