[Sonographic features of chromosomal defects at 11(+0) to 13(+6) weeks of gestation].
Each chromosomal defect has its own syndromal pattern of detectable abnormalities. The authors describe the sonographic features of trisomy 21 and other major chromosomal defects in the first trimesters of pregnancy. At 11(+0) - 13(+6) weeks, all major chromosomal defects are associated with increased NT thickness. In trisomies 21, 18 and 13 the pattern of increase in NT is similar and the average NT in these defects is about 2.5 mm above the normal median for crown-rump length. In Turner syndrome, the median NT is about 8 mm above the normal median. In addition to increased NT there are sonographic features that are often seen in some affected fetuses at 11(+0) - 13(+6) weeks. In trisomy 21 fetuses have absent nasal bone, short maxilla and abnormal Doppler waveforms in the ductus venosus. In trisomy 18, there is early onset fetal growth restriction, a tendency for bradycardia, exomphalos, absent nasal bone and single umbilical artery. In trisomy 13, there is tachycardia, early onset fetal growth restriction, megacystis, holoprosencephaly and exomphalos. In Turner syndrome, there is tachycardia and early onset fetal growth restriction. In triploidy, there is early onset asymmetrical fetal growth restriction, bradycardia, holoprosencephaly, exomphalos, posterior fossa cyst and molar changes in the placenta.


Portopulmonary hypertension: an update.
Portopulmonary hypertension represents a serious lung vascular disorder, defined as the presence of pulmonary arterial hypertension that is associated with portal hypertension, with or without the presence of significant liver disease. Transthoracic echocardiography represents the single best initial tool for the diagnostic evaluation in portopulmonary hypertension, and right heart catheterization remains the gold standard for definitive diagnosis. Despite the lack of randomized controlled trials in portopulmonary hypertension, some therapies have demonstrated improvements in cardiopulmonary haemodynamics and right ventricular function as described in case reports and case series. Specialists should be able to recognize indications and contraindications for liver transplantation in the setting of portopulmonary hypertension, and this review focuses on the appropriate diagnostic approach and current advances in medical therapies. Recognition of patients eligible for liver transplantation is needed to improve quality of life and survival.


[Acute myocardial ischemia after carbon monoxide exposure: a case report].
We describe the case of a patient who was admitted to the internal ward because of carbon monoxide poisoning. The examined level of carboxyhemoglobin measured 32%. The patient did not complain of any chest pain, but the features of myocardial hypoxia were observed in the electrocardiogram and significantly increased level of troponin T was revealed in laboratory tests. The ischaemic abnormalities ceased after normalization of carboxyhemoglobin level and the stress test was negative. Within the submitted study we report the possible interaction between carbon monoxide and cardiovascular system.


Effects of roughage source and inclusion in beef finishing diets containing corn wet distillers' grains plus solubles.
Two experiments were conducted to determine the effects of roughage source and inclusion in diets containing wet distillers' grains plus solubles (WDGS) on finishing cattle performance and ruminal metabolism. In Exp. 1, 385 crossbred steer calves (initial BW = 346 kg [SD 29]) were used in a finishing trial. A control diet with no roughage inclusion was compared with 6 diets containing either alfalfa hay (ALF), corn silage (CSIL), or corn stalks (CSTK) at 2 inclusions as a 3 × 2 factorial. Alfalfa hay was included at 4 (low) or 8% (standard) of diet DM. Diets containing CSIL or CSTK were formulated to provide total dietary NDF equal to the low and standard ALF inclusion diets. The final diets contained 6.13 and 12.26% CSIL or 3.04 and 6.08% CSTK (DM basis). All diets contained 30% WDGS and a 1:1 mixture of dry-rolled and high-moisture corn (DM basis). Cattle fed no roughage had reduced ( < 0.01) DMI and tended ( ≤ 0.10) to have the lowest final BW and ADG compared with cattle fed roughage. There were no differences ( ≥ 0.11) in DMI, ADG, or G:F due to roughage source. Cattle fed a standard inclusion of roughage had greater ( ≤ 0.04) DMI and ADG compared with cattle fed diets with low inclusion, regardless of roughage source. Feed efficiency tended to be different among treatments ( = 0.09), with cattle fed no roughage having greater G:F than all treatments ( ≤ 0.06) except cattle fed the low level of CSTK, which had a similar G:F ( = 0.48). Feed efficiency was not affected by source of roughage ( = 0.23) or inclusion of roughage ( = 0.49). In Exp. 2, 6 ruminally fistulated steers (347 kg BW [SD 25]) were used in a 6 × 6 Latin square design. Treatments were arranged as a 2 × 3 factorial with ALF or CSTK included at zero, low, or standard levels similar to Exp. 1. Apparent total tract digestibility (%) of DM, OM, and NDF decreased linearly ( ≤ 0.07) due to increasing roughage inclusion. Average, maximum, and minimum ruminal pH increased linearly ( ≤ 0.09) as roughage inclusion was increased. Based on the results of this study, low levels of CSTK improved cattle performance relative to low inclusions of ALF or CSIL. Diets with standard inclusions of ALF, CSIL, or CSTK had similar performance. Roughage sources can be exchanged to provide equal NDF in finishing diets containing 30% WDGS without negatively impacting finishing cattle. Based on ADG, eliminating roughages when 30% WDGS was included in finishing diets was not beneficial.


[Emesis and the oculocardiac reflex. Drug prophylaxis with droperidol and atropine in children undergoing strabismus surgery].
Although droperidol is often used to prevent emesis, vomiting is still common in children undergoing strabismus surgery. METHODS. One hundred children aged 3 to 12 years admitted for strabismus surgery were enrolled in a randomised, double-blind study to investigate the influence of the timing of the administration of droperidol (75 micrograms/kg i.v.) and the effect of atropine (10 micrograms/kg i.v.) on postoperative vomiting and the occurrence of the oculocardiac reflex (OCR). Each child was prospectively assigned to one of the following groups: Group A: atropine and droperidol before the beginning of surgery (n = 25); Group B: atropine before the beginning, droperidol after completion of surgery (n = 25); Group C: no atropine, droperidol before the beginning of surgery (n = 25); Group D: no atropine, droperidol after completion of surgery (n = 25). After oral premedication with 0.4 mg/kg midazolam, anaesthesia was induced via a face mask by inhalation of halothane, nitrous oxide, and oxygen and 1 mg/kg succinylcholine was given to facilitate tracheal intubation. Gastric contents were aspirated by a gastric tube at the end of the operation. Vomiting and retching were recorded for 24 h; recovery from anaesthesia was assessed by a modified Steward score. RESULTS. The four groups were comparable regarding age, sex, body weight, duration of anaesthesia, and number of repaired eye muscles. Patients receiving droperidol before and after the end of surgery had a similar incidence of vomiting (groups A and C 60% vs. groups B and D 50%). There was no significant difference in the number of patients vomiting between groups A and B (58%) and groups C and D (52%). The incidence of the OCR was lower in the patients premedicated with atropine (18% vs. 60%, P < 0.01). There was no statistical relationship between the occurrence of the OCR and post-operative emesis. Younger children (3 to 6 years) vomited more often than older ones (7 to 12 years). The incidence of the OCR was higher in patients with more than two eye muscles repaired than in others. Recovery scores were slightly lower in patients with droperidol after completion of surgery; postoperative recovery times did not differ significantly between the study groups. CONCLUSIONS. The timing of the administration of droperidol (75 micrograms/kg) had no influence on postoperative vomiting. The application of atropine (10 micrograms/kg) prior to surgery did not influence vomiting after strabismus surgery. Atropine (10 micrograms/kg) reduced the incidence of the OCR significantly. There was no statistical relationship between the occurrence of the OCR and postoperative vomiting.


Experience with simultaneous pancreas-kidney transplantation.
With refinements in surgical techniques and increased clinical experience, there has been a resurgence of interest in vascularized pancreas transplantation. From December 1986 to April 1988, 30 whole-organ vascularized pancreas transplants with pancreatico duodenocystostomy were performed simultaneously with renal transplantation. The recipient population consisted of 20 men and ten women, with a mean age of 34.7 years (range of 25-53 years). The mean duration of insulin-dependent diabetes mellitus (IDDM) was 22.6 years (range of 10-37 years). The mean pancreas preservation time was 8.7 hours (range 3-19 years). All patients were immediately insulin-independent. Simultaneous pancreas-kidney engraftment was performed to both iliac fossae via a lower midline incision (n = 28) or through a bilateral lower abdominal incision (n = 2). The mean operating time was 5.9 hours, and packed cell transfusion requirement was 1.3 units. The mean length of hospital stay was 27.4 days. Recipients averaged 2.3 admissions (1-7), with ten patients (34.4%) requiring only one hospital admission. Postoperative immunosuppression consisted of cyclosporine, prednisone, azathioprine, and Minnesota antilymphoblast globulin (MALG). A total of 49 episodes of rejection occurred in 26 patients. Actuarial patient survival rate at two years is 96.3%. The kidney and pancreas survival rates for the same time interval is 94.0% and 84.0%, respectively. Mean serum creatinine at present is 1.75 mg/dl. In conclusion, renal transplantation in concert with pancreas transplantation has a dramatic positive impact on pancreas allograft survival. Combined engraftment does not appear to jeopardize renal allograft functional survival. In view of these results, simultaneous pancreas-kidney transplantation appears to be the treatment of choice for Type I diabetic patients.


Resource-based relative values. An overview.
Studies have been conducted over the past decade to develop a Resource-Based Relative Value Scale (RBRVS) for physicians' services. Policymakers view an RBRVS as a potential tool to pay physicians. The Physician Payment Review Commission, under a congressional mandate, has endorsed the general concept of a fee schedule based on resource costs for physician payment under Medicare. In this overview article, we present the policy context in which the RBRVS may play a role and describe the approach taken to develop this scale, specifically consultation with clinicians, researchers, and insurers and data gathering, including a national survey of physicians. We discuss underlying elements that are necessary to constructing an RBRVS, each of which is described more fully in subsequent articles: measuring the work (intraservice work) of performing medical services and procedures, estimating preservice and postservice work, comparing work across specialties, measuring practice costs, extrapolating from surveyed services, and establishing an RBRVS for evaluation/management services and for invasive procedures. Overall results are presented in a companion article.


Biotin supply affects expression of biotin transporters, biotinylation of carboxylases and metabolism of interleukin-2 in Jurkat cells.
Biotin supply may affect transcription of genes and biotinylation of proteins in cells. In this study, Jurkat cells were used to model effects of biotin supply on biotin homeostasis and interleukin-2 metabolism in immune cells. Cells were cultured in media containing deficient (25 pmol/L), physiologic (250 pmol/L), or pharmacologic concentrations (10,000 pmol/L) of biotin for 4 wk. Activities of the biotin-dependent enzyme propionyl-CoA carboxylase paralleled the biotin concentrations in media [pmol bicarbonate fixed/(min x 10(6) cells)]: 1.9 +/- 0.7 (25 pmol/L biotin) vs. 19 +/- 1.2 (250 pmol/L biotin) vs. 40 +/- 2.0 (10,000 pmol/L biotin). Cells responded to biotin deficiency with increased expression of biotin transporter genes. Biotin-deficient cells maintained normal biotinylation of histones but contained reduced levels of biotinylated carboxylases, suggesting compartmentalization of intracellular biotin distribution. Rates of cell proliferation and activities of the apoptotic enzyme caspase-3 were similar among treatment groups, suggesting that net proliferation was not affected by biotin status. Net secretion of interleukin-2 by Jurkat cells was inversely associated with the biotin concentration in media [kU/(L x 24 h x 10(6) cells)]: 21 +/- 1.8 (25 pmol/L biotin) vs. 15 +/- 5.4 (250 pmol/L biotin) vs. 6.1 +/- 1.8 (10,000 pmol/L biotin), suggesting increased secretion or decreased internalization of interleukin-2 by biotin-deficient cells. This study provides evidence that biotin supply affects biotinylation of proteins, gene expression and metabolism of interleukin-2 in Jurkat cells. The physiological significance of effects of biotin status on metabolism of interleukin-2 remains to be elaborated.


Plant Lectins and Lectin Receptor-Like Kinases: How Do They Sense the Outside?
Lectins are fundamental to plant life and have important roles in cell-to-cell communication; development and defence strategies. At the cell surface; lectins are present both as soluble proteins (LecPs) and as chimeric proteins: lectins are then the extracellular domains of receptor-like kinases (LecRLKs) and receptor-like proteins (LecRLPs). In this review; we first describe the domain architectures of proteins harbouring G-type; L-type; LysM and malectin carbohydrate-binding domains. We then focus on the functions of LecPs; LecRLKs and LecRLPs referring to the biological processes they are involved in and to the ligands they recognize. Together; LecPs; LecRLKs and LecRLPs constitute versatile recognition systems at the cell surface contributing to the detection of symbionts and pathogens; and/or involved in monitoring of the cell wall structure and cell growth.


Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1.
In Old World primates, TRIM5-alpha confers a potent block to human immunodeficiency virus type 1 (HIV-1) infection that acts after virus entry into cells. Cyclophilin A (CypA) binding to viral capsid protects HIV-1 from a similar activity in human cells. Among New World primates, only owl monkeys exhibit post-entry restriction of HIV-1 (ref. 1). Paradoxically, the barrier to HIV-1 in owl monkey cells is released by capsid mutants or drugs that disrupt capsid interaction with CypA. Here we show that knockdown of owl monkey CypA by RNA interference (RNAi) correlates with suppression of anti-HIV-1 activity. However, reintroduction of CypA protein to RNAi-treated cells did not restore antiviral activity. A search for additional RNAi targets unearthed TRIMCyp, an RNAi-responsive messenger RNA encoding a TRIM5-CypA fusion protein. TRIMCyp accounts for post-entry restriction of HIV-1 in owl monkeys and blocks HIV-1 infection when transferred to otherwise infectable human or rat cells. It seems that TRIMCyp arose after the divergence of New and Old World primates when a LINE-1 retrotransposon catalysed the insertion of a CypA complementary DNA into the TRIM5 locus. This is the first vertebrate example of a chimaeric gene generated by this mechanism of exon shuffling.


5-(pyrrolidin-2-yl)-1H-tetrazole and 5-[(pyrrolidin-2-yl)methyl]-1H-tetrazole: proline surrogates with increased potential in asymmetric catalysis.
Catalytic enantioselective methodology has dramatically been enriched by the re-discovery of the simple amino acid proline as a chiral catalyst in the year 2000. Although no catalyst offers such a simple and broad access to quite complex reaction products, as does proline, its synthetic potential is not unrestricted, what is especially connected to its poor solubility in organic media. Exchange of the carboxylic moiety by a tetrazole unit leads to proline surrogates, that by far outperform proline with respect to yield, enantioselectivity, reaction time, substrate and solvent scope, catalyst loading, and stoichiometry of the compounds used in excess. These factors are discussed and critically compared with selected representative proline-catalyzed reactions.


Enrichment of conjugated linoleic acid (CLA) in hen eggs and broiler chickens meat by lactic acid bacteria.
1. The aim of this work was to compare conjugated linoleic acid (CLA) concentrations in chickens supplemented with 4 American Tissue Culture Collection (ATCC) bacterial strains, Lactobacillus plantarum, Lactobacillus lactis, Lactobacillus casei and Lactobacillus fermentum, and 4 isolates of Lactobacillus reuteri from camel, cattle, sheep and goat rumen extracts. 2. Micro-organisms were grown anaerobically in MRS broth, and 10(6) CFU/ml of bacteria were administered orally to mixed-sex, 1-d-old broiler chickens weekly for 4 weeks and to 23-week-old layer hens weekly for 6 weeks. 3. The 4 strains were evaluated for their effects on synthesis of CLA in hen eggs and broiler meat cuts. 4. Administration of pure Lactobacillus and isolated L. reuteri strains from camel, cattle, goat and sheep led to significantly increased CLA concentrations of 0.2-1.2 mg/g of fat in eggs and 0.3-1.88 mg/g of fat in broiler chicken flesh homogenates of leg, thigh and breast. 5. These data demonstrate that lactic acid bacteria of animal origin (L. reuteri) significantly enhanced CLA synthesis in both eggs and broiler meat cuts.


A six-year descriptive study of hospital-associated infection in trauma patients: demographics, injury features, and infection patterns.
Hospital-associated infection (HAI) is of concern to surgeons providing care for traumatized patients, as such patients have a higher rate of infection than other patients. Infection surveillance programs often study trauma patients within other populations (e.g., intensive care unit [ICU], surgery), and important issues may be missed. Information identifying trauma patients at risk, most frequent infection sites, and pathogens is of importance for surveillance and infection control. Measurement is essential to improving care. We evaluated the HAI rate, demographics, injury characteristics, and HAI patterns (microorganisms, sites, antibiotics) in trauma patients (1996-2001). We used two-tailed Mann-Whitney and Fisher exact tests for univariate analysis and a stepwise multivariable logistic regression model for association of multiple variables with the development of HAI. The incidence of HAI was 501 (9.1%) in 5,537 patients. Trauma patients with HAI were older (p < 0.001), more severely injured (p < 0.001), and more likely to have multi-system trauma (p = 0.027). Development of HAI was associated with all injury sites except the face. The most common pathogens were gram-positive cocci, and the most common infection sites were urinary and respiratory, with 157 of 501 (31%) being ventilator-associated pneumonia. The antibiotics most commonly used were cephalosporins and fluoroquinolones. Of 5,537 trauma patients, 19 (0.3%) had Staphylococcus aureus resistant to methicillin, which was higher (p < 0.001) than in the non-trauma patients (176 in 146,727 [0.1%]). Hospital-associated infections occur frequently in trauma patients. This paper identifies populations to target for surveillance and HAI control initiatives. With increased interest in adverse event prevention and continuing quality of care improvement, these data provide a benchmark for this institution and others.


Structure-preserving low-dose computed tomography image denoising using a deep residual adaptive global context attention network.
Low-dose computed tomography (LDCT) scans can effectively reduce the radiation damage to patients, but this is highly detrimental to CT image quality. Deep convolutional neural networks (CNNs) have shown their potential in improving LDCT image quality. However, the conventional CNN-based approaches rely fundamentally on the convolution operations, which are ineffective for modeling the correlations among nonlocal similar structures and the regionally distinct statistical properties in CT images. This modeling deficiency hampers the denoising performance for CT images derived in this manner. In this paper, we propose an adaptive global context (AGC) modeling scheme to describe the nonlocal correlations and the regionally distinct statistics in CT images with negligible computation load. We further propose an AGC-based long-short residual encoder-decoder (AGC-LSRED) network for efficient LDCT image noise artifact-suppression tasks. Specifically, stacks of residual AGC attention blocks (RAGCBs) with long and short skip connections are constructed in the AGC-LSRED network, which allows valuable structural and positional information to be bypassed through these identity-based skip connections and thus eases the training of the deep denoising network. For training the AGC-LSRED network, we propose a compound loss that combines the L1 loss, adversarial loss, and self-supervised multi-scale perceptual loss. Quantitative and qualitative experimental studies were performed to verify and validate the effectiveness of the proposed method. The simulation experiments demonstrated the proposed method exhibits the best result in terms of noise suppression [root-mean-square error (RMSE) =9.02; peak signal-to-noise ratio (PSNR) =33.17] and fine structure preservation [structural similarity index (SSIM) =0.925] compared with other competitive CNN-based methods. The experiments on real data illustrated that the proposed method has advantages over other methods in terms of radiologists' subjective assessment scores (averaged scores =4.34). With the use of the AGC modeling scheme to characterize the structural information in CT images and of residual AGC-attention blocks with long and short skip connections to ease the network training, the proposed AGC-LSRED method achieves satisfactory results in preserving fine anatomical structures and suppressing noise in LDCT images.


Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome.
The nucleolus is the site of rRNA gene transcription, rRNA processing, and ribosome biogenesis. However, the nucleolus also plays additional roles in the cell. We isolated nucleoli using fluorescence-activated cell sorting (FACS) and identified nucleolus-associated chromatin domains (NADs) by deep sequencing, comparing wild-type plants and null mutants for the nucleolar protein NUCLEOLIN 1 (NUC1). NADs are primarily genomic regions with heterochromatic signatures and include transposable elements (TEs), sub-telomeric regions, and mostly inactive protein-coding genes. However, NADs also include active rRNA genes and the entire short arm of chromosome 4 adjacent to them. In nuc1 null mutants, which alter rRNA gene expression and overall nucleolar structure, NADs are altered, telomere association with the nucleolus is decreased, and telomeres become shorter. Collectively, our studies reveal roles for NUC1 and the nucleolus in the spatial organization of chromosomes as well as telomere maintenance.


Right ventricle functional parameters estimation in arrhythmogenic right ventricular dysplasia using a robust shape based deformable model.
Assessment of cardiac right-ventricle functions plays an essential role in diagnosis of arrhythmogenic right ventricular dysplasia (ARVD). Among clinical tests, cardiac magnetic resonance imaging (MRI) is now becoming the most valid imaging technique to diagnose ARVD. Fatty infiltration of the right ventricular free wall can be visible on cardiac MRI. Finding right-ventricle functional parameters from cardiac MRI images contains segmentation of right-ventricle in each slice of end diastole and end systole phases of cardiac cycle and calculation of end diastolic and end systolic volume and furthermore other functional parameters. The main problem of this task is the segmentation part. We used a robust method based on deformable model that uses shape information for segmentation of right-ventricle in short axis MRI images. After segmentation of right-ventricle from base to apex in end diastole and end systole phases of cardiac cycle, volume of right-ventricle in these phases calculated and then, ejection fraction calculated. We performed a quantitative evaluation of clinical cardiac parameters derived from the automatic segmentation by comparison against a manual delineation of the ventricles. The manually and automatically determined quantitative clinical parameters were statistically compared by means of linear regression. This fits a line to the data such that the root-mean-square error (RMSE) of the residuals is minimized. The results show low RMSE for Right Ventricle Ejection Fraction and Volume (≤ 0.06 for RV EF, and ≤ 10 mL for RV volume). Evaluation of segmentation results is also done by means of four statistical measures including sensitivity, specificity, similarity index and Jaccard index. The average value of similarity index is 86.87%. The Jaccard index mean value is 83.85% which shows a good accuracy of segmentation. The average of sensitivity is 93.9% and mean value of the specificity is 89.45%. These results show the reliability of proposed method in these cases that manual segmentation is inapplicable. Huge shape variety of right-ventricle led us to use a shape prior based method and this work can develop by four-dimensional processing for determining the first ventricular slices.


[Significance expression and relationships with endothelin-1, matrix metalloproteinase-9 in the laryngeal carcinoma].
To evaluate the expression of endothelin-1(ET-1) and matrix metalloproteinase-9 (MMP-9) in laryngeal carcinoma and their correlations with clinical features. The expression of ET-1 and MMP-9 was detected by immunohistochemical method in 58 specimens of laryngeal carcinoma, 28 specimens of polyps of vocal cord and 19 specimens of normal laryngeal tissues. The expressions of ET-1, MMP-9 in laryngeal carcinoma were remarkably higher,compared to polyps of vocal cord and normal laryngeal tissues (P < 0.05). The expression of ET-1, MMP-9 was associated with clinical stage, T stage and lymph node metastasis. Expression levels of ET-land MMP-9 correlated significantly with each other (r(s) = 0.693, P < 0.05). The expression of ET-1 and MMP-9 may be the vital indexes in laryngeal carcinoma.


Foxj1 expressing ependymal cells do not contribute new cells to sites of injury or stroke in the mouse forebrain.
The stem cell source of neural and glial progenitors in the periventricular regions of the adult forebrain has remained uncertain and controversial. Using a cell specific genetic approach we rule out Foxj1+ ependymal cells as stem cells participating in neurogenesis and gliogenesis in response to acute injury or stroke in the mouse forebrain. Non stem- and progenitor-like responses of Foxj1+ ependymal cells to injury and stroke remain to be defined and investigated.


High frequency, single-dose model of renal adenoma/carcinoma induction using dimethylnitrosamine in Crl:(W)BR rats.
Following discovery that the type of kidney neoplasm induced in protein-deprived Wistar rats by a single dose of dimethylnitrosamine (DMN) was age-dependent, this study aimed to refine the system in order to develop a high frequency model for the induction of cortical epithelial tumors with low mesenchymal tumor incidence. Using outbred female Crl:(W)BR (Charles River Wistar) rats, DMN at a dose of 30 mg/kg was administered at 9-10 weeks of age following a 5-day period of high-carbohydrate/no-protein diet. From a total of 49 rats, 43 survived the early toxicity and 91% of these developed renal tumors. Mesenchymal tumors were present in only 9% of the tumor-bearing animals. In contrast, 70% of the rats developed epithelial tumors of the tubules classifiable on a size and histological basis as adenocarcinomas/carcinomas in response to DMN. A further 21% of rats had smaller proliferative lesions designated as adenomas, making the total cortical epithelial tumor incidence in excess of 90%. The malignant potential of the epithelial tumors was underscored by the presence of metastatic invasion, mainly involving the lungs, in 15% of the tumor-bearing rats. Metastatic behavior correlated with progressive growth of the carcinomas over a period of time exceeding 1.5 years to dimensions usually exceeding 2.9 cm diameter. Of the tumors approaching or exceeding this size, the metastatic rate was almost 50%. Thus, the administration of DMN to 65-70 days old, protein-deprived Wistar rats provides a potent, single dose model for the study of renal epithelial carcinogenesis with insignificant mesenchymal tumor induction and without the continuing toxicity which perturbs regimens based on repeated or continuous exposures.


Histochemical detection of osteocalcin in normal and pathological human bone.
We investigated the immunohistochemical localization of osteocalcin in demineralized, paraffin-embedded normal and pathological human bone. Acid decalcification protocols appeared to be more suitable for osteocalcin detection than mild chelating agents. In normal lamellar bone, osteocalcin was detected in osteocytes and along the lamellar bone matrix in fine granular deposits. Under pathological conditions (osteomyelitis, neoplasia), appositional bone showed immunoreactivity in osteoblasts and osteocytes but not in the provisory woven bone matrix. Intense immunoreactivity could be seen at the cell borders of osteoclasts and the bone margins of Howship lacunae. In primary bone-forming tumors, osteocalcin immunoreactivity was detected in osteoblasts and their malignant counterparts. On the basis of these results, we conclude that optimal preservation of osteocalcin is obtained through mild acid decalcifiers. Osteocalcin is deposited in bone matrix, especially that of metabolically inactive bone. In neoplasms, osteocalcin could be a marker of osteoblastic differentiation.


Ethics, organ donation and tax: a reply to Quigley and Taylor.
A national opt-out system of post-mortem donation of scarce organs is preferable to an opt-in system. Unfortunately, the former system is not always feasible, and so in a recent JME article we canvassed the possibility of offering people a tax break for opting-in as a way of increasing the number of organs available for donation under an opt-in regime. Muireann Quigley and James Stacey Taylor criticize our proposal. Roughly, Quigley argues that our proposal is costly and, hence, is unlikely to be implemented, while Taylor contests our response to a Titmuss-style objection to our scheme. In response to Quigley, we note that our proposal's main attraction lies in gains not reflected in the figures presented by Quigley and that the mere fact that it is costly does not imply that it is unfeasible. In response to Taylor, we offer some textual evidence in support of our interpretation of Taylor and responds to his favoured interpretation of the Titmuss-style objection that many people seem to want to donate to charities even if they can deduct their donations from their income tax. Finally, we show why our views do not commit us to endorsing a free organ-market.


PROLONGED GASTROESOPHAGEAL REFLUX MONITORING BY IMPEDANCE-PHMETRY: A REVIEW OF THE SUBJECT PONDERED WITH OUR EXPERIENCE WITH 1,200 CASES.
Prolonged monitoring increased our knowledge on gastroesophageal reflux (GER), and the disease became known as gastroesophageal reflux disease (GERD). Prolonged reflux monitoring permits the diagnosis of GERD when endoscopic findings are not enough to characterize it. The objective of this paper is to review the current knowledge on impedance-pH monitoring, taking into account the published literature and the authors experience with 1,200 exams. The different types of prolonged reflux monitoring, namely: conventional pHmetry, catheter-free pHmetry and impedance-pHmetry will be briefly described. The new possibilities of evaluation with impedance-pHmetry are emphasized, namely: the study of symptomatic patients in use of proton pump inhibitors (PPIs); evaluation of patients with symptoms suggestive of GERD although with normal endoscopy and normal pHmetry, diagnostic elucidation of patients with atypical symptoms or supra-esophageal symptoms, mainly chronic cough, study of patients complaining of belch, differentiating gastric and supra-gastric belching, and the proper work-up before anti-reflux surgery. When impedance was associated to pH monitoring, an impressive technological evolution became apparent, when compared to pH monitoring alone. The main advantages of impedance-pHmetry are: the ability to detect all types of reflux: acid, non-acid, liquid, gaseous. In addition, other important measurements can be made: the ability of the esophagus in transporting the bolus, the measurement of basal mucosal impedance and the evaluation of primary peristalsis post reflux. Impedance-pHmetry is a promising method, with great advantages over conventional pHmetry. The choice between these two types of monitoring should be very judicious. The authors suggest the importance of careful evaluation of each reflux episode by the physician responsible for the examination, necessary for the correct interpretation of the tracings.


[Application Value of Abbreviated Comprehensive Geriatric Assessment in Elderly Female Breast Cancer Patients].
Objective To evaluate the application value of abbreviated comprehensive geriatric assessment(aCGA)in elderly female breast cancer patients. Methods Eight aspects of the traditional CGA were simplified to form the aCGA assessment table,based on which the patients were classified into three grades of A,B and C according to the total scores.This study enrolled the elderly female patients with breast cancer aged 70 years and above who were treated in PUMC Hospital from June 2018 to January 2020.Eastern Cooperative Oncology Group(ECOG)scoring and aCGA grading were performed respectively,and the results of the two methods were compared. Results Of the 162 patients,111(68.5%)were classified by the aGGA method as grade A,43(26.5%)as grade B,and 8(5.0%)as grade C;131(80.9%)cases have concurrent diseases,and the most common complications were hypertension(n=89),cardiovascular diseases(n=47)and diabetes mellitus(n=39).The ECOG score was 0-1 in 133(82.0%)cases,2 in 24(14.8%)cases and 3 in 5(3.2%)cases.The ECOG score showed 133(82.0%)cases with good status and 29 cases with poor status.However,according to the aCGA classification,111 cases were in good health status and 51 cases were in poor health status;the difference in the result between the two groups was statistically significant(χ 2=14.24,P<0.001).Conclusion Compared with ECOG score,aCGA grading can more comprehensively evaluate the health status of elderly female breast cancer patients and can be applied to the patients aged 70 and above.


Antibody validation.
Antibodies are among the most frequently used tools in basic science research and in clinical assays, but there are no universally accepted guidelines or standardized methods for determining the validity of these reagents. Furthermore, for commercially available antibodies, it is clear that what is on the label does not necessarily correspond to what is in the tube. To validate an antibody, it must be shown to be specific, selective, and reproducible in the context for which it is to be used. In this review, we highlight the common pitfalls when working with antibodies, common practices for validating antibodies, and levels of commercial antibody validation for seven vendors. Finally, we share our algorithm for antibody validation for immunohistochemistry and quantitative immunofluorescence.


Chlamydia and Reiter's syndrome.
The role of Chlamydia trachomatis in Reiter's syndrome (RS) is reviewed. Chlamydia is an obligate, intracellular parasite which can be isolated from urethral smears in 36% of patients with RS. Two separate surveys carried out on RS patients in France, in 1977-78 and in 1982-83 showed that antibodies to C. trachomatis could be detected by a microimmunofluorescence test in 55% and 64% of subjects, respectively, and this is significantly higher than the levels found in rheumatoid or healthy controls. Further studies are indicated to evaluate the role of Chlamydia in RS.


Ulocladium cantlous sp. nov. isolated from northwestern China: its morphology and molecular phylogenetic position.
A new species of Ulocladium was isolated from diseased leaves from two Cucumis sp. growing in Sinkiang and Gansu provinces of China. Conidia were isolated from necrotic leaves and used to establish single-spore pure cultures. Conidia were harvested from cultures 7 d after incubation for morphological comparisons. The morphology of this species resembles that of U. botrytis and U. consortiale. However it is distinguished from these two species by the sizes of obovoid to broadly ellipsoidal conidia and longer conidiophores. A taxonomic description of U. cantlous, comparison with related species in this genus, and a species phylogeny based on the partial nucleotide sequence of the glyceraldehyde-3-phosphate dehydrogenase (gpd) gene and the Alternaria alternata major allergen (Alt a 1) gene are provided.


Isolation, selection, and characterization of highly ethanol-tolerant strains of Oenococcus oeni from south Catalonia.
Twenty-one strains of Oenococcus oeni were isolated during the malolactic fermentation of wines from south Catalonia. Due to their high ethanol tolerance (14 %, or more), these strains may serve as promising starters. The strains were screened by assays in a wine-like medium and by their co-inoculation in wine, resulting in the selection of well-performing strains, subsequently shown not to produce the main biogenic amines and lacking the genes involved in their synthesis. The genetic diversity of the isolates was studied by multilocus sequence typing (MLST), in which seven housekeeping genes were sequenced. Although the concatenated allelic profile of some strains was the same, the profiles obtained by random amplification of polymorphic DNA together with the variable number of tandem repeats at several loci showed that none of the strains were identical. A phylogenetic tree was constructed based on MLST with the seven genes and clearly showed two phylogroups, in accordance with previous studies. The best-performing strains occurred in members of both subgroups, suggesting that the grouping of housekeeping genes is not directly related to adaptation and ethanol tolerance.


Effects of physical exercise in sarcopenia. A systematic review.
From the third decade of life and due to multiple causes, muscle mass and strength are gradually lost, which affects the function of the musculoskeletal system. This combined loss of muscle mass and strength with aging is called sarcopenia, and is associated with greater morbidity and mortality in the elderly. Early treatment is therefore essential, and physical exercise is the therapeutic approach that has given the best results. This literature review intended to analyze the effect of physical exercise, excluding the role that other treatments proposed, including the nutritional approach, could play in the treatment of sarcopenia, refers to 12 articles. In studies including high intensity strength exercises in isolation, either alone or combined with aerobic exercise, improvements were seen in muscle mass, muscle strength, and functional test times. There is also a significant increase in fat-free mass in individuals who exercised more frequently (more than two sessions per week). Current evidence shows that strength-resistance training and its combination in multimodal programs with aerobic exercise show significantly beneficial effects on anthropometric and muscle function parameters. Programs of prescribed exercises including strength exercises adequate to the characteristics should therefore be adapted to the characteristics of each individual and replace the usual practice of prescribing aerobic exercises (walking) only.


Online Extra Trees Regressor.
Data production has followed an increased growth in the last years, to the point that traditional or batch machine-learning (ML) algorithms cannot cope with the sheer volume of generated data. Stream or online ML presents itself as a viable solution to deal with the dynamic nature of streaming data. Besides coping with the inherent challenges of streaming data, online ML solutions must be accurate, fast, and bear a reduced memory footprint. We propose a new decision tree-based ensemble algorithm for online ML regression named online extra trees (OXT). Our proposal takes inspiration from the batch learning extra trees (XT) algorithm, a popular and faster alternative to random forest (RF). While speed and memory costs might not be a central concern in most batch applications, they become crucial in data stream data learning. Our proposal combines subbagging (sampling without replacement), random tree split points, and model trees to deliver competitive prediction errors and reduced computational costs. Throughout an extensive experimental evaluation comprising 22 real-world and synthetic datasets, we compare OXT against the state-of-the-art adaptive RF (ARF) and other incremental regressors. OXT is generally more accurate than its competitors while running significantly faster than ARF and expending significantly less memory.


Calcaneal Avulsion Fractures: An Often Forgotten Diagnosis.
The calcaneus is the primary weight bearing bone in the heel, and its many surface contours render it a relatively difficult bone to visualize in its entirety. The stabilizing ligaments that hold the calcaneus in place occupy very specific locations, and the Achilles tendon enthesis is in a relatively constant location; therefore, avulsion fractures occur in reproducible locations. The mechanisms of injuries include overuse and neuropathic conditions, although most cases are related to trauma.


Association of catastrophizing and fatigue: a systematic review.
Catastrophizing is an exaggerated negative evaluation and attention to specific symptoms such as pain or fatigue. A number of studies consistently support the significant role of catastrophizing in pain. However, the role of catastrophizing in fatigue is less frequently investigated. This article provides a critical review of published studies investigating this association. Using the keyword "Fatigue AND Catastrophizing", we performed a search in PubMed, SCOPUS, PsycINFO, and EMBASE. Fourteen studies were reviewed and all except one were found to provide empirical support for an association between high catastrophizing and high fatigue. Most of these reviewed articles also show the large impact of catastrophizing on fatigue severity. Two longitudinal studies found that fatigue catastrophizing level before cancer treatment is a significant predictor of post-treatment fatigue. Studies also demonstrated that persons who had higher scores for catastrophizing recalled fatigue more accurately than those with lower scores. In spite the differences of its definition and the measurements used, a similar significant association between catastrophizing and fatigue was reported. Because this observation was based on 14 studies with limited types of patients, further studies are recommended to examine the role of catastrophizing in fatigue from other clinical populations and to investigate its utility as a behavioral marker for central fatigue.


[Postoperative complications and mortality in acute intestinal obstruction].
496 case reports of patients operated upon for various kinds of intestinal obstruction were analysed. Complications were studied in 202 (40.6%) patients. 93 patients died (19.7%). Peritonitis remains to be the main cause of death postoperatively (49.5 per cent to all lethal issues).


Anabolic effects of leucine-rich whey protein, carbohydrate, and soy protein with and without β-hydroxy-β-methylbutyrate (HMB) during fasting-induced catabolism: A human randomized crossover trial.
Protein-rich beverages are widely used clinically to preserve muscle protein and improve physical performance. Beverages with high contents of leucine or its keto-metabolite β-hydroxy-β-methylbutyrate (HMB) are especially anabolic in muscle, but it is uncertain whether this also applies to catabolic conditions such as fasting and whether common or separate intracellular signaling cascades are involved. To compare a specific leucine-rich whey protein beverage (LWH) with isocaloric carbohydrate- (CHO), soy protein (SOY), and soy protein +3 g HMB (HMB) during fasting-induced catabolic conditions. Eight healthy lean male subjects underwent four interventions (LWH, CHO, SOY, and HMB) using a randomized crossover design. Each trial included a 36 h fast and consisted of a 3 h basal fasting period and a 4 h 'sipping' period. Forearm net balances of phenylalanine (NBphe, measure of net protein loss) improved for all groups (p < 0.05), but more prominently so for LWH and HMB compared with SOY (p < 0.05). Muscle protein phosphorylation of mammalian target of rapamycin (mTOR) and its downstream targets eukaryotic translation factor 4E-binding protein 1 (4EBP1) and ribosomal S6 kinase 1 (S6) were distinctly increased during LWH consumption (p < 0.05). The ratio between autophagy protein microtubule-associated protein 1 light chain-3β II and I (LC3II/LC3I, a measure of autophagy activity) was decreased during LWH and SOY intake compared with the fasting period (p < 0.05). LWH and HMB have superior anabolic effects on muscle protein kinetics after 36 h of fasting, and LWH distinctly activates the mTOR pathway. These novel findings suggest that leucine-rich whey protein and/or HMB are specifically beneficial during fasting-induced catabolic conditions.


Effects of somatostatin analogs on uptake of radiolabeled somatostatin analogs on imaging: a systematic review and meta-analysis.
The imaging of somatostatin receptors (SSTRs) plays a significant role in imaging neuroendocrine tumors (NETs). However, there has been no clear definition on whether it is necessary to withdraw somatostatin analogs (SSAs) before SSTRs imaging. We aimed to assess whether nonradioactive SSAs affect the uptake of radiolabeled SSAs on imaging for NETs patients. The databases of PubMed, Embase, and Web of Science (WoS) were searched until March 12, 2022 to identify eligible studies. Maximum standardized uptake values (SUVmax) in tumor and normal tissues were extracted, pooled, and compared before and after SSAs treatment. The change of tumor-to-background/liver ratio was also described. The quality of each study was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 9 articles involving 285 patients were included and 5 studies using Gallium-68-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid]-D-Phe1-Tyr3-Thr8-octreotide (68Ga-DOTATATE) were used for pooled evaluation. We found a significantly decreased SUVmax in the liver (9.56±2.47 vs. 7.62±2.12, P=0.001) and spleen (25.74±7.14 vs. 20.39±6.07, P=0.006) after SSAs treatment whereas no significant differences were observed in the uptake of thyroid, adrenal, and pituitary gland. For either primary tumor sites or metastases, the SUVmax did not change significantly before and after SSAs treatment. The tumor-to-liver/background ratio increased following SSAs therapy. High heterogeneity was observed across the studies, mainly due to inherent diversity of study design, sample size, and scanning technique. Based on current evidence, long-acting SSAs therapy before imaging has no effect on the uptake of radiolabeled SSAs at tumor primary sites and metastatic lesions, but results in a significant reduction of uptake in the liver and spleen. These findings may implicate the unnecessary discontinuation of SSAs before radiolabeled SSAs imaging.


Synthesis and antibacterial and antifungal activities of N-(tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazones of substituted 4-formylsydnones.
Sydnone is a heterocycle that exhibits remarkable pharmacological activities, including antimicrobial, anti-inflammatory, analgesic, antipyretic and antioxidant activities. Thiosemicarbazones are of compounds that contain the -NHCSNHN=C< linkage group and are considerable interest because they exhibit important chemical properties and potentially beneficial biological activities. Similarly, thiosemicarbazones having carbohydrate moieties also exhibit various significant biological activities. The compounds of 3-formyl-4-phenylsydnones were obtained by Vilsmeyer-Haack's formylation reaction and were transformed into thiosemicarbazones by condensation reaction with N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazide. Reaction were performed in the presence glacial acetic acid as catalyst using microwave-assisted heating method. Reaction yields were 43‒85 %. The antimicrobial activities of these thiosemicarbazones were screened in vitro by using agar well diffusion and MIC methods. Among these thiosemicarbazones, compounds 4k, 4l, 4m and 4n were more active against all tested bacterial strains, especially against S. epidermidis, B. subtilis and E. coli. The MIC values in these cases are 0.156, 0.156 and 0.313 μg/mL, respectively. All compounds showed weak to moderate antifungal activity against C. albicans and A. niger than nystatin (MIC = 0.156‒0.625 μg/mL vs. MIC = 0.078 μg/mL of nystatin), and thiosemicarbazones 4l, 4m and 4n exhibited significant activity with MIC = 0.156 μg/mL. These compounds also had good antifungal activity against F. oxysporum similarly to nystatin (MIC = 0.156 μg/mL). Among the tested compounds having halogen group 4k, 4l, 4m and 4n showed highest activity against three strains of fungal organisms. In summary, we have developed a clean and efficient methodology for the synthesis of novel thiosemicarbazone derivatives bearing sydnone ring and d-glucose moiety; the heterocyclic and monosaccharide system being connected via ‒NH‒C(=S)NH‒N=C< linker using molecular modification approach. The methodology could be further extended and used for the synthesis of other thiosemicarbazones of biological importance. 4-Formyl-3-arylsydnone N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)thiosemicarbazones have been synthesized under microwave-assisted heating conditions. Almost all obtained compounds showed remarkable activities against the tested microorganisms. Among the tested compounds having halogen group 4k, 4l, 4m and 4n showed highest activity against all tested strains of bacterial and fungal organisms. Graphical abstract:Synthesis and antibacterial and antifungal activities of N-(tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazones of substituted 4-formylsydnones.


Acute and Short-Term Autonomic and Hemodynamic Responses to Transcranial Direct Current Stimulation in Patients With Resistant Hypertension.
Previously, we demonstrated that acute transcranial direct current stimulation (tDCS) reduced blood pressure (BP) and improved autonomic modulation in hypertensives. We hypothesized that acute and short-term tDCS intervention can promote similar benefits in resistant hypertensive patients (RHT). We assessed the impact of one (acute intervention) and ten (short-term intervention) tDCS or SHAM (20 min, each) sessions on BP, pulse interval (PI) and systolic blood pressure variabilities, humoral mechanisms associated with BP regulation, and cytokines levels. True RHT subjects (n = 13) were randomly submitted to one and ten SHAM and tDCS crossing sessions (1 week of "washout"). Hemodynamic (Finometer®, Beatscope), office BP, and autonomic variables (accessed through spectral analysis of the pulse-to-pulse BP signal, in the time and frequency domain - Fast Fourrier Transform) were measured at baseline and after the short-term intervention. 24 h-ambulatory BP monitoring was measured after acute and short-term protocols. Acute intervention: tDCS reduced BP, cardiac output, and increase high-frequency band of PI (vagal modulation to the heart). Short-term protocol: tDCS did not change BP and cardiac output parameters. In contrast, central systolic BP (-12%), augmentation index (-31%), and pulse wave velocity (34%) were decreased by the short-term tDCS when compared to SHAM. These positive results were accompanied by a reduction in the low-frequency band (-37%) and an increase of the high-frequency band of PI (+62%) compared to SHAM. These findings collectively indicate that short-term tDCS concomitantly improves resting cardiac autonomic control and pulse wave behavior and reduces central BP in RHT patients, https://ensaiosclinicos.gov.br/rg/RBR-8n7c9p.


Listeria monocytogenes infection in patients with rheumatic diseases on TNF-alpha antagonist therapy: the Spanish Study Group experience.
The prognosis of patients with rheumatic diseases has improved considerably following the use of biological therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these therapies. In the present study we aimed to assess the frequency of Listeria monocytogenes infection in a large series of patients with rheumatic diseases on treatment with tumor necrosis factor (TNF)-alpha blockers because of active disease refractory to conventional therapy, included in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) of the Spanish Society for Rheumatology. Assessment of the incidence of infection due to Listeria monocytogenes in the Spanish Registry Study (BIOBADASER) per 1000 patient-years and 95% confidence intervals (95% CIs) was performed. Rate from this registry was compared with that from the general population in Europe and with the rate found in patients with rheumatoid arthritis (RA) from the Spanish Rheumatoid Arthritis Registry Cohort Study (EMECAR) that assessed morbidity and clinical expression of RA and included patients treated in most cases with conventional therapies. Six patients on treatment with TNF-alpha antagonists were diagnosed as having Listeria monocytogenes infection. The incidence of this infection per 1000 patient-year (95% CI) was 0.256 (95% CI: 0.115-0.570). This was greater than the incidence observed in the general population from Europe and in the EMECAR study. Despite the benefits associated to the use of TNF-alpha antagonists, a high level of surveillance is required to reduce the potential risk of infections related to the use of these drugs.


Successful treatment of soft tissue calcifications in uremia.
The appearance of soft tissue calcifications in patients with chronic renal failure has been recognised as one of the serious complications of uremia. An elevated serum calcium-phosphate product has almost invariably been detected, although the exact mechanisms of precipitation are still not fully understood. Among the factors responsible for triggering the precipitation process are: hyperphosphatemia, secondary hyperparathyroidism, hypercalcemia, treatment with vitamin D3, etc. Phosphate binders have been used to prevent, among other things, soft tissue calcifications, and parathyroidectomy has most frequently been applied as the therapy of choice, once precipitation of calcium salts has occurred. We present a case of soft tissue calcifications in the gluteal regions of a chronic haemodialysis female patient. The therapy we chose was a combination of biphosphonate and deferoxamine. The patient was treated for two months. The regression of the soft tissue calcifications was very significant, as registered both clinically and radiologically. The exact mechanism by which this reversal was achieved needs further investigation.


Crystallization and preliminary X-ray diffraction analysis of an Escherichia coli tRNA(Gly) acceptor-stem microhelix.
The tRNA(Gly) and glycyl-tRNA synthetase (GlyRS) system is an evolutionary special case within the class II aminoacyl-tRNA synthetases because two divergent types of GlyRS exist: an archaebacterial/human type and an eubacterial type. The tRNA identity elements which determine the correct aminoacylation process are located in the aminoacyl domain of tRNA(Gly). To obtain further insight concerning structural investigation of the identity elements, the Escherichia coli seven-base-pair tRNA(Gly) acceptor-stem helix was crystallized. Data were collected to 2.0 A resolution using synchrotron radiation. Crystals belong to space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 35.35, c = 130.82 A, alpha = beta = 90, gamma = 120 degrees and two molecules in the asymmetric unit.


[The determination of ligustilide in Ligusticum chuanxiong Hort. by supercritical fluid extraction].
In this study, a systematic method was used to optimize the supercritical fluid extraction (SFE) of ligustilide in Ligusticum chuanxiong Hort. Overall five variables (pressure, temperature, static extracting time, modifier concentration and CO2 dynamic extracting volume) were considered. To reduce the loss of volatile substance, a solid-liquid trap was developed for SFE collection. Comparisons were made on the solvent trap for SFE. The extracts were analyzed by high performance liquid chromatography (HPLC) with ultraviolet absorbance detection. The recoveries of 99.34% (RSD 1.70%) and 92.11% (RSD 5.72%) were achieved for solid-liquid trap and solvent trap, respectively. SFE conditions: temperature 40 degrees C, pressure 27.6 MPa, static extraction 3 min, dynamic extraction 7 ml and 0.1 ml CHCl3 as modifier. HPLC conditions: The HPLC column (3.9 mm x 150 mm) was packed with Nova-Pak C18(4 microns). Naphthalene was used as internal standard. The mobile phase was methanol--10% isopropyl alcohol solution (53:47 v/v). The detection wavelength was 280 nm and the flow rate was 0.8 ml.min-1.


Saturable accumulation of retinoic acid in neural and neural crest derived cells in early embryonic development.
Retinoic acid (RA) binds to a cytosolic protein distinguishable from the cellular retinol (R) binding protein. Recent studies, showing an influence by R and RA on genomic expression, suggest an interaction with the cell nucleus mediated by the specific binding proteins in a manner resembling that of steroid hormones. RA can irreversibly stimulate in vitro differentiation of teratocarcinoma cells and support early embryonic development in vitamin A depleted animals. This study demonstrates a saturable, highly specific and regional accumulation of RA in the neuroepithelium and developing CNS that occurs in early but not in late fetal development in the mouse. The results suggest that a binding protein, or some other cellular mechanism for accumulation of RA is expressed in the neural cells only during restricted periods of development. High levels are recorded also in regions where cranial neural crest cells are known to migrate, and later in the visceral arches and maxillary areas, the mesenchyme of which is known to be partly derived from migrating cranial neural crest cells. The specific accumulation of RA in embryonic neural and cranial neural crest cells is in line with animal experiments and human clinical data, showing that retinoids specifically impair CNS, eye, ear, and facial development.


Relationships between fluid and electrolyte hormones and plasma volume during exercise with training and detraining.
The purpose of this study was to investigate the relationship between training-induced alterations in plasma volume (PV) and changes in fluid and electrolyte regulatory hormones during prolonged exercise. Seven male subjects (VO2peak 49.2 +/- 2.4 mL.kg-1.min-1, X +/- SE) performed a cycling test before (C) and after (T) 6 d of training and after 6 d of detraining (DT). Training was conducted for 2 h.d-1 at 68% VO2peak at a room temperature between 26-28 degrees C. The 60-min exercise challenge included 20 min at 50%, 65%, and 75% VO2peak workloads. Training resulted in a calculated 13.8 +/- 1.6% PV expansion (P < 0.05) which recovered to C levels with DT (1.8 +/- 2.3%, P > 0.05). Compared with that at C, training resulted in a reduction of aldosterone (ALDO) concentration at all exercise intensities (P < 0.05) which normalized to C levels with DT. With T, epinephrine (EPI) concentrations were reduced at the highest power output only (365 +/- 51 vs 113 +/- 22 pg.mL-1; P < 0.05) and returned to C levels with DT. Arginine vasopressin (AVP) concentrations were also reduced at the highest workload only (20.2 +/- 3.2 pg.mL-1 vs 10.4 +/- 0.7 pg.mL-1; P < 0.05) and remained depressed after DT (11.8 +/- 1.3 pg.mL-1; P < 0.05). Atrial natriuretic factor (ANF) and norepinephrine (NOREPI) were not affected by T or DT. The results suggest that concentrations of ALDO, and to a lesser extent EPI, during exercise are related to PV levels, whereas ANF and NOREPI concentrations are not. AVP concentrations are related to other adaptive factors, the effects of which persist for a longer time course than do PV changes.


Degree of diversity of hepatitis C virus quasispecies and progression of liver disease.
We examined the quasispecies of the hepatitis C virus genome in 28 patients with liver disease of varying severity. Nucleotide sequences of the hepatitis C virus genome spanning the region from the core to envelope were used to calculate the nucleotide diversity: 0.58% +/- 0.88% in 5 patients with acute hepatitis, 0.85% +/- 0.62% in 5 patients with chronic persistent hepatitis, 1.79% +/- 0.92% in 11 patients with chronic active hepatitis, 3.05% +/- 1.26% in 4 patients with cirrhosis and 2.71% +/- 1.47% in 3 patients with cirrhosis complicated by hepatocellular carcinoma. Thus the intrapatient variation in nucleotides increased significantly with severity of liver disease (p < 0.01), except in those cases of cirrhosis complicated by hepatocellular carcinoma. Multivariate analysis including the histology, duration of infection, age, sex, history of blood transfusion and serum level of ALT at diagnosis as variables showed that the histological finding was the strongest independent factor of the nucleotide diversity (p = 0.003). Serial analysis of the genome in three patients demonstrated that the intra-patient variation in nucleotides increased with the progression of liver disease. The magnitude of the intrapatient variation in nucleotides deduced from the observed changes in the patients was correlated with the mean serum levels of ALT. These findings suggest that the degree of diversity of HCV quasispecies is related to the progression of liver disease.


[Infection diagnosis after knee-TEP-implantation].
In this study, the accuracy of antigranulocyte scintigraphy as a diagnostic means prior to revision in infected total knee replacement was compared to that of preoperative joint aspiration and laboratory parameters. The most efficient combination of all diagnostic methods was calculated and thus a diagnostic algorithm recommended. The value of PCR was compared to commonly used techniques of microbiological culturing. Preoperative diagnostic means for infection of 50 total knee replacements in 45 patients requiring revision surgery, were retrospectively analyzed. Inclusion criteria were the intraoperative microbiological and histological verification of infection. Sensitivity, specificity, negative and positive prediction value of C-reactive protein (CRP) and leukocytes, antigranulocyte scintigraphy with (99m)Tc-labeled antibodies, and preoperative joint aspiration were calculated. Furthermore, the accuracy of the different techniques of culturing was compared to that of the polymerase chain reaction (PCR) based on the intraoperative histological findings. Two blinded examiners evaluated specimens taken intraoperatively according to the criteria of Mirra. We observed a sensitivity of 1.0, a specificity of 0.82, a positive prediction value of 0.83 and a negative prediction value of 1.0 for the antigranulocyte scintigraphy. The sensitivity of preoperative joint aspiration was 0.5, the specificity 1.0, and the positive and negative prediction values were 1.0 and 0.5. Correlated to the intraoperative histological findings the accuracy of PCR and culturing was comparable. The highest accuracy was obtained for blood culture samples. Compared to preoperative joint aspiration the antigranulocyte scintigraphy proved to be more sensitive in the diagnosis an infected knee replacement while having a high specificity. An advantage of PCR compared to the common microbiological culturing techniques was not observed.


Fraser-Cryptophthalmos syndrome with cardiovascular malformations: a rare association.
Fraser-Cryptophthalmos syndrome is a multiple malformation disorder associated variably with cryptophthalmos (hidden eye), anomalies of the head, nose and ears; syndactyly, renal and genital malformations. In this report, we describe a case of Fraser syndrome with cardiovascular malformations: coarctation of aorta, an association not previously described.


Woronin bodies, their impact on stress resistance and virulence of the pathogenic mould Aspergillus fumigatus and their anchoring at the septal pore of filamentous Ascomycota.
Hyphae of filamentous Ascomycota consist of compartments that are connected via septal pores. To avoid a dramatic loss of cellular content after wounding, fungi developed mechanisms to occlude their septal pores. In most Pezizomycotina, so-called Woronin bodies are anchored in proximity to the pore. This is a prominent example for precise spatial positioning of organelles, but so far the underlying molecular organization has remained largely unknown. Using the pathogenic mould Aspergillus fumigatus, we provide evidence that Woronin bodies are important for stress resistance and virulence. Furthermore the molecular machinery anchoring them at the septum is described. Namely, we have identified Lah as the tethering protein and provide evidence that the Woronin body protein HexA binds to the septal pore in a Lah-dependent manner. Moreover, we demonstrate that a striking poly-histidine motif targets HexA to the septal cell wall. Thus, the axis HexA-Lah is an excellent candidate for the tether linking Woronin bodies to the septum. This model applies to A.fumigatus, but most likely also to the vast majority of the Pezizomycotina. Our findings shed light on the evolution of Woronin body anchoring and provide a basis for the development of novel strategies to combat fungal pathogens like A.fumigatus.


The impact of health education on treatment outcomes in heart failure patients.
In 2016 heart failure (HF) affected between 600,000 and 700,000 people in Poland being one of the most common causes of hospitalization and death. Health education is an elements of patient treatment aimed at improving the level of self-care and adherence to the treatment recommendations. To perform a systematic review and meta-analysis of the available literature in order to determine the role of health education in HF treatment and its impact on outcomes in patients with chronic HF. A search was performed in the MEDLINE, PubMed and Scopus databases from January 2010 to January 2019 for the impact of health education on treatment outcomes in HF patients. A total of 16 studies from 12 countries on 5 continents were analyzed. The meta-analysis focused on the impact of education on outcomes in 944 study group patients. We found that the overall impact of education on outcomes was positive (+1 standard deviation (SD); 95% confidence interval (95% CI) >0). After education was provided, the target patients improved in terms of self-care (mean change (MC) = 13.49; p = 0.003; I² = 99.47%). Self-care also improved in the controls, but the improvement was less marked (MC = 9.56; p = 0.001; I² = 98.33%). No impact of education on quality of life (QoL) was confirmed (95% CI = 0). The greatest benefit of education is seen in terms of adherence to pharmaceutical treatment and self-care, while QoL was not associated with education.


Influence of symmetry and balance on visual perception of a white female smile.
Clinicians and dental technicians may underestimate what is deemed esthetic by laypersons and dental professionals. The purpose of this study was to define the relative importance of symmetry, visual tension, and balance in the smile. Images of a white woman were altered to reproduce symmetry, various visual tensions, distinct tooth shapes, and color changes. A 12-question survey was presented to 128 individuals, including 81 dental professionals and 47 laypersons. The survey asked individuals to choose the most desirable and beautiful image in a choice of images. Raters were most influenced by the maxillary central incisors and then the canines and were more forgiving on visual tensions of the maxillary lateral incisors. Square-shaped teeth were preferred over ovoid and triangular ones. The more upright the canines, the more the smile was perceived as masculine. Teeth whiter than the sclera of the eyes were preferred, with lay individuals choosing the lightest shade available and dental professionals choosing the shade slightly lighter than the sclera. Although participants mostly preferred a symmetrical smile, they opted for the natural face as opposed to symmetrical ones. Location of visual tension plays a role in perceiving beauty. Symmetrical smiles were considered more pleasant but not symmetrical faces. Imperfections play an essential role in perceiving beauty because they express life, individuality, charisma, and charm.


A role for JAK2 mutations in myeloproliferative diseases.
Myeloproliferative disorders (MPDs) are characterized by a clonal expansion of myeloid cells. Over the past two years, the identification of the JAK2V617F mutation in most cases of polycythemia vera (PV) as well as approximately 50% of patients with essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) has greatly advanced our understanding of MPDs. The JAK2V617F mutation alters the JAK2 tyrosine kinase to confer constitutive activation and affect downstream signaling pathways. Data from mouse models demonstrate that the mutation is sufficient for development of PV, but additional work is needed to better understand how this allele functions in ET and IMF. Regardless of the various pathologies, the JAK2V617F discovery highlights the importance of JAK-STAT signaling in myeloid differentiation and focuses effort on developing a clinically relevant JAK2 inhibitor.


Concurrent Pacemaker Lead Perforation and Subacute Coronary Stent Thrombosis: A Case Report.
Stent thrombosis and lead perforation are important differentials for patients presenting with chest pain following recent coronary stent insertion and pacemaker insertion. In this report, we describe an unusual case of a 78-year-old male who presented with sharp chest pain one week after admission for posterior ST-elevation myocardial infarction (STEMI) and subsequent Mobitz type II block, for which he received primary percutaneous coronary intervention (PPCI) to the left circumflex artery (LCx) and dual chamber permanent pacemaker (PPM) insertion. Computed tomography (CT) chest and CT coronary angiogram (CTCA), respectively, showed he had concurrent lead perforation and stent thrombosis. On balance, the cause of chest pain was likely lead perforation. This diagnosis was reached by having a high index of suspicion for both of these important post-procedure complications and investigating appropriately.


[Informational cooperation of the complex of software and hardware tools in automatization of state disease control management].
Nowadays, taking into account new tasks, that should be resolved by the medical service, could be marked enlargement of informational cooperation at the expense of perspective program-technical solutions, put in the complex of program-technical means of automatization of administration of state disease control CPTMADC during it's creating. It's planed to elaborate an additional programmatic module for the purpose of using in CPTMADC the methodology of valuation of risk for resolving of tasks of socially-hygienic monitoring. Before it's elaborating, there was examined a capacity to conversion of patterns of weekly reports about the sanitarian condition of objects and it's following using for informational transporting using electronic means of connection of the complex CPTMADC by the way of including in patterns the data about the staff under the influence of adverse factor, and following rangering the objects by the level of risk for staff.


Microglia Are Indispensable for Synaptic Plasticity in the Spinal Dorsal Horn and Chronic Pain.
Spinal long-term potentiation (LTP) at C-fiber synapses is hypothesized to underlie chronic pain. However, a causal link between spinal LTP and chronic pain is still lacking. Here, we report that high-frequency stimulation (HFS; 100 Hz, 10 V) of the mouse sciatic nerve reliably induces spinal LTP without causing nerve injury. LTP-inducible stimulation triggers chronic pain lasting for more than 35 days and increases the number of calcitonin gene-related peptide (CGRP) terminals in the spinal dorsal horn. The behavioral and morphological changes can be prevented by blocking NMDA receptors, ablating spinal microglia, or conditionally deleting microglial brain-derived neurotrophic factor (BDNF). HFS-induced spinal LTP, microglial activation, and upregulation of BDNF are inhibited by antibodies against colony-stimulating factor 1 (CSF-1). Together, our results show that microglial CSF1 and BDNF signaling are indispensable for spinal LTP and chronic pain. The microglia-dependent transition of synaptic potentiation to structural alterations in pain pathways may underlie pain chronicity.


Diagnosis oligohydramnios-related pulmonary hypoplasia (Potter syndrome): value of portable voiding cystourethrography in newborns with respiratory distress.
Potter renal nonfunctional syndrome is an association of facial and limb anomalies, pulmonary hypoplasia, and fetal renal anomalies which lead to marked oligohydramnios, including renal agenesis (true Potter syndrome), renal cystic dysplasia, and obstructive uropathies. Some infants survive long enough to develop severe respiratory distress secondary to pulmonary hypoplasia. The underlying renal disease is often noted only at autopsy. We studied four infants, only one of whom had clinical signs of the renal nonfunction syndrome. Portable voiding cystourethrography revealed a tiny bladder in three infants with cystic dysplasia kidneys (two of these infants had reflux into unused ureters). Bladder hypertrophy and vesicoureteral reflux secondary to posterior uretral valves were noted in the fourth infant.


Administration of recombinant human interleukin 12 to chronically SIVmac-infected rhesus monkeys.
With the demonstration that interleukin 12 can enhance natural killer (NK) cell activity and drive CD4+ lymphocytes toward T helper type 1 (Thl) responses, there is a strong rationale for exploring the use of this cytokine as an immunomodulatory therapy in HIV-1-infected individuals. To assess its potential safety and effects on both immune and virologic aspects of HIV-1 infection, recombinant human IL-12 (rhIL-12) was assessed in rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques (SIVmac). The activity of rhIL-12 on rhesus monkey lymphocytes was confirmed with the demonstration that peripheral blood lymphocyte lysis of the NK-sensitive cell line Colo was enhanced by this recombinant cytokine. Further, rhIL-12 was shown to induce interferon-gamma production by rhesus monkey lymphocytes in vitro. Then, in separate studies, two treatment regimens of rhIL-12 were assessed in SIVmac-infected monkeys: a low-dose regimen (0.1 microg/kg, daily for 4 weeks) and a high-dose regimen (2.5 microg/kg, every 3-4 days, for 3 weeks). Both rhIL-12 treatment regimens were well tolerated by these virus-infected animals. The high-dose regimen of rhIL-12 induced transient decreases in circulating lymphocytes in the SIVmac-infected monkeys. Furthermore, no changes in lymphocyte-associated SIVmac DNA or SIVmac plasma RNA levels were seen in the treated monkeys. These studies indicate that short-term treatment with rhIL-12 is well tolerated and causes no measurable changes in virus load in chronically SIVmac-infected rhesus monkeys.


Survey of expiration dating policies for repackaged pharmaceuticals.
A national survey was conducted to determine the policies of hospital pharmacies regarding expiration dates for repackaged pharmaceuticals. A cover letter, questionnaire, and self-addressed stamped envelope were mailed to the directors of pharmacy of 360 randomly selected hospitals. Definitions of bulk and extemporaneous repackaging were provided. The response rate was 57%. Less than one third of the responding institutions followed the current FDA recommendations for dating oral solids repackaged in bulk. Almost one quarter used the manufacturer's date. Only 5.6% of the hospitals used more conservative dating. Similar percentages were found for the dating of oral liquids. One third of the hospitals used 30-90 days to date repackaged injectables ; however, a large range of expiration dates was reported. Almost one third of the hospitals applied the current FDA bulk repackaging dating recommendations to extemporaneous repackaging . A large percentage (29% for oral solids and 31% for oral liquids) used the manufacturer's date. A wide variety of arbitrarily assigned expiration dates are being used by hospital pharmacists in the bulk and extemporaneous repackaging of oral solids, liquids, and injections.


Agrobacterium-mediated RMCE approach for gene replacement.
We describe the site-directed integration (SDI) system for Agrobacterium-mediated transformation to precisely integrate a single copy of a desired gene into a predefined target locus by recombinase-mediated cassette exchange (RMCE). The system requires the selection of a transformed line with an integrated copy of a target cassette, and subsequent introduction of an exchange vector. The target cassette contains the npt and cod genes between oppositely orientated recognition sites (RS). The exchange vector T-DNA possesses an exchange cassette containing the gene of interest and a selectable marker gene, such as hpt, between oppositely orientated (inner) RS. Adjacent to the exchange cassette are ipt and recombinase (R) genes and an additional (outer) RS. The recombinase catalyses double-crossover between target RS and exchange inner RS to replace the integrated target cassette with the introduced exchange cassette. Transgenic plants that contain randomly integrated copies of the exchange vector T-DNA show an abnormal phenotype as a result of the overproduction of cytokinin from ipt gene expression. The recombinase can also act on the directly orientated outer RS to remove such randomly integrated copies. The system resulted in single-copy exchange into the target site only in regenerated tobacco at a frequency of 1%-3% per treated explant, or 4%-9% per regenerated line of normal phenotype. Thus, transgenic plants with only an exchanged copy can be efficiently accumulated and selected. Here, we show that the SDI system can efficiently replace the target cassettes with the exchange cassettes in a heterozygous or homozygous condition. The SDI system may be useful for precise comparisons of different gene constructs, the characterization of different chromosomal regions and the cost-effective screening of reliable transgenic plants.


Separation of the estrogen-activated growth-regulatory forms of alpha-fetoprotein in mouse amniotic fluid.
We have previously reported that murine fetal alpha-fetoprotein (AFP) incubated for 1.0 h at room temperature in the presence of high concentrations of estradiol (E2) generates a growth-regulatory product designated AFP/E2. Subsequently we developed a bioassay in the immature mouse uterus to measure both the growth-inhibitory and growth-enhancing properties of AFP. In the present study, we have employed this bioassay to monitor each of the amniotic fluid-derived AFP isolates fractionated by various chromatographic and electrophoretic techniques. The objective of this investigation was to partition and isolate the various molecular forms of AFP contained in amniotic fluid and determine whether the growth-regulatory activities resided with one or more of the fractions. AFP was fractionated by three different chromatographic/electrophoretic methods: E2 affinity chromatography, preparative polyacrylamide-gel electrophoresis (PAGE), and high-performance liquid chromatography (HPLC); and one immunoaffinity method: gel-entrapped antibody filtration (GAF). Whereas E2 affinity chromatography separated the biological activity of AFP into inhibitory and possibly enhancing activities, PAGE purification yielded three fractions: an inhibitor, an enhancer, and a fraction without growth-regulatory activity. Immunoaffinity separation yielded an AFP product with only inhibitory activities. In comparison, fractionation by HPLC produced seven AFP fractions in which only three displayed growth-regulatory activities: two inhibitory and one enhancing. After subsequent HPLC rechromatography of these fractions, none displayed any biological activity. Thus, murine AFP derived from amniotic fluid is composed of potential heterofunctional forms that, depending on their relative abundance in the preparation, constitute a mixture capable of either (a) growth inhibition, (b) no effect, or (c) growth enhancement.


Celastrol suppresses morphological and transcriptional responses in microglial cells upon stimulation with double-stranded RNA.
Despite the pivotal role of microglia in the immune system of the brain, a growing body of evidence suggests that excessive microglial activation provokes neuronal and glial damage, leading to neurodegenerative and neuroinflammatory disorders. Celastrol, a triterpene, is a potent anti-inflammatory and antioxidant compound derived from perennial creeping plants belonging to the Celastraceae family. In the current study, we have analyzed the effect of celastrol on morphological and transcriptional responses in microglial MG6 cells upon stimulation with double-stranded RNA, a strong activator of innate immune cells. In the presence of celastrol, morphological changes were inhibited in double-stranded RNA-stimulated microglia. It was also found that the treatment of microglia with celastrol led to a significant decrease in the double-stranded RNA-induced expression of proinflammatory cytokines and chemokines. These data demonstrate that celastrol inhibits morphological and transcriptional responses during microglial activation.


The Troublesome Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma.
Barrett's esophagus and esophageal adenocarcinoma diagnoses have increased markedly in recent decades. Recent research with patients diagnosed with Barrett's esophagus (the only known precursor for esophageal adenocarcinoma) and esophageal adenocarcinoma has identified several modifiable and nonmodifiable potential risk factors. Consistent risk factors for both disorders include increasing age, male sex, white non-Hispanic race/ethnicity, gastroesophageal reflux disease, lack of infection with Helicobacter pylori, smoking, abdominal obesity, and a Western diet. The authors present detailed discussions of these risk factors along with possible explanations for some apparent discrepancies and ideas for future study.


Bias in air sampling techniques used to measure inhalation exposure.
Factors have been evaluated which contribute to the lack of agreement between inhalation exposure estimates obtained by time-weighted averaging of samples taken with mini hi-volume samplers, and those measured by time integrating, low-volume, lapel mounted, personal monitors. Measurements made with real-time aerosol monitors on workers at a Be-Cu production furnace show that part of the discrepancy results from variability of the aerosol concentration within the breathing zone. Field studies of sampler inlet bias, the influences of the electrostatic fields around polystyrene filter holders, and resuspension of dust from work clothing, were done in three areas of a Be plant. No significant differences were found in Be air concentrations measured simultaneously by open and closed face cassettes, and "mini hi-volume" samplers mounted on a test stand. No significant influence on Be collection was detected between either positively or negatively charged monitors and charge neutralized control monitors. The effect of contaminated work clothing on dust collection by lapel mounted monitors is most important. Beryllium release from the fabrics affected air concentrations measured by fabric mounted monitors more than it affected concentrations measured by monitors positioned above the fabrics. The latter were placed 16 cm from the vertically mounted fabrics, to simulate the position of the nose or mouth. We conclude that dust resuspended from work clothing is the major source of the observed discrepancy between exposures estimated from lapel mounted samplers and time-weighted averages.


The costs of multiple sclerosis: a cross-sectional, multicenter cost-of-illness study in Italy.
To estimate the socio-economic impact of multiple sclerosis (MS) in Italy. Outpatients with MS were enrolled at 44 centres across Italy. Socio-demographic, clinical and resource utilization data were collected using a validated questionnaire. Each patient completed a weekly diary of expenses due to MS over a three-month period. Direct health care costs and indirect costs (lack of productivity for the patient and for caregivers) were assessed for the whole population and were compared among five groups, categorised by disease severity (EDSS score). An analysis of variance was carried out on socio-demographic variables. For the total population of 566 patients, the mean direct cost over three months was ITL 2,134,000, the mean indirect cost was ITL 7,775,000. Costs were significantly higher for male patients (p < 0.05) and showed a significant increase with increasing age (p < 0.0005), disease duration (p < 0.0005) and disease severity (p < 0.0005). Costs for patients in a progressive phase were significantly higher (p < 0.0005). There were no significant geographical differences among the regions of Italy. This study confirms that MS represents a high economic burden, with indirect costs greatly exceeding direct costs. Unpaid caregivers remain the culturally accepted mode of care for MS patients in Italy and this study illustrates the impact of their loss of earnings. As costs increase with disease progression, these findings suggest that treatment efforts should focus on patients in the early stages of MS, in order to slow down disease progression.


MicroRNA-143 inhibits tumorigenesis in hepatocellular carcinoma by downregulating GATA6.
MicroRNAs serve a critical role in human hepatocellular carcinoma (HCC) progression. However, the exact role of microRNA-143 (miR-143) in HCC remains unclear. The current study investigates the molecular mechanism of miR-143 in HCC. In cultured HepG2 and Bel7402 cell lines, miR-143 levels were raised by lentivirus transduction. This significantly inhibited HCC progression in terms of cell invasion and proliferation in both HepG2 and Bel7402 cell lines (P<0.05). MiR-143 also significantly decreased tumor implantation in vivo (P<0.05). Regulation of miR-143 on its direct target, GATA-binding factor 6 (GATA6), was investigated by multiple strategies, including dual-luciferase assay, quantitative polymerase chain reaction and western blot analysis. The results indicated that miR-143 was downregulated in both HCC cell lines and human tumors. GATA6 was identified as the downstream target of miR-143 in HCC, and overexpressing GATA6 was able to counter the tumor-suppressive effect of miR-143 on HCC in HepG2 and Bel7402 cells by significantly increasing proliferation and invasion rates (P<0.05). Therefore, a novel epigenetic pathway was identified in which miR-143 may suppress the malignancy of HCC by targeting GATA6.


Enhanced Thermal and Dynamic Mechanical Properties of Synthetic/Natural Hybrid Composites with Graphene Nanoplateletes.
The aim of the present research work is to enhance the thermal and dynamic mechanical properties of Kevlar/Cocos nucifera sheath (CS)/epoxy composites with graphene nano platelets (GNP). Laminates were fabricated through the hand lay-up method followed by hot pressing. GNP at different wt.% (0.25, 0.5, and 0.75) were incorporated with epoxy resin through ultra-sonication. Kevlar/CS composites with different weight ratios (100/0, 75/25, 50/50, 25/75, 0/100) were fabricated while maintaining a fiber/matrix weight ratio at 45/55. Thermal degradation and viscoelastic properties were evaluated using thermogravimetric analysys (TGA), differential scanning calorimetric (DSC) analysis, and a dynamic mechanical analyser (DMA). The obtained results revealed that Kevlar/CS (25/75) hybrid composites at 0.75 wt.% of GNP exhibited similar thermal stability compared to Kevlar/epoxy (100/0) composites at 0 wt.% of GNP. It has been corroborated with DSC observation that GNP act as a thermal barrier. However, DMA results showed that the Kevlar/CS (50/50) hybrid composites at 0.75 wt.% of GNP exhibited almost equal viscoelastic properties compared to Kevlar/epoxy (100/0) composites at 0 wt.% GNP due to effective crosslinking, which improves the stress transfer rate. Hence, this research proved that Kevlar can be efficiently (50%) replaced with CS at an optimal GNP loading for structural applications.


Bone disease in diabetes.
The relationship between diabetes and bone disease is complex. While low bone mineral density (BMD) is consistently observed in type 1 diabetes (T1DM), in type 2 diabetes (T2DM) bone mineral density is similar to or higher than in non diabetic subjects. Yet, for both types of diabetes bone appears to be more fragile for a given density. Recent meta-analyses and cohort studies confirm that T1DM and T2DM are associated with higher fracture risk. Many factors influence the probability of fractures. Diabetes can affect bone through multiple pathways including obesity, changes in insulin levels, higher concentrations of advanced glycation end products in collagen, increased urinary excretion coupled with lower intestinal absorption of calcium, inappropriate homeostatic response of parathyroid hormone secretion, complex alterations of vitamin D regulation, reduced renal function, lower insulin-like growth factor-I, microangiopathy, and inflammation. Data on cellular mechanisms and experimental models are extensive, but the relevance of each one of these factors to the clinical situation is unclear. In this article we review the pathophysiological mechanisms potentially involved in the altered BMD found in diabetic patients, show data on the increased risk of fractures, and speculate on the potential causes of the increased risk of fractures in this context. Finally, we comment on the prevention and treatment of osteoporosis in diabetes, although the lack of trials testing the use of pharmacotherapy on preventing fractures in this context is emphasized.


Pacinian corpuscle in the juxtaoral organ of Chievitz.
The juxtaoral organ of Chievitz (JOOC) is a normal permanent anatomical structure located within the soft tissue overlying the angle of the mandible in the buccotemporal space. Although the sensory organ nature of JOOC, repeatedly mentioned in German publications, has been neglected in the last decade by the American anatomists and pathologists, we incidentally found JOOC-type squamous epithelium accompanied by Pacinian corpuscles. This fortuitous finding appears to be the first report of the authentic Paciniform nerve endings within JOOC, supporting its mechanosensory function.


An rhl-like quorum-sensing system negatively regulates pyoluteorin production in Pseudomonas sp. M18.
Pseudomonas sp. M18, isolated from the watermelon rhizosphere, is antagonistic against a number of soil-borne pathogens. This strain produces an uncharacterized red pigment, pyoluteorin (Plt), and two N-acylhomoserine lactones (AHLs). A previously isolated red-pigment-defective mutant, M18-T510, contains an insert within a gene similar to rhlI in P. aeruginosa PAO1. The M18 rhlI gene product is responsible for the production of two AHL signals: N-butyryl-homoserine lactone and N-hexanoylhomoserine lactone. Mutants defective in either rhlI or rhlR showed enhanced Plt biosynthesis due to loss of transcriptional repression, which was mediated, at least in part, by suppressed expression of the activator PltR. A Plt-specific ABC transporter was also upregulated in the rhl mutants in a Plt-dependent manner. In comparison with the wild-type strain, the rhl mutants survived longer during stationary-phase growth.


Twenty years after childhood strabismus surgery.
Children with infantile or acquired esotropia often have surgery in the first few years of life. Many of these children have additional surgeries and may also be treated for amblyopia. As pediatric ophthalmologists, we do not often have the opportunity to learn the affect of this strabismus on their life as they have become adults, completed their education and chosen a career and during this time, what has happened to their eye alignment. The charts for all children having had surgery for esotropia by the author from 1977 to 1984 were obtained and attempts were made to contact the patients. Five hundred thirty-one charts were identified, 131 contacts were successfully made, and 37 patients were examined. Seventy-eight percent of the infantile esotropia patients did not change their alignment from the last regular office visit and 90% of the acquired esotropia patients continued their good alignment an average of twenty-four years following surgery. Patients treated for amblyopia maintained their treated best corrected vision. Most patients did not feel their "corrected" childhood strabismus affected their school or social accomplishments, and most felt they were good readers. Children with "corrected" childhood strabismus tend to maintain this into adult life and it does not affect school performance or their career choice.


Management of atrial fibrillation in the emergency department and following acute myocardial infarction.
Atrial fibrillation (AF) is the most common arrhythmia managed by emergency physicians and there is increasing evidence that selected patients with acute AF can be safely managed in the emergency department without the need for hospital admission. The principles of management are identification and treatment of precipitating or underlying causes, hemodynamic stabilization/rate control, reduction of thromboembolism risk and the conversion/maintenance of sinus rhythm. A strategy of rate or rhythm control should be chosen based on the patient's clinical status, the duration of AF, the experience of the treating physician and the status of anticoagulation. Before either electric or pharmacological cardioversion, anticoagulation should be considered. Most patients should be given heparin or low molecular weight heparin while preparing for cardioversion. All patients should be considered for long-term anticoagulation based on their thromboembolic risk and bleeding risk from antithrombotic therapy. Following restoration of sinus rhythm, a decision regarding the use of antiarrhyhmic drugs should be made based on the estimated frequency of recurrence and degree of symptoms. In the setting of acute myocardial infarction, beta-blockers should be administered whenever possible. If beta-blockers are contraindicated, the rate can be slowed with digoxin or amiodarone. Cardioversion should be performed if the patient is hemodynamically unstable. Class IC antiarrhythmic drugs should not be administered in this setting.


Platelet contribution to cancer cell growth and migration: the role of platelet growth factors.
Blood platelets contain several growth factors and inhibitors. The better known among them are named platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF beta), active as modulators of growth of normal mesenchymal and epithelial cells. Cancer cell growth in vitro seems to be independent of the effects of exogenous peptides, but dependent on the cell ability to release autocrine growth factors, similar to PDGF or TGF beta. In addition, platelet-associated growth factors and inhibitors, which are able to induce a fibrotic response in connective tissue cells, might also play a role to modulate the desmoplastic reaction surrounding the tumor.


Do ethnic disparities extend to subspecialty diabetes care?
It is unclear if disparities described in diabetes primary care extend to subspecialty diabetes care. This retrospective observational study examined disparities in diabetes outcomes in a subspecialty practice by assessing glycemic improvement in type 2 diabetes patients during the first year of enrollment. Electronic data were gathered on 3,945 subjects. The outcome was the proportion of white and minority (Asian, black, and Hispanic) subjects achieving a hemoglobin A1C (A1C) level of ≤7% after the first year of care. Logistic regression was used to identify factors associated with odds of achieving A1C ≤7%. Minority patients had greater diabetes duration, more social disadvantages and missed appointments, and worse control at presentation than whites. The proportion of patients reaching target A1C rose from 37 to 52% among white patients and from 28 to 40% among minority patients. Significant differences between whites and minorities in the rates of patients reaching A1C ≤7% were found only among those with higher initial A1C (iA1C) levels (32% vs. 20.9%; P = .002 in third iA1C quartile, and 28.2% vs. 17.9%; P = .0003 in fourth iA1C quartile). The interaction between race/ethnicity and the top two iA1C quartiles remained significant in the fully adjusted model. Reaching an A1C level of ≤7% depends strongly upon the glycemic level at initial presentation to specialty care, not race. However, minority patients with the highest baseline A1C levels do not improve to the same degree as white patients, and therefore should be targeted for more intensive diabetes care management.