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Value of next-generation sequencing in early diagnosis of patients with tuberculous meningitis

J Neurol Sci. 2021 Jan 7;422:117310. doi: 10.1016/j.jns.2021.117310. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the value of next-generation sequencing (NGS) technology in early diagnosis of patients with tuberculous meningitis (TBM).

METHODS: 56 patients with clinically suspected TBM who came to Shandong Provincial Chest Hospital from February 2, 2018 to August 2, 2018 were prospectively included, and the clinical diagnosis and treatment outcomes were followed up. NGS was performed for the cerebrospinal fluid specimens submitted for test on the BGISEQ-100 platform of Tianjin Huada Gene Research Institute and the obtained pathogen sequences were compared with the pathogen data to get the final results. The NGS results were positive for detecting the unique matching sequence of the Mycobacterium tuberculosis (MTB) complex and negative for no unique matching sequence. Patients confirmed with TBM should have at least one of the following four items: cerebrospinal fluid MTB culture positive, smear positive, Xpert MTB/RIF test positive, or MTB nucleic acid polymerase chain reaction (PCR) test positive; clinically diagnosed patients were those with clinically suspected TBM and effective anti-tuberculosis treatment; non-TBM patients were those with other pathogenic basis or clinical exclusion of TBM. The sensitivity and specificity of NGS in early diagnosis of TBM were analyzed.

RESULTS: 22 patients were confirmed with TBM, of which 13 were positive for Xpert MTB/RIF test, 6 were positive for cerebrospinal fluid MTB culture, 5 were positive for MTB nucleic acid PCR test, 12 patients were clinically diagnosed with TBM, and there were 16 cases of non-TBM patients. Among confirmed and clinically diagnosed patients, 20 cases of MTB complex were detected by NGS technology, with a sensitivity of 58.8% (20/34) and specificity of 100% (16/16). Among confirmed patients, the sensitivity of NGS was 63.6% (14/22). Of the 50 specimens that were simultaneously subjected to traditional methods, Xpert MTB/RIF test and NGS, the specificity of the three methods was 100% (16/16) based on clinical diagnosis, and the sensitivity was 29.4% (10/34), 38.2% (13/34), and 58.8% (20/34) respectively. The difference of sensitivity between the first two detection methods and NGS was statistically significant (McNemar test, p = 0.013, x2 = 5.786 and p = 0.065, x2 = 3.273). The sensitivity of traditional methods combined with NGS was as high as 82.4% (28/34).

CONCLUSIONS: NGS technology could rapidly detect the MTB complex in cerebrospinal fluid with significant sensitivity and specificity, which could be used as an early diagnosis index of TBM. NGS combined with MTB culture could increase the detection rate.

PMID:33631643 | DOI:10.1016/j.jns.2021.117310

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Occurrence and trophic transfer of synthetic musks in the freshwater food web of a large subtropical lake

Ecotoxicol Environ Saf. 2021 Feb 22;213:112074. doi: 10.1016/j.ecoenv.2021.112074. Online ahead of print.

ABSTRACT

Synthetic musks (SMs) have drawn worldwide attention, as they are persistent, bioaccumulative, and toxic to many organisms. There is not enough information on the bioaccumulation and trophodynamic behavior of SMs in freshwater food webs to reliably understand the associated ecological risks. In this study, the concentrations of six SM congeners in fifteen aquatic species from Lake Chaohu, China, was investigated. The total concentrations of the six SMs ranged from 0.29 to 59.7 ng/g dry weight (median, 4.41) in fish muscle tissue and in the whole body tissues of small fish species and shrimps. Galaxolide (HHCB) and tonalide (AHTN) were the predominant congeners, accounting for 65.0% and 28.5% of the total SM concentration, respectively. On the whole, the total concentrations of SMs in livers and gills were 0.18-32.8 and 0.84-254 times higher than those in muscle tissues in fish species, respectively. In the food web of Lake Chaohu, cashmeran (DPMI) and HHCB showed a trend towards trophic magnification, and AHTN tended to show trophic dilution, but these trends were not statistically significant. This suggested that the trophic transfer of these chemicals through the food web was strongly influenced by many factors, including tissue-specific distribution within individuals at higher trophic levels. More investigation into the trophic transfer of SMs in aquatic ecosystems and the factors influencing uptake is needed.

PMID:33631637 | DOI:10.1016/j.ecoenv.2021.112074

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Nevin Manimala Statistics

The legacy of redlining: Associations between historical neighborhood mapping and contemporary tobacco retailer density in Ohio

Health Place. 2021 Feb 22;68:102529. doi: 10.1016/j.healthplace.2021.102529. Online ahead of print.

ABSTRACT

In the 1930s United States, urban neighborhoods were graded on their desirability for investment (often based on race), a process known as “redlining.” This study examined how historical redlining relates to current disparities in an important health determinant: tobacco retailer density. Analyses were conducted for thirteen Ohio cities using negative binomial models that accounted for retailer spatial dependence and controlled for present-day sociodemographic characteristics. Findings indicated that as grades increased from “Best” to “Still Desirable” to “Definitely Declining” and “Hazardous,” retailer density increased monotonically. These results highlight the persisting impacts of redlining and how disparities, once intentionally created, can be perpetuated over time.

PMID:33631601 | DOI:10.1016/j.healthplace.2021.102529

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Learning of spatial configurations of a co-actor’s attended objects in joint visual search

Acta Psychol (Amst). 2021 Feb 22;215:103274. doi: 10.1016/j.actpsy.2021.103274. Online ahead of print.

ABSTRACT

Regarding the effects of joint action on visual memory, previous research has focused on the memory of a single object that a participant and their co-actor attended together (i.e., a shared situation), while the literature on memory has demonstrated that spatial regularity composed of multiple objects can also be learned. We aimed to examine whether the visuospatial regularity of the co-actor’s attended objects could be strongly encoded. We repeatedly presented the same configuration of two targets and two sets of distractors in different colors (i.e., blue and red) to participants. In Experiment 1, pairs of participants simultaneously searched for the same target in the joint group while individual participants searched for the target alone in the single group. As a result, greater facilitation in reaction time was observed in earlier epochs in the joint group, reinforced by the learning of visuospatial regularity, compared to the single group. Experiment 2 examined whether the co-actor’s attended context could be strongly encoded although two persons simultaneously searched for different targets (i.e., parallel situation) such that one searched for the blue target and the other for the red target. The results showed no evidence regarding participants’ learning visuospatial regularity of the co-actor’s attended objects, indicating that co-actor’s learning information cannot be shared in this situation. This study revealed that facilitation of visuospatial learning in joint action would require two individuals to attend to the same objects when they perform the task.

PMID:33631557 | DOI:10.1016/j.actpsy.2021.103274

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Telomerase reverse transcriptase promoter mutation- and O6-methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link?

Eur J Cancer. 2021 Feb 22;147:84-94. doi: 10.1016/j.ejca.2021.01.014. Online ahead of print.

ABSTRACT

AIM OF THE STUDY: Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on the prognostic role of the MGMT status in patients with glioblastoma.

METHODS: MGMT promoter methylation and TERT promoter mutation status were retrospectively assessed in a prospective cohort of patients with IDH-wild-type glioblastoma of the German Glioma Network (GGN) (n = 298) and an independent retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n = 302).

RESULTS: In the GGN cohort, but not in the Düsseldorf/Zurich cohort, TERT promoter mutation was moderately associated with inferior outcomes in patients with MGMT promoter-unmethylated tumours (hazard ratio 1.74; 95% confidence interval: 1.07-2.82; p = 0.026). TERT promoter mutations were not associated with better outcomes in patients with MGMT promoter-methylated tumours in either cohort. The two different TERT promoter hotspot mutations (C228T and C250T) were not linked to distinct outcomes.

CONCLUSIONS: Analysis of two independent cohorts of patients with glioblastoma did not confirm previous data, suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in patients with IDH-wild-type glioblastoma.

PMID:33631540 | DOI:10.1016/j.ejca.2021.01.014

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Does older subjective age predict poorer cognitive function and higher risk of dementia in middle-aged and older adults?

Psychiatry Res. 2021 Feb 15;298:113807. doi: 10.1016/j.psychres.2021.113807. Online ahead of print.

ABSTRACT

As a biopsychosocial marker of aging, subjective age (i.e., the age individuals feel regardless of their actual age) was related to many health issues in the elderly. The purpose of this study is to investigate whether subjective age is associated with subsequent cognition and dementia risk in middle-aged and older adults. Samples were drawn from the English Longitudinal Study of Ageing (ELSA). Participants reported their subjective ages at the baseline (2004/2005), and their cognitive functions were measured after 10 years (2014/2015). Newly diagnosed dementias were recorded between 2006/2007 to 2014/2015. Overall, 6,475 adults aged 50 years or older were included in the current analyses. The relationship between subjective age reported at baseline and cognition assessed ten years later was modeled using multiple linear regression models. Compared to participants who reported a younger subjective age, those who reported an older subjective age were more likely to have poorer cognition after ten years (β = -0.705, P = .002 for memory, β = -1.567, P = .001 for executive function). A Cox proportional hazard regression model suggested that older subjective age was an independent risk factor for incident dementia (HR = 1.737, 95% CI =1.060-2.848). Other than chronological age, subjective age could also be considered as an important predictor for the development of cognitive dysfunction.

PMID:33631534 | DOI:10.1016/j.psychres.2021.113807

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Incidence and impact of disseminated intravascular coagulation in COVID-19 a systematic review and meta-analysis

Thromb Res. 2021 Feb 17;201:23-29. doi: 10.1016/j.thromres.2021.02.010. Online ahead of print.

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is a novel infectious disease, with significant morbidity and mortality. This meta-analysis is to evaluate the prevalence of disseminated intravascular coagulation (DIC) in COVID-19 patients and to determine the association of DIC with the severity and prognosis of COVID-19.

METHODS: We searched the PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) database until August 12, 2020. The meta-analysis was performed using Stata 16.0 software.

RESULTS: 14 studies were included in our meta-analysis. The pooled analysis revealed that the incidence of COVID-19 patients developing DIC was 3% (95%: 1%-5%, P < 0.001). In addition, deaths were more likely to be associated with DIC (Log OR = 2.46, 95% CI: 0.94-3.99, P < 0.001) with statistical significance.

CONCLUSIONS: DIC is associated with the severity and poor prognosis of COVID-19 patients. Therefore, attention should be paid to coagulation dysfunction in COVID-19 patients. Monitoring of coagulation indicators may improve the prognosis of COVID-19 inpatients.

PMID:33631519 | DOI:10.1016/j.thromres.2021.02.010

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Can pulse steroid therapy increase the risk of infection by COVID-19 in patients with multiple sclerosis?

Clin Neurol Neurosurg. 2021 Feb 15;203:106563. doi: 10.1016/j.clineuro.2021.106563. Online ahead of print.

ABSTRACT

BACKGROUND: Iran is one of the countries with a high prevalence of multiple sclerosis (MS) and COVID-19.MS patients receiving the immunomodulatory or immunosuppressive therapy have a higher risk of infection. Due to the significance of determining the risk factors for getting COVID-19 among MS patients, the present study was designed to assess the risk of infection following the pulse steroid therapy.

METHODS: This cross-sectional study included all MS patients that received corticosteroids in Tehran from December 2019 to August 2020 during the COVID-19 pandemic spread. The subjects’ clinical records including their sex, age, the type of MS, the type of medication, the number of days using corticosteroids, the status of prednisolone intake, and the number of days receiving prednisolone after the corticosteroid therapy were obtained. Moreover, main outcomes such as COVID-19 infection and the occurrence of death were recorded by patient’s visits and follow-up phone calls. COVID-19 infection was confirmed by physicians according to the clinical performance of RT-PCR, chest CT scan, and antibody tests.

RESULTS: Totally, 133 MS cases participated in the study, and the pulse therapy was completed for 104 (78.2%) patients up to 5-7 days. 89 (66.9%) cases used the prednisolone tablet following the pulse therapy. Overall, the infection by Covid-19 was observed in 8 (6%) cases, among whom 5 (71.4%) cases received the pulse therapy for 5-7 days and 4 (57.1%) cases had a history of taking the prednisolone tablet. The age of less than 40 years (OR = 1.03; 95% CI (0.23-4.51)), male sex (OR = 0.35; 95% CI (0.03-3.34)), and the RRMS type (OR = 2.87; 95% CI (0.52-15.72)) had no effect on the risk of Covid-19 infection. In addition, there was not statistically significant difference between subjects with the short-term pulse therapy duration (3-4 days) (OR 0.68 (0.12-3.74) and those with the long-term pulse therapy duration (5-7 days). Similarly, no statistically significant difference was observed between subjects taking prednisolone (OR = 1.62 (0.34-7.61) and those not taking prednisolone. Furthermore, there was no significant association between different medication groups and the risk of Covid-19 infection (p < 0.05). No death occurred due to Covid-19 infection among the subjects.

CONCLUSION: COVID-19 infection was more common among female and younger patients as well as patients with a longer duration of the pulse therapy and prednisolone intake. There was no significant association between the pulse steroid therapy in MS patients and the risk of infection by COVID-19 in the Iranian population.

PMID:33631509 | DOI:10.1016/j.clineuro.2021.106563

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Evaluation of the cognitive impairments and depressive symptoms in patients with Parkinson’s disease: A case-control study from Iran

Clin Neurol Neurosurg. 2021 Feb 8;203:106549. doi: 10.1016/j.clineuro.2021.106549. Online ahead of print.

ABSTRACT

BACKGROUND: Parkinson’s disease is a progressive neurodegenerative disease and the second most common neurological disease in the world, which usually affects people mainly in later years of life. Cognitive impairments and depressive symptoms are important symptoms in these patients that are associated with a poor prognosis. The study will focus on the original data regarding the cognitive impairments and depressive symptoms in patients with Parkinson’s disease and control group.

METHODS: In a case-control study, a total of 100 Parkinson’s patients who were hospitalized in Rouhani Hospital and 200 non-Parkinson’s people (control group) from Amirkola Health and aging project (AHAP) Marras et al., Babol, Iran were enrolled between September 2019 to February 2020. Data were collected by simple random sampling. Data were collected using a four-part questionnaire, including demographic characteristics, Unified Parkinson Disease Rating Scale (UPDRS), Modified Hoehn and Yahr staging Scale (MHYSS), Mini-M ental State Examination (MMSE) and Geriatric Depression Scale (GDS). P-value less than 0.05 was considered as significant RESULTS: A total of 300 persons were enrolled in the study. The mean age of Parkinson’s patients and non-Parkinson’s people was 70.34 ± 7.76 and 70.87 ± 7.59 years, respectively. The mean MMSE score in Parkinson’s and non-Parkinson’s people was 24.80 ± 4.53 and 25.40 ± 3.1, respectively (p = 0.182). The mean GDS score in Parkinson’s and non-Parkinson’s people was 7.06 ± 4.06 and 4.31 ± 3.47, respectively (p = 0.001). There was a statistically significant relationship between depressive symptoms and cognitive impairments with disease severity (p = 0.022 and p = 0.012, respectively). In addition, variables, such as age and the education level were associated with cognitive impairments (p = 0.001 and p = 0.021, respectively), but these variables were not significantly associated with depressive symptoms (p = 0.843 and p = 0.411, respectively). There was a significant relationship between depressive symptoms and cognitive impairment in Parkinson’s patients and the control group (p = 0.001 and p = 0.003, respectively).

CONCLUSIONS: Cognitive impairments and depressive symptoms were significantly associated with an increase in the severity of Parkinson’s disease, and also, depressive symptoms in Parkinson’s patients was associated with an increase in cognitive impairments.

PMID:33631508 | DOI:10.1016/j.clineuro.2021.106549

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Corrigendum to “The neuroprotective effect of deep brain stimulation at nucleus basalis of Meynert in transgenic mice with Alzheimer’s disease” [Brain Stimul 12 (2019) 161-174]

Brain Stimul. 2021 Feb 22;14(2):389-390. doi: 10.1016/j.brs.2021.01.019. Online ahead of print.

NO ABSTRACT

PMID:33631486 | DOI:10.1016/j.brs.2021.01.019