Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis , osteoarthritis and fi bromyalgia

diseases Although pain is commonly the patients’ utmost priority and the reason most patients seek rheumatologic consultation, the medical community has historically had a poor understanding of the etiology, mechanisms and treatment of pain. Rheumatologists often consider pain a peripheral entity, but there is great discordance between pain severity and purported peripheral causes of pain, such as infl ammation and structural joint damage (for example, cartilage degradation, erosions). In recognition of the importance of pain in the rheumatic diseases, the American College of Rheumatology Pain Management Task Force established an initia tive to increase awareness and call for organized research and education [1]. Th is initiative emphasizes the need for high-quality, quantitative research to understand the mechanisms underlying individual diff erences in pain among patients with rheumatic disease. Currently, most advances in the study of pain mechanisms have been in non-infl ammatory diseases, such as fi bromyalgia [2]. Th ese studies have highlighted the role of central painprocessing mechanisms, such as loss of descending analgesic activity and central pain augmentation or sensitization. Some pain researchers also believe that these mechanisms may have a signifi cant impact on pain severity among patients with osteoarthritis (OA) and rheuma toid arthritis (RA), diseases that have historically been associated with peripheral pain due to joint damage and infl ammation. In the present review we give a brief overview of the basic biology of acute and chronic pain, including the role of central pain-processing defects. We discuss the role of these mechanisms in diseases commonly seen in rheumatology practices (for example, fi bromyalgia, OA and RA) and consider potential treatments that may correct defi cits in central pain processing.
Nephrolithiasis in Israel: Epidemiological Characteristics of Return Patients in a Tertiary Care Center.

BACKGROUND The prevalence and etiology of nephrolithiasis vary, depending on geography, gender and ethnicity. OBJECTIVES To analyze the demographic data of return nephrolithiasis patients in a tertiary care center. METHODS We retrospectively reviewed our prospective registry database of return patients seen at our outpatient clinic for nephrolithiasis. Data included gender, age at first visit, age at first stone event, body mass index (BMI), self-reported hypertension, diabetes mellitus (DM), and hyperlipidemia. All patients were seen at least twice and had undergone a metabolic workup. RESULTS A total of 260 return patients were seen during the period 2010-2015. The male:female ratio was 3.1:1. Mean age at the first stone event was 44.1 years. Median time elapsed since the first stone event to medical evaluation was 5 years (interquartile range 1-12 years). Hypertension was reported by 33.1% of the patients, DM by 23.5% and hyperlipidemia by 30.4%. All three diseases were reported by 11.5% of patients. The metabolic abnormalities detected were hypocitraturia (60%), low urine volume (LUV) (60%), hypercalciuria (40.8%), hyperoxaluria (24.2%), hyperuricosuria (16.5%) and hyperuricemia (13.5%). Stone compositions from most to least frequent were calcium-oxalate (81%), calcium-phosphate (11.9%) and uric acid (7.1%). We also found that 24.6% were obese (BMI ≥ 30 kg/m2) and showed higher rates of hypertension, DM, hyperlipidemia, hyperuricemia and hyperuricosuria compared with non-obese patients. Significantly higher rates of obesity and LUV were detected in females compared with males. Patients over age 45 had lower rates of hyperuricemia compared with patients ≥ 45 years old (P = 0.038). CONCLUSIONS Factors related to nephrolithiasis can potentially differ among populations and countries. Our findings emphasize the significance of individualized national health programs to address local issues.
Responses of photosensitive and photorefractory male white-crowned sparrows (Zonotrichia leucophrys gambelii) to synthetic mammalian luteinizing hormone releasing hormone (syn-LHRH).

To assess a possible role of the adenohypophysis in photorefractoriness, photosensitive and photorefractory adult male white-crowned sparrows (Zonotrichia Ieucophrys) were treated with single intravenous injections of 0, 0.5, 5, 20, 35, 50 or 500 ng of synthetic Iuteinizing hormone releasing hormone (Syn-LHRH) in 0.9% saline solution. Serial samples of plasma were taken immediately before and at 5, 20 and 60 mm after injection. The plasma level of immunoreactive luteinizing hormone (irLH) was not altered by the injection of saline solution alone, or by 0.5 or 5 ng Syn-LHRH in either photosensitive or photorefractory birds. Treatment with 20, 35, 50 or 500 ng Syn-LHRH, however, elicitedsignificant and approximately equal increases in plasma levels of irLH in both groups 5 mm after injection. These responses are consistent with the hypothesis that the site of photorefractoriness is at a level higher than the adenohypophysis.
Copolymerization of ethylene and alkyl vinyl ethers by a (phosphine- sulfonate)PdMe catalyst.

The neutral complex (PO−OMe)PdMe(py) (1, PO−OMe = 2-[bis(2-OMe−Ph)phosphino]-4-methylbenzenesulfonate) polymerizes ethylene to a linear polymer with 1−10 branches/103 carbons (mostly methyl) and vinyl and 2-olefin unsaturated end groups. Complex 1 copolymerizes ethylene and alkyl vinyl ethers (CH2CHOR, 2a−c: R = tBu (a), Et (b), Bu (c)) in toluene at 60−100 °C to linear copolymers containing up to 7 mol % of vinyl ether. Addition of CH2CHOR lowers the polymerization rate and the polymer molecular weight. The copolymer structures are similar to that of homopolyethylene generated under the same conditions. The major comonomer units are −CH2CH(OR)CH2− (I) and CH3CH(OR)CH2− (II). The ethylene/CH2CHOR copolymers can be converted to hydroxy- and bromo-polyethylene. The results of control experiments argue against cationic and radical mechanisms for the copolymerization, and an insertion mechanism is proposed. The reaction of base-free (PO−OMe)PdMe with CH2CHOEt yields the adduct (PO−OMe)PdMe(CH2CHOEt), which u.
Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees

To study determinants of clinical outcome following HCV infection, viral kinetics, immune events, and intrahepatic cytokine markers were compared in 10 naive chimpanzees. Four of the animals cleared HCV; 6 developed persistent infections. All animals developed similar acute infections with increasing viremia from 1 to 2 weeks, followed by alanine aminotransferase (ALT) elevations and seroconversion. This viremia pattern consisted of a biphasic increase, a rapid slope (mean doubling time [t2] = 0.5 days) followed by a slower slope after the second week (t2 = 7.5 days). This slowing of virus replication correlated in all animals with increased intrahepatic 2′5′ oligoadenylate synthetase 1 (2OAS‐1) messenger RNA (mRNA) levels and was independent of disease outcome. An effective control of virus replication was observed following increases in intrahepatic interferon γ (IFN‐γ) mRNA and ALT levels. Although this control was associated in all animals with a 2‐log decrease in virus titer, the timing occurred approximately 2 weeks later in the chronic group (P < .05). Additionally, while cleared infections were characterized by a continual decrease in virus titer, the titers in the persistent infections reached a steady state level of 104 to 105 RNA copies/mL. This inability of the immune response to sustain viral clearance in the persistent infections was associated with a reduced intrahepatic CD3e and monocyte‐induced protein 1α (MIP‐1α) mRNA induction. In conclusion, these data indicate that, regardless of outcome, chimpanzees generate responses that control HCV replication during the early and late acute phase. However, the pathogenesis of HCV may be determined by a more rapid onset of the induced response and the cell population that migrates to the liver. (HEPATOLOGY 2004;39:1709–1720.)
Perivascular Ancestors of Adult Multipotent Stem Cells

Independent studies by numerous investigators have shown that it is possible to harvest multipotent progenitor cells from diverse dissociated and cultured fetal, perinatal, and principally adult developed tissues. Despite the increasingly recognized medical value of these progenitor cells, the archetype of which remains the mesenchymal stem cell, this indirect extraction method has precluded the understanding of their native identity, tissue distribution, and frequency. Consistent with other researchers, we have hypothesized that blood vessels in virtually all organs harbor ubiquitous stem cells. We have identified, marked, and sorted to homogeneity by flow cytometry endothelial and perivascular cells in a large selection of human fetal, perinatal, and adult organs. Perivascular cells, including pericytes in the smallest blood vessels and adventitial cells around larger ones, natively express mesenchymal stem cell markers and produce in culture a long-lasting progeny of multilineage mesodermal progenitor cells. Herein, we review results from our and other laboratories that suggest a perivascular origin for mesenchymal stem cells and other adult progenitor cells. Recent experiments illustrate the therapeutic potential of human pericytes to regenerate skeletal muscle and promote functional recovery in the diseased heart and kidney.
The Relationship between Cancer and Alzheimer's Disease

To The Editor:-A negative association between Alzheimer’s disease and cancer found at autopsy has previously been observed’ in this hospital. In that series, those with Alzheimer’s disease were older than those without. We have subsequently studied the relationship between cancer and Alzheimer’s disease in our current population using clinical diagnoses. Age-matching was achieved by using a lower cut-off age of 73 so that the mean age of those with clinically diagnosed Alzheimer’s disease was 88.5 and of those without Alzheimer’s disease was 88.3. The diagnosis of primary degenerative dementia of Alzheimer’s type was made by a team using DSM IIIR criteria. The cancer diagnoses were from chart review. Observations were not blind. Among 63 patients (57 female) with Alzheimer’s disease, seven (1 1 %) currently had, or had undergone treatment for, cancer (1 meningioma, 3 breast, 2 colon, 1 basal cell of skin). Among 49 patients (45 female) without Alzheimer’s disease, 17 (35%) currently had, or had undergone treatment for, cancer (2 prostate, 3 breast, 3 colon and rectum, 1 cervix, 1 tongue, 2 squamous cell of skin, 5 basal cell of skin). Chi square with Yates correction = 7.76; P = CO.01. We still suggest caution in attributing these differences to a biological factor. They may be due to some demographic peculiarity of this population. We should be most interested to hear of the experiences of your readers in this matter.
Dietary insulin as an immunogen and tolerogen

We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin‐specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3–7 days and/or 3 months after delivery. After exclusive breast‐feeding, the children received either CM formula or casein hydrolysate during the first 6–8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non‐diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = −0.39, p = 0.013), and at 12 months of age in all children (r = −0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta‐cell autoimmunity when compared with autoantibody‐negative children (p = 0.030); this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast‐fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta‐cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance.
Minimal inhibitory concentration of azithromycin in Rhodococcus equi strains isolated from foals

Rhodococcus equi (R. equi) is a facultative intracellular Gram-positive organism that causes chronic pyogranulomatous pneumonia and enteritis in foals, mainly from 1 to 6 months-old (Giguère and Prescott, 1997). It is less frequently associated with others clinical signs in domestic species (Radostits et al., 2000; Takai et al., 2003). During the last years, the organism has emerged as an important opportunistic pathogen in immunosuppressed patients, especially those infected by the immunodeficiency virus (Severo et al., 2001). In Brazil, rhodococcosis is considered to be one the most important disease in foals (Ribeiro, 2005). Recently it has been described in human, including patient with aids (Severo et al., 2001). R. equi expresses different virulence factors, including intracellular maintenance in macrophages, presence of virulence-associated plasmids, and resistance to conventional antimicrobial therapy, which may lead to chronic infections difficult to be treated, and high mortality rates in foals (Takai, 1997; Ribeiro et al., 2002).
Ring opening of donor-acceptor cyclopropanes with the azide ion: a tool for construction of N-heterocycles.

A general method for ring opening of various donor-acceptor cyclopropanes with the azide ion through an SN 2-like reaction has been developed. This highly regioselective and stereospecific process proceeds through nucleophilic attack on the more-substituted C2 atom of a cyclopropane with complete inversion of configuration at this center. Results of DFT calculations support the SN 2 mechanism and demonstrate good qualitative correlation between the relative experimental reactivity of cyclopropanes and the calculated energy barriers. The reaction provides a straightforward approach to a variety of polyfunctional azides in up to 91 % yield. The high synthetic utility of these azides and the possibilities of their involvement in diversity-oriented synthesis were demonstrated by the developed multipath strategy of their transformations into five-, six-, and seven-membered N-heterocycles, as well as complex annulated compounds, including natural products and medicines such as (-)-nicotine and atorvastatin.
Innovation processes in SMEs: Exploring the influence of varying degrees of control

Previous research in the field of product innovation management has focused on large firms. This is unfortunate because small and medium-sized enterprises (SMEs) have features that clearly distinguish them from their larger counterparts and also play an important role in the global economy. In addition, SMEs often have more varying control of the whole innovation process – from identification of a customer need to delivering customer value – compared to larger companies. This article addresses this research gap by exploring how SMEs with growth ambitions, and varying degree of control, can leverage their innovation process. The article outlines results from a SWOT analysis utilizing data from a multiple case study of eight SMEs. Both ‘product owning’ companies (with either in-house or outsourced manufacturing) as well as manufacturing industry subcontractors were sampled. The results show indications of the influence of varying degree of control of the innovation process – relating to different phases, how knowledge and competence are considered and being reliant on others – and how SMEs and their offerings can be considered as parts of larger systems.
Spread of HIV infection in married monogamous women in India.

CONTEXT A high prevalence of human immunodeficiency virus (HIV) infection in female sex workers (FSWs) and men who attend sexually transmitted disease (STD) clinics poses a risk for spread of infection to other populations. OBJECTIVE To examine spread of HIV to a low-risk population by comparing prevalence of, and risk factors for, HIV and STDs in FSWs and non-FSWs. METHODS Women attending STD clinics in Pune, India, were assessed for STDs and HIV from May 13, 1993, to July 11, 1996. Demographic and behavioral information was collected, and clinical and laboratory assessment was performed. MAIN OUTCOME MEASURE Prevalence and risk determinants of HIV infection. RESULTS Of 916 women enrolled, 525 were FSWs and 391 were non-FSWs. Prevalence of HIV in FSWs and non-FSWs was 49.9% and 13.6%, respectively (P<.001). In multivariate analysis, inconsistent condom use and genital ulcer disease or genital warts were associated with prevalent HIV in FSWs. History of sexual contact with a partner with an STD was associated with HIV in non-FSWs. CONCLUSIONS Infection with HIV is increasing in non-FSWs, previously thought to be at low risk in India. Since history of sexual contact with their only sex partner was the only risk factor significantly associated with HIV infection, it is likely that these women are being infected by their spouses. This underscores the need for strengthening partner-notification strategies and counseling facilities in India.
Local immune response in Helicobacter pylori‐infected cats and identification of H. pylori in saliva, gastric fluid and faeces

Helicobacter pylori‐infected cats were screened by culture and polymerase chain reaction (PCR) for the presence of H. pylori in salivary secretions, gastric juice, gastric tissue and faeces. H. pylori was cultured from salivary secretions in six of 12 (50%) cats and from gastric fluid samples in 11 of 12 (91%) cats. A 298 base pair polymerase chain reactions (PCR) product specific for an H. pylori 26 000 MW surface protein was amplified from dental plaque samples from five of 12 (42%) cats and from the faeces of four of five (80%) cats studied. Analyses of serum and mucosal secretions by enzyme‐linked immunosorbent assay (ELISA) revealed an H. pylori‐specific immunoglobulin G (IgG) response, and elevated IgA anti‐H. pylori antibody levels in salivary and local gastric secretions. Immunohistochemical analyses of gastric tissue revealed the presence of IgM+ B cells assembled into multiple lymphoid follicles surrounded by clusters of CD4+ and CD8+ T cells. The lamina propria also contained single cells or aggregates of IgA+ and IgM+ B cells. These observations show that H. pylori can be identified in feline mucosal secretions, and that a localized IgA immune response develops in gastric tissue of H. pylori‐infected cats. The findings suggest a zoonotic risk from exposure to personnel handling H. pylori‐infected cats in vivaria.
Four cytotoxic N4-substituted thiosemicarbazones derived from 2-hydroxynaphthalene-1-carboxaldehyde.

The X-ray crystal structures are reported of four novel and potentially O,N,S-tridentate donor ligands that demonstrate antitumour activity. These ligands are 1-[(4-methylthiosemicarbazono)methyl]-2-naphthol, C(13)H(13)N(3)OS, (III), 1-[(4-ethylthiosemicarbazono)methyl]-2-naphthol, C(14)H(15)N(3)OS, (IV), 1-[(4-phenylthiosemicarbazono)methyl]-2-naphthol, C(18)H(15)N(3)OS, (V), and 1-[(4,4-dimethylthiosemicarbazono)methyl]-2-naphthol dimethyl sulfoxide solvate, C(14)H(15)N(3)OS.C(2)H(6)OS, (VI). These chelators are N4-substituted thiosemicarbazones, each based on the same parent aldehyde, namely 2-zhydroxynaphthalene-1-carboxaldehyde isonicotinoylhydrazone. Conformational variations within this series are discussed in relation to the optimum conformation for metal-ion binding.
Age and origin of major Smith-Lemli-Opitz syndrome (SLOS) mutations in European populations

Background: Smith-Lemli-Opitz syndrome (SLOS) (MIM 270 400) is an autosomal recessive multiple congenital anomalies/mental retardation syndrome caused by mutations in the Δ7-sterol reductase (DHCR7, E.C.1.3.1.21) gene. The prevalence of SLOS has been estimated to range between 1:15000 and 1:60000 in populations of European origin. Methods and results: We have analysed the frequency, origin, and age of DHCR7 mutations in European populations. In 263 SLOS patients 10 common alleles (c.964-1G>C, p.Trp151X, p.Thr93Met, p.Val326Leu, p.Arg352Trp, p.Arg404Cys, p.Phe302Leu, p.Leu157Pro, p.Gly410Ser, p.Arg445Gln) were found to constitute approximately 80% of disease-causing mutations. As reported before, the mutational spectra differed significantly between populations, and frequency peaks of common mutations were observed in North-West (c.964-1G>C), North-East (p.Trp151X, p.Val326Leu) and Southern Europe (p.Thr93Met). SLOS was virtually absent from Finland. The analysis of nearly 8000 alleles from 10 different European populations confirmed a geographical distribution of DHCR7 mutations as reported in previous studies. The common Null mutations in Northern Europe (combined ca. 1:70) occurred at a much higher frequency than expected from the reported prevalence of SLOS. In contrast the most common mutation in Mediterranean SLOS patients (p.Thr93Met) had a low population frequency. Haplotypes were constructed for SLOS chromosomes, and for wild-type chromosomes of African and European origins using eight cSNPs in the DHCR7 gene. The DHCR7 orthologue was sequenced in eight chimpanzees (Pan troglodytes) and three microsatellites were analysed in 50 of the SLOS families in order to estimate the age of the three major SLOS-causing mutations. Conclusions: The results indicate a time of first appearance of c.964-1G>C and p.Trp151X some 3000 years ago in North-West and North-East Europe, respectively. The p.Thr93Met mutations on the J haplotype has probably first arisen approximately 6000 years ago in the Eastern Mediterranean. Together, it appears that a combination of founder effects, recurrent mutations, and drift have shaped the present frequency distribution of DHCR7 mutations in Europe.
Lactating PTU Exposure: II-Alters Thyroid-Axis and Prooxidant-Antioxidant Balance in Neonatal Cerebellum

The aim of the present study was to evaluate the effect of lactating 6-propyl-2- thiouracil (PTU) on the interactions between the thyroid-axis and prooxidant/antioxidant markers in neonates. PTU was administered to female rats in drinking water (0.1% w/v) from birth to lactation day (LD) 30. The administration gave rise to a highly significant decrease in serum thyroxine (T4) and triiodothyronine (T3) levels and increase in serum thyrotropin (TSH) level in both dams and their offspring at LDs 20 and 30 relative to control group. Also, in PTU group, a marked depression was observed in serum of neonatal growth hormone (GH). In this hypothyroid state, obvious elevation of oxidative markers (protein carbonyls, lipid peroxidation, NO and H2O2) was observed at postnatal days (PNDs) 20 and 30, along with decreased activities of antioxidants markers (total thiol, glutathione, glutathione peroxidase, superoxide dismutase and catalase) in neonatal cerebellum with respect to control group. Also, the administration caused some histopathological changes in neonatal cerebellar cortex, such as oedema, vacuoles, reduction of the Purkinje cells, and cellular fragmentations at PND 30. Thus, hypothyroidism in lactating PTU impairs the neonatal neuroendocrine system via production of free radicals, and this, may cause damage of proteins and lipids at the plasma membrane and cellular components delaying cerebellum development.