Miracle-dz/UniFAR-FTUs huggingface dataset:
Regionally specific pattern of neurochemical pathology in schizophrenia as assessed by multislice proton magnetic resonance spectroscopic imaging.

OBJECTIVE Several single-voxel proton magnetic resonance spectroscopy (1H-MRS) studies of patients with schizophrenia have found evidence of reductions of N-acetyl-aspartate (NAA) concentrations in the temporal lobes. Multislice proton magnetic resonance spectroscopy imaging (1H-MRSI) permits simultaneous acquisition and mapping of NAA, choline-containing compounds (CHO), and creatine/phosphocreatine (CRE) signal intensities from multiple whole brain slices consisting of 1.4-ml single-volume elements. We have used 1H-MRSI to assess the regional specificity of previously reported changes of metabolite signal intensities in schizophrenia. Hippocampal volume was also measured to test the relationship between 1H-MRSI findings and tissue volume in this region. METHOD Ratios of areas under the metabolite peaks of the proton spectra were determined (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions in 10 inpatients with schizophrenia. RESULTS Patients showed significant reductions of NAA/CRE and NAA/CHO bilaterally in the hippocampal region and in the dorsolateral prefrontal cortex. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios in the hippocampal region and its volume. CONCLUSIONS NAA-relative signal intensity reductions in schizophrenia appear to be remarkably localized, involving primarily the hippocampal region and the dorsolateral prefrontal cortex, two regions implicated prominently in the pathophysiology of this disorder.
Factors associated with breast cancer clinical trials participation and enrollment at a large academic medical center.

PURPOSE The practice patterns of medical oncologists at a large National Cancer Institute Comprehensive Cancer Center in Detroit, MI were evaluated to better understand factors associated with accrual to breast cancer clinical trials. PATIENTS AND METHODS From 1996 to 1997, physicians completed surveys on 319 of 344 newly evaluated female breast cancer patients. The 19-item survey included clinical data, whether patients were offered clinical trial (CT) participation and enrollment, and when applicable, reasons why they were not. Multivariate analyses using logistic regression were performed to evaluate predictors of an offer and enrollment. RESULTS The patients were 57% white, 32% black, and 11% other/unknown race. One hundred six (33%) were offered participation and 36 (34%) were enrolled. In multivariate analysis, CTs were less likely offered to older women (mean age, 52 years for those offered v 57 years for those not offered; P =.0005) and black women (21% of blacks offered v 42% of whites; P =.0009). Women with stage 1 disease, poor performance status, and those who were previously diagnosed were also less likely to be offered trials. None of these factors were significant predictors of enrollment. Women were not offered trials because of ineligibility (57%), lack of available trials (41%), and noncompliance (2%). Reasons for failed enrollment included patient refusal (88%) and failed eligibility (12%). CONCLUSION It is important for cooperative groups to design studies that will accommodate a broader spectrum of patients. Further work is needed to assess ways to improve communication about breast cancer CT participation to all eligible women.
“12 weeks’ stopping rule” in the treatment of genotype 1 chronic hepatitis C: Two prognostic categories under the same label?

Objective. The current guidelines recommend maintenance of combined therapy for hepatitis C virus (HCV) genotype-1 chronic hepatitis when HCV-RNA is undetectable or ≤2 log10 of baseline after 12 weeks of therapy. The aim of this study was to investigate whether the probability of obtaining sustained viral (SVR) response is similar when HCV-RNA is undetectable or is present at ≤2 log10 level after 12 weeks of therapy. Material and methods. Retrospective analysis was carried out in 208 HCV genotype-1 chronic hepatitis patients treated with pegylated interferon and ribavirin with available data on HCV viral load after 12 weeks of therapy and definite data on the results of therapy. Results. Seventy-six (68.5%) out of 111 patients with undetectable HCV-RNA and 4 (11.8%) out of 34 patients with HCV-RNA ≤2 log10 from baseline at week 12 reached SVR (odds ratio 16.29, 95% CI 5.08–67.12; p<0.001). Sixty-three patients did not meet any of these criteria and therapy was discontinued. Conclusions. The “12-week stopping rule” includes two different categories of responders considered candidates for maintained therapy, but the probability of obtaining SVR is very low in patients with HCV-RNA that is still detectable at this time of treatment. We suggest that, in these partial responders, the prolongation of therapy should be decided on an individual basis.
Presence and function of a thick mucous layer rich in polysaccharides around Bacillus subtilis spores

This study was designed to establish the presence and function of the mucous layer surrounding spores of Bacillus subtilis. First, an external layer of variable thickness and regularity was often observed on B. subtilis spores. Further analyses were performed on B. subtilis 98/7 spores surrounded by a thick layer. The mechanical removal of the layer did not affect their resistance to heat or their ability to germinate but rendered the spore less hydrophilic, more adherent to stainless steel, and more resistant to cleaning. This layer was mainly composed of 6-deoxyhexoses, ie rhamnose, 3-O-methyl-rhamnose and quinovose, but also of glucosamine and muramic lactam, known also to be a part of the bacterial peptidoglycan. The specific hydrolysis of the peptidoglycan using lysozyme altered the structure of the required mucous layer and affected the physico-chemical properties of the spores. Such an outermost mucous layer has also been seen on spores of B. licheniformis and B. clausii isolated from food environments.
Comparison of DNA damage and repair following radiation challenge in buccal cells and lymphocytes using single‐cell gel electrophoresis

Purpose: To develop a reproducible single‐cell gel electrophoresis assay for DNA damage and repair in buccal mucosa and sublingual exfoliated cells. Materials and methods: Buccal mucosa and sublingual cells and lymphocytes from six individuals (three males, three females, aged 34–45 years) were challenged with increasing doses of gamma‐rays. DNA strand breaks and DNA repair were measured using the single‐cell gel electrophoresis assay. Results: Baseline DNA strand breaks were significantly greater in buccal mucosa and sublingual cells compared with lymphocytes. Buccal mucosa and sublingual cells did not differ from each other with respect to induction of DNA strand breaks by 2 or 4 Gy gamma‐rays. However, they showed a smaller increase in gamma‐ray‐induced DNA strand breaks compared with lymphocytes (32–53% less than lymphocytes; ANOVA p<0.0001). Unlike lymphocytes, which repaired 83% of DNA strand breaks, buccal mucosa and sublingual cells exhibited only a minimal capacity for DNA repair (approximately 0–14% of the level in lymphocytes). Conclusions: Buccal mucosa and sublingual cells exhibit an apparent resistance to the expression of radiation‐induced DNA strand breaks in vitro and an apparent lack of DNA strand break repair in the single‐cell gel electrophoresis assay.
Acquirement of Brown Fat Cell Features by Human White Adipocytes*

Obesity, i.e. an excess of white adipose tissue (WAT), predisposes to the development of type 2 diabetes and cardiovascular disease. Brown adipose tissue is present in rodents but not in adult humans. It expresses uncoupling protein 1 (UCP1) that allows dissipation of energy as heat. Peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivator 1α (PGC-1α) activate mouse UCP1 gene transcription. We show here that human PGC-1α induced the activation of the human UCP1 promoter by PPARγ. Adenovirus-mediated expression of human PGC-1α increased the expression of UCP1, respiratory chain proteins, and fatty acid oxidation enzymes in human subcutaneous white adipocytes. Changes in the expression of other genes were also consistent with brown adipocyte mRNA expression profile. PGC-1α increased the palmitate oxidation rate by fat cells. Human white adipocytes can therefore acquire typical features of brown fat cells. The PPARγ agonist rosiglitazone potentiated the effect of PGC-1α on UCP1 expression and fatty acid oxidation. Hence, PGC-1α is able to direct human WAT PPARγ toward a transcriptional program linked to energy dissipation. However, the response of typical white adipocyte targets to rosiglitazone treatment was not altered by PGC-1α. UCP1 mRNA induction was shown in vivo by injection of the PGC-1α adenovirus in mouse white fat. Alteration of energy balance through an increased utilization of fat in WAT may be a conceivable strategy for the treatment of obesity.
Aortic stiffness is reduced beyond blood pressure lowering by short-term and long-term antihypertensive treatment: a meta-analysis of individual data in 294 patients

Background Arterial stiffness is an independent predictor of cardiovascular events and mortality in hypertensive patients. The influence of different antihypertensive drug classes on improving arterial stiffness beyond blood pressure reduction is not widely available. We aimed to determine whether the artery stiffness can be improved because of antihypertensive treatments independently of blood pressure lowering. Methods We conducted a meta-analysis of individual data from 15 randomized, controlled, double-blind, parallel group trials performed in our laboratory between 1987 and 1994. The primary endpoint was the changes of carotid–femoral pulse wave velocity (PWV) after treatment in 294 patients with mild-to-moderate essential hypertension untreated. Treatments tested were placebo (n = 88), angiotensin-converting enzyme inhibitors (ACEIs) (n = 75), calcium antagonists (n = 75), beta-blocker (n = 30), and diuretic (n = 26). Results In the short-term and long-term trials, PWV decreased significantly by −0.75 and −1.3 m/s in the active treatment group compared with by +0.17 and −0.44 m/s in the placebo group, respectively. Active treatment was independently related to the changes in PWV and explained 5 and 4% of the variance in the short-term and long-term trials, respectively. In the short-term trials, ACEIs were more effective than calcium antagonists and placebo on improving arterial stiffness. In the long-term trials, ACEI, calcium antagonists, beta-blocker, and diuretic reduced significantly PWV compared to placebo. Conclusion Our study shows that antihypertensive treatments improve the arterial stiffness beyond their effect on blood pressure.
Possible Interactions between the NS-1 Protein and Tumor Necrosis Factor Alpha Pathways in Erythroid Cell Apoptosis Induced by Human Parvovirus B19

ABSTRACT Human erythroid progenitor cells are the main target cells of the human parvovirus B19 (B19), and B19 infection induces a transient erythroid aplastic crisis. Several authors have reported that the nonstructural protein 1 (NS-1) encoded by this virus has a cytotoxic effect, but the underlying mechanism of NS-1-induced primary erythroid cell death is still not clear. In human erythroid progenitor cells, we investigated the molecular mechanisms leading to apoptosis after natural infection of these cells by the B19 virus. The cytotoxicity of NS-1 was concomitantly evaluated in transfected erythroid cells. B19 infection and NS-1 expression induced DNA fragmentation characteristic of apoptosis, and the commitment of erythroid cells to undergo apoptosis was combined with their accumulation in the G2phase of the cell cycle. Since B19- and NS-1-induced apoptosis was inhibited by caspase 3, 6, and 8 inhibitors, and substantial caspase 3, 6, and 8 activities were induced by NS-1 expression, there may have been interactions between NS-1 and the apoptotic pathways of the death receptors tumor necrosis factor receptor 1 and Fas. Our results suggest that Fas-FasL interaction was not involved in NS-1- or B19-induced apoptosis in erythroid cells. In contrast, these cells were sensitized to tumor necrosis factor alpha (TNF-α)-induced apoptosis. Moreover, the ceramide level was enhanced by B19 infection and NS-1 expression. Therefore, our results suggest that there may be a connection between the respective apoptotic pathways activated by TNF-α and NS-1 in human erythroid cells.
The World of The Neo-Hittite Kingdoms: A Political and Military History

This book provides an account of the military and political history of the Neo-Hittite kingdoms, which developed in south-eastern Anatolia and northern Syria during the Iron Age following the collapse of the Late Bronze Age Hittite empire. The book is divided into three parts. Parts I begins with a chapter on the last decades of the empire and proceeds, in Chapters 2-4, from a treatment of the Hittites' Anatolian successors to a discussion of the chief features of the Neo-Hittite kingdoms and their possible links with the biblical Hittites. Part II deals with the individual Neo-Hittite kingdoms, their rulers, and their Luwian hieroglyphic inscriptions, and also with the contemporary Aramaean states and the other kingdoms of the age, notably the Neo-Assyrian empire. Part III integrates the histories of the various Neo-Hittite states with those of their neighbours and contemporaries up to the time when the last Neo-Hittite kingdom was absorbed into the Assyrian provincial administration. The overall aim of this Part is to provide a historical synthesis of the Neo-Hittites and their contemporaries in the period from the 12th to the late 8th century. Assyria will play a major role throughout this synthesis, but the focus will be primarily on the cities, states, and territories that made up the world of the Neo-Hittite kingdoms.
Three-Dimensional Structures of Soluble CD4-Bound States of Trimeric Simian Immunodeficiency Virus Envelope Glycoproteins Determined by Using Cryo-Electron Tomography

ABSTRACT The trimeric envelope glycoprotein (Env) spikes displayed on the surfaces of simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) virions are composed of three heterodimers of the viral glycoproteins gp120 and gp41. Although binding of gp120 to cell surface CD4 and a chemokine receptor is known to elicit conformational changes in gp120 and gp41, changes in quaternary structure of the trimer have only recently been elucidated. For the HIV-1 BaL isolate, CD4 attachment results in a striking rearrangement of the trimer from a “closed” to an “open” conformation. The effect of CD4 on SIV trimers, however, has not been described. Using cryo-electron tomography, we have now determined molecular architectures of the soluble CD4 (sCD4)-bound states of SIV Env trimers for three different strains (SIVmneE11S, SIVmac239, and SIV CP-MAC). In marked contrast to HIV-1 BaL, SIVmneE11S and SIVmac239 Env showed only minor conformational changes following sCD4 binding. In SIV CP-MAC, where trimeric Env displays a constitutively “open” conformation similar to that seen for HIV-1 BaL Env in the sCD4-complexed state, we show that there are no significant further changes in conformation upon the binding of either sCD4 or 7D3 antibody. The density maps also show that 7D3 and 17b antibodies target epitopes on gp120 that are on opposites sides of the coreceptor binding site. These results provide new insights into the structural diversity of SIV Env and show that there are strain-dependent variations in the orientation of sCD4 bound to trimeric SIV Env.
Morphological Characterization of Hantavirus HV114 by Electron Microscopy

Objective: This study was sought to investigate the propagation and morphogenesis of a new strain of hantavirus, HV114. Methods: The urine of patient with epidemic hemorrhagic fever was inoculated to Vero E6 cells for the virus isolation. Electron microscopy was used to observe the isolated virus, HV114 and the variation of infected Vero E6 cells. Results: According to our observations, the size (90–120 nm) of HV114 is smaller than that reported previously as 110– 160 nm. While ribosome-like particles associated with virions originating from rodent hantaviruses were not observed in HV114, virion budding was exhibited. It suggests that the dumbbell-shaped particles may generated from the process of virion budding. The budding processes suggest that there are several sites for HV114 assembly and maturation, including the host endoplasmic reticulum-Golgi compartment and the host plasma membranes. Conclusions: The HV114 isolated from the urine of the patient is differed from other hantaviruses which were isolated from rat organs. HV114 might undergo changes during the viral transmission process from rodents to humans.
Non-telomeric sites as evidence of chromosomal rearrangement and repetitive (TTAGGG)n arrays in heterochromatic and euchromatic regions in four species of Akodon (Rodentia, Muridae)

Comparative studies among four species – Akodonazarae (2n = 38), A. lindberghi (2n = 42), A. paranaensis (2n = 44) and A. serrensis (2n = 46) – employing classic cytogenetics (C- and G-bands) and fluorescence in situ hybridization with telomeric (TTAGGG)n sequencesare reported here. Non-telomeric signals in addition to the regular telomeric sites were detected in three species:A. azarae, A. lindberghi and A. serrensis. One interstitial telomeric site (ITS) was observed proximally at the long arm of chromosome 1 of A. azarae. The comparison of G-banding patterns among the species indicated that the ITS was due to a tandem fusion/fission rearrangement. Non-telomeric signals of A. lindberghi and A. serrensis were not related to chromosomal rearrangements; instead, the sequences co-localized with (i) heterochromatic regions of all chromosomes in A. serrensis; (ii) some heterochromatic regions in A. lindberghi, and (iii) both euchromatic and heterochromatic regions in the metacentric pair of A. lindberghi. These exceptional findings revealed that ITS in Akodon can be related to chromosomal rearrangements and repetitive sequences in the constitutive heterochromatin and that the richness of TTAGGG-like sequences in the euchromatin could be hypothesized to be a result of amplification of the referred sequence along the chromosome arms.
A head in virtual reality: Development of a dynamic head and neck model

Advances in computer and interface technologies have made it possible to create three‐dimensional (3D) computerized models of anatomical structures for visualization, manipulation, and interaction in a virtual 3D environment. In the past few decades, a multitude of digital models have been developed to facilitate complex spatial learning of the human body. However, there is limited empirical evidence to guide the development and integration of effective computer models for teaching and learning. The purpose of this article is to describe the development of a dynamic head and neck model with flexible displays (2D, 3D, and stereoscopic 3D) and interactive control features that can be later used to design and test the efficacy of computer models as a means of improving student learning. The model was created using computer tomography scans of a human cadaver. Anatomical structures captured on the scans were segmented into discreet areas, and then reconstructed in three‐dimensions using specialized software. The final model consists of 70 distinct anatomical structures that can be displayed in 2D, 3D, or stereoscopic 3D. In 3D mode, a mouse can be used to actively and continuously interact with the model by manipulating viewer orientation, altering surface transparency, superimposing 2D scans with 3D reconstructions, removing or adding structures sequentially, and customizing animated scenes to show complex anatomical pathways or relationships. Anat Sci Educ 2: 294–301, 2009. © 2009 American Association of Anatomists.
Iris indocyanine green videoangiography in diabetic iridopathy.

AIMS/BACKGROUND: Iris fluorescein angiography (IFA) is not commonly used in clinical practice, although its value has been demonstrated especially in cases of diabetic disease. IFA is able to show neovascular tufts in order to guide the laser treatment, and it is highly recommended in diabetic patients who need cataract surgery or vitrectomy. Nevertheless, IFA fails to demonstrate the iris vascular pattern in heavily pigmented iris and conspicuous leakage cases. The aim of the study was to evaluate the feasibility of iris indocyanine green videoangiography (IICGV) and to correlate its findings with those of IFA in diabetic iridopathy. METHODS: Thirty six patients affected in varying degrees by diabetic retinopathy underwent an ophthalmic examination including retinal fluorescein angiography, IFA, and IICGV. IICGV was performed using IMAGEnet System H1024. RESULTS: The results demonstrated that IICGV allows precise visualisation of the iris vascular pattern, also in cases of heavily pigmented iris. CONCLUSIONS: Three main findings seemed to be evident: firstly, iris neovascularisations are detected with IFA far more easily than IICGV; secondly, capillary dilatations and iris hypoperfusion are identified far more clearly using IICGV; thirdly, there is no evident relation between capillary dilatation or iris hypoperfusion, and degree of diabetic retinopathy.
Colorectal cancer screening: practices and attitudes of gastroenterologists, internists and surgeons.

BACKGROUND The Canadian Task Force on Preventive Health Care has recommended the use of annual or biennial fecal occult blood testing (FOBT) and flexible sigmoidoscopy in the periodic health examination of asymptomatic people over 50 years of age. Therefore, we decided to ascertain the current colorectal cancer (CRC) screening practices and attitudes of surgeons, gastroenterologists and internists. METHODS In June 2002 (with a final mailing in December 2002), a questionnaire was sent to all gastroenterologists, internists and surgeons in Alberta. It included items on demographic and practice characteristics, CRC screening practices and opinions about CRC screening. RESULTS Responses were received from 42 gastroenterologists, 83 internists and 68 surgeons. Overall, 141 of 187 respondents (75.4%, 95% confidence interval [CI] 68.6%-81.4%) recommended that average-risk adults undergo CRC screening. Internists were less likely to recommend screening than either gastroenterologists or surgeons (95% CI for the difference 7.2%-32.8%). The most commonly recommended screening test was colonoscopy (70%), followed by FOBT (65%), flexible sigmoidoscopy (47%) and air-contrast barium enema (31%). Colonoscopy was the only test recommended by 7 (22.6%) of 33 gastroenterologists, 9 (16.4%) of 59 surgeons and 3 (6.1%) of 49 internists. Respondents were more likely to list barriers to the use of colonoscopy (mean 5 barriers) for screening than for either FOBT or flexible sigmoidoscopy (mean 2 barriers for both tests). Only 3 respondents indicated that they themselves would not undergo screening. Colonoscopy was the only screening test that 135 (70.0%) of the 193 would themselves undergo. CONCLUSIONS The majority of Alberta specialists recommend CRC screening for average-risk adults. Colonoscopy was the most commonly recommended test, despite the perception of more barriers to that technique and the 2001 guidelines prepared by the Canadian Task Force for Preventive Health Care, which did not support colonoscopy.