Miracle-dz/UniFAR-FTUs huggingface dataset:
Human platelet lysate supplementation of mesenchymal stromal cell delivery: issues of xenogenicity and species variability

Immunogenicity of fetal bovine serum (FBS) poses a problem for its use in the propagation of autologous mesenchymal stromal cells (MSCs) for cell therapy. Human platelet lysate (hPL), an enriched growth factor solution containing mitogenic and angiogenic cues, has potential utility in replacing FBS for human MSC (hMSC) delivery strategies. Despite its potentiation of hMSC number in vitro, little is known concerning its capacity to supplement implanted hMSC‐seeded constructs and promote tissue regeneration in vivo. In this study, we tested the effects of incorporating hPL in cell‐seeded constructs implanted subcutaneously into immunocompromised rats, investigated in vitro interactions between hPL and rat MSCs (rMSCs) and determined interspecies variability in the PL product [hPL vs rat PL (rPL)] and its effect on cultured MSCs (hPL/hMSCs vs rPL/rMSCs). The overarching aim was to determine the utility of hPL to foster MSC survival in preclinical rodent models. Exposure to hPL‐supplemented media resulted in rMSC death, by a process attributable to heat‐labile proteins, but not membrane attack complex formation. In the in vitro syngeneic model, the rodent product proved fundamentally distinct from the human product, with rPL having substantially lower growth factor content than hPL. Moreover, contrary to the positive effects of hPL on hMSC expansion, rPL did not reduce rMSC doubling time for the serum concentrations examined. When tested in vivo, hPL did not improve cell survival within hydrogel constructs through 2 weeks postimplantation. In summary, this study highlights the many facets of xenogenicity and interspecies variability that must be considered in the preclinical evaluation of hPL. Copyright © 2016 John Wiley & Sons, Ltd.
The genetic epidemiology of bulimia nervosa.

OBJECTIVE The authors seek to clarify, from both an epidemiologic and genetic perspective, the major risk factors for bulimia nervosa and to understand the relationship between narrowly defined bulimia and bulimia-like syndromes. METHOD Personal structured psychiatric interviews were conducted with 2,163 female twins from a population-based register. Psychiatric disorders were assessed using DSM-III-R criteria. RESULTS Lifetime prevalence and risk for narrowly defined bulimia were 2.8% and 4.2%, respectively. Including bulimia-like syndromes increased these estimates to 5.7% and 8.0%, respectively. Risk factors for bulimia included 1) birth after 1960, 2) low paternal care, 3) a history of wide weight fluctuation, dieting, or frequent exercise, 4) a slim ideal body image, 5) low self-esteem, 6) an external locus of control, and 7) high levels of neuroticism. Significant comorbidity was found between bulimia and anorexia nervosa, alcoholism, panic disorder, generalized anxiety disorder, phobia, and major depression. Proband-wise concordance for narrowly defined bulimia was 22.9% in monozygotic and 8.7% in dizygotic twins. The best-fitting model indicated that familial aggregation was due solely to genetic factors with a heritability of liability of 55%. A multiple threshold model indicated that narrowly defined bulimia nervosa and bulimia-like syndromes represented different levels of severity on the same continuum of liability. CONCLUSIONS The liability to fully syndromal bulimia nervosa, which affects around one in 25 women at some point in their lives, is substantially influenced by both epidemiologic and genetic risk factors. The same factors that influence the risk for narrowly defined bulimia also influence the risk for less severe bulimia-like syndromes.
Which factors predict the long-term outcome in chronic patellofemoral pain syndrome? A 7-yr prospective follow-up study.

PURPOSE The aim of this prospective study was to determine which factors predict the long-term (7-yr) outcome of conservative treatment of chronic patellofemoral pain syndrome. METHODS The general predictors registered were age, gender, body composition, athletic activity, duration of symptoms, and follow-up time. The remaining 13 predictors were clinical or radiological measurements of the knee joint. In 45 consecutive patients, these predictors were measured at the beginning of the 6-wk treatment protocol (rest, NSAID, and intense isometric quadriceps exercises) and at the end of the follow-up. The outcome criteria were the 100-mm Visual Analog Scale (VAS) pain score, and the Lysholm and Tegner functional knee scores. RESULTS The extension strength of the affected knee was a significant predictor of the outcome scores (Lysholm score: r = 0.37, P < 0.05, and the Tegner score: r = 0.39, P < 0.01): the smaller the strength difference between the affected and unaffected knee, the better the outcome. In a multiple stepwise regression analysis, the variables pain in the patella apprehension test, patella crepitation at baseline and at follow-up, bilateral symptoms developed during the follow-up, and patient's age and height were also independent predictors of the final outcome and could together account 60% for the variation seen in the Lysholm score and 52% in the Tegner score, respectively. Neither the radiologic nor the magnetic resonance imaging changes at the affected knee had a clear association with the 7-yr outcome. CONCLUSIONS The results of the current and our previous (15) observations support the concept that restoration of good quadriceps strength and function to the affected extremity is important for good recovery of the patient. In addition, negative findings in the clinical tests of patellar pain and crepitation, nonappearance of bilateral symptoms during the follow-up, low body height, and young age are associated with good long-term outcome.
Roles of oxidative stress in activation of Kupffer and Ito cells in liver fibrogenesis

An increasing body of experimental evidence is emerging to incriminate oxidative stress as a pivotal signal for liver fibrogenesis. This paper reviews the results from our studies testing this hypothesis. In the rat model of alcoholic liver disease, the importance of oxidative stress was supported by marked accentuation of liver fibrosis by dietary supplementation of iron, a pro‐oxidant, and the significant correlation of the liver malondialdehyde (MDA) and 4‐hydroxynonenal (4HNE) levels with the hepatic collagen accumulation. Both MDA and 4HNE adduct epitopes were detected intensely and diffusely in close association with collagen deposition. The direct cause and effect relationship between MDA/4HNE and Ito cell stimulation was indicated by the demonstration of Ito cell collagen gene induction by these aldehydes in culture. In primary cultures of rat Kupffer cells (KC), addition of antioxidants such as α‐tocopherol acetate and succinate suppressed mRNA expression and the release of interleukin (IL)‐6 and tumour necrosis factor alpha (TNFα). In rats with biliary fibrosis, an increase in the liver MDA level was accompanied by enhanced mRNA expression of procollagen α 1 (I) and transforming growth factor β 1 in Ito cells; and that of TNFα and IL‐6 in KC. Furthermore, the gel shift assay of KC nuclear extracts showed enhanced NF‐kB DNA binding activity. These results support the proposal that enhanced oxidative stress constitutes an important signal for activation of Kupffer and Ito cells in experimental liver fibrogenesis.
Sentinel lymph node biopsy as guidance for central neck dissection in patients with papillary thyroid carcinoma

Occult lymph node metastasis of papillary thyroid carcinoma (PTC) can be detected by sentinel lymph node (SLN) biopsy, but studies in larger patient cohorts undergoing complete central neck dissection may be required to assess the diagnostic accuracy of SLN. Therefore, the authors prospectively assessed the usefulness of SLN biopsy for the detection of central lymph node metastasis in patients with differentiated PTC who had no suspicious cervical lymphadenopathy.
Racial disparities in breast cancer outcome

Since the 1970s, overall age‐adjusted breast cancer mortality rates in the U.S. have been higher among African American (AA) women than among Caucasian American (CA) women. The racial disparity is not fully explainable based on socioeconomic factors. Suspected biologic factors underlying this trend may be interpreted by both epidemiologic and clinical perspectives. Descriptive epidemiologic studies suggest that breast cancer may be a mixture of at least 2 main diseases and/or causal pathways. The first breast cancer is early‐onset, with peak incidence near age 50 years and generally more aggressive outcome. The second breast cancer is late‐onset, with peak incidence near age 70 years and more indolent course. The early‐onset type of breast cancer is overrepresented among AA women compared with CA women. Clinical studies suggest that the course of breast cancer may be characterized by a common pathway through sequential dormant and active states eventually resulting in clustered appearance of clinical metastases. A balance between tumor and host traits influences the pace of the common pathway. Therefore, the recurrence risk profile of a single patient is seemingly determined by a specific mix of hierarchical prognostic factors, resulting from the unique genetic, environmental, or behavioral traits of that individual, which may be affected by race‐related factors. We suggest that the components of the AA versus CA disparity not attributable to socioeconomic factors are a particular case of the more general issue of host‐tumor interaction and that epidemiologic and clinical views are complementary; each is observing biologic parameters, which are not completely captured by the other. A ‘unifying hypothesis’ incorporating findings from genetics, epidemiology, and clinical studies should be aggressively pursued. Cancer 2007. © 2007 American Cancer Society.
Cholangiocarcinoma in a Ring-Necked Pheasant (Phasianus colchicus): a case report

A case of cholangiocarcinoma in a two-year-old Ring-Necked Pheasant (Phasianus colchicus) is reported. The liver was enlarged and numerous white foci were seen in the liver parenchyma. Histopathologically, channels with or without lumens and separated from one another by thin connective tissue septa were observed. Tumour cells were strongly positive for cytokeratin, Ki-67 and proliferative cell nuclear antigen. This is the first report of colangiocarcinoma in pheasants.
Genetic and environmental causes of covariation among blood pressure, body mass and serum lipids during young adulthood: a twin study.

OBJECTIVE To determine the extent to which the correlation of systolic blood pressure, diastolic blood pressure, body mass, fasting total cholesterol and fasting triglycerides in young adulthood reflects common genetic or environmental influences. DESIGN Cardiovascular risk factors were measured in a community sample of 129 monozygotic and 67 dizygotic twin pairs, ages 18-30 years. METHODS Multivariate twin structural equation modelling allows estimation of the extent to which the covariation of two or more variables is attributable to common genetic and environmental factors and was used to analyse the correlation among systolic blood pressure, diastolic blood pressure, body mass index, fasting total cholesterol and triglycerides. RESULTS The covariation of risk factors was partially attributable to a single common genetic factor, while the covariation of systolic blood pressure, body mass index and triglycerides was also, in part, attributable to a common non-shared environmental factor. CONCLUSIONS Genetic and, to a lesser extent, non-shared environmental factors contribute to the covariation of cardiovascular risk factors in young adult twins. Nonetheless, it should be noted that these common influences account for a relatively small percentage of the variance in each risk factor compared to genetic and environmental factors that are risk factor-specific.
Electrically Controllable Light Trapping for Self-Powered Switchable Solar Windows

The ability to electrically control transparency and scattering of light is important for many optoelectronic devices; however, such versatility usually comes with additional unwanted optical absorption and power loss. Here we present a hybrid switchable solar window device based on polymer dispersed liquid crystals (PDLCs) coupled to a semiconducting absorber, which can switch between highly transmissive and highly scattering states while simultaneously generating power. By applying a voltage across the PDLC layer, the device switches from an opaque, light-scattering structure (useful for room light dimming, privacy, and temperature control) to a clear, transparent window. Further, enabled by the very low operating power requirements of the PDLC (<0.8 mW/cm2), we demonstrate that these switchable solar windows have the potential for self-powering with as little as 13 nm of a-Si.
Asymptotic Properties of Estimators for the Linear Panel Regression Model with Individual Effects and Serially Correlated Errors: The Case of Stationary and Non-Stationary Regressors and Residuals

This paper studies the asymptotic properties of standard panel data estimators in a simple panel regression model with error component disturbances. Both the regressor and the remainder disturbance term are assumed to be autoregressive and possibly non-stationary. Asymptotic distributions are derived for the standard panel data estimators including ordinary least squares, fixed effects, first-difference, and generalized least squares (GLS) estimators when both T and n are large. We show that all the estimators have asymptotic normal distributions and have different convergence rates dependent on the non-stationarity of the regressors and the remainder disturbances. We show using Monte Carlo experiments that the loss in efficiency of the OLS, FE and FD estimators relative to true GLS can be substantial.
Detection of putative adduct with fluorescence characteristics identical to 2,3-dihydro-2-(7'-guanyl)-3-hydroxyaflatoxin B1 in human urine collected in Murang'a district, Kenya.

Food samples collected in Murang'a district, Kenya are known to be contaminated with a mycotoxin, aflatoxin B1 (AFB), and a positive correlation exists between the dietary intake of AFB and the incidence of liver cancer. When urine samples collected in this district were analyzed for the presence of 2,3-dihydro-2-(7'-guanyl)-3-hydroxyaflatoxin B1 (AFB-GuaI) by h.p.l.c. , 6 of 81 samples had a detectable level of a compound whose fluorescence spectrum was identical to chemically synthesized AFB-GuaI as confirmed by photoncounting fluorescence spectrophotometry. These results are an indication of interaction between the ultimate carcinogenic form of AFB and cellular nucleic acids in vivo and further support the hypothesis that AFB may play an important role in the etiology of human liver cancer.
Metabolic Syndrome and Mammographic Density in Mexican Women

Metabolic syndrome has been associated with an increased risk of breast cancer; however, little is known about the association between metabolic syndrome and percent mammographic density, a strong predictor of breast cancer. We analyzed cross-sectional data from 789 premenopausal and 322 postmenopausal women in the Mexican Teacher's Cohort (ESMaestras). Metabolic syndrome was defined according to the harmonized definition. We measured percent density on mammograms using a computer-assisted thresholding method. Multivariable linear regression was used to estimate the association between density and metabolic syndrome, as well as its components by state (Jalisco, Veracruz) and menopausal status (premenopausal, postmenopausal). Among premenopausal women in Jalisco, women with metabolic syndrome had higher percent density than those without after adjusting for potential confounders including BMI [difference = 4.76; 95% confidence interval (CI), 1.72–7.81]. Among the metabolic syndrome components, only low high-density lipoprotein levels (<50 mg/dL) were associated with significantly higher percent density among premenopausal women in Jalisco (difference = 4.62; 95% CI, 1.73–7.52). Metabolic syndrome was not associated with percent density among premenopausal women in Veracruz (difference = −2.91; 95% CI, −7.19 to 1.38), nor among postmenopausal women in either state. Metabolic syndrome was associated with higher percent density among premenopausal women in Jalisco, Mexico, but was not associated with percent density among premenopausal women in Veracruz, Mexico, or among postmenopausal women in either Jalisco or Veracruz. These findings provide some support for a possible role of metabolic syndrome in mammographic density among premenopausal women; however, results were inconsistent across states and require further confirmation in larger studies. Cancer Prev Res; 6(7); 701–10. ©2013 AACR.
Neurochemical Correlates of Cocaine and Ethanol Self‐Administration a

Self-administration procedures have been an effective tool to study the neuropharmacology of psychostimulant and opiate reward.14 On the basis of this work, biological theories of drug reinforcement have emerged that center around the assumption that drugs of abuse directly or indirectly activate central “reward substrates” that mediate motivated behavior and reinfor~ement. ~-~ In particular, self-administration studies have established an important role for dopamine in the acute reinforcing effects of psychostimulant drugs including cocaine and &amphetamine. 10-13 Relative to the advances in identifjmg critical circuitries for psychostimulant reward, little is known about the neuropharmacological bases of ethanol reward. Progress toward the identification of neurobiological substrates of ethanol reward has been impeded, in part, by the difficulty in establishing orally presented ethanol as a reinforcer in the absence of food or fluid restrictions, or the addition of sweetenen (for review see re&. 14-16). However, novel procedures for the initiation of ethanol self-administration have recently been developed in which oral ethanol intake is maintained more clearly by pharmacological motivation rather than nutritional appetite or thirst.15. 17 These models may allow a systematic exploration of the physiological systems involved in ethanol preference and reward. A number of neuropharmacological investigations using these procedures have since suggested a role for dopamine neurotransrnission in low-dose ethanol reinforcementlsJ9 (Samson et al., this volume). The present series of experiments sought to extend previous work on the role of dopamine in cocaine and ethanol
No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARδ and PPAR&ggr; act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma

Objectives Regular continuous non-steroidal anti-inflammatory drug (NSAID) use has been associated with a reduction in risk of colorectal cancer. Our objective was to investigate whether or not a number of the polymorphic genes involved in the metabolism of NSAIDs, including cytochrome P450 s (CYPs), act as modifiers of this protective effect. Methods As part of a multi-centre case–control study, 478 colorectal cancer patients and 733 controls (433 matched case–control pairs) answered questions on NSAID use. These individuals were then genotyped for common polymorphisms in P450 CYP2C8, P450 CYP2C9, UDP-glucuronosyl transferase (UGT)1A6 and peroxisome proliferator-activated receptor isoforms δ and &ggr; (PPARδ and PPAR&ggr;). Results and conclusion Our study confirmed the reduction in risk of colorectal cancer with regular NSAID use (odds ratio (OR)=0.73, 95% confidence interval (CI) (0.56, 0.95)) but showed that none of the polymorphic genes studied appeared to modify the protective effect of regular NSAID use.
Interprofessional clinical education of medical and pharmacy students

Pharmacists have become increasingly involved in influencing prescribing. Pharmaceutical education has changed accordingly, with increased teaching in therapeutics, partly on hospitals wards, giving students an insight into diseases and helping communication with clinicians. To extend this idea we have designed joint therapeutics teaching sessions with pharmacy and medical students. The scheme involves final year pharmacy students who have completed a course in clinical pharmacy and medical students who have completed their second MB. Interdisciplinary pairs of students are assigned a patient with common medical and therapeutic problems, such as arthritis, diabetes and cardiac failure; patients on multiple drug treatments are preferred. They jointly obtain a history: the medical student performs basic clerking, while the pharmacy student obtains the medication history. The medical student subsequently presents a brief medical history, with a summary of the patient's current problems. For each problem, the pharmacy student presents the current therapy, its rationale and how it is to be monitored. Experience with 73 students over 3 years has shown that almost all found sessions with students from another discipline useful. Few felt that members of the pairs contributed unequally. The main problem appeared to be insufficient time (although 2 1/2 h were allowed). Most students favoured more such sessions. Little difference in ability appeared between the two disciplines; there was considerable co‐operation and little nascent ‘professional rivalry’. The medical students were more comfortable interviewing patients, and the pharmacy students more confident analysing drug therapy. It is concluded that such interdisciplinary sessions are a successful method of clinical teaching and should be encouraged.
Low CD49d expression and long telomere identify a chronic lymphocytic leukemia subset with highly favourable outcome

CD49d expression and telomere length (TL) represent novel prognostic markers for chronic lymphocytic leukemia (CLL) [1―7]. The prognostic information carried by CD49d expression and TL in CLL has its rationale in the disease biology. CD49d is an adhesion molecule mediating cell-to-cell and cell-to-extracellular matrix interactions [8]. In CLL cells, CD49d transmits prosurvival/antlapoptotic signals from the tumor microenvironment to tumor cells [9]. Telomeres ensure genetic stability and regulate critical cellular functions, including proliferation and senescence [10]. In CLL, short TL associates with a fast proliferative history of the leukemic cells [1,11,12]. Both CD49d expression and short TL have been associated with increased genetic instability of the CLL clone [3,13]. From a clinical standpoint, a peculiar feature shared by CD49d expression and short TL is the association with CLL proliferation markers, including expression of CD38, high lactate dehydrogenase (LDH), high β-2-microglobulin, short time to lymphocyte doubling, and short time to progression to a more advanced stage [1―7]. Here, we tested whether the concomitant presence of high CD49d expression and short TL in the same CLL patient may help refine disease stratification for treatment prediction in patients that presented in early to intermediate Binet stage (Binet A and B) and that are candidate to watch and wait as initial management.
Re‐evaluation of the L‐dopa loading effect on dopamine metabolism in rat striatum

Investigation by HPLC with electrochemical detection of dopamine (DA) metabolism in rat striatum after L‐dopa + benserazide treatment allowed quantification of the time course evolution of DA, 3,4‐dihydroxyphenylacetic acid and homovanillic acid levels. Furthermore, four peaks which did not appear in controls, were detected in treated striatum. One was identified as 3‐methoxytyrosine, the level of which was still high 9 h after treatment. 3‐Methoxytyrosine, has been detected previously in plasma of parkinsonian patients treated with L‐dopa, and the disturbance in DA metabolism could explain some of the side‐effects induced by that treatment.