Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental Trajectories of Marijuana Use among Men

Objectives: Examine whether young men who chronically use marijuana are at risk for engaging in drug-related and non-drug-related criminal offending and exhibiting psychopathic personality features in their mid-30s. Methods: Patterns of marijuana use were delineated in a sample of predominately Black and White young men from adolescence to the mid-20s using latent class growth curve analysis. Self-report and official records of criminal offending and psychopathic personality features were assessed in the mid-30s. Analyses controlled for multiple factors indicative of a preexisting antisocial lifestyle and co-occurring use of other substances and tested for moderation by race. Results: Four latent marijuana trajectory groups were identified: chronic high, adolescence-limited, late increasing, and low/nonusers. Relative to low/nonusers, chronic high and late increasing marijuana users exhibited more adult psychopathic features and were more likely to engage in drug-related offending during their mid-30s. Adolescence-limited users were similar to low/nonusers in terms of psychopathic features but were more likely to be arrested for drug-related crimes. No trajectory group differences were found for violence or theft, and the group differences were not moderated by race. Conclusions: Young men who engage in chronic marijuana use from adolescence into their 20s are at increased risk for exhibiting psychopathic features, dealing drugs, and enduring drug-related legal problems in their mid-30s relative to men who remain abstinent or use infrequently.
Advanced oxidation protein products induce apoptosis, and upregulate sclerostin and RANKL expression, in osteocytic MLO-Y4 cells via JNK/p38 MAPK activation

Advanced oxidation protein products (AOPPs) are recognized as novel markers of oxidative stress and contribute to various medical conditions, which are associated with secondary osteoporosis. However, little is currently known regarding the role of AOPPs in the development of secondary osteoporosis. As the commander cells of bone remodeling, osteocytes are involved in the pathogenesis of osteoporosis. The present study aimed to determine the cytotoxic mechanisms of AOPPs on osteocytic MLO-Y4 cells. The results demonstrated that treatment with AOPPs significantly triggered apoptosis of MLO-Y4 cells, in a dose- and time-dependent manner. Furthermore, exposure to AOPPs induced phosphorylation of c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK). Conversely, N-acetylcysteine inhibited the activation of JNK and p38 MAPK, thus suggesting that the AOPPs-induced activation of JNK/p38 MAPK is reactive oxygen species (ROS)-dependent. In addition, SB203580 and SP600125 suppressed apoptosis, but did not affect ROS production, following AOPPs treatment. Notably, AOPPs also induced a significant upregulation in the expression levels of sclerostin and receptor activator of nuclear factor kappa-B ligand (RANKL) in a JNK/p38 MAPK-dependent manner. These findings provide novel insights into the molecular mechanisms underlying AOPPs-mediated cell death, and suggest that modulation of apoptotic pathways via the MAPK signaling cascade may be considered a therapeutic strategy for the prevention and treatment of secondary osteoporosis.
The Kinetics of Skin Cancer: Progression of Actinic Keratosis to Squamous Cell Carcinoma

BACKGROUND Actinic keratoses (AKs) are intraepidermal skin tumors that have the potential to progress to squamous cell carcinomas (SCCs). SCCs are the second most common cancer with more than 200,000 cases each year in America. Approximately 10% of AKs will progress to SCCs. This progression is thought to be due to chronic sun exposure, specifically ultraviolet B sunlight. OBJECTIVE Understanding the kinetics of this developmental process can help physicians better evaluate and subsequently treat precancerous AKs. METHODS To determine the time scale of AK progression, we conducted a retrospective electronic medical record study of all patients diagnosed histopathologically with an SCC between July 1, 2003, and June 30, 2005. RESULTS Of a total patient population of 6,691, 91 had a histopathologically confirmed diagnosis of an AK at the same site as the subsequent SCC. The length of time for an AK to progress to an SCC was determined to be 24.6 months (95% confidence interval, 21.04–28.16 months). CONCLUSIONS Although a more controlled in vivo study is indicated, these data provide a good estimate of the time course from an AK to an SCC. In summary, of the estimated 10% of AKs that will develop into an SCC, the progression will take approximately 2 years.
Differing In Vitro Potencies of Tocolytics and Progesterone in Myometrium From Singleton and Twin Pregnancies

We compared the relaxant effect of 2 known tocolytics; indomethacin and atosiban and progesterone, on pregnant human myometrial spontaneous and oxytocin-induced contractions from singleton and twin pregnancies. All agents exerted a concentration-dependent relaxant effect on myometrial contractions. There was no significant difference in the concentration–response curves between singletons and twins for progesterone or indomethacin on spontaneous contractions or atosiban on oxytocin-induced contraction. Under oxytocin however, the concentration–response curves for indomethacin and progesterone were significantly shifted to the right for both amplitude of contraction (P < .01) and activity integral (P < .01). When compared to singleton myometrium however, the concentration–response curves were significantly shifted to the right in the twin myometrium group (P < .05 progesterone and P < .001 indomethacin). We conclude that a greater concentration of progesterone and indomethacin is required to inhibit oxytocin-induced myometrial contractions in twins compared to singletons in vitro. The differences noted in the tissue pharmacologies may have implications for the successful prevention or inhibition of preterm labor in twin pregnancy.
Plasma leptin levels are associated with abnormal fibrinolysis in men and postmenopausal women

Abstract. Söderberg S, Olsson T, Eliasson M, Johnson O, Ahrén B (Umeå University Hospital, Luleå County Hospital and Lund University, Malmö, Sweden). Plasma leptin levels are associated with abnormal fibrinolysis in men and postmenopausal women. J Intern Med 1999; 245: 533–543.
Disgust sensitivity in eating disorders: a preliminary investigation.

BACKGROUND Disgust is a basic emotion that has been relatively neglected in psychiatry in general and in eating disorders in particular. Nevertheless, there are features of disgust and its more complex derivatives (e.g., shame) which suggest that disgust may have a role to play in eating disorders. METHOD Seventy-four patients with a DSM-IV diagnosis of anorexia nervosa, bulimia nervosa, eating disorder not otherwise specified, and obese binge eater were compared with 15 control subjects on their levels of disgust sensitivity. RESULTS Overall, eating disorder patients did not appear to be more sensitive to disgust-eliciting stimuli than comparison subjects, although there was a tendency for patients to be more disgusted by body products. However, drive for thinness and bulimia scores were related to higher levels of disgust sensitivity to food, death, and magical contagion. General psychopathology did not appear to be related to levels of disgust sensitivity. DISCUSSION Although patients are not more sensitive than controls to the disgust-eliciting stimuli measured, disgust still has a positive relationship to eating disorder symptoms. Future studies will need to examine more precisely what this relationship might be.
Functional Analysis of Recombinant Calreticulin Fragment 39–272: Implications for Immunobiological Activities of Calreticulin in Health and Disease

Although calreticulin (CRT) is a major Ca2+-binding luminal resident protein, it can also appear on the surface of various types of cells and it functions as an immunopotentiating molecule. However, molecular mechanisms underlying the potent immunobiological activity of cell surface CRT are still unclear. In the present study, a recombinant fragment (rCRT/39–272) covering the lectin-like N domain and partial P domain of murine CRT has been expressed in Escherichia coli. The affinity-purified rCRT/39–272 assembles into homodimers and oligomers in solution and exhibits high binding affinity to various glycans, including carrageenan, alginic acids, and hyaluronic acids. Functionally, rCRT/39–272 is capable of driving the activation and maturation of B cells and cytokine production by macrophages in a TLR-4–dependent manner in vitro. It specifically binds recombinant mouse CD14, but not BAFFR and CD40. It is also able to trigger Ig class switching by B cells in the absence of T cell help both in vitro and in vivo. Furthermore, this fragment of CRT exhibits strong adjuvanticity when conjugated to polysaccharides or expressed as part of a fusion protein. Soluble CRT can be detected in the sera of patients with rheumatoid arthritis or systemic lupus erythematosus, but not in healthy subjects. We argue that CRT, either on the membrane surface of cells or in soluble form, is a potent stimulatory molecule to B cells and macrophages via the TLR-4/CD14 pathway and plays important roles in the pathogenisis of autoimmune diseases.
Fluoroscopy‐Guided Endovenous Foam Sclerotherapy Using a Microcatheter in Varicose Tributaries Followed by Endovenous Laser Treatment of Incompetent Saphenous Veins: Technical Feasibility and Early Results

OBJECTIVES To evaluate the technical feasibility and preliminary results of endovenous foam sclerotherapy using a microcatheter in varicose tributaries followed by endovenous laser treatment (EVLT) of incompetent saphenous veins. MATERIALS AND METHODS From July 2005 to August 2006, 312 patients (M:F=139:173, mean age 45.8) who presented with varicose veins with reflux in the saphenofemoral, saphenopopliteal junction or tributaries were enrolled. Under ultrasound or fluoroscopy guidance, selective microcatheterization and endovenous foam slcerotherapy were first performed in varicose tributaries, followed by EVLT (980 nm) of incompetent saphenous veins. Follow‐up at 1‐week and 1‐, 3‐, and 6‐month intervals was done. RESULTS Technical success was seen in 410 of 411 limbs (99%). Continued closure of the saphenous veins and the complete sclerosis of varicose tributaries were noted in 332 of 373 limbs (89%) at the 1‐month follow‐up, all 307 limbs (100%) at the 3‐month follow‐up, and all 274 limbs (100%) at the 6‐month follow‐up. No serious complication was noted. CONCLUSION Endovenous foam sclerotherapy using a microcatheter in varicose tributaries followed by EVLT in incompetent saphenous veins is a safe, effective, and technically feasible treatment for varicose veins. It not only reduces additional sclerotherapy and technical failure, but also makes multiple therapeutic sessions unnecessary. The authors have indicated no significant interest with commercial supporters.
Immunohistochemical Characterization of Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma

Myofibroblasts are differentiated contractile cells that can secrete extracellular matrix components, cytokines, proteases, and proangiogenic factors. In neoplastic processes such as oral squamous cell carcinoma (OSCC), myofibroblasts are recognized as cancer-associated fibroblasts (CAFs) and actively participate in tumor progression. As the presence of myofibroblasts in the stroma may be an important parameter of invasion and proliferation, the aim of this study was to evaluate the presence of CAFs in OSCC by immunophenotyping and their association with histologic classification and clinicopathologic parameters. A total of 34 formalin-fixed, paraffin-embedded samples of OSCC were analyzed for CAF histology and immunophenotype established on the basis of the simultaneous immunohistochemical expression of &agr;-SMA, fibronectin, FSP1, HHF35, and vimentin. According to the histologic classification of CAFs, 16 (47%) cases were classified as the mature subtype and 18 (53%) as the immature subtype. CAF immunophenotype was detected in 19 (56%) cases, and the immunophenotype was variable in 15 (44%) cases. The CAFs immunophenotype was significantly associated with the immature histologic subtype. Immunohistochemical expression of &agr;-SMA, fibronectin, FSP1, HHF35, and vimentin represents a suitable CAF immunophenotype in OSCC. The CAF immunophenotype is associated with the immature histologic subtype. The characterization of CAFs may identify tumors with a distinct biological profile in OSCC. Studies extending the investigation of CAFs to OSCC are needed to determine the actual role of this cell population as a possible prognostic marker.
Gastric acidity in older adults.

CONTEXT Early studies suggested that gastric acidity declines as people age. However, sequelae of achlorhydria are uncommon in older people, making this conventional wisdom unlikely. OBJECTIVE To ascertain the prevalence of basal gastric acidity and atrophic gastritis (indicated by serum pepsinogen ratio) in older adults. DESIGN Cross-sectional study in a volunteer sample. SETTING Retirement communities in suburbs of Kansas City, Mo. SUBJECTS A total of 248 white male and female volunteers aged 65 years or older living independently. MAIN OUTCOME MEASURES Presence of basal unstimulated gastric acid was evaluated noninvasively by having subjects swallow quininium resin. Gastric acid with a pH lower than 3.5 releases quinine, which is then absorbed and excreted into urine. Atrophic gastritis was defined as a ratio of serum pepsinogen I/pepsinogen II of less than 2.9. RESULTS Basal unstimulated gastric content was acidic (pH <3.5) in 208 (84%) of 248 elderly subjects. On retesting 66 subjects (35 normals and 31 hyposecretors), 28 (80%) of 35 had pH less than 3.5 both times, and 22 (71%) of 31 had pH of 3.5 or higher twice; in the remaining 16 subjects, low vs high gastric pH changed between tests. Weighted population prevalence estimates in this sample were 67% for consistent acid secretion, 22% for intermittent secretion, and 11% for consistent gastric pH higher than 3.5. Whereas 14 (67%) of 21 consistent hyposecretors had serum pepsinogen ratios of less than 2.9, indicating atrophic gastritis, only 2 (5%) of 44 consistent or intermittent secretors of acid had ratios in this range (P<.001). CONCLUSIONS In contrast to what is commonly stated, nearly 90% of elderly people in this study were able to acidify gastric contents, even in the basal, unstimulated state. Of those who were consistent hyposecretors of acid, most had serum markers of atrophic gastritis.
Prognosis of chronic myelomonocytic leukemia.

BACKGROUND Cytopenia caused by ineffective hematopoiesis and monocyte overproduction coexist in CMML, providing grounds for discussion to supporters of a dysplastic versus a proliferative identity for CMML. Follow-up information from a large series of patients may contribute to clarifying the position of this infrequent disease. METHODS We analyzed data from 77 patients followed in five institutions. Thirty-two variables were studied for their influence on survival and on progression to acute leukemia by univariate and multivariate analysis. For some parameters, we performed a quartile analysis to reveal a possible non-monotonic influence on survival. RESULTS Median survival was 17 months. Evolution to acute leukemia (ANLL) occurred in 11 patients (14%) within a median time of 8 months. Multivariate analysis assigned a poorer prognosis to patients presenting with thrombocytopenia, anemia and leukocytosis. Thrombocytopenia and the presence of circulating blasts were risk factors for transformation to ANLL, while raised serum aspartate transaminase at diagnosis seemed to be associated with a lower probability of blastic evolution. The Bournemouth score for CMML proved to be a valid tool for predicting survival but not acute transformation. CONCLUSIONS CMML is a severe disease. The prognostic independence of cytopenia (anemia, thrombocytopenia) and leukocytosis underlines the coexistence of aspects typical of myelodysplastic and myeloproliferative syndromes.
Homocysteine levels after acute levodopa intake in patients with Parkinson's disease

Levodopa (L‐dopa) administered with a dopadecarboxylase inhibitor (DDI) increases homocysteine plasma levels. This may support the onset of atherosclerosis‐related disorders and neuropsychiatric complications in patients with Parkinson's disease (PD). This homocysteine elevation is considered as long‐term effect of chronic L‐dopa/DDI treatment. Little is known about the acute effects of L‐dopa/DDI intake on homocysteine generation. The objective of this trial was to investigate the relations between L‐dopa and homocysteine after acute L‐dopa/DDI administration in PD patients with different L‐dopa metabolism. Thirty PD patients were divided into groups with superior (I) and less (II) L‐dopa absorption after standardized intake of 125 mg L‐dopa/benserazide with determination of L‐dopa, 3‐O‐methyl‐dopa (3‐OMD) and homocysteine in plasma at baseline, 30, 60, and 90 minutes. There was a homocysteine increase in Group I (F = 5; P = 0.005) and a moderate decrease in Group II (F = 4.27; P = 0.01). A rise of 3‐OMD (F = 10.51; P < 0.0001) appeared in Group I, but not in Group II (F = 0.91; P = 0.44), accordingly L‐dopa accumulation was better in Group I than in Group II. Thus, in conclusion, L‐dopa metabolism is an important component for homocysteine elevation after one time L‐dopa/DDI administration in PD patients. © 2009 Movement Disorder Society
Outcome of nonerosive gastro-esophageal reflux disease patients with pathological acid exposure.

AIM To assess the management and outcome of nonerosive gastro-esophageal reflux disease (NERD) patients who were identified retrospectively, after a 5-year follow-up. METHODS We included patients with gastro-esophageal reflux disease (GERD) symptoms who had a negative endoscopy result and pathological 24-h esophageal pH-monitoring while off therapy. We interviewed them after an average period of 5 years (range 3.5-7 years) by means of a structured questionnaire to assess presence of GERD symptoms, related therapy, updated endoscopic data and other features. We assessed predictors of esophagitis development by means of univariate and multivariate statistical analysis. RESULTS 260 patients (137 women) were included. Predominant GERD symptoms were heartburn and regurgitation in 103/260 (40%). 70% received a maintenance treatment, which was proton pump inhibitor (PPI) in 55% of cases. An average number of 1.5 symptomatic relapses per patient/year of follow-up were observed. A progression to erosive gastro-esophageal reflux disease (ERD) was found in 58/193 (30.0%) of patients undergoing repeat endoscopy; 72% of these were Los Angeles grade A-B. CONCLUSION This study shows that progression to ERD occurs in about 5% of NERD cases per year, despite therapy. Only two factors consistently and independently influence progression: smoking and absence of PPI therapy.
Theory of NMR signal behavior in magnetically inhomogeneous tissues: The static dephasing regime

This paper is devoted to a theory of the NMR signal behavior in biological tissues in the presence of static magnetic field inhomogeneities. We have developed an approach that analytically describes the NMR signal in the static dephasing regime where diffusion phenomena may be ignored. This approach has been applied to evaluate the NMR signal in the presence of a blood vessel network (with an application to functional imaging), bone marrow (for two specific trabecular structures, asymmetrical and columnar) and a ferrite contrast agent. All investigated systems have some common behavior. If the echo time TE is less than a known characteristic time tc for a given system, then the signal decays exponentially with an argument which depends quadratically on TE. This is equivalent to an R2* relaxation rate which is a linear function of TE. In the opposite case, when TE is greater than tc, the NMR signal follows a simple exponential decay and the relaxation rate does not depend on the echo time. For this time interval, R2* is a linear function of a) volume fraction ζ occupied by the field‐creating objects, b) magnetic field B0 or just the objects' magnetic moment for ferrite particles, and c) susceptibility difference Δχ between the objects and the medium.
Cytotoxicity of ketamine, xylazine and Hellabrunn mixture in liver-, heart- and kidney-derived cells from fallow deer.

OBJECTIVES Chemical restraint of wild animals is practiced to accomplish intended procedures such as capture, clinical examination, collection of diagnostic samples, treatment and/or transport. Extra-label use of animal medicinal drugs is often necessary in wildlife because most approved therapeutics do not list wild species on the labelling. Here, we used cellular in vitro models, a cutting-edge tool of biomedical research, to examine cytotoxicity of anaesthetic agents in fallow deer and extrapolate these data for anaesthetic risks in wildlife. METHODS We examined the cytotoxic effects of ketamine, xylazine, and ketamine-xylazine, i.e. the Hellabrunn mixture, on liver-, heart- and kidney-derived cell cultures prepared from a fallow deer (Dama dama) specimen. In line with preliminary studies we exposed cells to 10 µM, 50 µM, 100 µM, 1 mM, and 10 mM ketamine or xylazine. The combination of ketamine-xylazine was dosed at 0.025+0.02 mg/ml, 0.05+0.04 mg/ml, 0.75+0.06 mg/ml, 0.1+0.08 mg/ml, and 0.125+0.1 mg/ml per one well containing 10 000 cells. The quantification of cytotoxicity was based on lactate dehydrogenase activity released from damaged cells. RESULTS Liver-derived cells show higher sensitivity to the cytotoxic effects of both ketamine and xylazine administered as single drugs when compared with cells cultured from the heart and kidney. The Hellabrunn mixture induced significantly higher cytotoxicity for kidney-derived cells ranging from 16.78% to 35.6%. Single and combined exposures to ketamine and xylazine resulted only in high-dose cytotoxicity in the heart-derived cells. CONCLUSIONS Our results indicate that immobilization drugs significantly differ in their cytotoxic effects on cells derived from various organs of the fallow deer.
Enhancing insulin-use safety in hospitals: Practical recommendations from an ASHP Foundation expert consensus panel.

PURPOSE Consensus recommendations to help ensure safe insulin use in hospitalized patients are presented. SUMMARY Insulin products are frequently involved in medication errors in hospitals, and insulin is classified as a high-alert medication when used in inpatient settings. In an initiative to promote safer insulin use, the American Society of Health-System Pharmacists (ASHP) Research and Education Foundation convened a 21-member panel representing the fields of pharmacy, medicine, and nursing and consumer advocacy groups for a three-stage consensus-building initiative. The panel's consensus recommendations include the following: development of protocol-driven insulin order sets, elimination of the routine use of correction/sliding-scale insulin doses for management of hyperglycemia, restrictions on the types of insulin products stored in patient care areas, and policies to restrict the preparation of insulin bolus doses and i.v. infusions to the pharmacy department. In addition, the panelists recommended that hospitals better coordinate insulin use with meal intake and glucose testing, prospectively monitor the coordination of insulin delivery and rates of hypoglycemia and hyperglycemia, and provide standardized education and competency assessment for all hospital-based health care professionals responsible for insulin use. CONCLUSION A 21-member expert panel convened by the ASHP Foundation identified 10 recommendations for enhancing insulin-use safety across the medication-use process in hospitals. Professional organizations, accrediting bodies, and consumer groups can play a critical role in the translation of these recommendations into practice. Rigorous research studies and program evaluations are needed to study the impact of implementation of these recommendations.