TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Transforming growth factor beta 1 (TGFβ1) is strongly induced following brain injury and polarises microglia to an anti-inflammatory phenotype. Augmentation of TGFβ1 responses may therefore be beneficial in preventing inflammation in neurological disorders including stroke and neurodegenerative diseases. However, several other cell types display immunogenic potential and identifying the effect of TGFβ1 on these cells is required to more fully understand its effects on brain inflammation. Pericytes are multifunctional cells which ensheath the brain vasculature and have garnered recent attention with respect to their immunomodulatory potential. Here, we sought to investigate the inflammatory phenotype adopted by TGFβ1-stimulated human brain pericytes.', 'Microarray analysis was performed to examine transcriptome-wide changes in TGFβ1-stimulated pericytes, and results were validated by qRT-PCR and cytometric bead arrays. Flow cytometry, immunocytochemistry and LDH/Alamar Blue® viability assays were utilised to examine phagocytic capacity of human brain pericytes, transcription factor modulation and pericyte health.', 'TGFβ1 treatment of primary human brain pericytes induced the expression of several inflammatory-related genes (NOX4, COX2, IL6 and MMP2) and attenuated others (IL8, CX3CL1, MCP1 and VCAM1). A synergistic induction of IL-6 was seen with IL-1β/TGFβ1 treatment whilst TGFβ1 attenuated the IL-1β-induced expression of CX3CL1, MCP-1 and sVCAM-1. TGFβ1 was found to signal through SMAD2/3 transcription factors but did not modify nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation. Furthermore, TGFβ1 attenuated the phagocytic ability of pericytes, possibly through downregulation of the scavenger receptors CD36, CD47 and CD68. Whilst TGFβ did decrease pericyte number, this was due to a reduction in proliferation, not apoptotic death or compromised cell viability.\Question: Does tGF-beta1 regulate human brain pericyte inflammatory processes involved in neurovasculature function?

SOLUTION: TGFβ1 attenuated pericyte expression of key chemokines and adhesion molecules involved in CNS leukocyte trafficking and the modulation of microglial function, as well as reduced the phagocytic ability of pericytes. However, TGFβ1 also enhanced the expression of classical pro-inflammatory cytokines and enzymes which can disrupt BBB functioning, suggesting that pericytes adopt a phenotype which is neither solely pro- nor anti-inflammatory. Whilst the effects of pericyte modulation by TGFβ1 in vivo are difficult to infer, the reduction in pericyte proliferation together with the elevated IL-6, MMP-2 and NOX4 and reduced phagocytosis suggests a detrimental action of TGFβ1 on neurovasculature.

PROBLEM: Context: To investigate whether the association between APOE-epsilon4 and memory decline is modified by baseline cognition and age in a population-based elderly sample.', 'The study sample consisted of 1,243 subjects, 62 to 85 years old, with a Mini-Mental State Examination (MMSE) score between 21 and 30 and known APOE phenotypes. Memory performance was measured with an abbreviated Auditory Verbal Learning Test (AVLT) at baseline and repeated after 3 years (n = 854). Memory decline was defined as a decrease of at least 1 SD from the mean change score on immediate recall (IR), delayed recall (DR), and retention, based on the AVLT.', 'Multivariate logistic regression analyses showed that APOE-epsilon4 is associated with memory decline in cognitively impaired subjects (MMSE score, 21 to 26) (OR for decline on IR adjusted for age, sex, education, and baseline recall score, 3.8; 95% CI, 1.4 to 10.0; adjusted OR for decline on DR, 2.9; 95% CI, 1.2 to 7.0; adjusted OR for decline on retention, 3.3; 95% CI, 1.1 to 10. 1), but not in cognitively normal subjects (MMSE score, 27 to 30) (adjusted OR for decline on IR, 1.1; 95% CI, 0.6 to 2.0; adjusted OR for decline on DR, 1.0; 95% CI, 0.6 to 1.8; adjusted OR for decline on retention, 1.5; 95% CI, 0.7 to 3.0). In particular, cognitively impaired epsilon4 carriers older than 75 years were at high risk of memory decline (adjusted OR for decline on IR, 4.5; 95% CI, 1.4 to 13.8; adjusted OR for decline on DR, 3.6; 95% CI, 1.2 to 10.8; adjusted OR for decline on retention, 6.6; 95% CI, 1.5 to 29.7).\Question: Is aPOE-epsilon4 associated with memory decline in cognitively impaired elderly?

SOLUTION: APOE-epsilon4 was associated with memory decline in subjects with cognitive impairment, but not in normally functioning subjects. Contrary to AD studies, our study suggests that the risk of APOE-epsilon4 on memory decline does not decrease at higher ages.

PROBLEM: Context: To compare the safety and efficacy of patients undergoing dorsal penile plication with patients undergoing ventral and lateral plication.', 'A retrospective review was performed of all patients who underwent penile plication between 2007 and 2013. Plication was performed through a 2-cm longitudinal incision in the proximal or midpenile shaft without degloving. Plication sutures were placed in parallel opposite the angle of greatest curvature. Dorsal plication was performed with minimal displacement of the neurovascular bundle. Patient demographics, perioperative outcomes, and patient-reported outcomes were analyzed.', 'Of 215 patients who underwent penile plication, complete operative and patient-reported outcomes data were available for 118 (55%). Patients were grouped by location of plication: dorsal (n = 17 [14%]), ventral (n = 65 [55%]), and lateral (n = 36 [31%]). Mean age (52-58 years; P = .51) and preoperative curvature (36-51°; P = .78) were similar among the 3 groups. Each group required a similar number of sutures (8-9; P = .18) to achieve similar correction (37-45°; P = .33). Patients completed a satisfaction survey at a mean of 15 months (range, 1-41 months) after surgery. All groups reported equally high rates of satisfaction for penile curvature (P = .64), penile rigidity (P = .64), strength of erection (P = .98), and overall satisfaction (P = .75). Although each group reported subjective decrease in penile length (P = .10), objective length loss occurred on a small scale (mean length loss for all groups, 0.3-0.8 cm; P = .24).\Question: Is dorsal plication without degloving safe and effective for correcting ventral penile deformities?

SOLUTION:
Penile plication is a safe and effective technique for correcting all directions of curvature. Dorsal plication without degloving produces favorable objective and subjective results comparable to ventral and lateral plication.