Nevin Manimala

PLoS One. 2023 Mar 30;18(3):e0283313. doi: 10.1371/journal.pone.0283313. eCollection 2023.

ABSTRACT

Statistical physics is widely used to study the nonlinear mechanical behaviors of rock. For the limitations of existing statistical damage models and Weibull distribution, a new statistical damage with lateral damage is established. In addition, by introducing the maximum entropy distribution function and the strict constraint on damage variable, a expression of the damage variable matching the proposed model is obtained. Through comparing with the experimental results and the other two statistical damage models, the rationality of the maximum entropy statistical damage model is confirmed. The proposed model can better reflect the strain-softening behavior for rocks and respond to the residual strength, which provides a theoretical reference for practical engineering construction and design.

PMID:36996233 | DOI:10.1371/journal.pone.0283313

Alzheimers Res Ther. 2023 Mar 29;15(1):67. doi: 10.1186/s13195-022-01135-z.

ABSTRACT

BACKGROUND: Individuals from minority ethnic groups in the UK are thought to be at higher risk of developing dementia while facing additional barriers to receiving timely care. However, few studies in the UK have examined if there are ethnic disparities in survival once individuals receive a dementia diagnosis.

METHODS: We conducted a retrospective cohort study using electronic health record data of individuals diagnosed with dementia from a large secondary mental healthcare provider in London. Patients from Black African, Black Caribbean, South Asian, White British, and White Irish ethnic backgrounds were followed up for a 10-year period between 01 January 2008 and 31 December 2017. Data were linked to death certificate data from the Office of National Statistics to determine survival from dementia diagnosis. Standardised mortality ratios were calculated to estimate excess deaths in each ethnicity group as compared to the gender- and age-standardised population of England and Wales. We used Cox regression models to compare survival after dementia diagnosis across each ethnicity group.

RESULTS: Mortality was elevated at least twofold across all ethnicity groups with dementia compared to the general population in England and Wales. Risk of death was lower in Black Caribbean, Black African, White Irish, and South Asian groups as compared to the White British population, even after adjusting for age, gender, neighbourhood-level deprivation, indicators of mental and physical comorbidities. Risk of death remained lower after additionally accounting for those who emigrated out of the cohort.

CONCLUSIONS: While mortality in dementia is elevated across all ethnic groups as compared to the general population, reasons for longer survival in minority ethnic groups in the UK as compared to the White British group are unclear and merit further exploration. Implications of longer survival, including carer burden and costs, should be considered in policy and planning to ensure adequate support for families and carers of individuals with dementia.

PMID:36991518 | DOI:10.1186/s13195-022-01135-z

Hum Genomics. 2023 Mar 30;17(1):31. doi: 10.1186/s40246-023-00478-4.

ABSTRACT

BACKGROUND: Genome-wide association studies (GWAS) have highlighted over 200 autosomal variants associated with multiple sclerosis (MS). However, variants in non-coding regions such as those encoding microRNAs have not been explored thoroughly, despite strong evidence of microRNA dysregulation in MS patients and model organisms. This study explores the effect of microRNA-associated variants in MS, through the largest publicly available GWAS, which involved 47,429 MS cases and 68,374 controls.

METHODS: We identified SNPs within the coordinates of microRNAs, ± 5-kb microRNA flanking regions and predicted 3’UTR target-binding sites using miRBase v22, TargetScan 7.0 RNA22 v2.0 and dbSNP v151. We established the subset of microRNA-associated SNPs which were tested in the summary statistics of the largest MS GWAS by intersecting these datasets. Next, we prioritised those microRNA-associated SNPs which are among known MS susceptibility SNPs, are in strong linkage disequilibrium with the former or meet a microRNA-specific Bonferroni-corrected threshold. Finally, we predicted the effects of those prioritised SNPs on their microRNAs and 3’UTR target-binding sites using TargetScan v7.0, miRVaS and ADmiRE.

RESULTS: We have identified 30 candidate microRNA-associated variants which meet at least one of our prioritisation criteria. Among these, we highlighted one microRNA variant rs1414273 (MIR548AC) and four 3’UTR microRNA-binding site variants within SLC2A4RG (rs6742), CD27 (rs1059501), MMEL1 (rs881640) and BCL2L13 (rs2587100). We determined changes to the predicted microRNA stability and binding site recognition of these microRNA and target sites.

CONCLUSIONS: We have systematically examined the functional, structural and regulatory effects of candidate MS variants among microRNAs and 3’UTR targets. This analysis allowed us to identify candidate microRNA-associated MS SNPs and highlights the value of prioritising non-coding RNA variation in GWAS. These candidate SNPs could influence microRNA regulation in MS patients. Our study is the first thorough investigation of both microRNA and 3’UTR target-binding site variation in multiple sclerosis using GWAS summary statistics.

PMID:36991503 | DOI:10.1186/s40246-023-00478-4

J Cannabis Res. 2023 Mar 30;5(1):11. doi: 10.1186/s42238-023-00179-8.

ABSTRACT

INTRODUCTION: Cannabidiol (CBD) is a potential therapeutic for pain management. Yet, there exists a dearth of studies of its tolerability and efficacy, especially in special populations. Former elite athletes are a special population both susceptible to chronic pain and also highly trained and attuned to assess medication tolerability concerns. The purpose of the present open-label pilot study was to assess the tolerability of CBD in this population.

MATERIALS AND METHODS: Retrospective analysis was conducted in deidentified data from 20 individuals who were all previously professional athletes in US/American football, track and field, or basketball, with careers ranging from 4 to 10 years. Participants received topical CBD (10 mg twice daily by controlled dispenser) for chronic pain resulting from acute lower extremity injuries. Assessments of tolerability and secondary analyses of pain, pain-related disability, and activities of daily living were collected by self-report over the 6-week study period. Data were analyzed by descriptive statistics, pairwise t-test, and linear regression.

RESULTS: Seventy percent of participants completed the study. Of the individuals who completed the study, 50% reported minor adverse effects, none of which required medical attention, and 50% did not report any adverse effects. The mostly commonly reported effects were skin dryness (43% of study completers) and skin rash (21% of study completers), which rapidly resolved. There was a significant improvement in self-reported pain levels (intake mean 3.5 ± 0.29; exit mean 1.7 ± 0.23; P < 0.001) and pain-related disability, including family and home responsibilities, life support activities, occupational activities, recreational activities, self-care, sexual function, and social activities (all P < 0.001).

DISCUSSION: To the best of our knowledge, this is the first study to assess CBD treatment in elite athletes, who are disproportionally susceptible to disabling injuries. Topical administration of CBD was tolerated well by this population and resulted in only minor adverse effects. As elite athletes are trained and attuned to assess their own bodies due to their professional lives, this population is likely to detect tolerability concerns. However, this study was limited to a convenience sample and self-reported data. These pilot findings warrant further study of topical CBD in randomized and controlled studies of elite athletes.

PMID:36991501 | DOI:10.1186/s42238-023-00179-8

BMC Med Genomics. 2023 Mar 29;16(1):64. doi: 10.1186/s12920-023-01488-w.

ABSTRACT

BACKGROUND: Detection of appropriate receptor proteins and drug agents are equally important in the case of drug discovery and development for any disease. In this study, an attempt was made to explore colorectal cancer (CRC) causing molecular signatures as receptors and drug agents as inhibitors by using integrated statistics and bioinformatics approaches.

METHODS: To identify the important genes that are involved in the initiation and progression of CRC, four microarray datasets (GSE9348, GSE110224, GSE23878, and GSE35279) and an RNA_Seq profiles (GSE50760) were downloaded from the Gene Expression Omnibus database. The datasets were analyzed by a statistical r-package of LIMMA to identify common differentially expressed genes (cDEGs). The key genes (KGs) of cDEGs were detected by using the five topological measures in the protein-protein interaction network analysis. Then we performed in-silico validation for CRC-causing KGs by using different web-tools and independent databases. We also disclosed the transcriptional and post-transcriptional regulatory factors of KGs by interaction network analysis of KGs with transcription factors (TFs) and micro-RNAs. Finally, we suggested our proposed KGs-guided computationally more effective candidate drug molecules compared to other published drugs by cross-validation with the state-of-the-art alternatives of top-ranked independent receptor proteins.

RESULTS: We identified 50 common differentially expressed genes (cDEGs) from five gene expression profile datasets, where 31 cDEGs were downregulated, and the rest 19 were up-regulated. Then we identified 11 cDEGs (CXCL8, CEMIP, MMP7, CA4, ADH1C, GUCA2A, GUCA2B, ZG16, CLCA4, MS4A12 and CLDN1) as the KGs. Different pertinent bioinformatic analyses (box plot, survival probability curves, DNA methylation, correlation with immune infiltration levels, diseases-KGs interaction, GO and KEGG pathways) based on independent databases directly or indirectly showed that these KGs are significantly associated with CRC progression. We also detected four TFs proteins (FOXC1, YY1, GATA2 and NFKB) and eight microRNAs (hsa-mir-16-5p, hsa-mir-195-5p, hsa-mir-203a-3p, hsa-mir-34a-5p, hsa-mir-107, hsa-mir-27a-3p, hsa-mir-429, and hsa-mir-335-5p) as the key transcriptional and post-transcriptional regulators of KGs. Finally, our proposed 15 molecular signatures including 11 KGs and 4 key TFs-proteins guided 9 small molecules (Cyclosporin A, Manzamine A, Cardidigin, Staurosporine, Benzo[A]Pyrene, Sitosterol, Nocardiopsis Sp, Troglitazone, and Riccardin D) were recommended as the top-ranked candidate therapeutic agents for the treatment against CRC.

CONCLUSION: The findings of this study recommended that our proposed target proteins and agents might be considered as the potential diagnostic, prognostic and therapeutic signatures for CRC.

PMID:36991484 | DOI:10.1186/s12920-023-01488-w

Arthritis Res Ther. 2023 Mar 29;25(1):51. doi: 10.1186/s13075-023-03033-7.

ABSTRACT

OBJECTIVE: To estimate the global prevalence of hip osteoarthritis (HOA) through a systematic review and meta-analysis, and to determine by regression analysis the respective relationships between age and sex, and sex and prevalence.

METHODS: EMBASE, PubMed, Web of science, CINAHL, and SCOPUS were searched from inception until August 2022. Two authors independently extracted data and assessed the quality of the retrieved literature. Random-effects meta-analysis was performed to derive the pooled prevalence. Variations in the prevalence estimate in different subgroups, including diagnostic methods, region, and patient sex, were examined by subgroup meta-analysis. Meta-regression was used to construct the age-specific prevalence of HOA.

RESULTS: A total of 31 studies were included in our analysis, involving 326,463 participants. Quality evaluation showed that all studies included in the analysis had a Quality Score of at least 4. The most frequently used method for diagnosing HOA was the Kellgren-Lawrence (K-L) grade classification, accounting for 19/31 (61.3%) studies. The pooled prevalence of HOA diagnosed based on the K-L grade ≥ 2 criterion was 8.55% (95% CI 4.85-13.18) worldwide. The prevalence of HOA was lowest in Africa at 1.20% (95% CI: 0.40-2.38), followed by Asia at 4.26% (95% CI 0.02-14.93) and North America at 7.95% (95% CI 1.98-17.36), and highest in Europe at 12.59% (95% CI 7.17-19.25). There was no statistically significant difference in HOA prevalence between men (9.42%, 95% CI:4.81-15.34) and women at (7.94%, 95% CI: 3.57-13.81). The regression model showed a correlation between age and the prevalence of HOA.

CONCLUSION: HOA has high prevalence worldwide and increases with age. The prevalence varies significantly by region but not by patient sex. High-quality epidemiological studies are warranted to more accurately estimate the prevalence of HOA.

PMID:36991481 | DOI:10.1186/s13075-023-03033-7

BMC Endocr Disord. 2023 Mar 29;23(1):69. doi: 10.1186/s12902-023-01325-2.

ABSTRACT

BACKGROUND: A high resting heart rate (HR) has been associated with an increased risk of diabetes mellitus. This study explored the association between initial in-hospital HR and glycemic control in patients with acute ischemic stroke (AIS) and diabetes mellitus.

METHODS: We analyzed data from 4,715 patients with AIS and type 2 diabetes mellitus enrolled in the Chang Gung Research Database between January 2010 and September 2018. The study outcome was unfavorable glycemic control, defined as glycated hemoglobin (HbA1c) ≥ 7%. In statistical analyses, the mean initial in-hospital HR was used as both a continuous and categorical variable. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression analysis. The associations between the HR subgroups and HbA1c levels were analyzed using a generalized linear model.

RESULTS: Compared with the reference group (HR < 60 bpm), the adjusted ORs for unfavorable glycemic control were 1.093 (95% CI 0.786-1.519) for an HR of 60-69 bpm, 1.370 (95% CI 0.991-1.892) for an HR of 70-79 bpm, and 1.608 (95% CI 1.145-2.257) for an HR of ≥ 80 bpm. Even after adjusting for possible confounders, the HbA1c levels after admission and discharge among diabetic stroke patients increased significantly in the subgroups with higher HRs (p < 0.001).

CONCLUSIONS: High initial in-hospital HR is associated with unfavorable glycemic control in patients with AIS and diabetes mellitus, particularly in those with an HR of ≥ 80 bpm, compared with those with an HR of < 60 bpm.

PMID:36991469 | DOI:10.1186/s12902-023-01325-2

World J Emerg Surg. 2023 Mar 29;18(1):25. doi: 10.1186/s13017-023-00495-7.

ABSTRACT

BACKGROUND: In the last two decades, there have been major improvements in the trauma system in the United Arab Emirates (UAE). We aimed to study the changes in the incidence, type, severity, and outcome of trauma of hospitalized child-bearing age women in Al-Ain City, UAE, during that time.

METHODS: Data from two separate trauma registries of Al-Ain Hospital, which were prospectively collected from March 2003 to March 2006 and January 2014 to December 2017, were analyzed retrospectively. All women aged 15-49 years were studied. The two periods were compared.

RESULTS: Trauma incidence of hospitalized child-bearing age women was reduced by 47% during the second period. There were no significant differences in the mechanism of injury between the two periods. Road traffic collision was the main cause of injury (44% and 42%, respectively) followed by fall down (26.1% and 30.8%, respectively). The location of injury was significantly different (p = 0.018), with a strong trend of more home injuries in the second period (52.8% compared with 44%, p = 0.06). There was a strong statistical trend of mild traumatic brain injury (GCS 13-15) in the second period (p = 0.067, Fisher’s Exact test). Those who had normal GCS of 15 were significantly higher in the second period compared with those in the first period (95.3% compared with 86.4%, p < 0.001, Fisher’s Exact test) despite having more anatomical injury severity of the head (AIS 2 (1-5) compared with 1 (1-5), p = 0.025). The NISS was significantly higher in the second period (median (range) NISS 5 (1-45) compared with 4 (1-75), p = 0.02). Despite that, mortality was the same (1.6% compared with 1.7%, p = 0.99) while the length of hospital stay was significantly less (mean (SD) 5.6 (6.3) days compared with 10.6 (13.6) days, p < 0.0001).

CONCLUSIONS: The incidence of trauma in hospitalized child-bearing-age women was reduced by 47% over the last 15 years. Road traffic collisions and falls are the leading cause of injury in our setting. Home injuries increased over time. The mortality remained stable despite the increased severity of injured patients. More injury prevention efforts should target home injuries.

PMID:36991466 | DOI:10.1186/s13017-023-00495-7

BMC Womens Health. 2023 Mar 29;23(1):142. doi: 10.1186/s12905-023-02305-3.

ABSTRACT

PURPOSE: There is currently no information on how caregivers for women diagnosed with cervical cancer in Guatemala, particularly daughters, are affected by their supportive role. This study’s objective was to describe the support role of caregivers in the country, with a focus on daughters with a mother diagnosed with cervical cancer.

METHODS: This analysis utilizes data from a cross-sectional study which aimed to understand pathways to cervical cancer care. Women seeking cervical cancer treatment at the Instituto de Cancerologia (INCAN) in Guatemala City, Guatemala and their companions were surveyed. Descriptive statistics were calculated.

RESULTS: One hundred forty-five women seeking treatment and 71 companions participated in the study. Patient’s daughters were most frequently reported as the person who provided the most support (51%) and as the most reported to have encouraged the patient to seek care. Furthermore, daughters were noted as the person most reported to fulfill the major household and livelihood roles of the patient while they were seeking or receiving treatment (38.0%). Most daughters reported that they were missing housework (77%), childcare (63%), and income-earning activities (60%) to attend the appointment with their mothers.

CONCLUSION: Our study suggests that in Guatemala cervical cancer patient’s daughters have a significant support role in their mother’s cancer diagnosis. Furthermore, we found that while caring for their mothers, daughters in Guatemala are often unable to participate in their primary labor activities. This highlights the additional burden that cervical cancer has on women in Latin America.

PMID:36991461 | DOI:10.1186/s12905-023-02305-3

J Orthop Surg Res. 2023 Mar 30;18(1):259. doi: 10.1186/s13018-023-03744-2.

ABSTRACT

BACKGROUND: This paper aimed to propose a modified technique of bone transport. An annular frame combined with a retrograde tibiotalocalcaneal arthrodesis nail was used in this novel technique for treating large distal tibial periarticular osteomyelitis and associated defects.

METHODS: Our team conducted a retrospective research. Forty-three patients with large distal tibial periarticular bone loss were involved in this study. Sixteen patients were treated using the modified hybrid transport technique (MHT group) while 27 were subjected to traditional bone transport (BT group). The mean bone loss was 7.8 ± 2.4 cm in the MHT group and 7.6 ± 2.6 cm in the BT group. The external fixation index, time in transport frame, self-rating anxiety scale, bone healing results and postoperative complications were recorded.

RESULTS: The mean time in frame for the MHT group was 3.6 ± 1.5 months, while that of the BT group was 10.3 ± 2.7 months (p < 0.05). The mean external fixation index of MHT group was 0.46 ± 0.08 months/cm versus 1.38 ± 0.24 months/cm of the BT group (p < 0.05). There was no statistical difference for the bone healing results between the MHT and BT groups (p = 0.856). The self-rating anxiety scale and total complication incidence of the MHT group were significantly lower than that of BT patients (p < 0.05).

CONCLUSION: Compared to the traditional BT technique, our modified hybrid transport technique showed better clinical outcomes for treating large distal tibial periarticular bone loss, including less time in transport frame, lower external fixation index and complication incidence. Therefore, this modified technique should be further promoted and developed.

PMID:36991442 | DOI:10.1186/s13018-023-03744-2