Miracle-dz/UniFAR-FTUs huggingface dataset:
Baratin, a nonamidated neurostimulating neuropeptide, isolated from cockroach brain: Distribution and actions in the cockroach and locust nervous systems

During the purification of tachykinin‐related peptides from the brain of the cockroach Leucophaea maderae, a few other peptides were collected in adjacent high‐performance liquid chromatography fractions. Edman degradation, mass spectrometry, and chemical synthesis revealed that one of these peptides had the sequence DNSQWGGFA. This nonamidated nonapeptide was designated baratin and appears not to be related to any known insect peptide. Baratin was not found to be bioactive in the L. maderae hindgut or oviduct muscle contraction assay. (Both synthetic nonamidated and amidated baratin were tested.) To screen for possible sites of action, we raised a rabbit antiserum to baratin. We found baratin‐immunoreactive (BAR‐IR) interneurons throughout the cockroach central nervous system. Some prominent brain neuropils were supplied by BAR‐IR neuron processes: the central body, the calyx, and lobes of the mushroom bodies, parts of the optic lobe, and the tritocerebral neuropil. Additionally we found BAR‐IR neurosecretory cells in the median neurosecretory cell group with processes supplying the storage lobe of the corpora cardiaca. In each of the thoracic and abdominal ganglia processes of BAR‐IR projection neurons and local neurons were seen. The baratin antiserum also labeled neurons in the brain of the locust Locusta migratoria, some of which are similar to those of the cockroach. A prominent system of interganglionic BAR‐IR processes was found in the locust subesophageal, thoracic, and abdominal ganglia. This was formed by four large projection neurons with cell bodies in the abdominal ganglia A1–2. The processes of these BAR‐IR neurons are distributed dorsally and laterally in each of the ventral nerve cord ganglia. When baratin (10−6–10−4 M) was applied to desheathed abdominal ganglia of locusts and cockroaches, we could monitor bursts of action potentials in neurons with axons in the anterior abdominal nerve (nerve 1), but not in the posterior nerve (nerve 2). In ganglia displaying spontaneous rhythmic firing in units of nerve 1, baratin strengthened the rhythmic pattern. Thus baratin appears to have a role in modulation of motor patterns in abdominal ganglia. The immunocytochemical findings suggest further modulatory actions of baratin in different circuits of the brain and ventral nerve cord. J. Comp. Neurol. 422:267–286, 2000. © 2000 Wiley‐Liss, Inc.
Cholangiociliopathies: genetics, molecular mechanisms and potential therapies

Purpose of review The present review summarizes recent knowledge on polycystic liver diseases (PCLDs), mechanisms of hepatic cystogenesis and potential therapies for these conditions. Recent findings PCLD may be classified as cholangiociliopathies. In PCLD associated with polycystic kidney disease, cell proliferation is one of the major mechanisms of cystogenesis, whereas in isolated PCLD (autosomal dominant polycystic liver disease), disrupted cell adhesion may be more important in cyst progression. In cystic cholangiocytes, overexpression of ion transporters and water channels facilitates fluid secretion into the cystic lumen, and growth factors, estrogens and cytokines promote cholangiocyte proliferation. With age, cholangiocytes lining liver cysts acquire features of mesenchymal cells contributing to hepatic fibrocystogenesis. A novel mechanism of liver cyst expansion in PCLD involves microRNA regulatory pathways. Hyperproliferation of cystic cholangiocytes is linked to abnormalities in cell cycle progression and microRNA expression. Decreased levels of miR-15a are coupled to upregulation of its target – the cell cycle regulator, Cdc25A. Cholangiocyte cilia in liver cysts are structurally abnormal. Somatostatin analogues and sirolimus reduce liver cyst volume in PCLD patients. Summary Clarification of molecular mechanisms of hepatic cystogenesis provides an opportunity for the development of targeted therapeutic options in PCLD.
Problem-based learning in pre-clinical medical education: 22 years of outcome research

Purpose: To conduct a systematic review of problem-based learning (PBL) in undergraduate, pre-clinical medical education. Methods: A research librarian developed comprehensive search strategies for MEDLINE, PSYCINFO, and ERIC (1985–2007). Two reviewers independently screened search results and applied inclusion criteria. Studies were included if they had a comparison group and reported primary data for evaluative outcomes. One reviewer extracted data and a second reviewer checked data for accuracy. Two reviewers independently assessed methodological quality. Quantitative synthesis was not performed due to heterogeneity. A qualitative review with detailed evidence tables is provided. Results: Thirty unique studies were included. Knowledge acquisition measured by exam scores was the most frequent outcome reported; 12 of 15 studies found no significant differences. Individual studies demonstrated either improved clerkship (N = 3) or residency (N = 1) performance, or benefits on some clinical competencies during internships for PBL (N = 1). Three of four studies found some benefits for PBL when evaluating diagnostic accuracy. Three studies found few differences of clinical (or practical) importance on the impact of PBL on practicing physicians. Conclusions: Twenty-two years of research shows that PBL does not impact knowledge acquisition; evidence for other outcomes does not provide unequivocal support for enhanced learning. Work is needed to determine the most appropriate outcome measures to capture and quantify the effects of PBL. General conclusions are limited by methodological weaknesses and heterogeneity across studies. The critical appraisal of previous studies, conducted as part of this review, provides direction for future research in this area.
MINITRANSPLANTS: ALLOGENEIC STEM CELL TRANSPLANTATION WITH REDUCED TOXICITY

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is used for the treatment of selected hematological malignancies. Its curative potential is based on two very different mechanisms, involving the conditioning regimen and the graft-versus-host reactions, respectively. The highdose chemo-radiotherapy conditioning regimen is aimed at destroying tumor cells, ablating the host immune system (to prevent rejection) and eliminating the host bone marrow (to “make space” for donor stem cells). However, the definitive eradication of tumor cells is also largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versusleukemia (GVL) or graft-versus-tumor (GVT) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger (< 55 years) and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols based on a two step approach : first the use of immunosuppressive (but nonmyeloablative) conditioning regimens providing sufficient immunosuppression to achieve engraftment of allogeneic hematopoietic stem cells and, in a second step, destruction of malignant cells by the GVL effect. These transplants are called nonmyeloablative HSCT or reducedconditioning HSCT or minitransplants. Preliminary results show that minitransplants are feasible with a relatively low transplant-related mortality (TRM) even in patients up to 70 years. In addition, strong anti-tumor responses are observed in several hematological malignancies as well as in some patients with renal cell carcinoma. As the benefits of minitransplants over alternative forms of treatment remain to be demonstrated, this strategy should be restricted to patients included in clinical trials.
Properties of 2 Counterfactual Effect Definitions of a Point Exposure

As recognized for more than 2 decades, the way to define effects of an exposure may be unclear if the effects are conditional on occurrence of prior events. Since age-specific rates are inherently conditional on survival to the age for which rates are calculated, age-specific rate ratios may be misleading. We consider this problem in the context of a point exposure and an unmeasured risk factor that is independent of the exposure, together with potential outcome models and associated counterfactual effect definitions. The methods apply to a recurring exposure that “tracks” over time, as well as to more complicated situations (although additional issues may then arise). We identify and evaluate 2 seemingly-natural ways that the population effects of a point exposure might be defined. At least one definition of the population effects of a point exposure is identifiable, while another natural definition is not identifiable. We describe possible implications of these definitions for the distortion of time-specific rate ratios that can occur with passage of time. We discuss interpretation of effects for each definition, and how the definitions are related to selection bias as recently defined by Hernán et al (Epidemiology. 2004;15:615–625). We present implications for study design, and make several recommendations. Problems may be reduced or avoided by starting follow-up before onset of exposure and by using survival curves to compare exposed with unexposed.
Higher Healthy Eating Index-2005 scores are associated with better physical performance.

BACKGROUND Little is known regarding the relationship between overall diet quality and physical performance among older adults. We examined the association between overall diet quality, as measured by the US Department of Agriculture's Healthy Eating Index-2005 (HEI-2005), and physical performance, as measured by gait speed (n = 2,132) and knee extensor power (n = 1,392), among adults aged 60 years or older. METHODS Using data from the 1999-2002 National Health and Nutrition Examination Survey, multiple linear regression models controlling for age, gender, race/ethnicity, education, smoking status, comorbidities, medication use, cognitive function, body mass index, and physical activity were used in the analyses. RESULTS After adjusting for age, gender, race/ethnicity, education, and smoking status, total HEI-2005 scores were positively associated with both gait speed (p for trend = .02) and knee extensor power (p for trend = .05). Older adults with higher HEI-2005 scores had a faster gait speed (p = .03 for both Quartile 3 and Quartile 4 vs quartile 1) compared with those with HEI-2005 scores in the lowest quartile. Those with HEI-2005 scores in Quartile 4 had a greater knee extensor power compared with those with HEI-2005 scores in the lowest quartile (p = .04). The associations between HEI-2005 scores and physical performance remained after further adjustment for comorbidities, medication use, cognitive function, and body mass index. However, the associations were no longer statistically significant after further adjustment for physical activity. CONCLUSION Adherence to overall dietary recommendations is associated with better physical performance among older adults.
Pharmacokinetics and Pharmacodynamics of Gastroretentive Delivery of Levodopa/Carbidopa in Patients With Parkinson Disease

ObjectiveTo investigate, in patients with Parkinson disease, the pharmacokinetics and pharmacodynamics of levodopa/carbidopa delivered via 3 different extended-release (ER) tablet formulations. MethodsThis was a randomized, crossover study in patients with stable idiopathic Parkinson disease comparing a conventional ER tablet (C-ER) administered orally 3 times daily with 2 levodopa/carbidopa gastroretentive ER formulations administered orally twice daily, one with an immediate release (IR) component (IR/ER) and one without (ER). Blood samples were collected for pharmacokinetic (PK) analysis, and a finger-tapping test was performed to assess pharmacodynamics. Tolerability was evaluated by monitoring adverse events and measuring vital signs. PK modeling was performed to estimate steady-state levodopa concentrations. ResultsFourteen patients completed the study. Compared with C-ER, both gastroretentive ER tablets significantly extended the first maximum time (6.0 vs 2.5 h; P < 0.025) and had smoother plasma concentration-time profiles while achieving a similar maximum plasma concentration and area under the curve. The IR/ER formulation exhibited a significantly longer duration of concentration above the presumed efficacious threshold of 300 ng/mL (21 vs 18 h; P = 0.0027) compared with C-ER. PK modeling predicts a steady-state levodopa peak/trough ratio of 4 for both IR/ER and ER formulations and a ratio of 21 for C-ER. Furthermore, superior response in the finger tapping test was observed for the IR/ER and ER formulations compared with the C-ER formulation. ConclusionsThis study demonstrated that the gastroretentive ER formulations achieved more constant plasma levodopa concentrations and better pharmacodynamics with reduced dose frequency, potentially reducing the on-off phenomena that have been associated with fluctuations in plasma levodopa concentrations.
Electroacupuncture ameliorates abnormal defaecation and regulates corticotrophin-releasing factor in a rat model of stress

Objective To examine the effect of electroacupuncture (EA) treatment on abnormal defaecation in a rat model of chronic heterotypic stress (CHS) and investigate the underlying mechanisms. Methods 20 male Sprague-Dawley rats were randomly divided into three groups: normal (n=6), CHS (n=7), and CHS+EA (n=7). Rats in the CHS group and CHS+EA groups received four different types of stressors for 7 days. For rats in the CHS+EA group, EA was applied at ST36 in the bilateral hind legs for 30 min before each stress-loading session. Rats in the normal group did not receive stressors or EA treatment. The faecal pellets of each rat were collected and weighed at a fixed time every day. Protein expression of corticotrophin-releasing factor (CRF) in the hypothalamus and colorectal tissues was measured by Western blotting at the end of the experiment on the 7th day. Results After 7 consecutive days of CHS, the number of faecal pellets, faecal wet weight, and faecal water content were significantly increased in the CHS group compared with the normal group (p=0.035, p=0.008 and p=0.008, respectively). All three parameters were significantly decreased in CHS+EA versus CHS groups (p=0.030, p=0.011 and p=0.006, respectively). Stress significantly increased CRF expression in both the hypothalamus and colorectal tissues. The excessive CRF responses seen following CHS were significantly suppressed by EA treatment. Conclusions EA treatment can ameliorate stress loading induced abnormal defaecation in rats and decrease protein expression of CRF centrally (hypothalamus) and peripherally (colorectal tissues), suggesting a potentially therapeutic role for EA in stress-related responses.
Meta-analysis of the effectiveness of psychological and pharmacological treatments for binge eating disorder.

OBJECTIVE The aim of this study was to compute and compare mean effects of various treatments for binge eating disorder. METHOD A total of 38 studies with 1973 participants fulfilled the defined inclusion criteria. Effect sizes, odds ratios, and simple rates were integrated in fixed and random (mixed) effects categorical models. RESULTS From randomized controlled trials, psychotherapy and structured self-help, both based on cognitive behavioral interventions, were found to have large effects on the reduction of binge eating. Regarding pharmacotherapy, mainly comprising antidepressants, randomized controlled trials revealed medium effects for the reduction of binge eating. Uncontrolled studies on weight-loss treatments demonstrated moderate reductions of binge eating. Combination treatments did not result in higher effects compared with single-treatment regimens. Except for weight-loss treatment, none of the interventions resulted in a considerable weight reduction. DISCUSSION Psychotherapy and structured self-help, both based on cognitive-behavioral interventions, should be recommended as the first-line treatments.
Long-Term Effect of Magnesium Consumption on the Risk of Symptomatic Gallstone Disease Among Men

BACKGROUNDMagnesium deficiency can cause dyslipidemia and insulin hypersecretion, which may facilitate gallstone formation. However, the effect of long-term consumption of magnesium on the risk of gallstone disease is unknown.METHODSWe prospectively studied magnesium consumption and risk of gallstone disease in a cohort of 42,705 U.S. men from 1986 to 2002. Magnesium consumption was assessed using a validated semiquantitative food frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially.RESULTSWe documented 2,195 incident cases of symptomatic gallstones during 560,810 person-years of follow-up. The age-adjusted relative risks (RRs) for men with total magnesium intake and dietary magnesium, when the highest and lowest quintiles were compared, were 0.67 (95% confidence interval [CI] 0.59–0.77, P for trend <0.0001) and 0.67 (CI 0.59–0.76, P for trend <0.0001), respectively. After adjusting for multiple potential confounding variables, when extreme quintiles were compared, the multivariate RR of total magnesium intake (RR 0.72, CI 0.61–0.86, P for trend = 0.006) and dietary magnesium (RR 0.68, CI 0.57–0.82, P for trend = 0.0006) remained significant with a dose–response relationship.CONCLUSIONSOur findings suggest a protective role of magnesium consumption in the prevention of symptomatic gallstone disease among men.
Do Long Term Interest Rates Drive GDP and Inflation in Small Open Economies? Evidence from Poland

I show that the long term interest rate that includes a time-varying term premium stabilizes GDP and it does not affect significantly inflation volatility in Poland. I derive this result from an estimated DSGE model of a small open economy. GDP volatility would have been much higher if the endogenous part of the term premium had been switched off in the model, while the inflation volatility has not been affected by the presence of the term premium. At the same time, the term premium shock had only a minor impact on GDP and inflation volatilities which suggests that the QE programs conducted by the major central banks did not have a substantial impact on the Polish economy.
Coping with stress: its influence on periodontal therapy.

BACKGROUND Individual stress coping strategies appear to influence periodontal disease: individuals with inadequate stress behavior may be at greater risk of developing disease. The purpose of this 24-month prospective study was to examine the influence of different coping behaviors on a non-surgical periodontal therapy and on the course of periodontal disease. METHODS In 80 patients with chronic periodontitis, a non-surgical periodontal treatment was conducted after their individual stress coping strategies had been recorded. After 2 years of regular maintenance, their periodontal condition was evaluated. The stress coping questionnaire was used to obtain psychodiagnostic data. Clinical attachment loss (CAL) served as the clinical parameter. RESULTS Patients with a defensive coping style had statistically significant poorer attachment values (P= 0.000) after 2 years compared to patients with other coping behaviors. The percentage of sites with slight to moderate CAL (<5 mm) was significantly less in patients with a defensive coping style than in patients with other coping strategies (P = 0.000). The number of sites with severe advanced CAL (>5 mm) was significantly correlated with a suppressive coping style (P= 0.0001). None of the individual stress coping styles revealed significant overall changes over time. The subtest of drug use (alcohol, nicotine, tranquilizers) as well as changes in this subtest over time were significantly correlated with the CAL (P = 0.003); an increase in the t value of the subtest of drug use was accompanied by a significant increase in CAL. CONCLUSIONS The results of this study show that passive coping strategies were more pronounced in advanced disease as well as in cases of poor response to a non-surgical periodontal treatment, whereas patients with active coping modes had milder disease and a more favorable course of treatment. Thus, maladaptive behavior, especially in association with behavior-related risk factors such as smoking, are of great importance in the medical history, treatment, and maintenance of patients with periodontal disease.
Expression and subcellular localization of the AQP8 and AQP1 water channels in the mouse gall‐bladder epithelium

Background information. Transepithelial transport of water is one of the most distinctive functions by which the gall‐bladder rearranges its bile content. Water is reabsorbed from the gall‐bladder lumen during fasting, whereas it is secreted into the lumen following meal ingestion. Nevertheless, the molecular mechanism by which water is transported across the gall‐bladder epithelium remains mostly unclear.
The long-term prognosis of renal transplantation in patients with lupus nephritis.

BACKGROUND Few data are available about the long-term outcome of renal transplantation in patients with systemic lupus erythematosus (SLE). METHODS Between June 1982 and 2004, a total of 33 adults with lupus nephritis received 35 kidney allografts. Outcomes of these grafts and those of 70 controls matched for age, sex, and donor source who underwent transplantation during the same period were compared. RESULTS Mean follow-up after renal transplantation was 91 +/- 59 months for patients with lupus and 90 +/- 64 months for controls. Actuarial 15-year patient (80% versus 83%) and death-censored graft survival rates (69% versus 67%) were not significantly different between patients with lupus and controls. Risks for acute and chronic rejection, arterial hypertension, and infection were not different between the 2 groups. Mean serum creatinine levels also were similar in the 2 groups at the last follow-up visit. Intravascular thrombotic events occurred in 9 patients with SLE (26%) and 6 controls (8.6%; P = 0.038). In the SLE group, 6 of 7 antiphospholipid (aPL) antibody-positive versus 3 of 17 aPL antibody-negative patients experienced thrombotic events ( P = 0.015). Recurrence of lupus nephritis was documented in 3 renal grafts (8.6%), but no graft was lost because of recurrent lupus nephritis. CONCLUSION Long-term patient and graft survival probabilities were similar in patients with SLE and matched controls. The risk for thrombotic complications was greater in patients with SLE, particularly aPL-positive patients. Nephritis recurred in less than 10% of patients with SLE and did not influence graft survival.