Category: Nevin Manimala

Oncol Lett. 2023 Jun 22;26(2):343. doi: 10.3892/ol.2023.13929. eCollection 2023 Aug.

ABSTRACT

Triple-negative breast cancer (TNBC) is an aggressive subtype of BC characterized by extensive intratumoral heterogeneity. Compared with other types of BC, TNBC is more prone to invasion and metastasis. The aim of the present study was to determine whether adenovirus-mediated clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 system is capable of effectively targeting enhancer of zeste homolog 2 (EZH2) in TNBC cells and lay an experimental basis for the investigation of the CRISPR/Cas9 system as a gene therapy for BC. In the present study, EZH2 was knocked out in MDA-MB-231 cells using the CRISPR/Cas9 gene editing tool to create EZH2-knockout (KO) group (EZH2-KO group). Moreover, the GFP knockout group (control group), and a blank group (Blank group), were employed. The success of vector construction and EZH2-KO were verified by T7 endonuclease I (T7EI) restriction enzyme digestion, mRNA detection and western blotting. Changes in proliferation and migration ability of MDA-MB-231 cells following gene editing were detected by MTT, wound healing, Transwell and in vivo tumor biology assays. As indicated by the results of mRNA and protein detection, the mRNA and protein expression of EZH2 were significantly downregulated in the EZH2-KO group. The difference in EZH2 mRNA and protein between the EZH2-KO and the two control groups was statistically significant. MTT, wound healing and transwell assay suggested that the proliferation and migration ability of MDA-MB-231 cells in the EZH2-KO group were significantly decreased after EZH2 knockout. In vivo, the tumor growth rate in the EZH2-KO group was significantly lower than that in the control groups. In brief, the present study revealed that the biological functions of tumor cells were inhibited after EZH2 knockout in MDA-MB-231 cells. The aforementioned findings suggested that EZH2 can have a key role in the development of TNBC.

PMID:37427349 | PMC:PMC10326815 | DOI:10.3892/ol.2023.13929

Oncol Lett. 2023 Jun 28;26(2):350. doi: 10.3892/ol.2023.13936. eCollection 2023 Aug.

ABSTRACT

Intracranial meningiomas are the most common tumors of the central nervous system (CNS). Meningiomas account for up to 36% of all brain tumors. The incidence of metastatic brain lesions has not been determined. Up to 30% of adult patients with cancer of one localization or another suffer from a secondary tumor lesion of the brain. The vast majority of meningiomas have meningeal localization; >90% are solitary. The incidence of intracranial dural metastases (IDM) is 8-9% of cases, while in 10% of cases, the brain is the only localization, and in 50% of cases the metastases are solitary. Typically, the task of distinguishing between meningioma and dural metastasis does not involve difficulties. Periodically, there is a situation when the differential diagnosis between these tumors is ambiguous, since meningiomas and solitary IDM may have similar characteristics, in particular, a cavity-less solid structure, limited diffusion of water molecules, the presence of extensive peritumoral edema, and an identical contrast pattern. The present study included 100 patients with newly diagnosed tumors of the CNS, who subsequently underwent examination and neurosurgical treatment at the Federal Center for Neurosurgery with histological verification between May 2019 and October 2022. Depending on the histological conclusion, two study groups of patients were distinguished: The first group consisted of patients diagnosed with intracranial meningiomas (n=50) and the second group of patients were diagnosed with IDM (n=50). The study was performed using a magnetic resonance imaging (MRI) General Electric Discovery W750 3T before and after contrast enhancement. The diagnostic value of this study was estimated using Receiver Operating Characteristic curve and area under the curve analysis. Based on the results of the study, it was found that the use of multiparametric MRI (mpMRI) in the differential diagnosis of intracranial meningiomas and IDM was limited by the similarity of the values of the measured diffusion coefficient. The assumption, previously put forward in the literature, regarding the presence of a statistically significant difference in the apparent diffusion coefficient values, which make it possible to differentiate tumors, was not confirmed. When analyzing perfusion data, IDM showed higher cerebral blood flow (CBF) values compared with intracranial meningiomas (P≤0.001). A threshold value of the CBF index was revealed, which was 217.9 ml/100 g/min, above which it is possible to predict IDM with a sensitivity and specificity of 80.0 and 86.0%, respectively. Diffusion-weighted images are not reliable criteria for differentiating intracranial meningiomas from IDM and should not influence the diagnosis suggested by imaging. The technique for assessing the perfusion of a meningeal lesion makes it possible to predict metastases with a sensitivity and specificity close to 80-90% and deserves attention when making a diagnosis. In the future, in order to reduce the number of false negative and false positive results, mpMRI would require additional criteria to be included in the protocol. Since IDM differs from intracranial meningiomas in the severity of neoangiogenesis and, accordingly, in greater vascular permeability, the technique for assessing vascular permeability (wash-in parameter with dynamic contrast enhancement) may serve as a refining criterion for distinguishing between dural lesions.

PMID:37427340 | PMC:PMC10326821 | DOI:10.3892/ol.2023.13936

Indian J Psychol Med. 2023 Jul;45(4):338-344. doi: 10.1177/02537176221130252. Epub 2022 Oct 27.

ABSTRACT

BACKGROUND: Patients with dementia usually have multiple comorbidities. The presence of comorbidities may exacerbate the progression of dementia and decreases the patient’s ability to participate in health maintenance activities. However, there is hardly any meta-analysis estimating the magnitude of comorbidities among patients with dementia in the Indian context.

METHODS: We searched PubMed, Scopus, and Google Scholar, and relevant studies conducted in India were included. The risk of bias was assessed and a random-effects meta-analysis model was used in which I² statistics were calculated to measure heterogeneity among studies.

RESULTS: Fourteen studies were included in the meta-analysis based on the inclusion and exclusion criteria. Altogether, we found the coexistence of comorbid conditions such as hypertension (51.10%), diabetes (27.58%), stroke (15.99%), and factors like tobacco use (26.81 %) and alcohol use (9.19%) among patients with dementia in this setting. The level of heterogeneity was high due to differences in the methodologies in the included studies.

CONCLUSIONS: Our study found hypertension as the most common comorbid condition among patients with dementia in India. The observed lacuna of methodological limitations in the studies included in the current meta-analysis provides the urgent need for good quality research to successfully meet the challenges ahead while devising appropriate strategies to treat the comorbidities among patients with dementia.

PMID:37427307 | PMC:PMC7614734 | DOI:10.1177/02537176221130252

Arrhythm Electrophysiol Rev. 2023 Apr 12;12:e07. doi: 10.15420/aer.2022.34. eCollection 2023.

ABSTRACT

Stroke is a leading cause of death worldwide. With escalating healthcare costs, early non-invasive stroke risk stratification is vital. The current paradigm of stroke risk assessment and mitigation is focused on clinical risk factors and comorbidities. Standard algorithms predict risk using regression-based statistical associations, which, while useful and easy to use, have moderate predictive accuracy. This review summarises recent efforts to deploy machine learning (ML) to predict stroke risk and enrich the understanding of the mechanisms underlying stroke. The surveyed body of literature includes studies comparing ML algorithms with conventional statistical models for predicting cardiovascular disease and, in particular, different stroke subtypes. Another avenue of research explored is ML as a means of enriching multiscale computational modelling, which holds great promise for revealing thrombogenesis mechanisms. Overall, ML offers a new approach to stroke risk stratification that accounts for subtle physiologic variants between patients, potentially leading to more reliable and personalised predictions than standard regression-based statistical associations.

PMID:37427297 | PMC:PMC10326666 | DOI:10.15420/aer.2022.34

Front Public Health. 2023 Jun 20;11:1193475. doi: 10.3389/fpubh.2023.1193475. eCollection 2023.

ABSTRACT

BACKGROUND: Smoking is a common problem in university students worldwide. Smoking is one of the most dangerous social phenomena and has a significant impact on public health. This study investigated the beliefs and attitudes of medical students toward smoking in Sudan.

METHODS: A cross-sectional study was conducted among medical students at Al Neelain University, Sudan, from March to June 2022 using a web-based questionnaire. The questionnaire consisted of eight items on demographic characteristics and 13 on the beliefs and attitudes toward smoking. Other data included smoking status, smoking habits, the number of cigarettes smoked per day, and smoking duration. Data analysis was performed descriptively, and chi-square test and logistic regression were conducted using SPSS version 24. Statistical significance was set at 0.05.

RESULTS: A total of 336 students participated in this study, and the smoking prevalence was 48.8% (41.1% in men and 7.7% in women). In total, 76.8% reported smoking daily at a rate of 5-10 cigarettes per day. In terms of students’ beliefs about smoking, 86.8% disagreed with selling cigarettes at the university. Of the respondents, 68.4% did not approve smoking on campus. There was a relationship between smoking habits and the age group of 22-25 years, which was the highest smoking category among students (p-value = 0.01).

CONCLUSION: The prevalence of cigarette smoking among medical students is disturbing, particularly as they are future doctors. There is a need to include plans to reduce smoking among students that can be incorporated into courses and special programs.

PMID:37427282 | PMC:PMC10325783 | DOI:10.3389/fpubh.2023.1193475

Biom J. 2023 Jul 9:e2200125. doi: 10.1002/bimj.202200125. Online ahead of print.

ABSTRACT

This article proposes a new class of nonhomogeneous Poisson spatiotemporal model. In this approach, we use a state-space model-based prior distribution to handle the scale and shape parameters of the Weibull intensity function. The proposed prior distribution enables the inclusion of changes in the behavior of the intensity function over time. In defining the spatial correlation function of the model, we include anisotropy via spatial deformation. We estimate the model parameters from a Bayesian perspective, employ the Markov chain Monte Carlo approach, and validate this estimation procedure through a simulation exercise. Finally, the extreme rainfall in the southern semiarid region in northeastern Brazil is analyzed using the R10mm index. The proposed model showed better fit and prediction ability than did other nonhomogeneous Poisson spatiotemporal models available in the literature. This improvement in performance is mainly due to the flexibility of the intensity function that is achieved by allowing the incorporation, in time, of the climatic characteristics of this region.

PMID:37424029 | DOI:10.1002/bimj.202200125

Chin Med. 2023 Jul 10;18(1):82. doi: 10.1186/s13020-023-00737-5.

ABSTRACT

BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative joint condition that causes disability and pain in the elderly population. The prevalence of KOA among persons aged 63 or above is approximately 30%. Previous studies have reported the positive effects of Tui-na treatment and the Chinese herbal formula Du-Huo-Ji-Sheng Decoction (DHJSD) for KOA treatment. The current study aims to evaluate the add-on therapeutic effect of oral administration of DHJSD on KOA in addition to Tui-na.

METHODS: We conducted a prospective, randomized, controlled clinical trial. Seventy study subjects with KOA were randomly assigned to the treatment and control groups in a 1:1 ratio. Both two groups received eight sessions of Tui-na manipulation for 4 weeks. The DHJSD was only administered to the study subjects in the treatment group. The primary outcome measure was rated using the WOMAC at the end of treatment (4 weeks). Secondary outcomes were assessed using EQ-5D-5L, a health-related quality of life with 5-level EQ-5D version at end of treatment (week 4) and follow-up (week 8).

RESULTS: No statistically significant difference was found between two groups on WOMAC scores at the end of treatment. The mean WOMAC Pain subscale score was significantly lower in the treatment group than control group at week 8 follow up (mean difference, MD – 1.8, 95% CI – 3.5 to – 0.02, P = 0.048). The mean WOMAC Stiffness subscale score was significantly lower in the treatment group than in the control group at week 2 (MD 0.74, 95% CI 0.05 to 1.42, P = 0.035) and week 8 follow up (MD 0.95, 95% CI 0.26 to 1.65, P = 0.008). The mean EQ-5D index value was significantly improved in the treatment group than in the control group at week 2 (MD 0.17, 95% CI 0.02 to 0.31, P = 0.022). The analysis of WOMAC scores and EQ-5D-5L in both groups showed statistically significant improvement with time. No significant adverse effect was found during the trial.

CONCLUSION: DHJSD may have an add-on effect in addition to Tui-na manipulation relieving pain and improving stiffness as well as quality of life (QOL) in patients with KOA. The combined treatment was generally safe and well tolerated. Trial registration The study was registered at the ClinicalTrials.gov (website: https://clinicaltrials.gov/ct2/show/NCT04492670 , registry number: NCT04492670), registered on 30 July 2020.

PMID:37424023 | DOI:10.1186/s13020-023-00737-5

BMC Biol. 2023 Jul 10;21(1):151. doi: 10.1186/s12915-023-01641-y.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) accelerates atherosclerosis, but the mechanisms remain unclear. Tyrosine sulfation has been recognized as a key post-translational modification (PTM) in regulation of various cellular processes, and the sulfated adhesion molecules and chemokine receptors have been shown to participate in the pathogenesis of atherosclerosis via enhancement of monocyte/macrophage function. The levels of inorganic sulfate, the essential substrate for the sulfation reaction, are dramatically increased in patients with CKD, which indicates a change of sulfation status in CKD patients. Thus, in the present study, we detected the sulfation status in CKD patients and probed into the impact of sulfation on CKD-related atherosclerosis by targeting tyrosine sulfation function.

RESULTS: PBMCs from individuals with CKD showed higher amounts of total sulfotyrosine and tyrosylprotein sulfotransferase (TPST) type 1 and 2 protein levels. The plasma level of O-sulfotyrosine, the metabolic end product of tyrosine sulfation, increased significantly in CKD patients. Statistically, O-sulfotyrosine and the coronary atherosclerosis severity SYNTAX score positively correlated. Mechanically, more sulfate-positive nucleated cells in peripheral blood and more abundant infiltration of sulfated macrophages in deteriorated vascular plaques in CKD ApoE null mice were noted. Knockout of TPST1 and TPST2 decreased atherosclerosis and peritoneal macrophage adherence and migration in CKD condition. The sulfation of the chemokine receptors, CCR2 and CCR5, was increased in PBMCs from CKD patients.

CONCLUSIONS: CKD is associated with increased sulfation status. Increased sulfation contributes to monocyte/macrophage activation and might be involved in CKD-related atherosclerosis. Inhibition of sulfation may suppress CKD-related atherosclerosis and is worthy of further study.

PMID:37424015 | DOI:10.1186/s12915-023-01641-y

Thyroid Res. 2023 Jul 10;16(1):23. doi: 10.1186/s13044-023-00165-5.

ABSTRACT

BACKGROUND: Thyroid cancer (TC) patients are understudied but appear to be at risk for poor physical and psychosocial outcomes. Knowledge of the course and determinants of these deteriorated outcomes is lacking. Furthermore, little is known about mediating biological mechanisms.

OBJECTIVES: The WaTCh-study aims to; 1. Examine the course of physical and psychosocial outcomes. 2. Examine the association of demographic, environmental, clinical, physiological, and personality characteristics to those outcomes. In other words, who is at risk? 3. Reveal the association of mediating biological mechanisms (inflammation, kynurenine pathway) with poor physical and psychological outcomes. In other words, why is a person at risk?

DESIGN AND METHODS: Newly diagnosed TC patients from 13 Dutch hospitals will be invited. Data collection will take place before treatment, and at 6, 12 and 24 months after diagnosis. Sociodemographic and clinical information is available from the Netherlands Cancer Registry. Patients fill-out validated questionnaires at each time-point to assess quality of life, TC-specific symptoms, physical activity, anxiety, depression, health care use, and employment. Patients are asked to donate blood three times to assess inflammation and kynurenine pathway. Optionally, at each occasion, patients can use a weighing scale with bioelectrical impedance analysis (BIA) system to assess body composition; can register food intake using an online food diary; and can wear an activity tracker to assess physical activity and sleep duration/quality. Representative Dutch normative data on the studied physical and psychosocial outcomes is already available.

IMPACT: WaTCh will reveal the course of physical and psychosocial outcomes among TC patients over time and answers the question who is at risk for poor outcomes, and why. This knowledge can be used to provide personalized information, to improve screening, to develop and provide tailored treatment strategies and supportive care, to optimize outcomes, and ultimately increase the number of TC survivors that live in good health.

PMID:37424010 | DOI:10.1186/s13044-023-00165-5

BMC Public Health. 2023 Jul 10;23(1):1313. doi: 10.1186/s12889-023-16243-0.

ABSTRACT

INTRODUCTION: Cardiovascular disease and obesity are both significantly influenced by physical inactivity. A rapidly expanding corpus of research contends that features of the built environment might encourage adolescents to lead active lives. There are still issues with the present evidence for determining which aspects of the built environment give adolescents the opportunity to engage in leisure-time physical activity (LTPA). This study looked at the relationship between the characteristics of the built environment and moderate-to-vigorous leisure-time physical activity (Leisure-time MVPA) of adolescents.

METHODS: 2628 adolescents between the ages of 11 and 18 were chosen as study participants from 19 Suzhou urban communities. They must have resided in the neighborhood for longer than six months and be permanent residents there. The International Physical Activities Questionnaire (n = 2628) and the Neighborhood Environment Walkability Scale for Chinese Children (NEWS-CC) were used to collect the data. LTPA are connected to different modes: Walking, leisure-time MPA, and leisure-time VPA. Univariate analysis and multinomial logistic regression were used to screen for potential associations between the built environment and the leisure-time MVPA in adolescents.

RESULTS: Univariate analysis of the general demographic and built environment showed statistically significant differences in gender, residential density, accessibility, pedestrian safety, aesthetic and security (P < 0.05). Step by walking reference category, security (P < 0.05, OR = 1.131) were associated with adolescents’ leisure-time MPA, aesthetics (P < 0.05, OR = 1.187) were associated with adolescents’ leisure-time VPA, they both have a significant positive correlation.

CONCLUSION: Security was positively associated with adolescents’ leisure-time MPA, aesthetics was positively associated with adolescents’ leisure-time VPA. This suggests that built environment may associated with leisure-time MVPA of Suzhou adolescents.

PMID:37424006 | DOI:10.1186/s12889-023-16243-0