Miracle-dz/UniFAR-FTUs huggingface dataset:
Alpha‐synuclein promoter haplotypes and dementia in Parkinson's Disease

Dementia is a common complication of Parkinson's disease (PD). It correlates significantly with the presence of cortical, limbic or nigral Lewy bodies, mainly constituted of alpha‐synuclein. Mutations of the alpha‐synuclein gene (SNCA) have been linked to rare familial forms of PD, while association studies on the promoter polymorphisms have given conflicting results in sporadic patients. We have performed a case control study to investigate whether genetic variability in the promoter of the alpha‐synuclein gene could predispose to dementia in PD. A total of 114 demented patients and 114 non‐demented patients with sporadic PD were included in the study. Six polymorphic loci (including the Rep1 microsatellite) in the promoter of the SNCA gene were examined. Each marker, taken individually, did not show association to dementia and no significant differences were observed in the inferred haplotype frequencies of demented and non‐demented patients. Our data suggest the lack of involvement of the SNCA promoter in the pathogenesis of dementia in PD. Further studies in other populations are needed to confirm these results. © 2007 Wiley‐Liss, Inc.
Comparing the Validity of Self-Reported Recent Drug Use Between Adult and Juvenile Arrestees

Abstract A large body of literature has explored the validity of self-reported drug use among criminal populations. These works have typically revealed strong underreporting of recent illicit drug use. To date, however, no studies have compared the validity of self-reported drug-using behaviors between adult and juvenile offenders. The authors overcome this limitation by assessing the validity of self-reported recent drug use with data collected from 1,425 adult and 551 juvenile Los Angeles arrestees surveyed through the Arrestee Drug Abuse Monitoring (ADAM) Program in 1997. Kappa statistics were computed and tests for specificity and sensitivity were conducted utilizing urinalysis as the reference standard. Results suggest that adult arrestees are more inclined to underreport their recent use of illicit drugs. Implications for drug use research are assessed in light of the current findings.
Heterogeneous rates for birth defects in Latin America: Hints on causality

The aim of this work was to disclose risk factors associated with birth defects which were heterogeneously distributed in the different geographic regions sampled by the Latin American Collaborative Study of Congenital Malformations (ECLAMC). The material included 2,159,065 hospital births, delivered in the 1967–1989 period in 24 geographic regions of Latin America. Birth defect types with 50 case‐control pairs or more were analyzed. A risk factor was defined as that available variable with differential geographic rates, correlated with those of a given birth defect type. Identified factors were tested by case‐control multivariate logistic regression to confirm their role in the occurrence of the defect. Altitude and maternal acute illness during first trimester of pregnancy, named influenza, were risk factors for microtia. Prenatal drug exposure, mainly sex hormones, were connected with the occurrence of hypospadias in low frequency areas, while Native ancestry was a “protective” factor in the same regions. Acute (influenza), and chronic (epilepsy and syphilis) maternal illness during first trimester of pregnancy and gravidity higher than four were risk factors for cleft lip. The independence of these variables from maternal age suggested that low maternal socioeconomic level could explain the high birth defect order and, perhaps, syphilis in mothers. Postaxial polydactyly was associated with parental consanguinity, as well as Afro‐American ancestry, suggesting genetic heterogeneity. © 1996 Wiley‐Liss, Inc.
Whole-body heat exchange during heat acclimation and its decay.

PURPOSE The purpose of this study was to quantify how much whole-body heat loss increases during heat acclimation and the decay in these improvements after heat acclimation. METHODS Ten males underwent a 14-d heat acclimation protocol that consisted of 90 min of cycling in the heat (40°C, 20% relative humidity) at approximately 50% of maximum oxygen consumption. Before (day 0), during (day 7), and at the end (day 14) of the heat acclimation protocol as well as 7 and 14 d after heat acclimation (days 21 and 28), whole-body heat exchange (evaporative and dry) was measured using direct calorimetry during three bouts of 30-min exercise at 300 (Ex1), 350 (Ex2), and 400 W·m (Ex3), each separated by 10 and 20 min of recovery, respectively, at 35°C and 16% relative humidity. Concurrent measurements of metabolic heat production (indirect calorimetry) allowed for the direct calculation of change in body heat content (ΔHb). RESULTS After accounting for an increase in net dry heat gain, increases in whole-body evaporative heat loss were evident for Ex2 and Ex3 on day 7 (Ex2, 4.9 ± 5.6%; Ex3, 9.0 ± 6.0%; both P ≤ 0.05) and all heat loads on day 14 (Ex1, 7.6 ± 8.3%; Ex2, 7.7 ± 5.5%; Ex3, 11.2 ± 4.6%; all P ≤ 0.05) relative to day 0 (Ex1, 494 ± 27 W; Ex2, 583 ± 21 W; Ex3, 622 ± 36 W). As a result, a lower cumulative ΔHb was measured on day 7 (-18 ± 8%, P ≤ 0.001) and day 14 (-26 ± 10%, P ≤ 0.001) compared with that measured on day 0 (1062 ± 123 kJ). Most of these improvements were retained after 2 wk of nonexposure to the heat. CONCLUSIONS This is the first study to quantify how much 14 d of heat acclimation can increase whole-body evaporative heat loss, which can improve by as much as approximately 11%.
Seed predation and defleshing in the agouti-dispersed palm Astrocaryum standleyanum

Abstract: The agouti (Dasyprocta punctata) meticulously defleshes Astrocaryum standleyanum palm seeds before scatter hoarding. On Barro Colorado Island, Panama, we experimentally tested three hypotheses on how this behaviour could reduce seed predation to the mutual benefit of the tree and the rodent. The first and established hypothesis – that defleshing reduces seed predation by bruchid beetles by intercepting larvae – was rejected. Experiments in which manually defleshed seeds or entire fruits were incubated at different times showed that defleshing reduced bruchid infestation before fruit fall but not after fruit fall. The second hypothesis – that defleshing reduces cache pilferage by making seeds less conspicuous – was supported. An experiment in which intact fruits and manually defleshed seeds were placed in mimicked agouti caches and followed showed that seeds with flesh were pilfered at higher rates than defleshed seeds. The third hypothesis – that defleshing reduces post-dispersal infestation of cached seeds – was rejected. An experiment in which intact fruits and manually defleshed seeds were placed in mammal exclosures and later collected to assess infestation showed that burial reduced seed infestation but defleshing did not. Thus, seed defleshing reduced palm seed predation, but in a different way than previously believed. We also found that (1) bruchid beetles can be pre-dispersal rather than post-dispersal seed predators, (2) seed infestation by scolytid beetles may control bruchid larvae, and (3) scolytids rather than bruchids are the main invertebrate seed predators of this palm.
Allergic contact dermatitisPierre

Article accepted on 15/4/2004 Contact dermatitis is an inflammatory skin condition induced by exposure to an environmental agent. Eczema and dermatitis are used synonymously to denote a polymorphous pattern of skin inflammation characterized at least in its acute phase by erythema, vesiculation and pruritus. Substances responsible for contact dermatitis after single or multiple exposures are non protein chemicals, i.e. haptens, that induce skin inflammation through activation of innate skin immunity (irritant contact dermatitis) or both innate and acquired specific immunity (allergic contact dermatitis). The present review will focus on allergic contact dermatitis, a delayed-type hypersensitivity reaction, which is mediated by hapten-specific T cells. Recent advances in the pathophysiology of ACD have shown that the occurrence of ACD, as well as its magnitude and duration, is controlled by the opposite functions of CD8 effector T cells and CD4 regulatory T cells. From these studies ACD can be considered as a breakdown of cutaneous immune tolerance to haptens.
Vibrio cholerae O395 Outer Membrane Vesicles Modulate Intestinal Epithelial Cells in a NOD1 Protein-dependent Manner and Induce Dendritic Cell-mediated Th2/Th17 Cell Responses*

Background: Vibrio cholerae, the etiologic agent of cholera, secretes outer membrane vesicles (OMVs) that are internalized into host cells. Results: OMVs activate an inflammatory response in intestinal epithelial cells (ECs) via a NOD1-dependent pathway that activates dendritic cells (DCs) and promotes T cell polarization toward Th2/Th17 responses. Conclusion: OMVs stimulate EC-DC cross-talk in generating an inflammatory response. Significance: Findings are important for the development of efficient vaccine strategies with OMVs. Like other Gram-negative pathogens, Vibrio cholerae, the causative agent of the diarrheal disease cholera, secretes outer membrane vesicles (OMVs). OMVs are complex entities composed of a subset of envelope lipid and protein components and play a role in the delivery of effector molecules to host cells. We previously showed that V. cholerae O395 cells secrete OMVs that are internalized by host cells, but their role in pathogenesis has not been well elucidated. In the present study, we evaluated the interaction of OMVs with intestinal epithelial cells. These vesicles induced expression of proinflammatory cytokines such as IL-8 and GM-CSF and chemokines such as CCL2, CCL20, and thymic stromal lymphopoietin in epithelial cells through activation of MAPK and NF-κB pathways in NOD1-dependent manner. Epithelial cells stimulated with OMVs activated dendritic cells (DCs) in a direct co-culture system. Activated DCs expressed high levels of co-stimulatory molecules; released inflammatory cytokines IL-1β, IL-6, TNF-α, and IL-23 and chemokines CCL22 and CCL17; and subsequently primed CD4+ T cells leading to IL-4, IL-13, and IL-17 expression. These results suggest that V. cholerae O395 OMVs modulate the epithelial proinflammatory response and activate DCs, which promote T cell polarization toward an inflammatory Th2/Th17 response.
Effect of papaya supplementation on oxidative stress markers in Parkinson's disease

Objective: In Parkinson’s disease (PD), oxidative processes occur that are probably involved in the progression of neuronal damage. Recent studies suggest that regular consumption of antioxidant-rich foods or supplementation with functional foods like fermented papaya, may reduce cellular oxidative stress and protect against many age-related diseases by strengthening the physiological antioxidant barrier. Our study aims to assess the antioxidant properties of a commercial fermented papaya preparation (FPP) in PD by evaluation of its effects on a wide panel of oxidative stress markers in blood and urine. Methods: A group of parkinsonian voluntary patients (T, n = 15) were treated 9 months with FPP and compared with a control group (NT, n = 12). The efficacy of FPP in increasing the physiological antioxidant barrier was evaluated at the times 0, 6 and 9 months with the analysis of 23 oxidative markers including total radical oxygen species, homocysteine, biological antioxidant potential, glutathione, superoxide dismutase, uric acid, total bilirubin, iron, ferritin, coenzyme Q10, 3-nitrotyrosine, total lipoperoxide, 4-hydroxy-nonenal, 8-hydroxydeoxyguanosine (8-OHdG) and 2-deoxyguanosine (2-dG). Results: Among the considered markers, twenty not showed significant differences at times 0, 6 and 9 months between T and NT patients, demonstrating a consequent non-significant effect of FPP supplementation. Instead, three urinary markers of oxidative stress on nucleic acids, 8-OHdG/2-dG, 2-dG/uric acid and 2-dG/creatinine showed statistical significant interactions between ‘time’ and ‘treatment’, highlighting an effective better response to oxidative attack for T than NT. Conclusions: Papaya supplementation for a medium-long time seems able to affect positively the turnover of oxidized nucleic acids helping to restore the normal nitrogenous bases into nucleotide chains and to replace those altered by radicals’ attack.
survey overweight and obesity worldwide : international Establishing a standard definition for child

Objective To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points. Design International survey of six large nationally representative cross sectional growth studies. Setting Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States. Subjects 97 876 males and 94 851 females from birth to 25 years of age. Main outcome measure Body mass index (weight/height). Results For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2-18 years. Conclusions The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
Patients’ experience with ambulatory urodynamics

Objective. To assess emotional variables in patients who underwent ambulatory urodynamic monitoring (AUM). Material and methods. A total of 33 females and 7 males aged 23–72 years with an overactive bladder who had undergone three consecutive AUM sessions were included in the study on a prospective basis. Patients completed a self-administered questionnaire before and immediately after each procedure. Answers were given using a visual analog scale. Results. The pre-procedural level of anxiety did not differ significantly with respect to sex, age, education level or income. The degree of bother experienced by patients aged ≥ 50 years was higher than for those aged < 50 years: 5 vs 2.5 (p=0.030). As income increased, the degrees of pain (p=0.016), bother (p=0.013) and boredom (p=0.010) decreased. Other emotional aspects did not differ significantly according to age or income (p>0.05). Only the subjective bother score influenced the examiner-rated degree of intolerance during AUM (p=0.007). A total of 34 patients (85.0%) indicated that they would be willing to return for a further session of AUM. The degree of intolerance decreased at the second (p=0.006) and third (p=0.049) AUM sessions, whereas other parameters were not significantly different. Conclusion. Our results demonstrate that AUM is acceptable and well tolerated by patients with bladder dysfunction.
TGF-beta production regulates the development of the 2,4,6-trinitrophenol-conjugated keyhole limpet hemocyanin-induced colonic inflammation in IL-2-deficient mice.

A severe, Th1-mediated experimental colitis with similarities to inflammatory bowel disease in humans can be induced by a single injection of 2,4,6-trinitrophenol (TNP)-substituted protein plus adjuvant in IL-2-/- mice. To determine the early events involved in the pathogenesis of IL-2-/-colitis, we compared the function of lamina propria (LP) T cells from IL-2-/- and IL-2+/+ mice subjected to disease-inducing (TNP-conjugated keyhole limpet hemocyanin [TNP-KLH]) and disease-inhibiting (anti-CD3) immunization protocols. We show that LP T cells in TNP-KLH-immunized IL-2-/- mice fail to produce TGF-beta early (day 2), whereas LP T cells in TNP-KLH-immunized IL-2+/+ mice exhibit an approximately eightfold rise in TGF-beta secretion. The critical importance of local TGF-beta production was further substantiated by the following findings. 1) LP T cells from TNP-KLH-immunized IL-2-/- mice administered anti-CD3 (i.p.) exhibit a significant rise in TGF-beta, production but fail to produce IFN-gamma, and such mice do not develop colitis. 2) TNP-KLH-immunized IL-2-/- mice administered anti-CD3 and coadministered anti-TGF-beta mAb again give rise to IFN-gamma-producing LP cells, and such mice develop colitis. 3) TNP-KLH-immunized IL-2+/+ mice administered anti-TGF-beta mAb exhibit pockets of mononuclear cell infiltrates in the LP. These results indicate that the disposition of IL-2-/- mice to develop chronic colonic inflammation is due to a Th1 cell response in the LP that is not appropriately counter-regulated by the production of the suppressor cytokine, TGF-beta.
Development of Cutaneous Toxicities During Selective Anti-BRAF Therapies: Preventive Role of Combination with MEK Inhibitors.

Activated BRAF mutations affecting the mitogen-activated protein kinases (MAPK) pathway are present in 50% of metastatic melanomas. Targeted therapies have been developed to block such mutations (1, 2). There is a risk of other components of the MAPK signalling pathway, such as MEK, being reactivated after the use of BRAF inhibitors (3–5). Given the evidence of drug resistance and side-effects of BRAF inhibitors, combined treatments with BRAF and MEK inhibitors are being tested in clinical trials for metastatic melanoma. Trametinib is one of these MEK inhibitors. Skin toxicities from BRAF inhibitors, such as photosensitivity, palmoplantar keratoderma (PPK) and keratosis pilaris (KP), have been reported (4, 6–11). Also, non-melanoma skin cancers (NMSC) are considered one of the most significant sideeffects (3, 11). We report here the profile of skin toxicities from vemurafenib, dabrafenib alone, or dabrafenib and trametinib combined treatment.
Apoptosis in prostatic adenocarcinomas; a study of relationship to Ki-67 and Bcl-2 protein expression.

BACKGROUND Tissue samples from patients with prostatic adenocarcinoma (PCA) were examined for relationship between apoptosis and expression of Ki-67 and bcl-2 protein. MATERIALS AND METHODS Prostatic tissue was obtained from 29 prostatic cancer patients with no prior therapy. The number of apoptotic cells (apoptotic index; AI) and the percentage of Ki-67 stained cells (Ki-67 labeling index; LI) were compared with the expression of bcl-2 which was evaluated by the proportion and intensity of tumor cell immunostaining. RESULTS Both AI and LI of moderately and poorly differentiated PCAs were significantly higher than those of well differentiated PCAs. There was a significant correlation between AI and LI. Bcl-2 protein was expressed less in moderately and poorly differentiated PCAs than in well differentiated PCAs. Moreover, there was no correlation between the bcl-2 protein expression and the AI. CONCLUSIONS The results suggest that, in PCAs, the degree of apoptosis is correlated with the cellular proliferation, and that expression of bcl-2 protein is not a critical factor that determines the degree of apoptosis.
Prostaglandin E 2 – Induced Aldosterone Release Is Mediated by an EP 2 Receptor

Prostaglandin E2 (PGE2) is an endogenous hormone of adrenal zona glomerulosa cells and is released in response to stimulation by agonists such as angiotensin II (Ang II). It stimulates the release of aldosterone from cultured bovine adrenal zona glomerulosa cells. These studies were designed to determine whether this steroidogenic effect of PGE2 was mediated by an EP1, EP2, or EP3 receptor. Prostaglandin E2 and 11-deoxy PGE1, an EP2-selective agonist, stimulated aldosterone release in a concentration-related manner with an ED50 of 300 nmol/L for PGE2 and 2 mmol/L for 11-deoxy PGE1. The maximal effect of PGE2 was less than that of angiotensin II. 17-Phenyl trinor PGE2, an EP1-selective agonist, required concentrations of 100 mmol/L to stimulate aldosterone release and sulprostone, an EP3/EP1-selective agonist, failed to alter aldosterone release. The EP1-selective antagonist SC19220 failed to alter basal or PGE2-stimulated aldosterone release over a range of concentrations. PGE2 and 11-deoxy PGE1 also stimulated an increase in both intracellular and extracellular cAMP. This increase was timeand concentration-related. The ED50 for PGE2 was 9.8 mmol/L. 17-Phenyl trinor PGE2 and sulprostone were without effect. Using fura-2 loaded cells, PGE2 (2 mmol/L), dibutyryl cAMP (2 mmol/L), and Ang II (2 mmol/L) increased intracellular calcium over basal concentrations by 5.5-fold, 3-fold, and 6.2-fold, respectively. Like PGE2, dibutyryl cAMP also stimulated aldosterone release. PGE2and dibutyryl cAMP–induced aldosterone release were blocked by the calcium channel inhibitor diltiazem. These studies indicate that PGE2 is a potent stimulus for aldosterone release and that the effect is mediated by EP2 receptors. Both cAMP and calcium appear to mediate the steroidogenic effect of PGE2 and calcium seems to be distal to cAMP. (Hypertension. 1998;31:575-581.)
Impaired uptake of β-carotene by Caco-2 human intestinal cells in the presence of iron

At present, there are conflicting data regarding whether or not β-carotene has a positive effect on iron absorption. This study was undertaken to evaluate possible interactions involved in the uptake of β-carotene and iron in a human intestinal cell model (Caco-2). The Caco-2 cells were incubated with test solutions containing different amounts of ferrous chloride (10–50 µM) and β-carotene (0.3–2.5 µM) incorporated in synthetic micelles. In the absence of iron, cellular accumulation of β-carotene from synthetic micelles was proportional (r2=0.97, P <0.001) to the β-carotene concentration in the test solution. However, with addition of ferrous chloride (30 µM), the β-carotene uptake was significantly reduced (P <0.05), on average by 22%. There was also an inverse relationship between the β-carotene uptake and iron concentration in the test solution (r2=0.93, P <0.05). Iron provided in physiological amounts inhibited the uptake of β-carotene in the in vitro Caco-2 cell system.
MEASUREMENT OF MENSTRUAL BLOOD LOSS IN PATIENTS COMPLAINING OF MENORRHAGIA

A study has been made of menstrual blood loss measured in 50 women with unexplained heavy loss (more than 80 ml). Twelve of these women had an average menstrual loss greater than 200 ml, five women in excess of 450 ml. There was no relation between the duration of menstruation and the total menstrual blood loss. Compared to women with normal menstrual loss there was no difference either in the proportion of total menstrual loss passed on each day of menstruation in women bleeding heavily (92 per cent of the total menses being lost in the first three days) or in the coefficient of variation for menstrual blood loss from one period to the next. There was a reduction in menstrual blood loss in the first period following uterine curettage but no effect thereafter.
Magnetic-susceptibility and electrical-resistivity measurements on RPdSn (R=Ce-Yb) compounds.

Magnetic-susceptibility and electrical-resistivity measurements have been carried out on equiatomic ternary compounds, RPdSn (R=Ce-Yb), in the temperature range 4.2 and 300 K. The compounds EuPdSn and YbPdSn have been synthesized. As-cast RPdSn (R=Ce-Yb) compounds crystallize in the orthorhombic TiNiSi-type structure. However, on annealing at 950 °C, Er- and Tm-containing compounds transform to hexagonal Fe2P-type structure. Magnetic-susceptibility measurements reveal that the compounds with R=Ce, Sm, Eu, Gd, Tb, Dy, and Er order antiferromagnetically with Neel temperatures (TN) of 7.5, 11, 13, 14.5, 23.5, 11.4, and 5.6 K, respectively. The compounds with R=Pr, Nd, Ho, and Tm are paramagnetic down to 4.2 K. Susceptibility of YbPdSn shows Curie-Weiss behavior between 300-150 K with μeff=1. 45μB and deviates considerably from it below 150 K. The electrical resistivity of all these compounds exhibits metallic behavior and shows a sharp drop at the respective Neel temperatures. The TN of the RPdSn series does not follow de Gennes scaling and, instead, peaks at Tb. This behavior of TN can be understood on the basis of crystalline-electric-field effects.