Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome‐Wide Analysis of Genes Related to Kidney Stone Formation and Elimination in the Calcium Oxalate Nephrolithiasis Model Mouse: Detection of Stone‐Preventive Factors and Involvement of Macrophage Activity

We previously established a mouse kidney stone formation model and showed that mice have a higher tolerance to stone formation than rats. Furthermore, we showed that the generated calcium oxalate crystal deposits could be eliminated after several days. This study investigated the transcriptome of stone formation and elimination in the mouse kidney based on gene selection using a microarray technique. Eight‐week‐old male C57BL/6N mice were administered 80 mg/kg glyoxylate for 15 days, and kidney calcium oxalate crystal depositions had increased by day 6; thereafter, depositions decreased gradually and had almost disappeared by day 15. On microarray analysis, mRNA expression in the crystal‐formed kidneys showed the significant expression of 18,064 genes. Thirty‐one, 21, and 25 genes showed at least a 2‐fold increased expression during the experimental course (days 3–15), stone formation phase‐specific (days 3–6), and stone elimination phase‐specific (days 9–15) stages, respectively. Among these genes, those related to chemotaxis and monocyte/macrophage activation were identified. Gene ontology analysis to identify overexpressed genes highlighted categories related to inflammation, immune reactions and the complement activation pathway. Quantitative PCR of 17 previously reported stone‐related genes with a significant expression on microarray analysis showed significantly increased chemokines, stone matrix proteins, and their receptors; the significant decrease of several types of transporters and superoxide dismutase; and the persistently high expression of Tamm‐Horsfall protein throughout the experiment. In conclusion, inflammation and immune reactivity through macrophage migration are involved in stone formation and elimination in mouse kidneys.
Thrombophilia and pregnancy outcomes

Summary. Pregnancy complications are still a challenge for physicians, because knowledge of pathomechanisms and prophylactic measures is still limited. In recent years thrombophilia as a risk factor for pregnancy complications has gained much attention in the scientific community. However, data on this topic in the literature are conflicting. Besides an established association between antiphospholipid antibodies and pregnancy loss, available data suggest additional associations for antithrombin deficiency, hyperhomocysteinemia and also for factor (F)V Leiden, prothrombin G20210A variation, and protein S‐deficiency. The contribution of thrombophilia to the risk of pre‐eclampsia is less well established and recent studies did not confirm earlier data suggesting an association between thrombophilia and pre‐eclampsia. A limited number of prospective studies have failed to reveal an increased risk of pregnancy complications in unselected women with thrombosis risk factors. Low‐molecular weight heparin (LMWH) seems to have a positive effect on pregnancy outcome after single or recurrent abortions, however, data from only one controlled trial are available. Experience in the prevention of pre‐eclampsia by prophylactic heparin is very limited, and in addition, data on pregnancy complications in women with known heritable thrombophilia or a history of thrombosis are inconsistent. These women will usually have a favorable pregnancy outcome referring to the European Prospective Cohort on Thrombophilia Study. In conclusion, thrombophilia screening might be justified in women with pregnancy loss and treatment with LMWH might be considered in those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed.
Effect of Shenfu injection on nuclear factor-kappaB during myocardial ischemia/reperfusion injury in rats.

OBJECTIVE To investigate effects of Shenfu injection on the concentrations of plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), activity of Nuclear Factor kappa B (NF-kappaB) and heart tissue ultrastructure during myocardial ischemia/reperfusion (I/R) injury in rats and its potential mechanism. METHODS Myocardial ischemia/reperfusion (I/R) was produced by ligation and release of the left anterior descending coronary artery. Ischemia lasted for 30 min and reperfusion for 60 min. Twenty-four healthy male SD rats weighing 230-280 g were randomly divided into three groups (n = 8, each): Group I (Sham-operation group); Group II (I/R group); Group III (Shenfu group), in which Shenfu injection (10 ml/kg) was intraperitoneally injected 30 min before ischemia in animals with I/R. The plasma concentrations of IL-6 and TNF-alpha were measured by ELISA, and the heart was harvested for determination of NF-kappaB levels by Ecl-western blot analysis. Electron microscopy was used to study its ultrastructure. RESULTS After reperfusion, NF-kappaB binding activity in myocardial nuclei and the plasma concentrations of IL-6 and TNF-alpha were significantly increased in Group II, compared with Group I (P < 0.01), and they were markedly reduced in Group III, compared with Group II (P < 0.01). In addition, electron microscopic examination showed more serious injury of the myocardium ultrastructure in Group II, while in Group III the myocardial ultrastructure was similar to normal state. CONCLUSIONS Shenfu injection inhibits NF-kappaB activity in I/R myocardium and leads to down-regulation of proinflammatory cytokine expression, which might be one of the molecular mechanisms of Shenfu injection in cardioprotection.
Oritavancin: an investigational lipoglycopeptide antibiotic.

PURPOSE The pharmacology, unique pharmacokinetic-pharmacodynamic profile, and potential future role of oritavancin in combating multidrug-resistant infections are reviewed, with an emphasis on efficacy data from Phase II and III clinical trials. SUMMARY Oritavancin has been shown to have potent in vitro activity against vancomycin-resistant enterococci (VRE) and staphylococci, methicillin-resistant Staphylococcus aureus (MRSA), and gram-positive anaerobic bacteria. Oritavancin exhibits excellent tissue penetration and concentrates well in macrophages; its prolonged plasma half-life (195.4 hours) and extended in vitro postantibiotic effect (2.4- 7.7 hours for MRSA and 1.9-4.3 hours for VRE) might allow once-daily or alternate-day dosing. Oritavancin has been shown to have synergistic activity with several antibiotics (e.g., ampicillin, gentamicin, linezolid) against certain infections. In two Phase III clinical trials involving a total of about 1800 patients with complicated skin and skin structure infections (cSSSIs), i.v. oritavancin therapy was shown to have bactericidal activity and a safety profile comparable to those of i.v. vancomycin (plus optional oral cephalexin stepdown therapy) while requiring a significantly shorter duration of therapy; however, the compiled evidence was considered insufficient to justify marketing approval by the Food and Drug Administration, which requested additional safety and efficacy data. Two ongoing Phase III trials evaluating oritavancin for the treatment of acute bacterial SSSIs are expected to be completed in early 2013. During the clinical trials to date, the most commonly reported adverse effects among oritavancin users were headache, nausea, constipation, and phlebitis. CONCLUSION Oritavancin is an investigational semisynthetic antibiotic classified as a second-generation lipoglycopeptide, with promising activity against multidrug-resistant gram-positive pathogens.
Combination chemotherapy containing mitoguazone, ifosfamide, methotrexate, etoposide (MIME) and G-CSF efficiently mobilize peripheral blood progenitor cells in heavily pre-treated relapsed lymphoma patients.

In this study we explored whether a standard chemotherapy regimen consisting of mitoguazone, ifosfamide, methotrexate and etoposide (MIME) combined with 5 micrograms/kg or 10 micrograms/kg G-CSF was capable of mobilizing peripheral blood progenitor cells (PBPC) in lymphoma patients. Thirty-three patients with Hodgkin's disease (HD) and 108 patients with non-Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were heavily treated with different chemotherapy regimens receiving a median of 11 cycles (range 3-40) of chemotherapy prior to mobilization. Eight of 141 patients failed to mobilize PBPC and bone marrow was harvested. In addition, 10 patients obtained a harvest of < 2.0 x 10(6) CD34+ cells/kg. More than 2.0 x 10(6) CD34+ cells/kg were achieved in all HD patients and in 83% of the NHL patients. Fifty-eight per cent of the patients harvested > or = 5 x 10(6) CD34+ cells/kg. Eleven per cent of the patients developed neutropenic fever during the mobilization and 3% had nadir platelet values below 20 x 10(9)/L. An inverse correlation was observed in high-grade NHL (H-NHL) patients between the number of chemotherapy cycles given before mobilization and yield of CD34+ cells. Such an association was not seen among patients with HD, transformed and low-grade NHL. When G-CSF 10 micrograms/kg was used in combination with MIME, this correlation was no longer seen in patients with H-NHL. There was also association between CD34+ cell yield and prior radiotherapy in patients with HD or transformed NHL or low-grade NHL. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF, can be successfully used to mobilize PBPC. Although no significant effect of increased dose of G-CSF was found, our data suggest that MIME/G-CSF 10 micrograms/kg should preferentially be used to mobilize PBPC in H-NHL patients pre-treated with > or = 12 cycles of chemotherapy, in irradiated HD patients and in all low-grade and transformed lymphomas.
Maximum voluntary activation in nonfatigued and fatigued muscle of young and elderly individuals.

BACKGROUND AND PURPOSE Researchers studying central activation of muscles in elderly subjects (> or = 65 years of age) have investigated activation in only the nonfatigued state. This study examined the ability of young and elderly people to activate their quadriceps femoris muscles voluntarily under both fatigued and nonfatigued conditions to determine the effect of central activation failure on age-related loss of force. SUBJECTS AND METHODS Twenty young subjects (11 men, 9 women; mean age = 22.67 years, SD = 4.14, range = 18-32 years) and 17 elderly subjects (8 men, 9 women; mean age = 71.5 years, SD = 5.85, range = 65-84 years) participated in this study. Subjects were seated on a dynamometer and stabilized. Central activation was quantified, based on the change in force produced by a 100-Hz, 12-pulse electrical train that was delivered during a 3- to 5-second isometric maximum voluntary contraction (MVC) of the quadriceps femoris muscle. Next, subjects performed 25 MVCs (a 5-second contraction with 2 seconds of rest) to fatigue the muscle. During the last MVC, central activation was measured again. RESULTS In the nonfatigued state, elderly subjects had lower central activation than younger subjects. In the fatigued state, this difference became larger. DISCUSSION AND CONCLUSION Central activation of the quadriceps femoris muscle in elderly subjects was reduced in both the fatigued and nonfatigued states when compared with young subjects. Some part of age-related weakness, therefore, may be attributed to failure of central activation in both the fatigued and nonfatigued states.
Greenwich Papers in Political Economy When complexity meets finance : A contribution to the study of the macroeconomic effects of complex financial systems

In the last decade, complexity economics has emerged as a powerful approach to the understanding of the most relevant factors influencing economic development. The concept of economic complexity has been applied to the study of different economic issues such as economic growth, technological change and inequality. With this work we aim at extending the application of this concept to the study of the financial side of the economy, and, in particular, of the macroeconomic effects of rising financial complexity. In this paper, we present an agent-based model integrating an increasingly complex financial sector with a real side of the economy populated, among other sectors, by heterogeneous households. We test the systemic impact that the increasing complexity of both the financial system and the financial products it manufactures bear on economic growth, macroeconomic stability and inequality. We find mixed results with respect to the positive economic implications the existing literature ascribes to products complexity and deepening production capabilities. Despite higher financial complexity may lead to faster growth, our model suggests that this comes at the cost of heightened financial fragility, a more crisis-prone economic system, and increasing levels of income and wealth inequality. According to these findings, and consistently with pioneering insights from Minsky, we claim that rising complexity does not always entail positive consequences for the well-being of the economy. This is particularly true when it comes to financial innovations and financial complexity.
The composition of house dust mite is critical for mucosal barrier dysfunction and allergic sensitisation

Background House dust mite (HDM) allergens have been reported to increase airway epithelial permeability, thereby facilitating access of allergens and allergic sensitisation. Objectives The authors aimed to understand which biochemical properties of HDM are critical for epithelial immune and barrier responses as well as T helper 2-driven experimental asthma in vivo. Methods Three commercially available HDM extracts were analysed for endotoxin levels, protease and chitinase activities and effects on transepithelial resistance, junctional proteins and pro-inflammatory cytokine release in the bronchial epithelial cell line 16HBE and normal human bronchial cells. Furthermore, the effects on epithelial remodelling and airway inflammation were investigated in a mouse model. Results The different HDM extracts varied extensively in their biochemical properties and induced divergent responses in vitro and in vivo. Importantly, the Greer extract, with the lowest serine protease activity, induced the most pronounced effects on epithelial barrier function and CCL20 release in vitro. In vivo, this extract induced the most profound epithelial E-cadherin delocalisation and increase in CCL20, CCL17 and interleukin 5 levels, accompanied by the most pronounced induction of HDM-specific IgE, goblet cell hyperplasia, eosinophilic inflammation and airway hyper-reactivity. Conclusions This study shows the ability of HDM extracts to alter epithelial immune and barrier responses is related to allergic sensitisation but independent of serine/cysteine protease activity.
Cloning and characterization of a gene required for assembly of the Bacillus subtilis spore coat

During endospore formation in Bacillus subtilis, approximately a dozen proteins are synthesized and assembled around the prespore to form a protective coat. Little is known about the assembly process, but several of the genes encoding these coat proteins are expressed in the mother cell compartment, where the proteins accumulate on the outer side of the developing endospore. Transcription of these genes is directed by the mother cell-specific sigma factor, sigma K, during the later stages of endospore development. sigma E may direct expression of the genes that encode proteins that function in the earliest stages of coat assembly. By screening for sigma E-dependent promoters, we cloned a gene, designated spoVID, required for assembly of a normal spore coat. Expression of spoVID was initiated at about the second hour of sporulation and continued throughout development from a sigma E-dependent promoter. The spoVID gene was located on the B. subtilis chromosome just downstream of the previously characterized hemAXCDBL operon and is predicted to encode an extremely acidic protein with 575 residues. Insertion mutants of spoVID produced refractile spores that were resistant to heat and to chloroform but were sensitive to lysozyme. Electron microscopic examination of sporulating spoVID mutant cells revealed normal morphological development up to about the third hour of sporulation. However, during the later stages of development the coat proteins assembled into aberrant structures that occurred freely in the mother cell cytoplasm and that consisted of reiterations of the single inner and outer layers that normally make up the spore coat.
Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans.

BACKGROUND After the age of 60, isolated cardiac amyloidosis is four times more common among blacks than whites in the United States; 3.9 percent of blacks are heterozygous for an amyloidogenic allele of the normal serum carrier protein transthyretin in which isoleucine is substituted for valine at position 122 (Ile 122). We hypothesized that the high prevalence of transthyretin Ile 122 is at least partially responsible for the increased frequency of senile cardiac amyloidosis among blacks. METHODS Paraffin blocks of cardiac tissue were obtained from an earlier study of 52,370 autopsies in Los Angeles and were examined by immunohistochemical and DNA analyses. Samples were available from 32 of 55 blacks and 20 of 78 whites over 60 years of age with isolated cardiac amyloidosis and from two control groups (228 cases). RESULTS Transthyretin amyloidosis was identified in 31 of the 32 cardiac-tissue samples from the black patients and in 19 of the 20 samples from the white patients. Six of the 26 analyzable DNA samples (23 percent) from the black patients and none of the 19 samples from the white patients were heterozygous for the Ile 122 variant. Four of 125 DNA samples obtained at autopsy (3.2 percent) from a second, more recent, age-matched cohort of blacks without amyloidosis at the same institution were heterozygous for the transthyretin Ile 122 allele. On reexamination the cardiac tissue from these four patients contained small amounts of amyloid not detected at the initial autopsies. All subjects with the Ile 122 variant had ventricular amyloid. CONCLUSIONS The assessment of elderly black patients with unexplained heart disease should include a consideration of transthyretin amyloidosis, particularly that related to the Ile 122 allele.
Sensitization of meningeal nociceptors: inhibition by naproxen

Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non‐selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non‐selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single‐unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non‐selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of Aδ‐ and C‐units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX‐2 inhibitor N‐[2‐(cyclohexyloxy)‐4‐nitrophenyl]‐methanesulfonamide (NS‐398) onto the dural receptive field of Aδ‐ and C‐unit nociceptors also reversed the neuronal hyper‐responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache.
A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.

PURPOSE To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. METHODS A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. RESULTS Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. CONCLUSIONS Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.
Gene expression analysis of major lineage‐defining factors in human bone marrow cells: Effect of aging, gender, and age‐related disorders

Adult bone marrow cells (BMCs) include two populations:;mesenchymal stem cells (MSCs), which can differentiate into bone, cartilage, and fat; and hematopoietic stem cells (HSCs), which produce all mature blood lineage. To study the effect of aging, gender, and age‐related disorders on lineage differentiation, we performed quantitative RT‐PCR to examine mRNA expression of the major factors defining BMC lineage, cbfa1 for osteoblasts, ppar‐gamma for adipocytes, sox9 for chondrocytes, and rankl for osteoclasts, in bone marrow from 80 healthy subjects and patients (14–79 years old) with two age‐related disorders: osteoarthritis (OA) and rheumatoid arthritis (RA). Two apoptosis‐related genes, bcl‐2 and drak1, were studied. RANKL and PPAR‐Gamma levels exhibited a clear positive correlation with age in female patients, but not in males, with a slight age‐related decline in CBFa1 transcripts. DRAK1 expression showed an age‐associated ascending trend with significantly greater transcripts of RANKL and DRAK1 in females (p < 0.01). Compared with age‐matched controls, RA patients exhibited increased RANKL, PPAR‐Gamma, and DRAK1 mRNA levels (p < 0.05), and OA showed the higher RANKL and PPAR‐Gamma transcripts (p < 0.05). Furthermore, SOX9 and DRAK1 expressions in the RA group were higher than in the OA group (p < 0.05). Our data indicate that aging and age‐related disorders affect gene expressions differently, suggesting that in aging, the lineage of bone marrow cells was modified with prominent changes in decreased bone marrow osteoblastogenesis, increased adipogenesis and osteoclastogenesis, while in age‐related disorders, marrow adipogenesis and the activity or number of osteoclasts may play an important role in the pathogenesis of arthritic bone loss. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:910–917, 2008