Miracle-dz/UniFAR-FTUs huggingface dataset:
Aging of the brain, entropy, and Alzheimer disease

Sporadic Alzheimer disease (AD) is related to advancing age far more than to any other risk factor and ultimately affects almost half of the population over age 85. Despite its remarkable prevalence among the elderly, it has been regarded as a specific disease, distinct from “normal aging. ” This view is supported in large part by clinical and pathologic similarities to early-onset, dominantly inherited familial AD, where genetic mutations related to β-amyloid have been identified. There is much evidence that sporadic AD overlaps with normal aging in many clinical and pathologic features. Some of the many molecular age-related changes (ARCs) affecting the brain, both intrinsic (programmed) and extrinsic (stochastic), are reviewed, with discussion of the effects they have singly and collectively on neuronal viability and vulnerability. The effect of ARCs on the brain is seen as the biologic manifestation of increasing entropy, an approach that helps to explain the progressive decline of neural and cognitive function over time; the ability of multiple, varied ARCs to summate as individuals age; the transitional relationship between normal aging, mild cognitive impairment, and AD; and the apparent differences between normal aging and AD. Increasing entropy, manifest through a complex network of interacting ARCs, is seen as the fundamental driving cause of neural and cognitive decline in the elderly, as well as the overriding etiologic principle in further transition to sporadic AD. Research on sporadic AD has largely focused on finding a single causal metabolic disorder or genetic mutation. Multiple ARCs contribute to declining function and increased frailty in the aging brain, however, and to the catastrophic disintegration of sporadic AD. Effective prevention or treatment will depend on recognizing the contributions of a multiplicity of ARCs to AD and reducing the burden of as many as possible. The role of amyloid is seen as one element in the larger network of senescent changes involving the aging brain.
Antimicrobial photodynamic therapy as an adjunct to non-surgical treatment of aggressive periodontitis: a split-mouth randomized controlled trial.

BACKGROUND The management of aggressive periodontitis (AgP) represents a challenge for clinicians because there are no standardized protocols for an efficient control of the disease. This randomized controlled clinical trial evaluated the effects of repeated applications of antimicrobial photodynamic therapy (aPDT) adjunctive to scaling and root planing (SRP) in patients with AgP. METHODS Using a split-mouth design, 20 patients with generalized AgP were treated with aPDT + SRP (test group) or SRP only (control group). aPDT was applied at four periods. All patients were monitored for 90 days. Clinical, microbiologic, and immunologic parameters were statistically analyzed. RESULTS In deep periodontal pocket analysis (probing depth [PD] ≥ 7 mm at baseline), the test group presented a decrease in PD and a clinical attachment gain significantly higher than the control group at 90 days (P < 0.05). The test group also demonstrated significantly less periodontal pathogens of red and orange complexes and a lower interleukin-1β/interleukin-10 ratio than the control group (P < 0.05). CONCLUSION The application of four sessions of aPDT, adjunctive to SRP, promotes additional clinical, microbiologic, and immunologic benefits in the treatment of deep periodontal pockets in single-rooted teeth in patients with AgP.
Early Life Stress Triggers Persistent Colonic Barrier Dysfunction and Exacerbates Colitis in Adult IL-10−/− Mice

Background:It has become increasingly evident that disease flares in the human inflammatory bowel diseases are influenced by life stress. It is known that life stress can trigger disturbances in intestinal barrier function and activate proinflammatory signaling pathways, which are important contributors to intestinal inflammation and clinical disease; however, the exact mechanisms of stress-induced inflammatory bowel disease exacerbations remain to be elucidated. Here, we presented a model of early life stress–induced exacerbation of colitis in interleukin (IL)-10−/− mice. Methods:C57Bl/6 wild-type and IL-10−/− mice were exposed to neonatal maternal separation (NMS) stress on postnatal days 1 to 18 and reared under normal conditions until 10 to 12 weeks of age. At this time, histopathology, colitis scores, intestinal barrier function, proinflammatory cytokine expression, and mast cell activity were evaluated. Results:NMS increased the severity of colitis IL-10−/− mice indicated by greater colitis scores and colonic proinflammatory cytokine concentrations. NMS and IL-10−/− increased colonic permeability; however, NMS alone did not induce colitis. Increased mast cell activation and colonic tryptase release were observed in IL-10−/− mice exposed to NMS, indicating mast cell activation. Conclusions:This study demonstrates that colitis in IL-10−/− mice can be exacerbated by NMS stress. The precise mechanisms of enhanced colitis severity in NMS IL10−/− mice are unclear but persistent defects in intestinal barrier function likely play a contributing role. NMS serves as a novel model to investigate the mechanisms by which early life stress influences the development and course of inflammatory bowel disease in adulthood.
Prevalence and Mental Health Treatment of Suicidal Ideation and Behavior Among College Students Aged 18-25 Years and Their Non-College-Attending Peers in the United States.

OBJECTIVE College students have been the focus of many studies on suicidal ideation with or without suicidal behavior. Little attention has been given to their non-college-attending peers on these issues. We examined the 12-month prevalence and mental health treatment of suicidal ideation with or without suicidal behavior among college students aged 18-25 years and their non-college-attending peers in the United States. METHODS We assessed data from 135,300 persons aged 18-25 years who participated in the 2008-2013 National Surveys on Drug Use and Health. Descriptive analyses and multivariate logistic regression models were applied. RESULTS Compared with full-time college students, high school students, those not enrolled in a school or college, and part-time college students were more likely to attempt suicide with a plan (model-adjusted prevalence = 0.67% vs 1.09%, 1.06%, and 1.07%, respectively). The mental health treatment rate among full-time college students with suicidal ideation with or without suicidal behavior was similar to the rates among the other 3 counterparts. The effects of race/ethnicity and serious mental illness on receipt of mental health treatment were significantly larger among those who did not perceive unmet treatment need than among those who perceived unmet treatment need (P = .019 and P = .001, respectively). CONCLUSIONS Compared to full-time college students, non-college-attending young adults and part-time college students were at higher risk for attempting suicide with a plan. Suicide prevention and intervention strategies should emphasize increasing access to mental health treatment among both college students with suicidal ideation with or without suicidal behavior and their non-college-attending peers (particularly among minorities and those who seem to be at low risk because they are without serious mental illness and report no need for mental health treatment).
Expected Returns and the Business Cycle: Heterogeneous Goods and Time-Varying Risk Aversion

This paper proposes a representative agent habit-formation model where preferences are defined for both luxury goods and basic goods. The model matches the equity risk premium, risk-free rate, and volatilities. From the intratemporal first-order condition, one can substitute out basic good consumption and the habit level, yielding a stochastic discount factor driven by two observable risk factors: luxury good consumption and the relative price of the two goods. I estimate these processes and find them to be heteroskedastic, implying time variation in the conditional volatility of the stochastic discount factor. These dynamics occur both at the business cycle frequency and at a lower, "generational" frequency. The findings reveal that the time variation in aggregate stock market and Treasury bond risk premiums are consistent with the predictions of the model. The Author 2009. Published by Oxford University Press on behalf of The Society for Financial Studies. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org, Oxford University Press.
Lack of association between depressive symptoms and markers of immune and vascular inflammation in middle-aged men and women

Background. Disturbed immune activity and vascular inflammation are associated both with clinical depression and coronary atherogenesis, and may constitute a mechanism through which depression contributes to coronary heart disease. If this is the case, then non-clinical depressive symptoms and psychological distress should be associated with immune activation and vascular inflammation. We tested this hypothesis in a healthy middle-aged sample. Method. Measures of depressive symptoms and hopelessness were obtained from 226 volunteers (122 men, 104 women) aged 47–59 years, drawn from the Whitehall II epidemiological cohort. C-reactive protein, fibrinogen, plasma interleukin-6, tumour necrosis factor alpha, interleukin-1 receptor antagonist, and T- and B-lymphocyte, and natural killer cells numbers and percentages were assessed. Results. There were no associations between measures of depressive symptoms or hopelessness and markers of immune activation or inflammatory response. Conclusions. Factors such as the measures of depressive symptoms, the choice of inflammatory and immune indices, and sample size, are unlikely to be responsible for these null effects. Associations may be confined to clinically depressed or older age populations, but there are problems of confounding by co-morbidity and health compromising behaviours in this literature. We conclude that disturbances of immune function and inflammatory processes are unlikely to be primarily responsible for the associations between depressive symptoms and coronary heart disease described in the literature, and that other pathways are involved.
Put-Call Parity in Equity Options Markets: Recent Evidence

There have been various studies of potential violations of put-call parity in US equity options markets, and the purpose of this study is to examine one potential explanation of these anomalous results. Cremers and Weinbaum [1] indicate a potential trading strategy that can obtain excess returns of up to 50 basis points per week, which is quite remarkable. However, none of these studies consider the fact that options markets have historically maintained different trading hours than those of their underlying security markets. While the US stock market has traditionally closed at 3:00 PM CST, options markets have variously closed between 3:10 and 3:02 PM CST over the past two decades. Using over ten million individual options implied volatility estimations since 1996, it is documented that these anomalies have all but disappeared since stock and option markets synchronized their trading hours. Beginning in the late 1990’s, stock prices often move slightly or to a larger degree in “after-hours” trading, enabled by the advent of electronic trading platforms. Options markets that are still open may adjust to subsequent stock market movements, although closing stock prices are reported as of 3:00 PM CST. Prior studies may have ignored these effects, and this is the first study to indicate that apparent deviations from put-call parity have decreased markedly over recent years, if they were ever economically significant at all.
Self‐renewal and differentiation of a basic fibroblast growth factor‐dependent multipotent hematopoietic cell line derived from embryonic stem cells

Despite the accumulation of information on the origin of hematopoietic stem cells, it is still unclear how these cells are generated in ontogeny. Isolation of cell lines equivalent to early embryonic hematopoietic progenitor cells can be helpful. A multipotent hematopoietic progenitor cell line, A‐6, was isolated from H‐1 embryonic stem (ES) cells. The self‐renewal of A‐6 cells was supported by basic‐fibroblast growth factor (b‐FGF) and their differentiation into definitive erythroid cells, granulocytes and macrophages was induced after co‐culture with ST‐2 stromal cells. A‐6 cells were positive for the surface markers of hematopoietic stem cell, c‐kit, CD31, CD34, Flt3/Flk2, PgP‐1, and HSA, but were negative for that of the differentiated cells. Reverse transcription‐polymerase chain reaction analysis showed that A‐6 cells produced mRNA from SCL/tal‐1 and GATA‐2 genes. Among various cytokines examined, only stem cell factor (SCF) and Flt3/Flk2 ligand (FL) supported the proliferation of A‐6 cells instead of b‐FGF. The FL, as well as b‐FGF, supported the self‐renewal of A‐6 cells, whereas SCF induced differentiation into myeloid cells. A‐6 cells will be useful for the characterization of hematopoietic progenitor cells derived from ES cells and provide a model system to realize the control mechanisms between self‐renewal and differentiation of hematopoietic stem cells.
Intrinsic membrane properties and morphological characteristics of interneurons in the rat supratrigeminal region

The membrane properties and morphological features of interneurons in the supratrigeminal area (SupV) were studied in rat brain slices using whole‐cell patch clamp recording techniques. We classified three morphological types of neurons as fusiform, pyramidal, and multipolar and four physiological types of neurons according to their discharge pattern in response to a 1‐sec depolarizing current pulse from −80 mV. Single‐spike neurons responded with a single spike, phasic neurons showed an initial burst of spikes and were silent during the remainder of the stimulus, delayed‐firing (DF) neurons exhibited a slow depolarization and delay to initial spike onset, and tonic (T) neurons showed maintained a discharge throughout the stimulus pulse. In a subpopulation of neurons (10%), membrane depolarization to around −44 mV produced a rhythmic burst discharge (RB) that was associated with voltage‐dependent subthreshold membrane oscillations. Both these phenomena were blocked by the sodium channel blocker riluzole at a concentration that did not affect the fast transient spike. Low doses of 4‐AP, which blocks low‐threshold K+ currents, transformed bursting into low‐frequency tonic discharge. In contrast, bursting occurred with exposure to cadium, a calcium‐channel blocker. This suggests that persistent sodium currents and low‐threshold K+ currents have a role in intrinsic burst generation. Importantly, RB cells were most often associated with multipolar neurons that exhibited either a DF or a T discharge. Thus, the SupV contains a variety of physiological cell types with unique morphologies and discharge characteristics. Intrinsic bursting neurons form a unique group in this region. © 2007 Wiley‐Liss, Inc.
Extensive Fatal Intracoronary Thrombosis During Percutaneous Coronary Intervention With Bivalirudin

The authors describe 2 cases of extensive intracoronary thrombus formation leading to acute closure of the left main where bivalirudin (Angiomax) was used as the anticoagulant during percutaneous coronary intervention leading to mortality. Both cases had similarity in the cascade of complications of coronary dissection leading to slow flow and prolonged procedure time with compromise of antegrade flow in the coronary artery and a final catastrophic development of extensive intracoronary thrombosis extending into the left main and nonintervened vessel (left anterior descending or circumflex) followed by ventricular fibrillation and death. Bivalirudin has reversible anticoagulant pharmacodynamics because the bivalirudin molecule is cleaved by the thrombin molecule. In situations when the antegrade flow is compromised, delivery of fresh circulating bivalirudin to replenish the catalysis of bivalirudin by thrombin is diminished, allowing thrombin activity to regenerate, thereby creating a prothrombotic milieu in these coronary segments. This can lead to extensive intracoronary thrombus formation in situations of slow flow precipitated by coronary dissection and prolonged dwell time with intracoronary hardware (wires, balloons, and stents). Interventionalists should be aware of the potential risk of this fatal complication and should be proactive in recognizing the scenarios where this is likely to occur. In such anticipated circumstances, the interventionalist may judiciously switch the anticoagulant to heparin and/or use additional glycoprotein IIb/IIIa inhibitor because freshly formed intracoronary thrombus is susceptible to lysis by glycoprotein IIb/IIIa inhibitors.
Instructional Scaffolding to Improve Students’ Skills in Evaluating Clinical Literature

Objective. To implement and assess the effectiveness of an activity to teach pharmacy students to critically evaluate clinical literature using instructional scaffolding and a Clinical Trial Evaluation Rubric. Design. The literature evaluation activity centered on a single clinical research article and involved individual, small group, and large group instruction, with carefully structured, evidence-based scaffolds and support materials centered around 3 educational themes: (1) the reader's awareness of text organization, (2) contextual/background information and vocabulary, and (3) questioning, prompting, and self-monitoring (metacognition). Assessment. Students initially read the article, scored it using the rubric, and wrote an evaluation. Students then worked individually using a worksheet to identify and define 4 to 5 vocabulary/concept knowledge gaps. They then worked in small groups and as a class to further improve their skills. Finally, they assessed the same article using the rubric and writing a second evaluation. Students’ rubric scores for the article decreased significantly from a mean pre-activity score of 76.7% to a post-activity score of 61.7%, indicating that their skills in identifying weaknesses in the article's study design had improved. Conclusion. Use of instructional scaffolding in the form of vocabulary supports and the Clinical Trial Evaluation Rubric improved students’ ability to critically evaluate a clinical study compared to lecture-based coursework alone.
The effects of human growth hormone (GH) administration in GH-deficient adults: a 20-day metabolic ward study.

The early effects of human GH administration in GH-deficient (GHD) adults on protein, electrolyte homeostasis, and body composition were investigated in a metabolic ward study. Four patients were studied. In addition to a constant caloric and nitrogen (N)-sufficient diet, the patients received GH for 15 days in dosages of 12.5-25 micrograms/kg.day, with a maximum of 1.48 mg (4 IU)/day. GH replacement therapy was well tolerated by all patients. There was a slowly increasing effect on IGF-I levels, which reached a maximum after 8-12 days. The lowered IGFBP-3 levels normalized quicker, reaching maximum circulating concentrations 3 days after the start of GH treatment. Insulin concentrations maximally increased after 5 days, after which they leveled off. Insulin-like growth factor-binding protein-1 levels were maximally suppressed after 2 days of treatment. N balance became positive in all patients (mean, +2.8 +/- 0.2 g/day). Maximal N retention occurred after 2-5 days of GH administration, after which adaptation occurred. This degree of N retention represents a formation of 20 g muscle/day, which would mean an increase of 3.6 kg muscle over a period of 6 months of GH replacement therapy. A rapidly occurring positive sodium balance was observed within 24-72 h. Maximal sodium retention amounted to 61 mmol/day. It slowly decreased spontaneously over the subsequent 12 days. In parallel, rapid changes in bioelectrical impedance analysis (BIA) were observed. There was a close parallel between the net cumulative sodium retention and the decrease in BIA in these patients during the first 15 days of GH therapy. This suggests that the calculation of body composition compartments on the basis of BIA measurements during the initial phase of GH replacement does not represent actual changes in fat mass. This was substantiated with measurements of body composition using dual energy x-ray absorptiometry. In conclusion, measurements of early metabolic changes in GHD adults during the first 15 days after the start of GH replacement indicate that IGF-I values reach maximal levels only after 8-12 days, that the measurements of changes in IGFBP-1 and IGFBP-3 levels probably do not contribute to a determination of the optimal GH replacement dose, that maximal N-retaining effects occur within 2-5 days, after which adaptation occurs, that massive sodium retention occurs during this period, which spontaneously levels off, and that cumulative sodium retention closely correlates during this period with changes in BIA. (ABSTRACT TRUNCATED AT 400 WORDS)
Prevalence and characteristics of clinically significant retained common bile duct stones after laparoscopic cholecystectomy for symptomatic cholelithiasis

Purpose To investigate the prevalence and clinical features of retained symptomatic common bile duct (CBD) stone detected after laparoscopic cholecystectomy (LC) in patients without preoperative evidence of CBD or intrahepatic duct stones. Methods Of 2,111 patients who underwent cholecystectomy between September 2007 and December 2014 at Seoul Metropolitan Government-Seoul National University Boramae Medical Center, 1,467 underwent laparoscopic cholecystectomy for symptomatic gallbladder stones and their medical records were analyzed. We reviewed the clinical data of patients who underwent postoperative endoscopic retrograde cholangiopancreatography (ERCP) for clinically significant CBD stones (i.e., symptomatic stones requiring therapeutic intervention). Results Overall, 27 of 1,467 patients (1.84%) underwent postoperative ERCP after LC because of clinical evidence of retained CBD stones. The median time from LC to ERCP was 152 days (range, 60–1,015 days). Nine patients had ERCP-related complications. The median hospital stay for ERCP was 6 days. Conclusion The prevalence of clinically significant retained CBD stone after LC for symptomatic cholelithiasis was 1.84% and the time from LC to clinical presentation ranged from 2 months to 2 years 9 months. Therefore, biliary surgeons should inform patients that retained CBD stone may be detected several years after LC for simple gallbladder stones.