Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurobiological Correlates of Autism: A Review of Recent Research

This review paper integrates recent structural and functional imaging, postmortem, animal lesion, and neurochemical research about the pathophysiology of autism. An understanding of the neurobiological correlates of autism is becoming increasingly important as more children are diagnosed with the condition and funding for well-targeted interventions increases. Converging evidence suggests that autism involves abnormalities in brain volume, neurotransmitter systems, and neuronal growth. In addition, evidence firmly links autism with abnormalities in the cerebellum, the medial temporal lobe, and the frontal lobe. Potential implications of these findings and suggestions for future research are reviewed.
Dental anxiety and temperament in 15-year olds.

OBJECTIVE The aim of the present study was to analyze the prevalence of dental anxiety and its association with temperament, sociodemographic factors and previous painful and unpleasant experiences of dental care among 15-year old individuals. MATERIALS AND METHODS The sample included 263 randomly selected 15-year old individuals living in the municipality of Jönköping, Sweden. The school, parental and adolescent consent was acquired. Three self-reported questionnaires were used, one included items of sociodemography, while the others dealt with dental anxiety assessed by the Dental Fear Survey (DFS) and temperament assessed by an adapted version of The EAS Temperament Survey for Children modified for adults, the EASI temperament survey. RESULTS The results showed that 6.5% of the adolescents were classified as dentally anxious and with girls proportionally more fearful than boys. The three temperaments activity, impulsivity and emotionality were significantly correlated with dental anxiety. A hierarchical multiple linear regression analysis showed that pain at the last dental appointment or previous pain experiences during dental care treatment were the strongest predictors regarding dental anxiety in 15-year olds. The temperament dimensions activity and impulsivity were also significantly predictive of dental anxiety. CONCLUSIONS Although some of the temperament dimensions are correlated with dental anxiety, which may emphasize an important finding with regard to personality, this study showed that previous pain experiences during dental care treatment is a strong predictor for high dental anxiety in 15-year olds.
Randomized study of biennial screening with a faecal occult blood test: results after nine screening rounds

Background: Two large true population studies in Europe have shown a significant reduction in mortality from colorectal cancer (CRC) by screening with a faecal occult blood test. In one trial conducted in Funen County, 61,933 individuals (aged 45–75 years) were randomly allocated either to a control group or to receive a biennial Hemoccult‐II test. Methods: These individuals were followed from 1985 to 2002 and 9 screening rounds were performed. Results: First screening was accepted by 67% (20,672). Positivity rates varied between 0.8% and 3.8%, and the cumulative proportion of the test group having colonoscopy was 5.3%. Screen‐detected CRC was early (Dukes' A) in 36% compared to 11% among controls. Incidence of CRC was unchanged, but mortality was reduced by 11%. This figure increased to 43% in persons participating in all 9 rounds. No more than 8,558 were screened at the 9th round. Patients with CRC detected between screenings had better survival than controls. Death rates from causes other than CRC among participants never became higher than among controls. Conclusion: The lesser reduction in mortality from CRC of 11% compared to 18% after 5 screening rounds may be explained by the decrease in the number screened. Efficacy in those screened supports the introduction of countrywide screening in Denmark, but it must be ascertained that acceptability, proportion of early CRC and logistics all reach the same standard as in the randomized trial.
Presenilin/γ‐secretase activity regulates protein clearance from the endocytic recycling compartment

The presenilin (PS)/γ‐secretase complex proteolytically cleaves more than 20 different proteins in addition to the amyloid precursor protein (APP). These substrates are almost exclusively type I membrane proteins. Many undergo internalization from the cell surface followed by degradation or recycling back to the plasma membrane through the endo‐cytic recycling compartment (ERC). Evidence shows that the PSs also regulate intracellular trafficking of APP and its C‐terminal fragments (CTFs). To investigate whether PS/γ‐secretase activity is required for normal endosomal recycling, we performed live cell imaging experiments with fluorescently labeled transferrin, reported to specifically traffic through the ERC. By using pharmacological γ‐secretase inhibitors or cell lines lacking functional PS/γ‐secretase, here we show that PS/γ‐secretase activity is required for clearance of transferrin from the ERC. Interestingly, lack of PS/γ‐secretase function also resulted in the accumulation of APP and APP‐CTFs in the ERC in addition to the cell surface. Familial Alzheimer's disease mutations in APP‐CTFs did not affect endocytic recycling of these proteins. Our results suggest that PS/γ‐secretase activity is required for normal endosomal recycling of soluble and membrane‐associated proteins through the ERC and propose a new mechanism by which impaired PS/γ‐secretase function may eventually contribute to neurodegeneration. —Zhang, M. , Haapasalo, A. , Kim, D. Y. , MacKenzie Ingano, L. A. , Pettingell, W. H. , and Kovacs, D. M. Presenilin/γ‐secretase activity regulates protein clearance from the endocytic recycling com‐partaient. FASEB J. 20, E271‐E280 (2006)
Effect of osteogenic protein‐1 on the development and mineralization of primary cultures of avian growth plate chondrocytes: Modulation by retinoic acid

Osteogenic protein‐1 (OP‐1), a member of the TGF‐β family of proteins, induces endochondral bone formation. Here we studied the effect of OP‐1 on the development of primary cultures of avian growth plate (GP) chondrocytes in either serum‐free or serum‐containing medium, in the absence or presence of retinoic acid (RA). OP‐1 was added on day 7 of culture and continued for 7 days, or until the cultures were harvested, typically on day 21. Alone, OP‐1 caused ∼2‐fold increase in proteoglycan synthesis into both the medium and the cell:matrix layer. Additionally, OP‐1 caused a dosage‐dependent increase in alkaline phosphatase (ALP) activity, and an increase in protein, when given from days 7–14 and examined on day 14. This stimulation was greater in cells grown in serum‐free than in serum‐containing media (3–5‐fold vs. 2–3‐fold increase in ALP; ∼40% vs. ∼20% increase in protein). Such stimulation of ALP activity and proteoglycan (PG) synthesis in cultured GP cells indicates that OP‐1 elicits differentiation of chondrocytes. OP‐1 minimally affected cell division (DNA content); however, a slight increase was seen when examined early in the culture. Alone, OP‐1 increased mineral (Ca and Pi) content of the cultures by ∼2‐fold in both types of media. As early as day 14, clusters of mineral encircled many of the OP‐1 treated cells. Thus, as in vivo, OP‐1 strongly promoted mineral formation by the cultured GP chondrocytes. When present together, OP‐1 and RA generally blocked the action of the other. Separately OP‐1 and RA each stimulated protein synthesis, ALP activity, and Ca2+ deposition; together they were inhibitory to each. Also, RA blocked the stimulation of PG synthesis induced by OP‐1; whereas OP‐1 decreased cell division engendered by RA. Thus, this GP chondrocyte culture system is a good model for studying factors that influence differentiation and mineral deposition during bone growth in vivo. J. Cell. Biochem. 67:498–513, 1997. © 1997 Wiley‐Liss, Inc.
Ethanol impairs intestinal barrier defense by modulation of immunoglobulin A transport.

BACKGROUND Increased epithelial permeability may contribute to septic complications after alcohol intoxication. Prior ethanol (EtOH) exposure leads to structural and functional effects on cytoskeletal components important in maintaining barrier integrity. The cytoskeleton is also important in the transcellular transport of proteins including the polymeric immunoglobulin receptor (pIgR) mediated transport of immunoglobulin A (IgA) to the luminal surface of mucosal tissues. We (1) investigated the effects of acute EtOH exposure on cell monolayer barrier integrity and IgA transport and (2) assessed the importance of microtubule function on these functions in vitro. METHODS Confluent Madin-Darby canine kidney (MDCK) epithelial cells transfected with pIgR cDNA were exposed to 1% or 5% EtOH, and transcytosis of dimeric IgA was measured. Paclitaxel was used to pretreat a subset of MDCK cells. Results. EtOH exposure resulted in a concentration and time dependent decrease in IgA transcytosis. This was associated with physical derangements in the integrity of the cell monolayer. Pretreatment with paclitaxel completely abrogated these effects. CONCLUSIONS EtOH causes both physical and immune derangement of epithelial cell barrier function. Decreased secretory IgA at mucosal surfaces may initiate septic complications after EtOH intoxication.
Massive pulmonary embolism: surgical embolectomy versus thrombolytic therapy--should surgical indications be revisited?

OBJECTIVES The treatment of massive pulmonary embolism (PE) is a matter of debate. We present our institutional experience of patients suffering from massive PE with the aim of comparing the early results, the outcome and quality of life (QoL) between patients primarily assigned to either pulmonary surgical embolectomy (SE) or thrombolytic therapy (TL). A subgroup of patients (TS) with failed responses to TL requiring SE was separately analysed. METHODS All consecutive patients (January 2001-December 2007) with computed tomography (CT)-scan-confirmed massive bilateral central or paracentral PE were reviewed. All clinical data were retrieved from our patients' registry and completed by the evaluation of the CT-scan-derived right ventricle/left ventricle ratio (RV/LV ratio). Follow-up focused on clinical outcome and QoL was obtained. RESULTS Eighty patients were analysed including 28 SE (35%) and 52 TL (65%), of whom 11 (21%) required TS. Demographics and preoperative characteristics were similar between SE and TL. Analysis of the RV/LV ratio revealed a ratio of 1.66 for SE and 1.44 for TL. The early mortality rate was not significantly different between the two groups (SE: 3.6% versus TL: 13.5%), whereas early mortality was 27% in those patients treated initially with thrombolysis and subsequently requiring SE (TS-group). Severe bleeding complications were lower in the SE-group (3.6% versus 26.5% P = 0.013). Intracerebral bleeding rates and neurological events were not statistically different. After a mean follow-up of 63 ± 21 months, the mortality rate was 17.9% in the SE-group and 23.1% in the TL-group. CONCLUSIONS SE is an excellent treatment option in massive PE with comparable early mortality rates and significantly less bleeding complications than TL. Patients having surgery after inefficient thrombolysis have the worst early outcome. The RV/LV CT-scan ratio might serve as a predictor to differentiate patients, who could profit from direct surgical intervention than thrombolytic treatment attempts. Further studies are required to confirm these results.
Na+‐Phosphate Cotransport in Mouse Distal Convoluted Tubule Cells: Evidence for Glvr‐1 and Ram‐1 Gene Expression

While there is considerable evidence for phosphate (Pi) reabsorption in the distal tubule, Pi transport and its regulation have not been well characterized in this segment of the nephron. In the present study, we examined Na+‐dependent Pi transport in immortalized mouse distal convoluted tubule (MDCT) cells. Pi uptake by MDCT cells is Na+‐dependent and, under initial rate conditions, is inhibited by phosphonoformic acid (41 ± 3% of control), a competitive inhibitor of Na+‐Pi cotransport. The transport system has a high affinity for Pi (Km = 0.46 mM) and is stimulated by lowering the extracellular pH from 7.4 to 6.4 and inhibited by raising the pH from 7.4 to 8.4. Exposure to Pi‐free medium for 21 h increased Na+‐Pi cotransport from 2.1 to 5.5 nmol/mg of protein/5 minutes (p < 0.05) while parathyroid hormone, forskolin, and phorbol 12‐myristate 13‐acetate failed to alter Pi uptake in MDCT cells. Reverse transcriptase polymerase chain reaction of MDCT cell RNA provided evidence for the expression of the Npt1 but not the Npt2 Na+‐Pi cotransporter gene. However, preincubation of MDCT cells with Npt1 antisense oligonucleotide led to only 20% inhibition of Na+‐Pi cotransport, suggesting that other Na+‐Pi cotransporters are operative in MDCT cells. Indeed, we showed, by ribonuclease protection assay, that MDCT cells express the ubiquitous cell surface receptors for gibbon ape leukemia virus (Glvr‐1) and amphoteric murine retrovirus (Ram‐1) that also function as Na+‐Pi cotransporters. In summary, we demonstrate that the pH dependence and regulation of Na+‐Pi cotransport in MDCT cells is distinct from that in the proximal tubule and suggest that different gene products mediate Na+‐Pi cotransport in the proximal and distal segments of the nephron.
High ethanol preferring rats fail to show dependence following short- or long-term ethanol exposure.

AIMS The high ethanol preferring (HEP) rat shows high total ethanol consumption, high spontaneous activity and high consumption of novel tastants. Because these animals consume large quantities of ethanol daily, we sought to determine whether they could become alcohol-dependent by repeated exposures of varying lengths and withdrawals of alcohol, both in short- and long-term ethanol exposure. METHODS Male and female HEP rats were subjected to short (14 days) or long (20 weeks) exposure to 10% ethanol in a two choice (vs. water) test. During the short- and long-term ethanol exposures, the animals were repeatedly deprived of ethanol for 5 days followed by reinstatement of the two-choice test. Moreover, pharmacological interventions (morphine and naltrexone), adulteration of ethanol by quinine and addition of saccharine to water were applied to test the lability of a possible alcohol deprivation effect. RESULTS In every case, deprivation produced a high initial intake of ethanol that lasted 0.5 h, but thereafter no significant increase in alcohol consumption, compared to predeprivation. Even after several months of continuous drinking of large amounts of ethanol, the animals were sensitive to adulteration of the alcohol solution by quinine, that reduced the intake, and still preferred a saccharine solution when presented as a free choice with the alcohol solution. Pretreatment with morphine increased ethanol consumption in the first 0.5 h following deprivation, whereas naltrexone reduced it. CONCLUSIONS Taste reinforcement is probably a major component of alcohol drinking by the HEP rats, and that while these rats consume large quantities of ethanol both in the short- and long-term, they do not show a robust alcohol deprivation effect.
Effects of maternal exposure to thiamazole on behavioral development in infant cynomolgus monkeys

Thiamazole, an anti‐hyperthyroidism agent, was administered orally to pregnant cynomolgus monkeys at doses of 2.0 and 3.5 mg/kg per day from GD 120 to GD 150 to investigate effects on behavioral development of their infants. Swelling of the throat region due to enlargement of the thyroid glands was observed at birth in thiamazole‐treated infants, and it returned to normal around postnatal day (PND) 30. At necropsy of infants at 12 months of age, thyroidal weight in the thiamazole groups was increased. This finding suggested the likelihood that administration of thiamazole to maternal animals during the late gestational period induced thyroid goiter in fetal/infant monkeys through placental transfer of thiamazole. No clear changes were noted in thyroid histopathology or serum thyroid hormone levels in maternal animals or infants, but goiter formation might have been indicative of exposure to high thyroid stimulating hormone (TSH) and low T3 or T4 in utero from maternal treatment with thiamazole. Age‐related changes were observed in the control in behavioral development tests, while infants at 3.5 mg/kg showed no age‐related decrease in contact behavior and no increase in exploratory activity on PND 90 or PND 170. In addition, the number of eye contacts between PND 210 and PND 240 was less frequent. This indicated that maternal exposure to thiamazole induced mental retardation‐like behaviors in infants. Thiamazole may directly inhibit thyroid hormone synthesis in the fetus by placental transfer. From these results, it was speculated that oral administration of thiamazole to maternal animals during the late gestational period induced retardation of behavioral development in their infants.
Species specificity of the Listeria monocytogenes InlB protein

InlA and InlB mediate L. monocytogenes entry into eukaryotic cells. InlA is required for the crossing of the intestinal and placental barriers. InlA uses E‐cadherin as receptor in a species‐specific manner. The human E‐cadherin but not the mouse E‐cadherin is a receptor for InlA. In human cells, InlB uses Met and gC1qR as receptors. By studying the role of InlB in vivo, we found that activation of Met by InlB is species‐specific. In mice, InlB is important for liver and spleen colonization, but not for the crossing of the intestinal epithelium. Strikingly, the virulence of a ΔinlB deletion mutant is not attenuated in guinea pigs and rabbits. Guinea pig and rabbit cell lines do not respond to InlB, although expressing Met and gC1qR, but support InlB‐mediated responses upon human Met gene transfection, indicating that InlB does not recognize or stimulate guinea pig and rabbit Met. In guinea pig cells, the effect of human Met gene transfection on InlB‐dependent entry is increased upon cotransfection with human gc1qr gene, showing the additive roles of gC1qR and Met. These results unravel a second L. monocytogenes species specificity critical for understanding human listeriosis and emphasize the need for developing new animal models for studying InlA and InlB functions in the same animal model.
Fully Electronic CMOS DNA Detection Array Based on Capacitance Measurement with On-Chip Analog-to-Digital Conversion

An 8 times 16 array of sensing micro-sites employs a fully-electrical label-free technique for DNA recognition using capacitance measurement and is fabricated in 0.5mum CMOS with added noble metal. Repeatability and parallel detection capability have been demonstrated. The DNA-chip is suitable for low-cost, fully-integrated point-of-care applications
MIGRATION AND SUICIDE

In keeping with studies conducted elsewhere, suicide rates among Immigrants to Australia are substantially higher than those prevailing in their countries of origin and among the Australian‐born population. However, not all racial groups show this tendency, which is most pronounced among Immigrants from Great Britain, Ireland and New Zealand. Southern European immigrants, in contrast, show rates lower than those existing in Australia.
Quality of care for hospitalized medicare patients at risk for pressure ulcers.

BACKGROUND No state peer review organization has attempted to identify processes of care related to pressure ulcer prediction and prevention in US hospitals. OBJECTIVE To profile and evaluate the processes of care for Medicare patients hospitalized at risk for pressure ulcer development by means of the Medicare Quality Indicator System pressure ulcer prediction and prevention module. METHODS A multicenter retrospective cohort study with medical record abstraction was used to obtain a total of 2425 patients aged 65 years and older discharged from acute care hospitals after treatment for pneumonia, cerebrovascular disease, or congestive heart failure. Six processes of care for prevention of pressure ulcers were evaluated: use of daily skin assessment; use of a pressure-reducing device; documentation of being at risk; repositioning for a minimum of 2 hours; nutritional consultation initiated for patients with nutritional risk factors; and staging of pressure ulcer. The associations between processes of care and incidence of pressure ulcer were determined with Kaplan-Meier survival analyses. RESULTS National estimates of compliance with process of care were as follows: use of daily skin assessment, 94%; use of pressure-reducing device, 7.5%; documentation of being at risk, 22.6%; repositioning for a minimum of 2 hours, 66.2%; nutritional consultation, 34.3%; stage 1 pressure ulcer staged, 20.2%; and stage 2 or greater ulcer staged, 30.9%. CONCLUSION These results suggest that US hospitals and physicians have numerous opportunities to improve care related to pressure ulcer prediction and prevention.
Expression Cloning of lsc, a Novel Oncogene with Structural Similarities to the Dbl Family of Guanine Nucleotide Exchange Factors*

In a screen for genes with oncogenic potential expressed by the murine B6SUtA1 myeloid progenitor cell line, we isolated a 2.5-kilobase pair cDNA whose expression causes strong morphological transformation and deregulated proliferation of NIH 3T3 cells. The transforming cDNA encodes a truncated protein (designated Lsc) with a region of sequence similarity to the product of the lbc oncogene. This region includes the tandem Dbl homology and pleckstrin homology domains that are hallmarks of the Dbl-like proteins, a family of presumptive or demonstrated guanine nucleotide exchange factors that act on Rho family GTPases. Lsc requires intact Dbl homology and pleckstrin homology domains for its oncogenic activity. The transforming activity of Lsc in NIH 3T3 cells is reduced by cotransfection with p190 (a GTPase activating protein for Rho family GTPases) and the Rho family dominant-negative mutants RhoA(19N), CDC42(17N), and Rac1(17N). These results indicate a role for the Rho family of GTPases in mediating the transforming activity of Lsc and are consistent with the exchange specificities that have been attributed to Dbl family members. The lsc gene is expressed in a variety of tissues and is particularly abundant in hemopoietic tissues (thymus, spleen, and bone marrow). Lsc is a member of a growing family of proteins that may function as activators of Rho family GTPases in a developmental or tissue-specific manner.
Proteomic analysis of Fasciola hepatica excretory‐secretory products

This paper describes a global investigation of the components of Fasciola hepatica excretory‐secretory (ES) products by a proteomic approach. Despite the absence of a F. hepatica genome sequencing project we have shown that it was possible to identify 29 of the 60 prominent proteins found using two‐dimensional gel electrophoresis. As well as cathepsin L proteases, a number of enzymes implicated in parasite protection from the host immune system were also found to be present in relatively large abundance. These included superoxide dismutase, thioredoxin peroxidase, glutathione S‐transferases and fatty acid binding proteins, all of which may play a part in the detoxification of reactive oxygen intermediates. Interestingly, ovine superoxide dismutase was the only protein from the host identified on the gel. We suggest that the relative abundance and protective nature of the components of the ES products of this organism play an important role in its survival within the host. The precise identification, to individual NCBI database entries, of a number of glutathione S‐transferases and cathepsin Ls from F. hepatica, by peptide mass fingerprinting, was hampered by multidatabase submissions of the two protein superfamilies from this organism.