Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease.

OBJECTIVES Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. DESIGN Cross-sectional, multicenter, clinical study. PARTICIPANTS A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. MEASUREMENTS All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. RESULTS Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N = 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N = 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. CONCLUSIONS The authors' study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms.
25-vitamin D, 1,25-vitamin D, parathyroid hormone, fibroblast growth factor-23 and cognitive function in men with advanced CKD: a veteran population

Abstract. Cognitive impairment is common in advanced chronic kidney disease (CKD), but little is known about its relation with abnormalities in mineral metabolism. Methods: The longitudinal association between plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), intact parathyroid hormone (iPTH), and fibroblast growth factor-23 (FGF-23) levels and cognitive function was assessed in 605 patients (67 ± 12 years) with advanced CKD not requiring dialysis (n = 247) or end-stage renal disease (ESRD; n = 358) who participated in the Homocysteine Study Cognitive Function Substudy (HOSTCOG)). Cognitive function was assessed using the Telephone Interview for Cognitive Status-modified (TICSm; mean follow-up 3.1 years) and associated with baseline mineral metabolite levels using linear regression analyses. Results: In unadjusted analyses, increasing log 1,25(OH)2D and decreasing log iPTH and FGF-23 levels were associated with worse cognitive status (p < 0.05). In fully adjusted multivariate analyses, the associations were no longer significant. Log 25(OH)D levels were not associated with cognitive function in unadjusted or adjusted analyses. Results were similar when analyzed by tertile or separately within CKD and ESRD groups. Conclusions: These results suggest that mineral metabolism dysregulation does not mediate the impairment in cognitive function common in advanced CKD.
Social Validation of Everyday Knowledge: Heterogeneity and Consensus Functionality

This article presents evidence supporting the idea that laypeople use specific types of informational cues about the composition of groups to derive and attribute validity to the knowledge conveyed by these groups. A pilot study and two experimental studies analyzed the role of consensus and heterogeneity information when participants attribute validity to the positions of opposing groups. We predicted that consensus information is moderated by heterogeneity information. When two groups are described as equally consensual, greater validity is attributed to the more heterogeneous group, while when one group is described as more consensual than the other heterogeneity information will not contribute to the validation of groups’ opinions. Our studies support this prediction in different scenarios and with different manipulations of groups’ composition in terms of their internal heterogeneity. These findings are discussed in the context of the role played by social metacognitive beliefs in everyday knowledge validation.
Capsaicin Sensitive Afferents Contribute to Acute Airway Edema following Tracheal Instillation of Hydrochloric Acid or Gastric Juice in the Rat

The formation of acute edema in the tracheobronchial mucosa following local instillation of hydrochloric acid or gastric juice was studied in rats. Protein extravasation using the Evans blue technique was measured and used to indicate edema formation. A pH dependent Evans blue extravasation was observed whereby pH 2 produced a small, pH 1,5 an intermediate, and pH 1 a pronounced effect. Also, gastric juice (pH 1.3 ± 0.1) induced a marked Evans blue extravasation in the tracheobronchial mucosa. Rats which had been pretreated with capsaicin (100 mg/kg s.c.) had a much lower Evans blue extravasation following local instillation of both hydrochloric acid and gastric juice. Thus, the increase in Evans blue content induced by acid at pH 1.5 was abolished while about 50% of the response remained at pH 1. The protein extravasation caused by gastric juice was reduced by about 70% after capsaicin treatment. Terbutaline (73 nmol/kg, iv) or emprophylline (25 μmol/kg, iv) injected intravenously 10 min before, as well as hydrocortisone injected immediately after the intratracheal instillation of gastric juice, did not influence the magnitude of edema formation. Beta-methasone (0.25 mg/kg ip) pretreatment 24 h prior to the gastric juice exposure enhanced tracheal extravasation. In conclusion, acute protein extravasation in the lower airway mucosa induced by hydrochloric acid or gastric juice is mainly dependent on capsaicin sensitive sensory nerves, suggesting that local release of mediators, such as tachykinins, play a key role in this reaction.
The Role of Toll‐like Receptor 4 Asp299Gly and Thr399Ile Polymorphisms and CARD15/NOD2 Mutations in the Susceptibility and Phenotype of Crohn's Disease

Background: We investigated the influence of 2 common Toll‐like receptor 4 (TLR4) polymorphisms on susceptibility and disease characteristics of Crohn's disease (CD). Methods: Genomic DNA from 204 patients with CD and 199 unrelated controls was analyzed for the presence of 2 single nucleotide polymorphisms in the TLR4 gene, resulting in the amino acid substitutions Asp299Gly and Thr399Ile. In addition, the carrier status for the 3 common CD‐associated CARD15/NOD2 gene mutations, Arg702Trp, Gly908Arg, and 1007fs, was determined. The frequency of the different genotypes was compared, and a detailed genotype‐phenotype correlation was performed. Results: An almost 2‐fold increase in the frequency of the TLR4 Asp299Gly phenotype was observed in patients with CD (14.2%) compared with healthy controls (7.5%, P = 0.038, odds ratio = 2.03). The prevalence of a stricturing phenotype was increased in patients heterozygous for 1 of the TLR4 polymorphisms studied (Asp299Gly, 34.5%; Thr399Ile, 36.7%) compared with patients with wild‐type TLR4 (17.1% and 16.7%; P = 0.04 and 0.02, respectively). The presence of the Asp299Gly polymorphism in the absence of CARD15/NOD2 mutations was a particularly strong predictor of the stricturing disease phenotype that was present in 47.4% of the patients with Asp299Gly+/NOD2− compared with 10.1% of the patients with the Asp299Gly−/NOD2+ status (P = 0.0009; P = 0.0004 for Thr399Ile+/NOD2− versus Thr399Ile−/NOD2+). In contrast, there was a trend toward a higher prevalence of the penetrating phenotype in the TLR4−/NOD2+ group (71.6%) compared with the TLR4+/NOD2− group (47.4%, P = 0.059). Conclusions: The TLR4 Asp299Gly polymorphism is a risk factor for CD. TLR4 and CARD15/NOD2 mutations may contribute to distinct disease phenotypes.
The Plant-Derived Chalcone 2,2′,5′-Trihydroxychalcone Provides Neuroprotection against Toll-Like Receptor 4 Triggered Inflammation in Microglia

Chalcones are plant metabolites with potential for therapeutic exploitation as antioxidant, anti-inflammatory, and antiproliferative agents. Here we explored the neuroprotective effects of 2,2′,5′-trihydroxychalcone (225THC), a potent antioxidant with radical-scavenging properties. 225THC was found to be a potent inhibitor of apoptosis in stimulated primary rat neuronal cultures. This was likely mediated by an anti-inflammatory effect on microglial cells since 225THC inhibited LPS-stimulated TNF-α and IL-6 secretion from primary rat microglia and modulated the cytokine/chemokine profile of BV2 microglial cells. Additionally, 225THC inhibited LPS-evoked inducible nitric oxide synthase expression but did not influence endogenous superoxide generation. Microglial flow cytometric analyses indicated the 225THC treatment induced a shift from an M1-like phenotype to a more downregulated microglial profile. Taken together these data suggest that the chalcone 2,2′,5′-trihydroxychalcone can modulate neuroinflammatory activation in brain-derived microglia and holds promise as a therapeutic in neuroinflammatory conditions.
Induction and differential expression of certain novel proteins in Anabaena L31 under UV-B radiation stress

For examining how UV-B radiation alters the proteome of the N2-fixing cyanobacterium, Anabaena L31, we extracted proteins from cultures irradiated with UV-B + white light and controls (white light irradiated) and analyzed the proteins using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Twenty one proteins, including two hypothetical proteins (HPs) were identified and placed in eight functional categories. However several of the proteins were housekeeping proteins involved in key metabolic processes such as carbon, amino acid biosynthesis and energy metabolism, certain proteins seem to have a role in stress (antioxidative enzymes), translation, cellular processes and reductases. Two novel HPs (all3797 and all4050) were characterized in detail. These two were over-expressed after UV-B irradiation and characterized as FAS 1 (all3797) and PRC barrel-like (all4050) proteins. Bioinformatics analysis revealed that the genes of both the HPs have promoter regions as well as transcription binding sites in their upstream region (UTR). Promoters present in all3797 genes suggest their crucial role against UV-B and certain other abiotic stresses. To our knowledge these novel proteins have not been previously reported in any Anabaena strains subjected to UV-B stress. Although we have focused our study on a limited number of proteins, results obtained shed light on the highly complicated but poorly studied aspect of UV-B radiation-mediated changes in the proteome and expression of proteins in cyanobacteria.
One-carbon metabolism in psychiatric illness

The cost of psychiatric illness to the UK economy was recently estimated at £77 billion annually. Despite years of research no firm aetiological explanation exists, and with no physiological or biochemical markers diagnosis is made entirely on a behavioural basis. All current pharmacological therapies are associated with serious long-term side effects. Substantial evidence supports the involvement of one-carbon cycle dysregulation in psychiatric illness, but this is not currently used as a basis for diagnosis or treatment. The present paper reviews the evidence for one-carbon cycle dysregulation in schizophrenic, bipolar, depressed and autistic patients. Also presented are novel findings from the field of epigenetics, which demonstrate how the one-carbon cycle-derived methyl donor S-adenosylmethionine influences the expression of key genes in the brain affecting memory, learning, cognition and behaviour, genes whose expression is reduced to varying degrees in these patient groups. Clinical evidence that nutritional supplements can rectify one-carbon cycle activity, and restore normal gene expression, suggests a novel approach to the development of biochemical tests and simple, non-harmful treatments for some psychiatric patients. Conversely, evidence from animal studies highlights the dangers of exposing the unborn fetus to very high dietary levels of folic acid, a one-carbon cycle cofactor. Fetal adaptations to a high-folate environment may interfere with folate metabolism postnatally, with serious consequences for the epigenetic regulation of gene expression. The public health implications of these diverse scenarios indicate an urgent need for further research in this field.
Changes in Diagnostic Approach and Factors Affecting Treatment and Survival of Pancreatic Carcinoma in a Retrospective Series over Twelve Years

Aims Identify the following aspects of pancreatic carcinoma: 1) the prevalence of some risk factors, 2) the accuracy of the diagnostic tecniques and the pattern of their utilization over the years, 3) the factors affecting the therapeutic choice and mortality. Methods Retrospective study on all patients with a final diagnosis of pancreatic carcinoma seen at the Ospedale di Busto Arsizio, from January 1978 to August 1989. Results There were 155 patients, 68 ±11.6 years old, with a 1.2 male to female ratio. Antemortem pathologic confirmation was obtained in 127 cases (82%); 45% were smokers and 45% drinkers. Diabetes mellitus, a history of peptic disease, a past neoplasm and gallstone disease were respectively present in 36.1%, 12.3%, 11% and 8.2% of the cases; 61.9% 23.8% and 9% of the tumors were located respectively in the head, body and tail; 1.3%, 40% and 51.5% were respectively in stage II, III and IV. Ultrasound abdominal scanning and computerized tomography sensitivity were respectively 67.5% and 72.5% (p = NS). In addition, carcinoembryonic antigen, fine needle aspiration biopsy and percutaneous transhepatic cholangiography showed respectively a 66.6%, 88.9% and 93% sensitivity. Together the non-invasive imaging procedures dramatically decreased the number of unnecessary exploratory laparotomies over the years (p = 0.005) without changing the stage at diagnosis or survival. Among the tested variables (age, sex, year of diagnosis, past diseases, co-morbidity, location and stage of the tumor), only the head location and a less advanced stage were significantly related to a surgical choiche (p< 0.001). Overall one-year survival rate was 13.4%, and among the tested variables, only a less advanced stage and the aggressive treatment were associated to a longer survival (p< 0.001). Conclusions The prevalence of diabetes mellitus in patients with pancreatic carcinoma may be higher than previously expected; the wide use of diagnostic imaging, dramatically reduced the number of unnecessary exploratory laparotomies over the years; aggressively treated patients with a less advanced stage have a slight, but significant improvement in survival.
Influences of Sex and Activity Level on Physiological Changes in Individual Adult Sockeye Salmon during Rapid Senescence

A noninvasive biopsy protocol was used to sample plasma and gill tissue in individual sockeye salmon (Oncorhynchus nerka) during the critical life stage associated with spawning—arrival at a spawning channel through senescence to death several days later. Our main objective was to characterize the physiological changes associated with rapid senescence in terms of the physiological stress/cortisol hypersecretion model and the energy exhaustion model. Salmon lived an average of 5 d in the spawning channel, during which time there were three major physiological trends that were independent of sexual status: a large increase in plasma indicators of stress and exercise (i.e., lactate and cortisol), a decrease in the major plasma ions (i.e., Cl− and Na+) and osmolality, and a decrease in gross somatic energy reserves. Contrary to a generalized stress response, plasma glucose decreased in approximately 2/3 of the fish after arrival, as opposed to increasing. Furthermore, plasma cortisol levels at spawning‐ground arrival were not correlated with the degree of ionoregulatory changes during rapid senescence. One mechanism of mortality in some fish may involve the exhaustion of energy reserves, resulting in the inability to mobilize plasma glucose. Sex had a significant modulating effect on the degree of physiological change. Females exhibited a greater magnitude of change for gross somatic energy, osmolality, and plasma concentrations of Cl−, Na+, cortisol, testosterone, 11‐ketotestosterone, 17,20β‐progesterone, and estradiol. The activity level of an individual on the spawning grounds appeared to influence the degree of some physiological changes during senescence. For example, males that received a greater frequency of attacks exhibited larger net decreases in plasma 11‐ketotestosterone while on the spawning grounds. These results suggest that rapid senescence on spawning grounds is influenced by multiple physiological processes and perhaps behavior. This study provides some of the first data to look at sex differences in senescence in Pacific salmon.
European public opinion and the Lisbon earthquake

At the end of November 1755, news of the Lisbon earthquake spread rapidly to all capital cities of Europe. Horrific reports gave rise to a wealth of sensational journalism. As Samuel Johnson and others attest, this was particularly marked in Great Britain. The catastrophe remained a popular subject of flysheets, newspapers, and engravings for months on end. The event was magnified many times over in the eyes and minds by the popular press, which led to forms of public distress. For the first time in the western world, the press, on the occasion of the Lisbon earthquake, helped create the illusion of proximity and unity between the peoples of different nations in Europe. As Voltaire said, ‘L'Europe ressemblait à une grande famille réunie après ses différences’.
Routines as multilevel mechanisms

Abstract: It is argued that routines can be fruitfully conceived of as multilevel mechanisms. The merits of viewing routines as multilevel mechanisms are that it helps in putting together a coherent picture of what routines are, what routines do, and how they do it. In particular, it helps in getting a clearer picture of how skills and routines are ontologically (rather than metaphorically) related to each other. It allows us to see that while routines are generative mechanisms producing recurrent patterns of firm behavior, as multilevel mechanisms they themselves are at the same time recurrent patterns of interaction within firms. Because of its ‘behavioral’ spirit, viewing routines as multilevel mechanisms (rather than as, for example, unobservable dispositions of firms to energize patterns of behavior in firms) greatly facilitates further empirical research on crucial, as yet unresolved issues, such as how stable and robust routines are and to what extent firm behavior is routine.
ACE I/D and MMP-7 A-181G variants and the risk of end stage renal disease

The variants of angiotensin converting enzyme (ACE) and matrix metalloproteinases (MMPs) genes might be involved in the pathogenesis of end stage renal disease (ESRD) and hypertension. We studied the ACE insertion/deletion (I/D) and MMP-7 A-181G variants in 99 unrelated ESRD patients and 117 individuals without renal complications from Western Iran with Kurdish ethnic background. The frequency of ACE I/D variants was not significantly different between ESRD patients and controls. However, the presence of ACE D allele increased the risk of hypertension in ESRD patients by 2.14-fold (P=0.036). The MMP-7 -181 AG genotype increased the risk of ESRD by 2.04 times (P=0.026). The present study indicated the absence of an association between the ACE I/D polymorphism with the risk of ESRD. However, the ACE D allele increased the risk of hypertension in ESRD patients. Also, the present study suggests a role for MMP-7 AG genotype in the pathogenesis of ESRD.
Intrusion Detection : Content Analysis of Packet Data

This paper presents a network intrusion detection system based on the content analysis of the packets. A majority of the current intrusion detection systems use packet header information for developing classification rules or scan the content for specific signatures based on previous known attacks. There has been some recent work on developing behavior based classification rules based on the content of the data. The models used in these systems are based on the frequency of characters that occur in the content of the packet. This characterization does not capture the sequence of the characters that we believe is more critical compared to the frequency of characters. We analyze the existing approach and attempt to address some of the limitations of the previous approaches. The results of this investigation are presented in this paper.
A Micropuncture Investigation of the Whole Tissue Mechanism of Electrolyte Secretion by the In Vitro Rabbit Pancreas

Micropuncture techniques have been used to examine electrolyte secretion by the in vitro rabbit pancreas. The concentration profiles of the major secreted ions and digestive protein and the electrical potential profile within the pancreatic ductal system have been determined during spontaneous and secretin-stimulated secretion. The active transport of both Na and HCO3 are the rate-controlling steps in primary secretion. Spontaneous secretion is produced primarily within the intralobular ducts. The anion composition of this primary secretion depends on the secretion rate with HCO3 ranging from about 70 meq/liter at low rates to about 110 meq/liter at high rates. With secretin stimulation the smaller extralobular ducts also secrete and this extralobular secretion has a higher HCO2 content than that of the intralobular secretion. In the main collecting duct the anion composition of the juice is modified further by Cl-HCO3 exchange which appears to be a passive process depending on the average residence time of the juice in the main duct.
Communication Intervention in Children with Severe Disabilities and Multilingual Backgrounds: Perceptions of Pedagogues and Parents

Increasing global population movement has resulted in a corresponding increase of children with severe and multiple disabilities and complex communication needs who at home are exposed to languages different from the language used at school. The aim of this study was to highlight facilitating as well as limiting factors for effective communication intervention for these children both in school and within the family. Based on observations, qualitative research interviews and analysis in the tradition of grounded theory the results indicate that the quality of parent-teacher-interaction is central to effective communication intervention and culturally sensitive use of communication aids. Challenges for teachers as well as parents to achieve a mutually satisfying interaction are addressed, and issues regarding the language use with children with severe disabilities and a multilingual and multicultural background and the inclusion of their parents in school based activities are discussed.