Objective
The aim of this study was to investigate the mediating role of child brain structure in the relationship between prenatal gestational diabetes mellitus (GDM) exposure and child adiposity.
...Methods
This was a cross‐sectional study of 9– to 10‐year‐old participants and siblings across the US. Data were obtained from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study®. Brain structure was evaluated by magnetic resonance imaging. GDM exposure was self‐reported, and discordance for GDM exposure within biological siblings was identified. Mixed effects and mediation models were used to examine associations among prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates.
Results
The sample included 8521 children (7% GDM‐exposed), among whom there were 28 sibling pairs discordant for GDM exposure. Across the entire study sample, prenatal exposure to GDM was associated with lower global and regional cortical gray matter volume (GMV) in the bilateral rostral middle frontal gyrus and superior temporal gyrus. GDM‐exposed siblings also demonstrated lower global cortical GMV than unexposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers.
Conclusions
The results identify brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM.
Global cortical gray matter volume mediating the associations between maternal diabetes exposure and child adiposity
Micturition requires precise control of bladder and urethral sphincter via parasympathetic, sympathetic and somatic motoneurons. This involves a spino-bulbospinal control circuit incorporating ...Barrington's nucleus in the pons (Barr). Ponto-spinal glutamatergic neurons that express corticotrophin-releasing hormone (CRH) form one of the largest Barr cell populations. Barr
neurons can generate bladder contractions, but it is unknown whether they act as a simple switch or provide a high-fidelity pre-parasympathetic motor drive and whether their activation can actually trigger voids. Combined opto- and chemo-genetic manipulations along with multisite extracellular recordings in urethane anaesthetised CRH
mice show that Barr
neurons provide a probabilistic drive that generates co-ordinated voids or non-voiding contractions depending on the phase of the micturition cycle. CRH itself provides negative feedback regulation of this process. These findings inform a new inferential model of autonomous micturition and emphasise the importance of the state of the spinal gating circuit in the generation of voiding.
Prostate tumors were induced in Lobund-Wistar rats by treatment with N-methyl-N-nitrosourea (MNU) and testosterone propionate (TP). Androgen receptor (AR) expression was confirmed in 16 (100%) of the ...primary prostate cancers, with strong uniform staining in well-differentiated tumors and more variable AR immunoreactivity in poorly differentiated tumors. Epithelial cell lines were established from nine of the tumors. At early passages, four of the tumor cell lines tested were strongly immunoreactive for AR; however, only two of the cell lines, E2(A) and F2, have remained AR-positive. These cell lines specifically bind$^{3}H-DHT$at 40 and 19 fmol/mg protein, respectively, and express a 110 kDa AR immunoreactive protein. Proliferation in in vitro culture of both E2(A) and F2 cells was increased in the presence of$5\alpha-dihydrotestosterone$(DHT). The antiandrogen, hydroxyflutamide was able to prevent the DHT-induced growth of E2(A) but not F2 cells. Furthermore, hydroxyflutamide alone increased proliferation of F2 cells, suggesting that the androgen signalling pathway in this cell line may be abnormal. Tumorigenicity of the AR-expressing and nonexpressing cell lines was confirmed by xenograft formation following subcutaneous inoculation into intact male nude mice. In summary, carcinogen-induced prostate tumors of Lobund-Wistar rats express AR and two of nine cell lines derived from the tumors express AR. Further evaluation of AR structure in primary prostate tumors forming spontaneously or following MNU and TP induction will determine whether, as in human prostate cancers, disease progression in Lobund-Wistar rats is associated with mutations in the AR gene.
Update on C3 glomerulopathy Barbour, Thomas D; Ruseva, Marieta M; Pickering, Matthew C
Nephrology, dialysis, transplantation,
05/2016, Letnik:
31, Številka:
5
Journal Article
Recenzirano
Odprti dostop
C3 glomerulopathy refers to a disease process in which abnormal control of complement activation, degradation or deposition results in predominant C3 fragment deposition within the glomerulus and ...glomerular damage. Recent studies have improved our understanding of its pathogenesis. The key abnormality is uncontrolled C3b amplification in the circulation and/or along the glomerular basement membrane. Family studies in which disease segregates with structurally abnormal complement factor H-related (CFHR) proteins demonstrate that abnormal CFHR proteins are important in some types of C3 glomerulopathy. This is currently thought to be due to the ability of these proteins to antagonize the major negative regulator of C3 activation, complement factor H (CFH), a process termed 'CFH de-regulation'. Recent clinicopathological cohort studies have led to further refinements in case definition, culminating in a 2013 consensus report, which provides recommendations regarding investigation and treatment. Early clinical experience with complement-targeted therapeutics, notably C5 inhibitors, has also now been published. Here, we summarize the latest developments in C3 glomerulopathy.
Abstract Osteoarthritis (OA) causes bony shape changes within the knee. Furthermore, the risk of developing OA increases with age. However, age alone does not cause OA. It is therefore important to ...understand the healthy age‐related trajectories of knee shape before attributing these changes to OA. The aim of this study was to determine the association between bony knee shape and age using statistical‐shape modelling (SSM). 96 participants received a CT scan of their knee. Three‐dimensional models were created using manual segmentation. Separate SSM's for the distal femur and proximal tibia were created. Linear regression models were used to assess the association between age and femoral and tibial shape. Fourteen modes of the femoral and tibial SSM's captured 68% and 73% shape variation, respectively. Only femoral mode 3 and tibial mode 7 were associated with age. Increasing age was related to larger femoral bone volume and deepening of the femoral trochlear groove. Furthermore, increased age was associated with medial tibial plateau expansion. Aspects of bony femoral and tibial shape were significantly associated with aging, including femoral and tibial bone size, femoral trochlear groove, and medial tibial plateau area. Changes in knee morphology occur as a normal process of aging without osteoarthritis development. This may be a response to mechanical loading over time . Further research investigating the effect of these changes on loading in the knee may provide valuable information for knee health in older age.
The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine ...against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1) and IgG(3) from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic.
Background
Intraoperative parathyroid hormone (iPTH) testing is often used to confirm successful removal of hypersecreting parathyroid glands during parathyroidectomy. Unfortunately, the iPTH test ...can be a time-consuming and highly variable process that occurs while the patient is under anesthesia. We set out to improve iPTH lab efficiency and variability.
Methods
We performed a retrospective review of 85 patients who underwent parathyroidectomy at our institution from October 2017 to October 2019. Each step of the iPTH lab reporting process was recorded and analyzed. Three simulations were performed of the entire process. We then established interventions to modify inefficiencies in the process and studied 21 patients who underwent parathyroidectomy at our institution from November 2019 to March 2020.
Results
Twenty-five minutes of time inherent to the process were identified. Four critical steps were identified as modifiable steps in the process:
1. Operating room (OR) blood draw ---> lab receipt.
2. Lab receipt ---> placement on centrifuge.
3. Removal from centrifuge ---> placement on PTH machine.
4. PTH machine result ---> OR verbal report.
We improved iPTH lab efficiency by 19%, decreasing the average lab result from 45 to 36 minutes (P = .001). We improved iPTH lab variability by 62%, decreasing the standard deviation from 21 to 8 minutes (P = .001).
Discussion
Utilizing a team-based approach to identify and expedite critical steps in the iPTH lab process can make a significant improvement in iPTH lab efficiency, improving patient care by decreasing total anesthesia time.
Much research in bilingualism has addressed the question of the extent to which lexical information is shared between languages. The present study investigated whether syntactic information is shared ...by testing if syntactic priming occurs between languages. Spanish-English bilingual participants described cards to each other in a dialogue game. We found that a participant who had just heard a sentence in Spanish tended to use the same type of sentence when describing the next card in English. In particular, English passives were considerably more common following a Spanish passive than otherwise. We use the results to extend current models of the representation of grammatical information to bilinguals.
Mutations in the complement regulatory proteins are associated with several different diseases. Although these mutations cause dysregulated alternative pathway activation throughout the body, the ...kidneys are the most common site of injury. The susceptibility of the kidney to alternative pathway-mediated injury may be due to limited expression of complement regulatory proteins on several tissue surfaces within the kidney. To examine the roles of the complement regulatory proteins factor H and Crry in protecting distinct renal surfaces from alternative pathway mediated injury, we generated mice with targeted deletions of the genes for both proteins. Surprisingly, mice with combined genetic deletions of factor H and Crry developed significantly milder renal injury than mice deficient in only factor H. Deficiency of both factor H and Crry was associated with C3 deposition at multiple locations within the kidney, but glomerular C3 deposition was lower than that in factor H alone deficient mice. Thus, factor H and Crry are critical for regulating complement activation at distinct anatomic sites within the kidney. However, widespread activation of the alternative pathway reduces injury by depleting the pool of C3 available at any 1 location.
The transmission soil transmitted helminths (STH) occurs via ingestion of or contact with infective stages present in soil contaminated with human faeces. It follows therefore that efforts to reduce ...faecal contamination of the environment should help to reduce risk of parasite exposure and improvements in water, sanitation and hygiene (WASH) are seen as essential for the long-term, sustainable control of STH. However, the link between WASH and STH is not always supported by the available evidence from randomised controlled trials, which report mixed effects of WASH intervention on infection risk. This review critically summarises the available trial evidence and offers an interpretation of the observed heterogeneity in findings. The review also discusses the implications of findings for control programmes and highlights three main issues which merit further consideration: intervention design, exposure assessment, and intervention fidelity assessment.
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