Category: Nevin Manimala

Mol Immunol. 2022 Jan 14;143:50-57. doi: 10.1016/j.molimm.2022.01.005. Online ahead of print.

ABSTRACT

Asthma is a disease with complicated network of inflammatory responses of cytokines and ImmunoglobulinE (IgE). The aim of this study was to explore the clinical characteristics, cytokine profile and plasma IgE in the Malaysian population. This is a cross-sectional study involving physician-diagnosed asthma patients (n = 287) recruited from the Chest Clinic, University of Malaya Medical Centre (UMMC). Blood (8 mL) was taken after consent was obtained. The peripheral blood leucocytes (PBL) were cultured in presence of a mitogen for 72 h to quantify cytokines [Interleukin-5(IL-5), Interleukin-9 (IL-9), Interleukin-12 Beta (IL-12ꞵ) and granulocyte-macrophage colony-stimulating factor (GM-CSF)] and plasma was used to quantify IgE levels with commercial ELISA kits. Results were compared against the same biomarkers in healthy subjects (n = 203). In addition, the amount of the biomarkers in the asthma patients were compared with their disease severity and clinical characteristics. Statistical tests in the SPSS software (Mann-Whitney U test and the Kruskal Wallis) were used to compare cytokine production and plasma IgE levels. The mean plasma IgE level was markedly higher (p < 0.0001) in asthmatics compared to controls. There were higher levels of IL-5, IL-9, IL-12ꞵ and GM-CSF (p < 0.0001) produced by cultured PBL from asthma patients compared to controls. However, our results did not expose a significant association between these cytokine levels and severity and clinical symptoms of asthma. However, there was a marked association between asthma severity and blood lymphocyte count [ꭓ²(2) = 6.745, p < 0.05]. These findings support the roles played by cytokines and IgE in the airway inflammation in asthma. The findings of this study provide new information about inflammatory cytokines in Malaysian asthma patients.

PMID:35038659 | DOI:10.1016/j.molimm.2022.01.005

J Environ Manage. 2022 Jan 14;306:114495. doi: 10.1016/j.jenvman.2022.114495. Online ahead of print.

ABSTRACT

Accelerating the development of renewable energy is seen as an effective way for achieving the goals of carbon peak and carbon neutrality. The polices of Renewable Electricity Standard (RES) and Renewable Energy Certificates (REC) play increasing and important roles in developing renewable energy. In this paper, we develop an analytical model to analyze the impacts of the interaction of RES and REC polices on the renewable energy investment levels of an electricity generation firm and the carbon emissions. Our analysis reveals several interesting insights. First, we find that the green tags price under REC policy has a non-monotonic effect on the renewable energy investment, which highly depends on the quota (i.e., the required percentage of renewable electricity consumption on total electricity consumption) under the RES policy. Specifically, when the quota in RES policy is set too high, an increase in the green tags price will increase renewable energy investment; otherwise it will reduce the electricity generation firm’s incentive to invest in renewable energy. Second, we show that the green tags price also has a non-monotonic effect on the carbon emissions. Specifically, when the quota in RES policy is set small enough, an increase in the green tags price will decrease the carbon emission. However, when the quota in RES policy is high enough, an increase in the green tags price will increase the carbon emission.

PMID:35038670 | DOI:10.1016/j.jenvman.2022.114495

Semin Arthritis Rheum. 2022 Jan 10;52:151952. doi: 10.1016/j.semarthrit.2022.151952. Online ahead of print.

ABSTRACT

BACKGROUND: There is growing evidence from case reports that methotrexate (MTX) therapy may impair bone metabolism in individual patients leading to low bone mass, atraumatic stress fractures and immobilizing bone pain – referred to as ‘MTX osteopathy’. However, the clinical features, risk factors and treatment options of this condition are still elusive.

METHODS: A systematic review was conducted according to PRISMA guidelines. Two databases (MEDLINE, Embase) were searched for published cases of MTX osteopathy in patients with rheumatic musculoskeletal diseases (RMD). Data from the included publications were extracted and descriptive statistical analysis was performed.

RESULTS: We report data from 32 studies describing 80 adult RMD patients with stress fractures in MTX osteopathy. Most cases were found in elderly women with longstanding RMD, especially rheumatoid arthritis (72.5%). MTX osteopathy commonly presented as stress fracture of the distal tibia (51.3%), calcaneus (35.0%) and proximal tibia (27.5%), mimicking arthritis in some cases. Although a majority of the patients met the densitometric criteria for osteoporosis (58.1%), typical osteoporotic fractures (e.g., vertebral fractures) were rarely seen. Patients frequently suffered from bilateral (55.0%), multiple (71.3%) and recurrent fractures (25.0%). Fractures mainly occurred at low to moderate doses of MTX therapy (45.0%). It should be noted that half (48.8%) of the patients did not receive systemic steroid therapy for at least 3 years.

CONCLUSIONS: Low-dose MTX therapy in RMD may result in atraumatic stress fractures of the lower extremity that can mimic arthritis. MTX osteopathy is characterized by a pathognomonic type of stress fractures with band- or meander-shaped appearance along the growth plate.

PMID:35038641 | DOI:10.1016/j.semarthrit.2022.151952

Comput Methods Programs Biomed. 2022 Jan 10;215:106625. doi: 10.1016/j.cmpb.2022.106625. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Promoter is a component of the gene, which can specifically bind with RNA polymerase and determine where transcription starts, and also determine the transcription efficiency of the gene. Promoters can be divided into strong promoters and weak promoters because their structures and the interaction time interval are quite different. The functional variation of the promoter can lead to a variety of diseases. Therefore, identifying promoters and their strength is necessary and has important biological significance. A novel and promising model based on deep learning is proposed to achieve it.

METHODS: In this work, we build a power model named iPro-GAN for identification of promoters and their strength. First, we collect benchmark datasets and independent datasets for training and testing. Then, Moran-based spatial auto-cross correlation method is used as feature extraction method. Finally, deep convolution generative adversarial network with 10-fold cross validation is applied for classifying. The first layer of the model is used to identify the promoter and the second layer is used to determine its type.

RESULTS: On the benchmark data set, the accuracy of the first layer predictor is 93.15%, and the accuracy of the second layer predictor is 92.30%. On the independent data set, the accuracy of the first layer predictor is 86.77%, and the accuracy of the second layer predictor is 91.66%. In particular, breakthrough progress has been made in the identification of promoters’ strength.

CONCLUSIONS: These results are far higher than the existing best predictor, which indicate that our model is serviceable and practicable to identify promoters and their strength. Furthermore, the datasets and source codes are available from this link: https://github.com/Bovbene/iPro-GAN.

PMID:35038653 | DOI:10.1016/j.cmpb.2022.106625

Soc Sci Med. 2022 Jan 5;294:114694. doi: 10.1016/j.socscimed.2021.114694. Online ahead of print.

ABSTRACT

Some evidence indicates under-perception of overweight is associated with lower levels of weight loss. This might be due to ‘visual normalisation’ of overweight through comparisons made in communities where average body mass index (BMI) is high, resulting in under-perception of overweight, which in turn, may protect against negative weight-related self-perceptions and/or reduce motivation to lose weight. Evidence in support of this hypothesis was found initially in a precision-weighted multilevel logistic regression analysis of 3729 overweight Australians aged >18 y, after adjusting for age, sex and area-level disadvantage. Participants whose BMI was -1 kg/m² or less than the community mean BMI had lower odds of weight-related dissatisfaction (OR = 0.64, 95%CI = 0.51-0.80) and perceived overweight (OR = 0.56, 95%CI = 0.45-0.70), compared with peers whose BMI was within ± 1 kg/m² of the community mean. Moreover, participants whose BMI was 1 kg/m² or greater than the community mean BMI had higher odds of weight-related dissatisfaction (OR = 1.97, 95%CI = 1.69-2.30) and perceived overweight (OR = 2.81, 95%CI = 2.41-3.28) when compared to the same reference group. These findings were consistent for men and women; however, they were attenuated towards the null and rendered statistically insignificant after adjustment for personal BMI. Overall, these results indicate that among adults who are overweight, personal BMI, rather than the relative difference between personal and community BMI, is the stronger determinant of weight-related perception and satisfaction.

PMID:35038633 | DOI:10.1016/j.socscimed.2021.114694

Public Health. 2021 Dec 9;203:100-109. doi: 10.1016/j.puhe.2021.12.003. Online ahead of print.

ABSTRACT

OBJECTIVES: Countries throughout the world are experiencing COVID-19 viral load in their populations, leading to potential transmission and infectivity of asymptomatic COVID-19 cases. The current systematic review and meta-analysis aims to investigate the role of asymptomatic infection and transmission reported in family clusters, adults, children and health care workers, globally.

STUDY DESIGN: Systematic review and meta-analysis.

METHODS: An online literature search of PubMed, Google Scholar, medRixv and BioRixv was performed using standard Boolean operators and included studies published up to 17 August 2021. For the systematic review, case reports, short communications and retrospective studies were included to ensure sufficient asymptomatic COVID-19 transmission data were reported. For the quantitative synthesis (meta-analysis), participant data from a collection of cohort studies focusing on groups of familial clusters, adults, children and health care workers were included. Inconsistency among studies was assessed using I² statistics. The data synthesis was computed using the STATA 16.0 software.

RESULTS: This study showed asymptomatic transmission among familial clusters, adults, children and health care workers of 15.72%, 29.48%, 24.09% and 0%, respectively. Overall, asymptomatic transmission was 24.51% (95% confidence interval [CI]: 14.38, 36.02) among all studied population groups, with a heterogeneity of I² = 95.30% (P < 0.001). No heterogeneity was seen in the population subgroups of children and health care workers. The risk of bias in all included studies was assessed using the Newcastle Ottawa Scale.

CONCLUSIONS: For minimising the spread of COVID-19 within the community, this study found that following the screening of asymptomatic cases and their close contacts for chest CT scan (for symptomatic patients), even after negative nucleic acid testing, it is essential to perform a rigorous epidemiological history, early isolation, social distancing and an increased quarantine period (a minimum of 14-28 days). This systematic review and meta-analysis supports the notion of asymptomatic COVID-19 infection and person-to-person transmission and suggests that this is dependent on the varying viral incubation period among individuals. Children, especially those of school age (i.e. <18 years), need to be monitored carefully and follow mitigation strategies (e.g. social distancing, hand hygiene, wearing face masks) to prevent asymptomatic community transmission of COVID-19.

PMID:35038628 | DOI:10.1016/j.puhe.2021.12.003

Public Health. 2021 Dec 18;203:110-115. doi: 10.1016/j.puhe.2021.12.010. Online ahead of print.

ABSTRACT

OBJECTIVES: At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI).

STUDY DESIGN: We undertook an ecological study using routinely available national data.

METHODS: We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure.

RESULTS: Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity.

CONCLUSIONS: These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.

PMID:35038629 | DOI:10.1016/j.puhe.2021.12.010

Early Hum Dev. 2022 Jan 14;165:105535. doi: 10.1016/j.earlhumdev.2021.105535. Online ahead of print.

ABSTRACT

BACKGROUND: Breast milk feeding (BMF) improved neurodevelopment in children born very preterm (VPT, <32 weeks of gestation), but knowledge about its effect on other mental health outcomes remains limited.

OBJECTIVE: To estimate the association of BMF practices with behavioral and emotional problems at preschool age in children born VPT.

METHODS: We studied 263 children born VPT during 2011-12 and enrolled in the Portuguese EPICE cohort. At the age of 3, information on BMF initiation and duration was collected and behavioral and emotional problems were assessed using the parents’ completed Child Behavior Checklist 1.5-5 years (CBCL/1½-5). Children were categorized for all CBCL/1½-5 sub-scales and for Diagnostic and Statistical Manual of Mental Disorders (DSM5)-oriented scales. Risk ratios were estimated to assess the association of BMF with subclinical/clinical problems, fitting a Poisson regression.

RESULTS: Behavioral or emotional subclinical/clinical problems were found in almost 20% of children (11.8% in the clinical range). BMF was consistently associated with lower adverse behavioral and emotional outcomes, particularly risks of externalizing problems, somatic complaints, aggressive behavior, as well as autism spectrum and attention deficit/hyperactivity symptoms, although the magnitude of the unadjusted risks was attenuated by adjustment for relevant confounders and wider confidence intervals included the null.

CONCLUSION: Lower exposure to BMF seemed to increase the risk of adverse behavioral and emotional outcomes at preschool age in children born VPT. These results raise questions about explanatory pathways and strengthen evidence underpinning BMF promotion for VPT children.

PMID:35038626 | DOI:10.1016/j.earlhumdev.2021.105535

J Ethnopharmacol. 2022 Jan 14:114991. doi: 10.1016/j.jep.2022.114991. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Platycodon grandiflorus (Jacq.) A.DC. (PG) is a common natural medicine with a history of thousands of years. The processing products were mainly recorded as raw, honey-processed, wine-fried, yellow-fried, and bran-fried PG, which were respectively used for different clinical purposes. Therefore, it is necessary to study the chemical composition and pharmacological activity of PG after processing.

AIM OF THE STUDY: To explore the effects of different processing methods on the composition and biological activity of PG using metabonomics and pharmacologic design.

MATERIALS AND METHODS: UPLC-QTOF-MS combined with multivariate statistical analysis was used to identify different metabolites before and after the processing of PG. Network pharmacology was used to construct the metabolite-target-disease network. CCK-8 assay, flow cytometry, and western blotting were used to detect cell viability, apoptosis, and the expression of related proteins, respectively.

RESULT: A total of 43 differentially expressed metabolites (VIP >10) were detected and identified in the analyzed groups. Based on their chemical nature, these metabolites were divided into five categories, namely, saccharolipids, flavonoid glycosides, alkynes, saponins, and lipids (including fatty acids, phospholipids, fatty aldehydes, and sterols). The content of lipids in the five processed groups (CH, FC, JZ, MZI, and MZG) was found to be higher than that in raw PG. In particular, the processing approaches explored herein increased the contents of many phospholipids, namely, glycerophosphoinositols, phosphatidic acids, and lysophosphatidyle·thanolamines. In total 8 metabolites were found by venn diagram to distinguish different processed products (metabolites 2, 6, 19, 20, 21, 26, 28, and 38). The results of network pharmacology analysis showed that the primary anti-cancer targets of 43 metabolites of PG processing products are PIK3CA, Akt, and STAT3, and based on CCK-8 assay, MZI-processed PG has a significant killing effect on A549 cells, compared to other processing techniques. Moreover, flow cytometry analysis showed that the cells treated with MZI-processed PG exhibit significantly increased cell apoptosis, and that the effect is dose-dependent. Finally, the western blots performed herein demonstrated that the MZI-processed PG effectively inhibits the expression of p-Akt and p-STAT3, which is consistent with the network pharmacology results.

CONCLUSION: Depending on the processing technique, the contents of 43 different metabolites in PG vary significantly. Specifically, the contents of phospholipids and fatty acids increase, whereas the contents of large Mw saponins decrease. Compared to the other investigated processing methods, MZI increases the potential of PG in inducing cell apoptosis and inhibiting cell proliferation by affecting the Akt and STAT3 signaling pathways. The increased levels of 3-O-β-glucopyranosyl polygalacic acid and platycoside F after honey-frying confirm these results.

PMID:35038566 | DOI:10.1016/j.jep.2022.114991

Spine J. 2022 Jan 14:S1529-9430(22)00009-2. doi: 10.1016/j.spinee.2022.01.008. Online ahead of print.

ABSTRACT

BACKGROUND CONTEXT: The ethics of industry payments to physicians and the potential impact on healthcare costs and research outcomes have long been topics of debate. Industry payments to spine surgeons are frequently scrutinized. Transparency of industry relationships with physicians provides insight into their possible impact on clinical decision-making and utilization of care.

PURPOSE: To analyze trends in medical industry payments to spine surgeons and all physicians from 2014 to 2019, and further evaluate whether specific payments to spine surgeons vary based on company size.

STUDY DESIGN/SETTING: Cross-sectional investigation of publicly reported Center for Medicare and Medicaid Services (CMS) Open Payments Database (OPD) Population Sample: All US providers listed as receiving industry payments with further evaluation of payments to neurosurgeons and orthopaedic spine surgeons.

OUTCOME MEASURES: Main measures were the magnitude and trends of industry general and research payments and subcategories of general payments, such as royalty/license and consulting fees, to spine surgeons and comparison to all physicians over the six-year period. Variations in payment patterns among spine device manufacturers with the highest reported level of spine surgeon payments in 2019.

METHODS: 2014 to 2019 publicly reported general and research industry payments in the CMS OPD were analyzed. Trends in payments to all physicians were compared to trends in payments to neurosurgeons and orthopaedic spine surgeons. Trends in payment patterns among spine device manufacturers with the highest payments in 2019 were determined. Linear regression analysis was completed to find statistically significant outcomes.

RESULTS: Our investigation found an aggregate of $42,710,365,196 general and research payments reported to all physicians over the six-year period, 2.6% ($1,112,936,203) of which went to spine surgeons. Industry general and research payments to spine surgeons decreased by 17.5% ($195,571,109, 2014; $161,283,683, 2019), while increasing by 8.7% ($6,706,208,391, 2014; $7,288,003,832, 2019) to all physicians. Industry research payments to spine surgeons were notably low each year and decreased to only 0.5% of research payments made to all physicians in 2019. Median payment received by spine surgeons as well as the overall distribution of payments to the 75^th and 95^th percentile significantly increased over the six-year period in comparison to the stable distribution of payments to all physicians. Top eight spine device manufactures with the highest level of spine surgeon payments accounted for 72.9% payments in 2014 but decreased payments by 17.6% to 2019 ($120,409,083.75, 2014; $99,283,264.49, 2019).

CONCLUSIONS: Industry general and research payments to all physicians increased from 2014 to 2019 but decreased to spine surgeons, largely due to decreasing payments from eight device manufacturers with the highest level of surgeon payments. A small subset of spine surgeons continues to receive increasing payments. The implications of decreasing investments in research by industry and of large payments made to a small group of spine surgeons bears cautious oversight, both for the future of the specialty and any impact on patient care outcomes.

PMID:35038572 | DOI:10.1016/j.spinee.2022.01.008