Analysis of Clostridium beijerinckii NCIMB 8052's transcriptional response to ferulic acid and its application to enhance the strain tolerance

Background: Plant-based cellulose presents the best source of renewable sugars for biofuel production. However, the lignin associated with plant cellulose presents a hurdle as hydrolysis of this component leads to the production of inhibitory compounds, such as ferulic acid. Results: The impacts of ferulic acid, a phenolic compound commonly found in lignin hydrolysates, on the growth, solvent production, and transcriptional responses of Clostridium beijerinckii NCIMB 8052 were determined. Addition of ferulic acid to growing cultures resulted in a decrease in the growth and solvent production by 30% and 25%, respectively, when compared to the control cultures. To better understand the toxicity of this compound, microarray analyses were performed using samples taken from these cultures at three different growth states. Several gene ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified showing significant change at each status, including ATP-binding cassette (ABC) transporters, two component system, and oxidoreductase activity. Moreover, genes related with efflux systems and heat shock proteins were also strongly up-regulated. Among these, expression of the groESL operon was induced by more than fourfold and was consequently selected to improve C. beijerinckii tolerance to ferulic acid. Real-time quantitative PCR (RT-qPCR) analysis confirmed that C. beijerinckii harboring the plasmid, pSAAT-ptb_Gro, had a two-to fivefold increased groESL operon expression during growth of these cultures. Moreover, this strain was more tolerant to ferulic acid as the growth of this recombinant strain and its bioconversion of glucose into solvents were both improved. Conclusions: Using transcriptomics, we identified numerous genes that are differentially expressed when C. beijerinckii cultures were exposed to ferulic acid for varying amounts of time. The operon expressing groESL was consistently up-regulated, suggesting that this gene cluster may contribute to strain tolerance. This was confirmed as recombinant cultures showed both an enhanced growth and solvent yield in the presence of 0.5 g/L ferulic acidopen00

The Interplay of Variants Near LEKR and CCNL1 and Social Stress in Relation to Birth Size

Background We previously identified via a genome wide association study variants near LEKR and CCNL1 and in the ADCY5 genes lead to lower birthweight. Here, we study the impact of these variants and social stress during pregnancy, defined as social adversity and neighborhood disparity, on infant birth size. We aimed to determine whether the addition of genetic variance magnified the observed associations. Methodology/Principal Findings We analyzed data from the Northern Finland Birth Cohort 1986 (n = 5369). Social adversity was defined by young maternal age (<20 years), low maternal education (<11 years), and/or single marital status. Neighborhood social disparity was assessed by discrepancy between neighborhoods relative to personal socio-economic status. These variables are indicative of social and socioeconomic stress, but also of biological risk. The adjusted multiple regression analysis showed smaller birth size in both infants of mothers who experienced social adversity (birthweight by −40.4 g, 95%CI −61.4, −19.5; birth length −0.14 cm, 95%CI −0.23, −0.05; head circumference −0.09 cm 95%CI −0.15, −0.02) and neighborhood disparity (birthweight −28.8 g, 95%CI −47.7, −10.0; birth length −0.12 cm, 95%CI −0.20, −0.05). The birthweight-lowering risk allele (SNP rs900400 near LEKR and CCNL1) magnified this association in an additive manner. However, likely due to sample size restriction, this association was not significant for the SNP rs9883204 in ADCY5. Birth size difference due to social stress was greater in the presence of birthweight-lowering alleles. Conclusions/Significance Social adversity, neighborhood disparity, and genetic variants have independent associations with infant birth size in the mutually adjusted analyses. If the newborn carried a risk allele rs900400 near LEKR/CCNL1, the impact of stress on birth size was stronger. These observations give support to the hypothesis that individuals with genetic or other biological risk are more vulnerable to environmental influences. Our study indicates the need for further research to understand the mechanisms by which genes impact individual vulnerability to environmental insults

Patterns and associates of cognitive function, psychosocial wellbeing and health in the Lothian Birth Cohort 1936

BACKGROUND: Cognitive function, psychosocial wellbeing and health are important domains of function. Consistencies and inconsistencies in patterns of wellbeing across these domains may be informative about wellbeing in old age and the ways it is manifested amongst individuals. In this study we investigated whether there were groups of individuals with different profiles of scores across these domains. We also aimed to identify characteristics of any evident groups by comparing them on variables that were not used in identifying the groups. METHODS: The sample was the Lothian Birth Cohort 1936, which included 1091 participants born in 1936. They are a community-dwelling, narrow-age-range sample of 70-year-olds. Most had taken part in the Scottish Mental Survey 1947 at an average age of 11, making available a measure of childhood intelligence. We used latent class analysis (LCA) to explore possible profiles using 9 variables indicating cognitive functioning, psychosocial wellbeing and health status. Demographic, personality, and lifestyle variables – none of which were used in the LCA – were used to characterize the resulting profile groups. RESULTS: We accepted a 3-group solution, which we labeled High Wellbeing (65.3%), Low Cognition (20.3%), and Low Bio-Psychosocial (14.5%). Notably, the High Wellbeing group had significantly higher childhood IQ, lower Neuroticism scores, and a lower percentage of current smokers than the other 2 groups. CONCLUSION: The majority of individuals were functioning generally well; however, there was evidence of the presence of groups with different profiles, which may be explained in part in terms of cognitive ability differences. Results suggested that higher life-long intelligence, personality traits associated with less mental distress, and basic health practices such as avoiding smoking are important associates of wellbeing in old age

Increased Mortality in Metal-on-Metal versus Non-Metal-on-Metal Primary Total Hip Arthroplasty at 10 Years and Longer Follow-Up: A Systematic Review and Meta-Analysis

Analysis and Stochastic

The association between comorbidities and pain, physical function and quality of life following hip and knee arthroplasty

The aim of the study was to examine the relationship between comorbidities and pain, physical function and health-related quality of life (HRQoL) after total hip arthroplasty (THA) and total knee arthroplasty (TKA). A cross-sectional retrospective survey was conducted including 19 specific comorbidities, administered in patients who underwent THA or TKA in the previous 7–22 months in one of 4 hospitals. Outcome measures included pain, physical functioning, and HRQoL. Of the 521 patients (281 THA and 240 TKA) included, 449 (86 %) had ≥1 comorbidities. The most frequently reported comorbidities (>15 %) were severe back pain; neck/shoulder pain; elbow, wrist or hand pain; hypertension; incontinence of urine; hearing impairment; vision impairment; and cancer. Only the prevalence of cancer was significantly different between THA (n = 38; 14 %) and TKA (n = 52; 22 %) (p = 0.01). The associations between a higher number of comorbidities and worse outcomes were stronger in THA than in TKA. In multivariate analyses including all comorbidities with a prevalence of >5 %, in THA dizziness in combination with falling and severe back pain, and in TKA dizziness in combination with falling, vision impairments, and elbow, wrist or hand pain was associated with worse outcomes in most of the analyses. A broad range of specific comorbidities needs to be taken into account with the interpretation of patients’ health status after THA and TKA. More research including the ascertainment of comorbidities preoperatively is needed, but it is conceivable that in particular, the presence of dizziness with falling, pain in other joints, and vision impairments should be assessed and treated in order to decrease the chance of an unfavorable outcome

Survival Analysis of 3 Different Age Groups and Prognostic Factors among 402 Patients with Skeletal High-Grade Osteosarcoma. Real World Data from a Single Tertiary Sarcoma Center

Age is a known prognostic factor for many sarcoma subtypes, however in the literature there are limited data on the different risk profiles of different age groups for osteosarcoma survival. This study aims to provide an overview of survival in patients with high-grade osteosarcoma in different age groups and prognostic variables for survival and local control among the entire cohort. In this single center retrospective cohort study, 402 patients with skeletal high-grade osteosarcoma were diagnosed and treated with curative intent between 1978 and 2017 at the Leiden University Medical Center (LUMC). Prognostic factors for survival were analyzed using a Cox proportional hazard model. In this study poor overall survival (OS) and event-free survival (EFS) were associated with increasing age. Age groups, tumor size, poor histopathological response, distant metastasis (DM) at presentation and local recurrence (LR) were important independent prognostic factors influencing OS and EFS. Differences in outcome among different age groups can be partially explained by patient and treatment characteristics

Body composition and bone mineral density in craniopharyngioma patients: A longitudinal study over 10 years

Context: Patients with craniopharyngioma suffer from obesity and impaired bone health. Little is known about longitudinal changes in body composition and bone mineral density (BMD).Objective: To describe body composition and BMD (change).Design: Retrospective longitudinal study.Setting: Two Dutch/Swedish referral centers.Patients: Patients with craniopharyngioma (n = 112) with a dual X-ray absorptiometry (DXA) scan available (2 DXA scans, n = 86; median time 10.0 years; range 0.4-23.3) at age >= 18 years (58 [52%1 male, 50 [45%] childhood onset).Main outcome measures: Longitudinal changes of body composition and BMD, and associated factors of Delta Z-score (sex and age standardized).Results: BMI (from 28.8 +/- 4.9 to 31.2 +/- 5.1 kg/m(2), P< .001), fat mass index (FMI) (from 10.5 +/- 3.6 to 11.9 +/- 3.8 kg/m(2), P= .001), and fat free mass index (FFMI) (from 18.3 +/- 3.2 to 19.1 +/- 3.2 kg/m(2) , P< .001) were high at baseline and increased. Fat percentage and Z-scores of body composition did not increase, except for FFMI Z-scores (from 0.26 +/- 1.62 to 1.06 +/- 2.22, P< .001). Z-scores of total body, L2-L4, femur neck increased (mean difference 0.61 +/- 1.12, P< .001; 0.74 +/- 1.73, P< .001; 0.51 +/- 1.85, P= .02). Linear regression models for AZ-score were positively associated with growth hormone replacement therapy (GHRT) (femur neck: beta 1.45 [95% CI 0.51-2.39]); and negatively with radiotherapy (femur neck: beta -0.79 [-1.49 to -0.09]), glucocorticoid dose (total body: beta -0.06 (-0.09 to -0.02]), and medication to improve BMD (L2-L4: beta -1.06 [-1.84 to -0.28]).Conclusions: Z-scores of BMI, fat percentage, and FMI remained stable in patients with craniopharyngioma over time, while Z-scores of FFMI and BMD increased. Higher glucocorticoid dose and radiotherapy were associated with BMD loss and GHRT with increase.Development and application of statistical models for medical scientific researc