The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system.
Blood vessels and nerves are complex, branched structures that share a high degree of anatomical similarity. Guidance of vessels and nerves has to be exquisitely regulated to ensure proper wiring of both systems. Several regulators of axon guidance have been identified and some of these are also expressed in endothelial cells; however, the extent to which their guidance functions are conserved in the vascular system is still incompletely understood. We show here that the repulsive netrin receptor UNC5B is expressed by endothelial tip cells of the vascular system. Disruption of the Unc5b gene in mice, or of Unc5b or netrin-1a in zebrafish, leads to aberrant extension of endothelial tip cell filopodia, excessive vessel branching and abnormal navigation. Netrin-1 causes endothelial filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a repulsive netrin receptor in endothelial cells controlling morphogenesis of the vascular system.


Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms).
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and patients display an increased prevalence of cardiovascular events compared with essential hypertensives. To date, 3 familial forms of PA have been described and termed familial hyperaldosteronism types I, II, and III (FH-I to -III). The aim of this study was to investigate the prevalence and clinical characteristics of the 3 forms of FH in a large population of PA patients. Three-hundred consecutive PA patients diagnosed in our unit were tested by long-PCR of the CYP11B1/CYP11B2 hybrid gene that causes FH-I, and all of the available relatives of PA patients were screened to confirm or exclude PA and, thus, FH-II. Urinary 18-hydroxycortisol and 18-oxocortisol were measured in all of the familial PA patients. Two patients were diagnosed with FH-I (prevalence: 0.66%), as well as 21 of their relatives, and clinical phenotypes of the 2 affected families varied markedly. After exclusion of families who refused testing and those who were not informative, 199 families were investigated, of which 12 were diagnosed with FH-II (6%) and an additional 15 individuals had confirmed PA; clinical and biochemical phenotypes of FH-II families were not significantly different from sporadic PA patients. None of the families displayed a phenotype compatible with FH-III diagnosis. Our study demonstrates that familial forms of hyperaldosteronism are more frequent than previously expected and reinforces the recommendation of the Endocrine Society Guidelines to screen all first-degree hypertensive relatives of PA patients.


Hepatoprotective Effects of Sweet Cherry Extracts (cv. Saco).
Cancer is the second cause of death worldwide. Among cancers, hepatocellular carcinoma is one of the most prevalent. Evidence indicates that the daily consumption of fruits and vegetables can prevent the onset of various cancers due to the presence of bioactive compounds. Sweet cherries are known for their richness in phenolics, including anthocyanins, which are the major constituents, and presumably, the key contributors to their biological activity. Therefore, the present study aimed to evaluate the effects of three different cherry fractions on human hepatocellular carcinoma (HepG2) cells viability and effectiveness to improve the redox status of these cells under oxidative damage induced by nitric oxide radicals and hydrogen peroxide. Phenolic characterization of fractions was performed by Fourier transform infrared spectroscopy. The obtained results indicated that enriched phenolic fractions of sweet cherries (cv. Saco, can impair cell viability and suppress cells growth after 72 h of exposure, promoting necrosis at the highest tested concentrations (>50 µg/mL). Additionally, fractions also showed the capacity to protect these cells against oxidative injury by capturing radicals before they can attack cells' membrane and by modulating reactive oxygen and nitrogen species generation, as demonstrated by bioinformatic tools.


Dual pathways for agonist-stimulated arachidonic acid release in pancreatic acini: roles in secretion.
The present experiments were performed to determine pathways responsible for arachidonic acid release stimulated by cholecystokinin (CCK) and phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA), and the roles of pathways in the secretory response in dispersed acini from guinea pig pancreas. Both CCK-octapeptide (CCK-OP) and PMA increased intracellular arachidonic acid. To determine the source of released arachidonic acid, we measured the effects of PMA and CCK-OP on cellular 1,2-diacylglycerol and lysophosphatidylcholine (LPC) and of diglyceride lipase inhibitor RHC 80267 on [3H]arachidonic acid release. Both PMA and CCK-OP increased 1,2-diacylglycerol and LPC. RHC 80267 had no effect on LPC but inhibited the increase in [3H]arachidonic acid release with a concentration of CCK-OP that was maximal for enzyme secretion. The increase in [3H]arachidonic acid release with PMA or a supramaximal concentration of CCK-OP was not inhibited by RHC 80267. In parallel fashion, RHC 80267 inhibited amylase release caused by maximally effective concentrations of CCK-OP but not that caused by PMA or by supramaximally effective concentrations of CCK-OP. Arachidonic acid stimulated amylase release. Exogenous addition of phospholipase A2 caused increases in [3H]arachidonic acid release, LPC formation, and amylase release. The results indicate that there are at least two pathways responsible for the increase in free cellular arachidonic acid stimulated by pancreatic agonists. One is sequential action of phospholipase C and diglyceride lipase on phosphatidylinositol. The other is a phospholipase A action on phosphatidylcholine. The results also suggest a stimulatory role for both pathways in the secretory response.


T cells of patients with the Wiskott-Aldrich syndrome have a restricted defect in proliferative responses.
The Wiskott-Aldrich syndrome (WAS) is a disease of profound thrombocytopenia and severe immune defects caused by an unidentified defective X chromosome gene. In this study, T lymphocyte function is examined using a panel of allospecific WAS patient T cell lines, previously found to express the abnormal disease gene and the cytoarchitectural defect characteristic of the disease. Although T cell lines from normal individuals proliferate vigorously in response to immobilized anti-CD3 mAb OKT3 and SPV-T3b, five of seven WAS patient T cell lines failed to proliferate and two lines showed significantly decreased proliferation when challenged with the immobilized anti-CD3 mAb. The deficient responsiveness of the WAS T cell lines to immobilized anti-CD3 mAb is a restricted defect, because the cells proliferate normally when challenged with allospecific Ag, PHA, or PMA plus ionomycin. Addition of anti-CD28 mAb did not correct the deficient proliferation of the WAS cells challenged with immobilized anti-CD3. Deficient response of the WAS T cell lines to immobilized anti-CD3 was detected also when earlier events of the proliferation process, IL-2 production and up-regulation of activation Ag CD69 and CD28, were measured. On the other hand, WAS cell lines did not differ from normal cell lines in binding of anti-CD3 mAb, mobilization of Ca2+ in response to soluble OKT3, and tyrosine phosphorylation and GTP binding of the CD3 zeta-chain in response to OKT3. Cumulatively, these findings demonstrate a striking restricted defect in the proliferative response of WAS T cells, which because it is found in cell lines free of secondary changes that occur in the patient circulation must be a reflection of the inherited defective disease gene product.


Pathogenetic mechanisms of septic cardiomyopathy.
Sepsis is a serious complication after infection, whose further development may lead to multiple organ dysfunction syndrome and so on. It is an important cause of death in critically ill patients who suffered an infection. Sepsis cardiomyopathy is a common complication that exacerbates the prognosis of patients. At present, though the pathogenesis of sepsis cardiomyopathy is not completely clear, in-depth study of the pathogenesis of sepsis cardiomyopathy and the discovery of its potential therapeutic targets may decrease the mortality of sepsis patients and bring clinical benefits. This article reviews mitochondrial dysfunction, mitophagy, oxidation stress, and other mechanisms in sepsis cardiomyopathy.


[Preparation of NADPH-cytochrome P-450 reductase and the role in metabolism of xenobiotics].
NADPH-Cytochrome P-450 Reductase is the major part of MFO (mixed function oxidase) system of liver. A simple and economic method of preparation of reductase was introduced in this paper and it was certified that xenobiotics benzene, bichloroethylene, and asbestos can be oxidized by reductase and reconstituted cytochrome P-450 2B1. But the metabolites of the 3 compounds can not cause the changes of plasmid PBR322 DNA.


Survival and Healthcare Costs with Invasive Mechanical Ventilation versus Noninvasive Ventilation in Patients with Dementia Admitted with Pneumonia and Respiratory Failure.
Rationale: Invasive mechanical ventilation (IMV) may be burdensome for persons with advanced dementia. Research has shown that IMV use in persons with dementia has increased in the United States, Spain, and Canada. Objectives: To compare the outcomes and healthcare costs among hospitalized patients with advanced dementia treated with noninvasive ventilation (NIV) versus IMV. Methods: A retrospective cohort study was conducted among hospitalized patients aged 66 years and older with pneumonia, or septicemia with pneumonia, treated with either NIV or IMV between 2015 and 2017. Persons were included if they had Minimum Data Set (MDS) assessments between 1 and 120 days before hospitalization indicating that they had advanced dementia with four or more impairments in activities of daily living. Propensity-matched analysis was performed using clinical information from the MDS, Chronic Condition Warehouse indicators of chronic disease, and prior use measures. Main outcome measures were survival and healthcare costs up to 1 year after discharge. Results: Among 27,483 hospitalizations between 2015 and 2017, IMV was used in 12.5% and NIV in 8.2%. A propensity-matched model comparing IMV versus NIV using clinical data from the MDS, Chronic Condition Warehouse indicators of chronic diseases, and prior use revealed matches for 96.3% of hospitalizations with the use of IMV. NIV matched cases had a higher 30-day mortality rate compared with IMV cases (58.7% vs. 51.9%, P ⩽ 0.001), but this survival benefit did not persist, as 1-year mortality was slightly higher among subjects with IMV compared with those with NIV (86.5% vs. 85.9%, P > 0.05). One-year healthcare costs after matching were higher among those treated with IMV compared with NIV (mean, $57,122 vs. $33,696; P < 0.001). Conclusions: Among patients with advanced dementia hospitalized with pneumonia or septicemia with pneumonia, improvement in 30-day survival for those treated with IMV compared with NIV must be weighed against lack of 1-year survival benefit and substantially higher costs.


Non-communicating gastric duplication cyst in a 10-week-old Labrador Retriever puppy.
A 10-week-old male Labrador Retriever puppy was presented for acute onset of vomiting over a 48-h period. Ultrasound examination showed a cystic structure in the area of the pylorus that was impinging on gastric outflow. Surgery was performed to resect this structure. Histological examination showed the cystic structure to be composed of gastric mucosa surrounded by a smooth muscle wall. This finding, together with the intraoperative observations, led to a definitive diagnosis of a non-communicating gastric duplication cyst. Although rare, gastric duplication cyst is a differential diagnosis for acute-onset vomiting in a young dog. This report should aid in the decision-making process in future cases.


Versatile type miniature diamond anvil high-pressure cell.
A miniature diamond anvil high-pressure cell 42 mm in diameter, 18 mm thick, and 150 g in weight has been constructed. The cell is loaded into a piston-cylinder type pressing device with an alignment mechanism and compressed to a desired pressure. After the pressure is clamped by three screws, the cell part is taken out. Thereby, in spite of the small and simple cell, pressure can be generated easily and steadily up to 200 kbar. Because the cell is small and light enough to be mounted on a usual goniometer head, and has large openings towards both the top and bottom, it can widely be used as a versatile apparatus for research at high pressure.


Development of camelid single chain antibodies against Shiga toxin type 2 (Stx2) with therapeutic potential against Hemolytic Uremic Syndrome (HUS).
Shiga toxin (Stx)-producing Escherichia coli (STEC) infections are implicated in the development of the life-threatening Hemolytic Uremic Syndrome (HUS). Despite the magnitude of the social and economic problems caused by STEC infections, no licensed vaccine or effective therapy is presently available for human use. Single chain antibodies (VHH) produced by camelids exhibit several advantages in comparison with conventional antibodies, making them promising tools for diagnosis and therapy. In the present work, the properties of a recently developed immunogen, which induces high affinity and protective antibodies against Stx type 2 (Stx2), were exploited to develop VHHs with therapeutic potential against HUS. We identified a family of VHHs against the B subunit of Stx2 (Stx2B) that neutralize Stx2 in vitro at subnanomolar concentrations. One VHH was selected and was engineered into a trivalent molecule (two copies of anti-Stx2B VHH and one anti-seroalbumin VHH). The resulting molecule presented extended in vivo half-life and high therapeutic activity, as demonstrated in three different mouse models of Stx2-toxicity: a single i.v. lethal dose of Stx2, several i.v. incremental doses of Stx2 and intragastrical STEC infection. This simple antitoxin agent should offer new therapeutic options for treating STEC infections to prevent or ameliorate HUS outcome.


Risk factors for posttraumatic synostosis and outcomes following operative treatment of ankle fractures.
Distal tibiofibular synostosis is a known but poorly described complication of ankle fractures. The objective of this study was to evaluate the relationship between ankle fracture fixation method and other risk factors in the development of synostosis in posttraumatic operative ankle fractures. Outcomes of patients with no synostosis, incomplete bony bridging, or complete synostosis also were compared. All operative ankle fractures from a single surgeon's prospectively collected clinical database were evaluated for the presence of distal tibiofibular synostosis not earlier than 3 months postoperatively. All fractures were treated in a fracture-specific and ligament-specific fashion. Syndesmotic screws, when used, were routinely removed no sooner than 4 months after operation. Patient demographic and medical history data as well as injury and fixation profile were evaluated. Incidence of complications was also reviewed. Foot and Ankle Outcome Score (FAOS) and range of motion (ROM) were compared between the groups. Of the 564 ankle fractures included in the study, 91 demonstrated complete synostosis and 46 demonstrated incomplete bony bridging. Multivariate analysis revealed male sex (odds ratio [OR] = 2.82, P < .001), syndesmotic screw fixation (OR = 2.46, P < .001), and tibiotalar dislocation (OR = 1.74, P = .032) to remain significant independent risk factors for the development of incomplete bony bridging or complete synostosis while adjusting for confounding risk factors. Ankles with synostosis also demonstrated significant reduction in dorsiflexion (P = .017), plantarflexion (P = .024), and inversion (P < .001), though patient-reported outcome measures were equivalent with patients without synostosis. Syndesmotic screw fixation, male sex, and tibiotalar dislocation were significant risk factors in the formation of postoperative distal tibiofibular synostosis, though patient-reported outcome measures seemed equivalent among patients with and without synostosis. Level III, case control study of prospectively collected registry data.


Optimal Fermentation Conditions of Hyaluronidase Inhibition Activity on Asparagus cochinchinensis Merrill by Weissella cibaria.
This study was conducted to evaluate the hyaluronidase (HAase) inhibition activity of Asparagus cochinchinesis (AC) extracts following fermentation by Weissella cibaria through response surface methodology. To optimize the HAase inhibition activity, a central composite design was introduced based on four variables: the concentration of AC extract (X1: 1-5%), amount of starter culture (X2: 1-5%), pH (X3: 4-8), and fermentation time (X4: 0-10 days). The experimental data were fitted to quadratic regression equations, the accuracy of the equations was analyzed by ANOVA, and the regression coefficients for the surface quadratic model of HAase inhibition activity in the fermented AC extract were estimated by the F test and the corresponding p values. The HAase inhibition activity indicated that fermentation time was most significant among the parameters within the conditions tested. To validate the model, two different conditions among those generated by the Design Expert program were selected. Under both conditions, predicted and experimental data agreed well. Moreover, the content of protodioscin (a well-known compound related to anti-inflammation activity) was elevated after fermentation of the AC extract at the optimized fermentation condition.


A null mutation in the gene encoding a type I interferon receptor component eliminates antiproliferative and antiviral responses to interferons alpha and beta and alters macrophage responses.
To examine the in vivo role(s) of type I interferons (IFNs) and to determine the role of a component of the type I IFN receptor (IFNAR1) in mediating responses to these IFNs, we generated mice with a null mutation (-/-) in the IFNAR1 gene. Despite compelling evidence for modulation of cell proliferation and differentiation by type I IFNs, there were no gross signs of abnormal fetal development or morphological changes in adult IFNAR1-/- mice. However, abnormalities of hemopoietic cells were detected in IFNAR1 -/- mice. Elevated levels of myeloid lineage cells were detected in peripheral blood and bone marrow by staining with Mac-1 and Gr-1 antibodies. Furthermore, bone marrow macrophages from IFNAR1 -/- mice showed abnormal responses to colony-stimulating factor 1 and lipopolysaccharide. IFNAR1 -/- mice were highly susceptible to viral infection: viral titers were undetected 24 hr after infection of IFNAR1 +/+ mice but were extremely high in organs of IFNAR1 -/- mice, demonstrating that the type I IFN system is a major acute antiviral defence. In cell lines derived from IFNAR1 -/- mice, there was no signaling in response to IFN-alpha or -beta as measured by induction of 2'-5' oligoadenylate synthetase, antiviral, or antiproliferative responses. Importantly, these studies demonstrate that type I IFNs function in the development and responses of myeloid lineage cells, particularly macrophages, and that the IFNAR1 receptor component is essential for antiproliferative and antiviral responses to IFN-alpha and -beta.


Synthesis of Pyridine-Fused Siloles by Palladium-Catalyzed Intramolecular Bis-Silylation.
Silole derivatives are attracting significant attention as new functional materials with excellent electronic and photophysical properties. Thus, the development of synthesis methods to afford such derivatives is highly desirable. Herein, the synthesis of pyridine-fused siloles under the conditions of the Sonogashira coupling reaction is described. The reactions of 2-bromo-3-(pentamethyldisilanyl)pyridine (1) with ethynylbenzene derivatives in the presence of PdCl2(PPh3)2-CuI as a catalyst afforded the corresponding pyridine-fused siloles (2a-2c) through intramolecular trans-bis-silylation. DFT calculations were also performed to understand the reaction mechanism. This paper is the first to report on the successful use of palladium catalysts in the trans-bis-silylation of alkynes with disilanes.


Restraining mechanisms in regulating glottal closure during phonation.
Recent experimental studies showed that isotropic vocal fold models were often blown wide apart and thus not able to maintain adductory position, resulting in voice production with noticeable breathy quality. This study showed that the capability of the vocal fold to resist deformation against airflow and maintain adductory position can be improved by stiffening the body-layer stiffness or increasing the anterior-posterior tension of the vocal folds, which presumably can be achieved through the contraction of the thyroarytenoid (TA) and cricothyroid (CT) muscles, respectively. Experiments in both physical models and excised larynges showed that, when these restraining mechanisms were activated, the vocal folds were better able to maintain effective adduction, resulting in voice production with much clearer quality and reduced breathiness. In humans, one or more restraining mechanisms may be activated at different levels to accommodate the varying degree of restraining required under different voice conditions.


Synthesis of bis(N-arylcarboximidoylchloride)pyridine cobalt(II) complexes and their catalytic behavior for 1,3-butadiene polymerization.
A new family of bis(N-arylcarboximidoylchloride)pyridine cobalt(II) complexes with the general formula [2,6-(ArN=CCl)2C5H3N]CoCl2 (Ar = 2,4,6-Me3C6H2, 4a; 2,6-(i)Pr2C6H3, 4b; 2,6-Me2C6H3, 4c; C6H5, 4d; 4-Cl-2,6-Me2C6H2, 4e) and a typical Brookhart-Gibson-type reference complex [2,6-(2,4,6-Me3C6H2N=CMe)2C5H3N]CoCl2 (5a) were synthesized and characterized. Determined by X-ray crystallographic analysis, complexes 4a, 4c-e, and 5a adopted a trigonal bipyramidal configuration, and 4b adopted a distorted square pyramidal geometry. In combination with ethylaluminum sesquichloride (EASC), all the complexes were highly active towards 1,3-butadiene polymerization, affording polybutadiene with predominant cis-1,4 content (up to 96%). 4a with chlorine atoms at the imine groups exhibited higher catalytic activity than did 5a, indicating that the incorporation of chlorine atoms into the ligand improves the activity. The activity of the complexes in 1,3-butadiene polymerization was in the order of 4a > 4c ∼ 4e ∼ 4b > 4d, which is consistent with the trend of spatial opening degree around the metal center in the complexes as revealed by crystallographic data. Screening polymerization conditions proved that EASC was the most efficient among the cocatalysts examined.


Web Thermo Tables - an On-Line Version of the TRC Thermodynamic Tables.
It has long been understood that availability of thermophysical and thermochemical property data is vital to scientific research and industrial design. For over 65 years, the Thermodynamics Research Center (TRC) has been publishing tables of critically evaluated data covering physical and thermodynamic properties of pure compounds, TRC Tables-Hydrocarbons and TRC Tables-Non-Hydrocarbons. Over their long history, the TRC Tables have always been valued as a reputable source of evaluated thermophysical and thermodynamic data. To facilitate more flexible, convenient, and up-to-date access to the data, here, we present the release of the on-line version of the TRC tables, Web Thermo Tables (WTT). Presently, WTT contains data for 7838 compounds and over 950,000 evaluated data points. The tabulated information includes critical properties, vapor pressures and boiling temperatures, phase transition properties, volumetric properties, heat capacities and derived properties, transport properties, reaction state-change properties, as well as index of refraction, surface tension, and speed of sound. Various search options and data plotting capabilities are provided via the Web interface. WTT are distributed through the NIST Standard Reference Data Program [1].


Extraction of azadirachtin A from neem seed kernels by supercritical fluid and its evaluation by HPLC and LC/MS.
A new supercritical extraction methodology was applied to extract azadirachtin A (AZA-A) from neem seed kernels. Supercritical and liquid carbon dioxide (CO(2)) were used as extractive agents in a three-separation-stage supercritical pilot plant. Subcritical conditions were tested too. Comparisons were carried out by calculating the efficiency of the pilot plant with respect to the milligrams per kilogram of seeds (ms/mo) of AZA-A extracted. The most convenient extraction was gained using an ms/mo ratio of 119 rather than 64. For supercritical extraction, a separation of cuticular waxes from oil was set up in the pilot plant. HPLC and electrospray mass spectroscopy were used to monitor the yield of AZA-A extraction.


Clinical application of acupuncture in ophthalmology.
Acupuncture of 50 persons suffering from myopia, glaucoma, retinitis pigmentosa (degeneratio retinae pigmentosa), optic nerve atrophy, aged 5 to 71 was carried out. One to three courses were conducted, each consisting of 10-15 seances. All the patients were treated with acupuncture at these bilateral points: Extra 2, BL 2, GB 14, 4, TH 17, St 1. In cases of optic nerve atrophy, the authors also needled points T 15 and BL 60. By indirect electroacupuncture (by Chinese apparatus WQ 10), points BL 2 and St 1 were also stimulated. In all the patients, a subjective improvement of visual acuity was observed. In children with myopia, relative accommodation was enlarged. In patients with retinitis pigmentosa, an enlargement of the borders of the visual field, investigated by perimetry and isopter perimetry was observed, as well as light difference sensitivity established by static perimetry. Electrooculograms showed a reduction of the basic values and of Arden's ratio. 3 of the patients with glaucoma had a decrease in pressure of the eye, measured by Maklakow's tonometer.


Progressive conduction defects and cardiac death in late infantile neuronal ceroid lipofuscinosis.
This article reports the case of a female with late infantile neuronal ceroid lipofuscinosis who developed right and left anterior bundle branch blocks and episodic bradycardia at 23 years of age. Several episodes of supraventricular tachycardia manifested at 23 and 27 years of age. In addition, a transient second-degree atrioventricular conduction block also emerged at 27 years of age. Atrial fibrillation and aggravation of the atrioventricular conduction block resulted in progressive bradycardia and cardiac death at the age of 28 years. Cardiac involvement and accumulation of lipopigments in the myocardium and cardiac conduction system have been recognized in juvenile neuronal ceroid lipofuscinosis, but this is the first report to describe progressive conduction defects in a case of late infantile neuronal ceroid lipofuscinosis.


100th anniversary of the Fourth International Congress of Thalassotherapy in Opatija.
The authors of the text have been particularly interested into the organization, the procedure,the accompanying activities as well as the themes covered at 4th International Congress of Thalassotherapy in Opatija in 1908. The Congress was organised by the then head of the thermal spa resort Professor Dr.Julius Glax. The official languages at the Congress were German, French, English, and also Italian and Croatian as the languages of the hosting country. Each lecturer had twenty minutes time to give a lecture or a co-lecture, ten minutes for papers and five for a follow-up discussion. The participants could make use of the information centre of the Congress, in the centre of Opatija, the whole day. Unofficially, the Congress started on 27th September 1908 with the introductory evening for all the participants in Adria Club. The Congress officially began on 28th September 1908 when all the participants gathered at the theatre hall of Hotel Stephanie. The lectures were presented in the morning. In the afternoon, the participants were taken to visit some exhibitions (e.g. the medical exhibition at Hotel Palace, the exhibition of the native Istrian-Dalmatian home crafts and antiquates and the painting exhibition at Vila Angiolina), a short sea voyage through the bay of Kvarner. On the last day of the Congress, the participants observed the sanitary conditions in Opatija (the water supply, the sewer system, litter incinerator, and quarantine for infectious illnesses), three sanatoriums, Zander's Institute, the rehabilitating-heart paths and the Archduke Ludwig-Viktor's indoor baths. The round-Opatija tour was followed by the concluding meeting and the conclusion of the Congress. The authors of this research have established that there are no important differences in the organization and realization of the congresses in the past and now.


Regulation of RNA Synthesis by DNA-Dependent RNA Polymerases and RNases during Cold Acclimation in Winter and Spring Wheat.
Chromatin DNA-dependent RNA polymerases and RNases activities were measured in winter and spring varieties to understand the overall regulation of RNA synthesis during cold acclimation. We found that total RNA polymerase activities were significantly higher in chromatin isolated from winter wheat compared to the spring wheat during the acclimation period. This increase was parallel to the increase in protein and RNA contents during hardening. The ratio of RNA polymerase I to RNA polymerase II activity was higher than 2 in winter wheat after 30 days of hardening compared, to a ratio of 0.90 under the nonhardening conditions. The increase in activity and the ratio of polymerase I to polymerase II was maintained after the separation of the enzymes from the template, suggesting that RNA synthesis is regulated in part at the enzyme level. On the other hand, the chromatin associated RNase activity decreased in both varieties during acclimation, indicating a nonspecific inhibition caused by low temperature rather than a selective genetic response associated with cold acclimation.


Biochemical characterization of the exopolysaccharide purified from Laetiporus sulphureus mycelia.
The extracellular polysaccharide (EPS) was isolated from mycelial cultures of Laetiporus sulphureus var. miniatus and purified by DEAE cellulose and Sephadex G-50 column chromatography. The purified EPS (EPS-2-1) was composed of only glucose units and its molecular mass was 6.95 kDa. The chemical structure of EPS-2-1 consisted of a main chain containing (1-->4)-Glcp units with branches at the C-6 position of the chain carrying -Glcp-(1-->4)-linked residues. The effect of purified EPS on immunomodulatory genes and proteins of the Bcl-2 family was observed using cultured U937 human leukemia cells. Of note, the levels of Bax and Bad proteins treated with the EPS (4 mg/ml) were approximately 23- and 18-times higher than those in non-treated cells, respectively. These results may suggest that the EPS purified from the mushroom L. sulphureus is associated with the activation of immunomodulatory mediators, Bax and Bad proteins.


Study of stability and biophysical characterization of ranibizumab and aflibercept.
The anti-vascular endothelial growth factor (VEGF) agents such as ranibizumab (Lucentis®) and aflibercept (EyLea®) are currently used as monthly or bimonthly intravitreal injections to treat potentially retinal diseases such as wet age-related macular degeneration (AMD) or diabetic macular edema (DME). Because of the complications associated with repeated intra-vitreal injections, there is considerable interest in developing a sustained delivery system. The purpose of this study was to examine the stability of both therapeutic proteins under physiological conditions as well as when incorporated into drug delivery systems (DDS). First, thermotropic properties in physiological conditions and at different pH values were evaluated by differential scanning calorimetry (DSC) to determine the protein denaturation temperature. Second, the effects of pH and incubation time on conformational changes and aggregation were evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, and size-exclusion chromatography (SEC). Also, the ability of both proteins to bind to VEGF was tested in the aforementioned experimental conditions for up to 30 days. Finally, we investigated the stability of both proteins after a rapid screening method that simulates the first homogenizing step during the protein microencapsulation process. This method allowed the development of stable ranibizumab and aflibercept formulations that may be useful to entrap these proteins into microparticles selecting the most convenient organic solvent and protein stabilizers.


The Role of Maximal Locoregional Block in Autologous Breast Reconstruction.
Enhanced Recovery After Surgery (ERAS) has become the standard of care in microsurgical breast reconstruction. The current literature provides overwhelming evidence of the benefit of ERAS pathways in improving quality of recovery, decreasing length of hospital stay, and minimizing the amount of postoperative narcotic use in these patients. However, there are limited data on the role of using maximal locoregional anesthetic blocks targeting both the abdomen and chest as an integral part of an ERAS protocol in abdominally based autologous breast reconstruction. The aim of this study is to compare the outcomes of implementing a comprehensive ERAS protocol with and without maximal locoregional nerve blocks to determine any added benefit of these blocks to the standard ERAS pathway. Forty consecutive patients who underwent abdominally based autologous breast reconstruction in the period between July 2017 and February 2020 were included in this retrospective institutional review board-approved study. The goal was to compare patients who received combined abdominal and thoracic wall locoregional blocks as part of their ERAS pathway (study group) with those who had only transversus abdominis plane blocks. The primary end points were total hospital length of stay, overall opioids consumption, and overall postoperative complications. The use of supplemental thoracic wall block resulted in a shorter hospital length of stay in the study group of 3.2 days compared with 4.2 days for the control group (P < 0.01). Postoperative total morphine equivalent consumption was lower at 38 mg in the study group compared with 51 mg in the control group (P < 0.01). Complications occurred in 6 cases (15%) in the control group versus one minor complication in the thoracic block group. There was no difference between the 2 groups in demographics, comorbidities, and type of reconstruction. The maximal locoregional nerve block including a complete chest wall block confers added benefits to the standard ERAS protocol in microvascular breast reconstruction.


Toleration of amino acid substitutions within hepatitis B virus envelope protein epitopes established by peptide replacement set analysis. I. Region S(139-147).
B and T cell epitopes expressed on the surface of S-protein, a major constituent of the envelope of hepatitis B virus (HBV), are essential for eliciting protective immunity against HBV infection. A segment of the S-protein sequence encompassing residues S(139-147) is a portion of overlapping B and T cell epitopes. This sequence is conserved among distinct serological subtypes of HBV and has a 77.8% homology with an analogous sequence in S-proteins of nonhuman mammalian hepadnaviruses. Rare subtypes and variants of HBV having amino acid replacements within the S(139-147) sequence were discerned recently. The impact of amino acid replacements within this sequence on its immunological recognition at both the B and T cell levels was explored by peptide replacement set analysis. Results of the analysis permit discrimination between tolerated and forbidden amino acid replacements and provide a background for the development of reagents and immunogens specific for emerging HBV variants.


Propagation model for vector beams generated by metasurfaces.
A propagation model of vector beams generated by metasurfaces based on vector diffraction theory is established theoretically and verified experimentally. Considering the Pancharatnam-Berry phase introduced by the metasurface, analytical forms of vector beams for arbitrary incident polarization and topological charge of metasurfaces are found in the Fresnel and Fraunhofer diffraction regions, respectively. The complex amplitude of the resultant vector beam can be described in terms of a confluent hypergeometric function, with an intensity profile that manifests concentric rings in the Fresnel region and a single ring in the Fraunhofer one. Fraunhofer diffraction provides a method to create vector beams with simultaneously high purity and modal power. Further experiments verify the theoretical results.


[Hepatorenal syndrome].
Hepatorenal syndrome (HRS) is a particular form of functional renal failure which may develop in patients with liver cirrhosis. Recent advances in the understanding of the biology of vasoactive mediators and the physiology of microcirculation have allowed to better anticipate its pathophysiological mechanisms. To review new advances in the knowledge of epidemiology, diagnosis criteria, pathophysiological mechanisms and treatment of HRS. Review of literature using medical data bases (Medline) with the following key words: hepatorenal syndrome, pathophysiology, medical treatment, MARS, liver transplantation. During the course of cirrhosis, portal hypertension leads to splanchnic and systemic vasodilation, responsible for a reduction of effective arteriel blood volume. As a result, a state of intense renal vasoconstriction develops, leading to renal failure in the absence of any organic renal disease. At this stage, liver transplantation is the only definitive therapy able to reverse renal dysfunction. Pharmacologic and radiologic therapy is aimed at improving renal function to enable patients to survive until transplantation is possible. These therapies are based on vasoconstrictor drugs associated with intravenous albumin infusion and transjugular intrahepatic portosystemic shunt (TIPS). They improve circulatory function, normalize serum creatinine and may improve survival. Simple measures have been shown to reduce the risk of HRS in cirrhotic patients including the plasma volume expansion with albumin in patients with spontaneous bacterial peritonitis and optimal fluid management in patients undergoing large volume paracentesis.


Knowledge of, and attitudes towards, adult vaccination among General Practitioners in Piedmont, Italy: results from a cross-sectional study.
"Life-course immunization" is increasingly recognized as important. In Italy, adults are recommended to receive influenza; pneumococcal; tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap); and herpes zoster (HZ) vaccines at various ages. Cross-sectional study. To study the knowledge and attitudes of Italian general practitioners (GPs) towards adult vaccination, we surveyed 335 GPs in Piedmont from December 2019 through March 2020; and compared the results by GPs' age (≤50 vs >50 years). The most common vaccination information source was the regional/local educational courses (72.8%), with older vs younger GPs more likely to attend (79.4% vs 64.4%; p=0.002). Approximately half felt that they needed further information on vaccine co-administration (55.5%), duration of protection (49.6%), and safety/tolerability (48.7%), with older vs younger GPs being more interested in safety/tolerability. Overall, most respondents (86.0%) felt that information for the patient would most engage them, and 68.1% planned to co-administer vaccines. Respondents felt most comfortable proposing influenza, but were also comfortable about pneumococcal/Tdap/HZ vaccination. However, younger vs older GPs were more comfortable about proposing Tdap and HZ. The most common ways to inform patients about influenza or pneumococcal/Tdap/HZ vaccination eligibility were personally during a visit (42.7% or 54.3%, respectively) or via an information poster (30.7% or 17.9%). The surveyed GPs had favorable attitudes towards adult vaccination and were interested in ongoing education.


Age-related patterns in mental health-related complementary and alternative medicine utilization in Canada.
The aim of this study was to examine whether age-related differences in rates of use of complementary and alternative medicine (CAM) specifically for mental health problems parallel well-known age-related differences in use of conventional mental health services and medications. A sample of middle-aged (45-64 years; n = 10,762), younger-old (65-74; n = 4,113) and older-old adults (75 years and older; n = 3,623) was drawn from the 2001-2002 Canadian Community Health Survey (CCHS), Cycle 1.2, Mental Health and Wellbeing. Age-related utilization rates of conventional and complementary mental health services and medications/products were calculated. Logistic regression analyses were used to examine the strength of association between age group and utilization of services and medications or products in the context of other important sociodemographic and clinical characteristics. When considered in the context of other sociodemographic and clinical characteristics, older age was positively associated with mental health-related utilization of alternative health products. Older age was not significantly associated with mental health-related consultations with CAM providers. Overall, age-related patterns in mental health-related use of CAM did not directly correspond to age-related patterns in conventional mental health care utilization, suggesting different sets of predictors involved in seeking each type of care.


Real-world outcomes of patients with advanced intrahepatic cholangiocarcinoma treated with programmed cell death protein-1-targeted immunotherapy.
There is a lack of effective treatment to improve the prognosis of intrahepatic cholangiocarcinoma (ICC). Programmed cell death protein-1 (PD-1)-targeted immunotherapy has shown promising results in a variety of malignant tumours. However, in patients with advanced ICC, the safety and efficacy of anti-PD-1 agents remain unclear. Forty-two advanced ICC patients treated with anti-PD-1 agents from August 2018 to December 2020 were retrospectively analyzed. Tumour response, overall survival (OS), progression-free survival (PFS), and time to tumour progression (TTP) were evaluated. Adverse events were also recorded. The median duration of follow-up was 12.1 months, and the median time of treatment was 6.7 months for all patients. The median OS, median PFS, and median TTP for the whole cohort were 19.3 months, 11.6 months, and 11.6 months, respectively. The overall response rate (ORR) and disease control rate (DCR) for the whole cohort were 23.8% and 85.7%, respectively. Of the 42 evaluable individuals, two (4.8%) had hyperprogressive disease. The most common adverse events (AEs) were pain (n = 6; 14.3%), anorexia (n = 4; 9.5%), hypertension (n = 4; 9.5%), pyrexia (n = 3; 7.1%), cough (n = 3; 7.1%), and hypothyroidism (n = 3; 7.1%). The median OS of patients with albumin-bilirubin (ALBI) grade 1 was longer than that of patients with ALBI grade 2 (19.3 months vs. 14.7 months). The median PFS did not show a significant difference between ALBI grade 1 and grade 2 patients (13.6 months vs. 6.9 months). PD-1-targeted immunotherapy showed promising efficacy and safety in advanced ICC patients.Key messagesPD-1-targeted immunotherapy is a safe and effective treatment for advanced ICC patients.This study provides therapeutic strategy for advanced ICC patients.


Epidemiology of Serratia marcescens infections in NICU of a Teaching and Research Hospital in Northern Italy.
Serratia marcescens (Sm) is a known cause of infection and colonization in neonates receiving intensive care. The aim of this study was to identify the risk factors for colonization and infection with Sm in Neonatal Intensive Care Unit (NICU) of a tertiary care Hospital. A case-control study was conducted from January to December 2011 in neonates admitted to the NICU. Cases are patients with a microbiologically confirmed infection or colonization, controls were randomly chosen among patients admitted to the same NICU. Globally, 39 acquired infections or colonizations were identified. Among factors related to pregnancy, only premature delivery was independently associated to the risk of infection; as well as mechanical ventilation and catheterization for parenteral nutrition, considering indwelling devices. Prolonged administration with antibiotics were also related to the risk of infection. Among Sm strains which have been tested to antibiotics, all have been resistant to amoxicillin/clavulanic acid and to colistin. This study confirms the association between Sm infection or colonization and low gestational age. Invasive medical devices and medications, strictly necessary in care-support of preterm neonates, are likely related to Sm infection too. Preventive control strategies are expected to be effective in the control of Sm spread in NICUs.


A study of 6-year retention in methadone maintenance treatment among opioid-dependent patients in Xi'an.
We analyzed a 6-year methadone maintenance treatment (MMT) retention rate in 8 MMT clinics in Xi'an and the factors that influenced the retention rate. We conducted a 6-year retrospective dynamic cohort study of 5849 eligible patients from 2006 to 2011. Participants were serially enrolled on the basis of opioid addiction, age, residence status, and civil capacity. Cumulative retention in treatment was calculated using survival analyses (life tables) on the basis of the number of days in MMT. We also used the Cox proportional hazard regression model to analyze the factors that may influence treatment retention. The MMT retention varied from a less than 1 month to a maximum of 71.2 months; the average dose was 48.76 ± 17.03 mg/d. The cumulative retention for 12, 24, 36, 48, 60, and 72 months after MMT initiation were 0.87, 0.76, 0.66, 0.57, 0.49, and 0.43, respectively. The MMT retention rate was significantly associated with factors that included the particular clinic for MMT, the year when the subject initiated MMT, average daily dose, hidden drug use, sex, age, length of drug abuse history, needle sharing, living arrangements, and employment status. The 6-year retention rates for MMT in the 8 clinics in Xi'an were higher than those reported in other studies of other clinics. High therapeutic doses (>60 mg/d) could reduce the risk of patients withdrawing from treatment. Retention rates were relatively high in cohorts who were elderly, living with family, employed, or drug users, especially those with a long history of drug abuse.


A novel 3D technique to assess symmetry of hemi pelvises.
Anatomical reconstruction of pelvic fractures has been shown to affect functional outcome. Using the contra lateral side of the extremities to create a template for an ipsilateral reconstruction is common practice in orthopedic surgery. We aimed to assess whether hemi pelvises are symmetrical in terms of translation and rotation using 3D reconstruction, point to point mirroring and merging of the 3D created volumes, a method with previous proven high precision and accuracy. CT images of ten randomly selected patients were used. The DICOM images were converted to STL files. Three dimensional images of left hemi pelvis were reversed and merged with the right side. The posterior aspect of the pelvises was considered static and the anterior aspect as moving. Differences in translation and rotation were measured. There were no statistically significant differences between right and left hemi pelvis. The 95% confidence interval (CI) for all mean angular differences between right hemi pelvis and mirrored left hemi pelvis were - 2° to 1.5°. The 95% CI for all mean translational differences between these two objects were - 2.3 to 2.9 mm. Differences between the right hemi pelvis and the mirrored images of the left hemi pelvis for any patient greater than 3 mm or 2 degrees could be excluded with a 95% confidence. The left and right hemi pelvis of healthy adults are symmetrical enough. The pre-operative planning based on a healthy contra lateral side seems reasonable.


Effect of supplementation of calcium and vitamin D on bone mineral density and bone mineral content in peri- and post-menopause women; a double-blind, randomized, controlled trial.
Osteoporosis is a serious global health problem for the future, that is why improving diagnostic methods and prevention of this disease could be helpful. To assess the effects of calcium supplementations combined with Vitamin D on bone mineral density (BMD) and bone mineral content (BMC) in a representative sample of peri- and post-menopausal women in a double-blind, a randomized, controlled trial was untaken. A total of 120 women aged over 45 were included in a randomised placebo-controlled, double-blind trial on the effect of a daily dietary supplementation of calcium and Vitamin D on bone mineral density and bone mineral content; over a 30-month period. Dietary intake assessment; dual-energy X-ray absorptiometry to measure total body and segmental bone mineral density and bone mineral content at beginning of the study and every 15 months were undertaken. There was no significant change in dietary calcium or Vitamin D intakes in either of the treatment groups during the 30-month intervention period. The change in total BMD in the calcium group was significantly different from that in the placebo group (P <0.005). The placebo group lost a total BMD at a rate of about 0.4% per year. There was an inverse correlation between BMD and age. The effect of calcium and Vitamin D supplementation on bone mineral density of calcium has been demonstrated in this group of young adult women. Our results showed the positive effect of calcium and Vitamin D supplementation in women both peri- and post-menopausal status; for this reason a supplementation of calcium and Vitamin D should be recommended as a strategic option in helping to prevent early postmenopausal bone loss.


Solitary fibrous tumor of the pineal region in the elderly: A case report.
Solitary fibrous tumor (SFT) is a mesenchymal tumor with spindle cells that is often detected in the subcutaneous area and rarely in the central nervous system. Intracranial SFTs rarely occur in individuals older than 80 years, and there are only a few cases reports involving the pineal region. The present case was an 80-year-old man with lightheadedness, headache, and vomiting. Magnetic resonance imaging showed a tumor in the pineal region extending along the falx and tentorium cerebelli with homogenous enhancement. Subtotal resection was performed via the occipital transtentorial approach. A histopathological examination showed the proliferation of oval- to spindle-shaped tumor cells with bland nuclei arranged in a haphazard pattern and accompanied by staghorn-like branching vessels. Immunohistochemically, tumor cells were positive for CD34 (focal), CD99, and STAT6, but negative for epithelial membrane antigen (EMA) and S-100. Based on these findings, the tumor was diagnosed as SFT (WHO grade I). Although difficulties are associated with differentiating SFT from meningioma on imaging, recurrence and metastasis are more common with SFT than with meningioma; therefore, histological and immunohistochemical analyses are important. A correlation has been reported between postoperative adjuvant radiotherapy and longer progression-free survival; however, this needs to be confirmed in further studies. SFT involving the pineal region is rare in the elderly, but needs to be considered as a preoperative diagnosis. Since high rates of postoperative recurrence and metastasis have been reported, long-term follow-ups are required after surgery.


Asymmetric anatase TiO₂ nanocrystals with exposed high-index facets and their excellent lithium storage properties.
In this work, we demonstrate a unique organic solvent system to synthesize asymmetric anatase TiO(2) nanocrystals with a bipyramidal structure, where the upper pyramid is bound by (201) facets, and the lower pyramid is bound by (401) surfaces. Due to the high surface energy of these (401) high-index facets, the nanocrystals tend to assemble on these facets to minimize the free energy, leading to the formation of a dandelion-like hierarchical structure.


[Laser surface modification of medical titanium].
Titanium, by far one of the oldest materials in medical implants used for hard tissue replacement and rehabilitation, was used widely as implant material. The objective of the present study was to fabricate the TiN modified layer on the surface of medical pure titanium and improve its surface properties. Thus the wear resistance, biocompatibility and antisepsis were improved. A continuous-wave 2 kW Nd: YAG laser was used to irradiate the sample in the environment of N2 with concentration of 99.995%. Titanium nitride surface coatings had been extensively used as corrosion resistant and biocompatible layers on titanium and its alloys. The microstructure and composition of the laser nitrided coating were studied by scanning electron microscopy and X-ray diffraction. Microhardness of the modified sample was also analyzed by micro-hardmeter. TiN modified layer with the thickness of about 400 microm was obtained. TiN distributed gradually from surface to the substrate. There was a good metallurgical bonding between the nitrided layer and the substrate. The hardness of the modified layer was reduced from the surface to the inside. With optimum process parameters, a compact laser modified gradient coating reinforced with fine TiN was achieved on the surface of medical titanium.


A review of radio frequency identification technology for the anatomic pathology or biorepository laboratory: Much promise, some progress, and more work needed.
Patient safety initiatives throughout the anatomic laboratory and in biorepository laboratories have mandated increasing emphasis on the need for accurately identifying and tracking biospecimen assets throughout their production lifecycle and for archiving/retrieval purposes. However, increasing production volume along with complex workflow characteristics, reliance on manual production processes, and required asset movement to disparate destinations throughout asset lifecycles continue to challenge laboratory efforts. Radio Frequency Identification (RFID) technology, use of radio waves to communicate data between electronic tags attached to objects and a reader, shows significant potential to facilitate and overcome these hurdles. Advantages over traditional barcode labeling include readability without direct line-of-sight alignment to the reader, ability to read multiple tags simultaneously, higher data storage capacity, faster data transmission rate, and capacity to perform multiple read-writes of data to the tag. Most importantly, use of radio waves decreases the need to manually scan each asset, and at each step, identification or tracking event is needed. Temperature monitoring by on-board sensors and three-dimensional position tracking are additional potential benefits of using RFID technology. To date, barriers to implementation of RFID systems in the anatomic laboratory include increased associated costs of tags and readers, system software, data security concerns, lack of specific data standards for stored information, and potential for technological obsolescence during decades of specimen storage. Novel RFID production techniques and increased production capacity are projected to lower costs of some tags to a few cents each. Potentially, information security concerns can be addressed by techniques such as shielding, data encryption, and tag pseudonyms. Commitment by stakeholder groups to develop RFID tag data standards for anatomic pathology and biorepository laboratories could avoid or mitigate the "islands of data" dilemma presented by barcode usage where there are innumerable standards and a consequent paucity of hardware or software "plug and play" interoperability. Work remains to be done to establish the durability and appropriate shielding of individual tag types for use in harsh laboratory environmental conditions, and for long-term archival storage. Finally, given the requirements for long-term storage of biospecimen assets, consideration should be given to ways of mitigating data isolation due to eventual technological obsolescence of a particular RFID technology or software.


An evaluation of the "cloud" LINEAR KGT-3/4 buffer-whole tonometer.
During an 18-month period, we evaluated the LINEAR KGT 3/4 'cloud' tonometer and found the reproducibility of results in replicate assays to be excellent, with a narrow range of standard deviations. Equilibrium efficiency high, and temperature stability and pH re-equilibration were excellent. Whole-blood tonometry involved minimum exposure to the technologist and could be satisfactorily accomplished from a single blood pool for at least 22 hours. Consumption of calibration gases was low (less than 4 ml/min per level), operator time minimal, and cost per assay for aqueous-buffer samples estimated to be about $0.08.


A new VEP system for studying binocular single vision in human infants.
Visual evoked potentials (VEPs), that provide unequivocal objective evidence of cortical binocularity have been recorded from adults and young infants using a new VEP system developed for this purpose. The system uses alternating field stereoscopy (AFS) to present separate visual stimuli to each eye. With this system, the binocular image pairs to the right and left eyes alternate at a high rate on a single video monitor. The subject wears spectacles incorporating light-scattering liquid crystal lenses which alternate electronically between opaque and clear modes in synchrony with the video monitor. To detect cortical binocularity, the system analyzes VEP activity mathematically and identifies significant responses at test frequencies reflecting binocular cortical interactions exclusively. Three types of binocular stimuli were presented: (1) dynamic random dot correlograms (correlograms); (2) dynamic random dot stereograms (stereograms); and (3) dichoptic checkerboard stimuli. The correlograms are generated when moving random dot patterns presented to each eye alternate between two phases, correlated and anticorrelated. With the stereograms, portions of random dot patterns presented to each eye are shifted horizontally relative to each other at a fixed rate, alternately producing crossed and uncrossed binocular disparities. Subjectively, these patterns appear to shift in depth. Dichoptic checkerboard stimuli are regular checkerboard patterns which reverse at different rates (frequencies) for each eye. Binocular VEPs are generated due to cortical interactions at the difference (beat) frequency. Using this VEP system, we have recorded binocular VEPs from 10 normal adults and more than 40 infant subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


The future of esthetic dentistry.
The materials and techniques of esthetic dentistry are provoking reconsideration of the basic principles of operative dentistry. Cavity preparations can be minimized, demands on retention are altered, and prevention can be practiced. Problems remain, particularly in bonding and sealing to dentin. The newer materials have yet to prove themselves in terms of durability, especially in regard to fracture and wear.


[Psychiatric disorders of the contemporary battlefield].
This article presents the factors exerted an influence on psychiatric health status of participants of military missions and psychiatric disorders forming on the contemporary battlefield. The main stressors are threats being a result of duty in warfare, also hard climatic conditions, long-lasting separation from family, foreign language of local population, other customs, religion, caused alienation of mission personnel. Significant factors seem also dependences on duty and unofficial relationships prevailing in military environment. The consequence of survived psychiatric trauma being a result of short-lived incident or prolonged event are often acute stress disorder (ASD) or posttraumatic stress disorder (PTSD).


Rapid trafficking of membrane type 1-matrix metalloproteinase to the cell surface regulates progelatinase a activation.
Pericellular matrix degradation during cancer invasion and inflammation is dependent on activation of progelatinase A by membrane type 1-matrix metalloproteinase (MT1-MMP); a stoichiometric concentration of tissue inhibitor of metalloproteinase-2 (TIMP-2) is required. Activation of progelatinase A has generally been considered to be a slow process occurring as a result of enhanced expression of MT1-MMP. We herein report that ConA treatment of HT1080 fibrosarcoma cells is followed by MT1-MMP-induced activation of progelatinase A on the cell surface within 1 hour. Cell surface biotinylation, immunohistochemistry, and (125)I-labeled TIMP-2 binding to cell surface MT1-MMP were used to characterize the appearance and function of MT1-MMP on the plasma membrane. Treatment of HT1080 cells with ConA resulted in increased specific binding of (125)I-labeled TIMP-2 to cell surface receptors within 5 minutes. TIMP-2 binds almost exclusively to activated MT1-MMP on the surface of HT1080 cells. MT1-MMP function at the cell surface was also accelerated by treatment of cells with cytochalasin D, an inhibitor of actin filaments, PMA, a stimulator of protein kinase C, and bafilomycin A(1), an inhibitor of lysosome/endosome function. A functional pool of intracellular MT1-MMP available for trafficking to the cell surface was demonstrated by repetitive ConA stimulation. ConA-induced expression of MT1-MMP mRNA (Northern blot analysis) in HT1080 cells was a delayed event (>6 hours). These data suggest that presynthesized MT1-MMP is sorted to a transient storage compartment (trans-Golgi network/endosomes), where it is available for rapid trafficking to the plasma membrane and cell surface proteolytic activity.


Chlamydial antibody crossreactivity with peripheral blood mononuclear cells of patients with ankylosing spondylitis: the role of HLA B27.
We have previously reported the association of Chlamydia trachomatis with HLA B27+ related diseases. To investigate the possibility that chlamydial antibodies serve to localize the immune response in such diseases, we examined the crossreactivity of chlamydial antibodies (rabbit anti-D and anti-L2 serotypes) with peripheral blood mononuclear cells of patients with ankylosing spondylitis (AS) and anterior uveitis (AU) and with human and bovine ocular tissue and cells in culture. Our results indicate a significantly increased percentage binding of chlamydial antibody (D serotype) to the mononuclear cells of HLA B27+ patients with AS when compared with HLA B27- patients with AS (12.9% +/- 2.2 versus 5.4% +/- 2.2), B27+ controls (5.5% +/- 1.5) and B27- controls (6.1% +/- 1.0). There was no significant difference between controls and HLA B27+ patients with AU (6.6% +/- 1.9) and B27- patients with AU (8.7% +/- 1.1). This crossreactivity could not be blocked by monoclonal HLA B27 antibody. Chlamydial antibodies (D and L2) crossreact with human and bovine conjunctiva but not uvea, tissue culture derived iris fibroblasts or smooth muscle cells. Our results provide additional support for the concept of crossreactivity between antibodies to microbial agents and peripheral blood mononuclear cells of patients with HLA B27+ AS.


Disseminated lomentosporiosis in a heart transplant recipient: Case report and review of the literature.
Lomentospora prolificans (formerly S prolificans) is a saprophyte fungi that causes opportunistic infections in solid organ transplant (SOT) recipients. Resulting disseminated infections are difficult to treat and have a high mortality. Indications for antifungal prophylaxis after heart transplantation (HT) include CMV disease, reoperation, renal replacement therapy, extracorporeal membrane oxygenation (ECMO), and high environmental exposure to Aspergillus spores. However, the risk of breakthrough infections, such as Lomentosporiosis, remains a cause of concern. We report the clinical findings, microbiology, treatment and outcome of a disseminated Lomentosporiosis in a heart transplant recipient with ECMO and antifungal prophylaxis. A 25-year-old male with complex grown-up congenital heart disease (GUCHD) was admitted for HT. He presented severe post-surgical complications including acute kidney injury and right heart and respiratory failure requiring venoarterial-ECMO, continuous renal replacement therapy (CCRT) and later on (+14) a ventricular assist device (VAD). Ganciclovir, cotrimoxazole, and antifungal prophylaxis with anidulafungin at standard doses had been started on day + 3 post HT. The patient presented seizures (+4), pancytopenia with mild neutropenia (days + 6 to + 11), influenza B (+7), and bacteremic Pseudomonas aeruginosa ventilator associated pneumonia (VAP) (+10). On days + 14 to + 16 Lomentospora prolificans was recovered from blood cultures, broncho aspirate, catheter tip, and skin biopsy. Despite treatment with L-AMB, voriconazole and terbinafine the patients died on day 17 after HT. Necropsy revealed disseminated infection with fungal invasion in central nervous system, heart, lung, cutaneous, and subcutaneous tissue. Broth microdilution tests demonstrated resistance to all antifungals. Lomentosporiosis is a rare complication that may emerge as a breakthrough invasive fungal infection in heart transplant recipients on ECMO despite antifungal prophylaxis.


LRPAP1 autoantibodies in mantle cell lymphoma are associated with superior outcome.
Low-density lipoprotein (LDL) receptor-related protein-associated protein 1 (LRPAP1) had been identified by B-cell receptor (BCR) expression cloning and subsequent protein array screening as a frequent and proliferation-inducing autoantigen of mantle cell lymphoma (MCL). Of interest, high-titered and light chain-restricted LRPAP1 autoantibodies were detected in 8 of 28 patients with MCL. In the present study, LRPAP1 autoantibodies in sera of patients treated within the Younger and Elderly trials of the European MCL Network were analyzed regarding frequency, association with disease characteristics, and prognostic impact. LRPAP1 autoantibodies were detected in 41 (13%) of 312 evaluable patients with MCL. These LRPAP1 autoantibodies belonged predominantly to the immunoglobulin G (IgG) class and were clonally light chain restricted (27 with κ light chains, 14 patients with λ light chains). Titers ranged between 1:400 and 1:3200. The presence of LRPAP1 autoantibodies was not significantly associated with any baseline clinical characteristic, however, it was associated with a superior 5-year probability for failure-free survival (FFS) of 70% (95% confidence interval [CI], 57% to 87%) vs 51% (95% CI, 44% to 58%), P = .0052; and for overall survival (OS) of 93% (95% CI, 85% to 100%) vs 68% (95% CI, 62% to 74%), P = .0142. LRPAP1-seropositive patients had a Mantle Cell Lymphoma International Prognostic Index-adjusted hazard ratio for FFS of 0.48 (95% CI 0.27-0.83, P = .0083) and for OS of 0.47 (95% CI 0.24-0.94, P = .032). LRPAP1 autoantibodies were frequently detected in a large cohort of MCL patients treated within prospective multicenter clinical trials. Our results suggest better outcomes for LRPAP1-autoantibody seropositive patients.


[Diabetes mellitus: renal osmoregulating function].
To evaluate the kidney status from osmotic urine concentration in different stages of diabetes mellitus (DM) to define whether not only glomeruli and proximal tubules, but also renal medullary substance structures are involved into the pathological process, as well as their reaction to endogenous vasopressin production. Forty patients with a 1-to-28-year history of DM, including 18 with diabetic nephropathy, 10 with chronic renal failure, and 22 without diabetic nephropathy, were examined. Urine and blood osmolality were determined and renal osmoregulating function was estimated. Decreased glomerular filtration rate was found in relation to the duration of DM. The osmolality of nocturnal urine samples tended to diminish during short-term deprivation depending on the duration of DM. Increased diuresis in DM was shown to correlate with the higher reabsorption of osmotically free water. Diminished renal concentrating capacity in DM appears to depend on evolving renal failure rather than vasopressin resistance. The application of a new approach, by calculating the clearance of sodium-free water, suggests that its increased reabsorption favors normalization of serum osmolality in hyperglycemia.


The effects of age and spontaneous adenoma formation on trophic activity in the rat pituitary gland: a comparison with trophic activity in the human pituitary and in human pituitary adenomas.
The effects of ageing on trophic activity in the pituitary gland and the molecular events that underlie pituitary tumour formation are poorly understood. In the present study we have used an extremely accurate system to analyse trophic activity in human pituitary tumours and compared our findings with trophic activity in spontaneous rat pituitary adenomas and with changes in basal rates of turnover as the animals age. Thin, hematoxylin and eosin-stained pituitary sections from groups of male Wistar rats aged 6 weeks to 16 months, killed at 90-min intervals after receiving a single intraperitoneal bolus of colchicine to block cellular passage through mitosis, were evaluated histologically. Extremely accurate quantification of small changes in the prevalence of trophic events, and thus the rate of cell turnover, was achieved using a dedicated computerized aid to manual cell counting. Results were compared with the prevalence of mitotic activity in 24 spontaneous rat pituitary adenomas and with a series of 97 archival human pituitary adenomas and 24 normal human pituitary glands obtained at autopsy. In rats, average basal pituitary cell turnover declined by over 95% between 6 weeks and 16 months of age. Concurrent with this decline was a marked increase in the prevalence of adenoma formation. The prevalence of mitotic activity in spontaneous rat pituitary adenomas averaged almost twice that seen in normal, young rat pituitary and exceeded 16 times that seen in the pituitary of aged animals. In contrast, when compared to normal human pituitary tissue, average trophic activity in human pituitary adenomas remained extremely low.


Investigation on flavonoid composition and anti free radical potential of Sida cordata.
Sida cordata, a member of Family Malvaceae is used in folk medicine for various ailments including liver diseases. In this study we investigated, its flavonoid constituents, in vitro antioxidant potential against different free radicals and hepatoprotection against carbon tetrachloride (CCl4)-induced liver damage in rat. Dried powder of S. cordata whole plant was extracted with methanol and the resultant (SCME) obtained was fractionated with escalating polarity to obtain n-hexane fraction (SCHE), ethyl acetate fraction (SCEE), n-butanol fraction (SCBE) and the remaining soluble portion as aqueous fraction (SCAE). Diverse in vitro antioxidants assays such as DPPH, H2O2, •OH, ABTS, β-carotene bleaching assay, superoxide radical, lipid peroxidation, reducing power, and total antioxidant capacity were studied to assess scavenging potential of methanol extract and its derived fractions. On account of marked scavenging activity SCEE was selected to investigate the hepatoprotective potential against CCl4 induced toxicity in Sprague-Dawley male rats by assessing the level of serum markers (alkaline phosphatase, alanine transaminase, aspartate transaminase, lactate dehydrogenase, bilirubin, and γ-glutamyltransferase) and of liver antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione-S-transfers (GST), glutathione reductase (GSR), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH) and lipid peroxidation (TBARS). Histology of the liver was performed to study alteration in histoarchitecture. Existence of active flavonoids was established by thin layer chromatographic studies. Considerable amount of flavonoid and phenolic contents were recorded in the methanol extract and its derived fractions. Although the extract and all its derived fractions exhibited good antioxidant activities however, the most distinguished scavenging potential was observed for SCEE. Treatment of SCEE decreased the elevated level of serum marker enzymes induced with CCl4 administration whereas increased the activity of hepatic antioxidant enzymes (CAT, SOD, POD, GST, GSR and GSH-Px). Hepatic concentration of GSH was increased while lipid peroxidation was decreased with SCEE administration in CCl4 intoxicated rats. Presence of apigenin with some unknown compounds was observed in SCEE by using thin layer chromatography. These results revealed the presence of some bioactive compound in the ethyl acetate fraction, confirming the utility of S. cordata against liver diseases in folk medicine.


Biomolecular Interaction Assays Identified Dual Inhibitors of Glutaminase and Glutamate Dehydrogenase That Disrupt Mitochondrial Function and Prevent Growth of Cancer Cells.
Glutaminase (KGA/isoenzyme GAC) is an emerging and important drug target for cancer. Traditional methods for assaying glutaminase activity are coupled with several other enzymes. Such coupled assays do not permit the direct and stringent characterization of specific glutaminase inhibitors. Ebselen was identified as a potent 9 nM KGA inhibitor in the KGA/glutamate oxidase (GO)/horse radish peroxidase (HRP) coupled assay but showed very weak activity in inhibiting the growth of glutamine-dependent cancer cells. For rigorous characterization, we developed a direct kinetic binding assay for KGA using bio-layer interferometry (BLI) as the detection method; Ebselen was identified as a GDH inhibitor but not a KGA inhibitor. Furthermore, we designed and synthesized several benzo[d][1,2]selenazol-3(2H)-one dimers which were subjected to SAR analysis by several glutaminolysis specific biochemical and cell based assays. Novel glutamate dehydrogenase (GDH) or dual KGA/GDH inhibitors were discovered from the synthetic compounds; the dual inhibitors completely disrupt mitochondrial function and demonstrate potent anticancer activity with a minimum level of toxicity.


Specimen self-collection for SARS-CoV-2 testing: Patient performance and preferences-Atlanta, Georgia, August-October 2020.
Self-collected specimens can expand access to SARS-CoV-2 testing. At a large inner-city hospital 1,082 participants self-collected saliva and anterior nasal swab (ANS) samples before healthcare workers collected nasopharyngeal swab (NPS) samples on the same day. To characterize patient preferences for self-collection, this investigation explored ability, comfort, and ease of ANS and saliva self-collection for SARS-CoV-2 testing along with associated patient characteristics, including medical history and symptoms of COVID-19. With nearly all participants successfully submitting a specimen, favorable ratings from most participants (at least >79% in ease and comfort), and equivocal preference between saliva and ANS, self-collection is a viable SARS-CoV-2 testing option.


Predictors of Atrial Fibrillation Recurrences after a First Radiofrequency Catheter Ablation Intervention for Paroxysmal Atrial Fibrillation-Experience of a Low Volume Ablation Centre.
Background and Objectives: Atrial fibrillation recurrences (AFR) after radiofrequency catheter ablation (RFCA) are not uncommon, up to 65% of patients having relapses in the first year. However, current data are based mainly on studies from centres with a large volume of ablations, as they include technically inhomogeneous interventions, and populations with different types of AF. The aim of our study was to assess and stratify the risk at 6 and 12 months for AFR after a single RFCA, in patients with paroxysmal AF, in a centre with low volume activity. Materials and Methods: We enrolled 40 patients who underwent an initial RFCA, followed by continuous 48 h ECG monitoring at 1, 3, 6, and 12 months. Patients self-monitored their cardiac activity by random daily radial pulse palpation or in the presence of palpitations. Results: Ten independent predictors for late AFR were identified, and a 6-month risk score was computed using three of them: AFR duration in the first month, number of AFR between 1 and 3 months, and supraventricular ectopics per 24 h at 6 months. The score can explain 59% of the AFR (p = 0.001). A further 12-month assessment identified three independent predictors. The presence of AFR between 6-12 months is the most important of them (OR = 23.11, 95% CI = 3.87-137.83, p = 0.001), explaining 45% of AFR over 1 year. The risk scores at 6 and 12 months were internally validated. Conclusions: The 6-month score proved to be a useful tool in guiding further strategy for patients with a low risk, while a longer follow-up to 12 months may avoid unnecessary early reinterventions.


On the gastrocecal inhibitory reflex in the rat.
In rats anesthetized with urethane, the effects of distention of the stomach upon cecal motility and neural mechanisms which generate this effect were studied. Cecal motility was inhibited which generate this effect were studied. Cecal motility was inhibited when the pars glandularis of the stomach was distended by pressure ranging from 25 to 30 cm H2O. This inhibitory reflex was not affected by bilateral cervical vagotomy, but completely abolished following bilateral severance of the greater splanchnic nerves or after intravenous administration of guanethidine. After transection of the spinal cord at the level of the 5th thoracic segment the inhibitory reflex remained intact, but was abolished following pithing of the 6th thoracic segment and below. It may be concluded that the afferent and efferent path of the gastrocecal inhibitory reflex mainly pass through the greater splanchnic nerves and the reflex center is located in thoracic segments caudal to the 6th thoracic segment.


Proteomic Characterization of Reversible Thiol Oxidations in Proteomes and Proteins.
Reactive oxygen species are produced during normal metabolism in cells, and their excesses have been implicated in protein damage and toxicity, as well as in the activation of signaling events. In particular, hydrogen peroxide participates in the regulation of different physiological processes as well as in the induction of antioxidant cascades, and often the redox molecular events triggering these pathways are based on reversible cysteine (Cys) oxidation. Recent Advances: Increases in peroxides can cause the accumulation of reversible Cys oxidations in proteomes, which may be either protecting thiols from irreversible oxidations or may just be reporters of future toxicity. It is also becoming clear, however, that only a few proteins, such as the bacterial OxyR or peroxidases, can suffer direct oxidation of their Cys residues by hydrogen peroxide and, therefore, may be the only true sensors initiating signaling events. We will in this study describe some of the methodologies used to characterize at the proteome level reversible thiol oxidations, specifically those combining gel-free approaches with mass spectrometry. In the second part of this review, we will summarize some of the electrophoretic and proteomic techniques used to monitor Cys oxidation at the protein level, needed to confirm that a protein contains redox Cys involved in signaling relays, using as examples some of the best characterized redox sensors such as bacterial OxyR or yeast Tpx1/Pap1. While Cys oxidations are often detected in proteomes and in specific proteins, major efforts have to be made to establish that they are physiologically relevant. Antioxid. Redox Signal. 26, 329-344.


Vein of Galen vascular malformations in infants: clinical, radiological and therapeutic aspect.
A series of 14 vein of Galen vascular malformations diagnosed in the pediatric populations and treated at the Hospital for Sick Children-Necker, Paris, between 1988 and 1994 is presented. Five of the patients were diagnosed in the neonatal period, of whom 4 presented with life-threatening, intractable cardiac decompensation and high-flow arteriovenous fistulae. Embolization was performed on vital indications in 4 patients during the first week after birth. One embolization failed with fatal outcome. Of the 3 who were embolized, 2 succumbed within 1 week and 1 survived with marked improvement of cardiac symptoms. The older children presented with hydrocephalus and neurologic symptoms. The 10 patients older than 1 year were embolized. These procedures were successful in 90 %, with hemodynamic stabilization and improvement of clinical symptoms. In this group the mortality rate was 10 %. The total mortality rate was 29 %. Hydrocephalus was secondary to a compression of the Sylvian aqueduct in 44 % of cases. Five patients had ventricular drainage before embolization followed by a staged elective embolization. Transarterial embolizations were performed in 11 patients, whereas 2 patients were embolized via the transvenous route.


Investigation of TCDD half-life heterogeneity in veterans of Operation Ranch Hand.
The half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the contaminant of Agent Orange, has been recently estimated in 36 members of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam, as 7.1 yr with a 95% [corrected] confidence interval of 5.8-9.6 yr. We investigated the variability of TCDD half-life with percent body fat in these 36 Ranch Hand veterans who have two TCDD assay results from serum drawn in 1982 and 1987. Using a repeated measures linear model, we found a marginally significant change in half-life with percentage of body fat (p = .09) and no statistically significant change in half-life with relative changes in percentage of body fat from 1982 to 1987 (p = .60).


Plasma Levels of Proresolving and Prophlogistic Lipid Mediators: Association With Severity of Respiratory Failure and Mortality in Acute Respiratory Distress Syndrome.
Acute respiratory distress syndrome is characterized by an overly exuberant inflammatory state in the lung. Specialized proresolving mediators are endogenous agonists for the resolution of lung inflammation and injury in health, yet their association with acute respiratory distress syndrome severity and outcomes remains to be defined. In the current study, we investigate associations between plasma levels of specialized proresolving mediators and acute respiratory distress syndrome severity and mortality. Translational pilot study nested within a large prospective cohort of patients with risk factors for acute respiratory distress syndrome. ICU from a large medical center. Twenty-six Caucasian patients with acute respiratory distress syndrome and available plasma from early in critical illness. None. Here, in samples from 26 acute respiratory distress syndrome patients, we examined plasma levels of select specialized proresolving mediators that promote lung injury resolution in preclinical systems, namely lipoxin A4 and maresin 1, and select prophlogistic lipid mediators linked to acute respiratory distress syndrome pathogenesis, namely cysteinyl leukotrienes and thromboxane B2. These mediators were detected by sensitive enzyme-linked immunosorbent assay: lipoxin A4 (assay range) (8.2-5,000 pg/mL), maresin 1 (7.8-1,000 pg/mL), cysteinyl leukotrienes (7.8-1,000 pg/mL), and thromboxane B2 (15.6-2,000 pg/mL). Lower plasma levels of specialized proresolving mediators were associated with increased duration of ventilatory support and ICU length of stay. Even in this small sample size, trends were evident for increased cysteinyl leukotrienes to specialized proresolving mediator ratios (cysteinyl leukotrienes/maresin 1 and cysteinyl leukotrienes/lipoxin A4) in acute respiratory distress syndrome nonsurvivors. Lower specialized proresolving mediator levels in acute respiratory distress syndrome patients may disrupt timely resolution of lung inflammation and/or injury and contribute to clinical severity and mortality.


Low-dose ethanol alters the cardiovascular, metabolic, and respiratory compensation for severe blood loss.
Compensation for hemorrhage and shock requires coordination of responses and sufficient physiologic reserve capacity of the cardiovascular, respiratory, renal, and neuroendocrine systems. Intake of ethanol (EtOH) is known to degrade physiologic response to stress. The purpose of this study was to investigate how acute EtOH exposure changes responses to severe blood loss, shock, and resuscitation. Conscious male Duncan Hartley guinea pigs were given an intraperitoneal injection of either EtOH (1 g/kg) or an equal volume of water 30 minutes before controlled hemorrhage (60% blood volume), resuscitated after 30 minutes of hypovolemia with a lactated Ringer's solution volume equal to that of the shed blood volume, and observed for 24 hours. Hemodynamic (heart rate, arterial blood pressure), clinical laboratory (arterial blood gases, glucose, lactate, hematocrit), and metabolic gas exchange (oxygen consumption, carbon dioxide production) indicators of shock were monitored. Of the animals that survived 24 hours, changes in arterial pH and lactate were significantly greater in the experiment group than in the control group. Mortality at 24 hours was 77% in the experiment group (EtOH-treated) and 42% (p = 0.39) in the control group (water-treated). Acute EtOH exposure, with blood EtOH concentration similar to legal intoxication levels, limits physiologic reserve during hemorrhagic shock and resuscitation. In survivors of shock and resuscitation, compensation is compromised and physiologic reserve is adversely affected by acute EtOH intake.


Novel Correlation for Calculating Water Saturation in Shaly Sandstone Reservoirs Using Artificial Intelligence: Case Study from Egyptian Oil Fields.
The accurate determination of water saturation in shaly sandstone reservoirs has a significant impact on hydrocarbons in place estimation and selection of possible hydrocarbon zones. The available numerical equations for water saturation estimation are unreliable and depend on laboratory core analysis. Therefore, this paper attempts to use artificial intelligence methods in developing an artificial neural network model (ANN) for water saturation (Sw) prediction. The ANN model is developed and validated by using 2700 core measured points from the fields located in the Gulf of Suez, Nile Delta, and Western Desert of Egypt, with inputs including the formation depth, the caliper size, the sonic time, gamma rays (GRs), shallow resistivity (Rxo), neutron porosity (NPHI), the photoelectric effect (PEF), bulk density, and deep resistivity (Rt). The study results show that the optimization process for the ANN model is achieved by distributing the collected data as follows: 80% for training and 20% for testing processes, with an R 2 of 0.973 and a mean square error (MSE) of 0.048. In addition, a mathematical equation is extracted out of the ANN model that is used to estimate the formation water saturation in a simple and direct approach. The developed equation can be used incorporating with the existing well logs commercial software to increase the accuracy of water saturation prediction. A comparison study is executed using published correlations (Waxman and Smits, dual water, and effective models) to show the robustness of the presented ANN model and the extracted equation. The results show that the proposed correlation and the ANN model achieved outstanding performance and better accuracy than the existing empirical models for calculating the formation water saturation with a high correlation coefficient (R 2) of 0.973, lowest mean-square error (MSE) of 0.048, lowest average absolute percent relative error (AAPRE) of 0.042, and standard deviation (SD) of 0.24. To the best of our knowledge, the current study and the proposed ANN model establish a novel base in the estimation of formation water saturation.


A Yardstick for Danger: Developing a Flexible and Sensitive Measure of Risk Perception.
While individual perceptions of risk are central to many behavioral theories of hazard response and are of considerable interest in both conceptual and applied work surrounding risk, hazards, and decision making, there is currently no consensus on how perceived risk should best be measured. Several recent efforts have laid the groundwork for a conceptual model outlining four key factors that make up risk perception: exposure, susceptibility, severity, and affective response. In this article, we use an extensive scale-development process to develop empirically supported 3-4 item subscales to measure each of those four dimensions. Using cognitive interviewing techniques and several quantitative psychometric methods including exploratory and confirmatory factor analysis and item-response theory analyses, we reduce a large set of potential items to the highest-quality items to assess each subscale. These subscales can be used to make comparisons across perceived risk in different hazard contexts and populations.


Chronic hepatitis E in hematopoietic stem cell transplant patients in a low-endemic country?
Cases of chronic hepatitis E have been described in patients after kidney and liver transplantation. In addition, hepatitis E virus (HEV) reactivation was reported after hematopoietic stem cell transplantation (HSCT). We here evaluated if HEV infection might explain elevated liver enzymes in a well selected cohort of allogeneic HSCT patients with biochemical evidence of hepatitis (n = 52). Of note, none of the subjects tested positive for HEV RNA, including 2 HSCT patients who had been infected with HEV already before transplantation. Thus, both chronic courses of HEV infections and HEV reactivations seem to be rather rare events in HSCT patients in a non-endemic country.


Increased mast cell number in human hypertensive nephropathy.
Mast cells have recently been related to nonallergic chronic organ damage and fibrosis. In the present study, we analyzed mast cell number, localization, and maturation in the kidney of a relatively unique group of middle-aged accident victims with primary essential hypertension and in normotensive controls (n=8 per group, Caucasians, predominantly male). Hypertensive kidneys showed a significantly higher degree of arteriolosclerosis. However, glomerular and tubulointerstitial matrix accumulation did not differ significantly to normotensive controls indicating a relatively early stage of hypertensive nephropathy. Using toluidine blue staining, renal mast cell number was found to be fivefold higher in hypertensive subjects compared with normotensive controls. Mast cells were primarily located in the peritubular interstitial spaces, some perivascular, but not in glomeruli. In a series of immunohistological staining studies, mast cell maturation grading showed that expression of early hematopoietic precursor cell marker CD34 did not differ between both groups. In contrast, mast cells were mostly positive for IgE receptor, tryptase, and chymase indicating a mature, differentiated cell phenotype in hypertensive nephropathy. Renal expression of stem cell factor was markedly upregulated in primary hypertension. Kidney macrophage and lymphocyte numbers were similar in both groups. In conclusion, human hypertensive kidney disease shows an early and conspicuous upregulation of stem cell factor along with an increased number of mature mast cells. The results suggest that renal mast cell accumulation may play a role in the pathogenesis of human hypertensive nephropathy.


Kinematic head and trunk strategies used by hemiplegic stroke patients crossing over obstacles of different heights.
[Purpose] The purpose of this study was to compare kinematic data regarding the head, trunk, and pelvis strategies used by individuals with hemiplegia when crossing over obstacles of different heights. [Subjects and Methods] Nine adults with hemiplegia from stroke (7 males and 2 females) participated in this study. A motion analysis system with six infrared cameras was used to measure the kinematic data of the head, trunk, and pelvis while the subjects crossed over obstacles of different heights. Repeated measures ANOVA analysis was performed to compare the resulting kinematic data. [Results] An increase in the magnitude of the kinematic data of the head, trunk, and pelvis of the hemiparetic stroke patients was observed when the height of the obstacles, which they crossed over, increased. [Conclusion] This study described the kinematic strategies, with regard to the head, trunk, and pelvis, used by hemiplegic patients crossing over obstacles of different heights. The results indicate that these kinematic strategies primarily change when the obstacle height was 20% of the height of the subjects.


Use of 16S rRNA Gene-Targeted Group-Specific Primers for Real-Time PCR Analysis of Predominant Bacteria in Mouse Feces.
Mouse models are widely used for studying gastrointestinal (GI) tract-related diseases. It is necessary and important to develop a new set of primers to monitor the mouse gut microbiota. In this study, 16S rRNA gene-targeted group-specific primers for Firmicutes, Actinobacteria, Bacteroidetes, Deferribacteres, "Candidatus Saccharibacteria," Verrucomicrobia, Tenericutes, and Proteobacteria were designed and validated for quantification of the predominant bacterial species in mouse feces by real-time PCR. After confirmation of their accuracy and specificity by high-throughput sequencing technologies, these primers were applied to quantify the changes in the fecal samples from a trinitrobenzene sulfonic acid-induced colitis mouse model. Our results showed that this approach efficiently predicted the occurrence of colitis, such as spontaneous chronic inflammatory bowel disease in transgenic mice. The set of primers developed in this study provides a simple and affordable method to monitor changes in the intestinal microbiota at the phylum level.


Binding of the Streptococcus gordonii DL1 surface protein Hsa to the host cell membrane glycoproteins CD11b, CD43, and CD50.
Infective endocarditis is frequently attributed to oral streptococci. The mechanisms of pathogenesis, however, are not well understood, although interaction between streptococci and phagocytes are thought to be very important. A highly expressed surface component of Streptococcus gordonii, Hsa, which has sialic acid-binding activity, contributes to infective endocarditis in vivo. In the present study, we found that S. gordonii DL1 binds to HL-60 cells differentiated into monocytes, granulocytes, and macrophages. Using a glutathione S-transferase (GST) fusion to the NR2 domain, which is the sialic acid-binding region of Hsa, we confirmed that the Hsa NR2 domain also binds to differentiated HL-60 cells. To identify which sialoglycoproteins on the surface of differentiated HL-60 cells are receptors for Hsa, intrinsic membrane proteins were assessed by bacterial overlay and far-Western blotting. S. gordonii DL1 adhered to 100- to 150-kDa proteins, a reaction that was abolished by neuraminidase treatment. These sialoglycoproteins were identified as CD11b, CD43, and CD50 by GST pull-down assay and immunoprecipitation with each specific monoclonal antibody. These data suggest that S. gordonii DL1 Hsa specifically binds to three glycoproteins as receptors and that this interaction may be the initial bacterial binding step in infective endocarditis by oral streptococci.


Programmed endothelial cell death induced by an avian hemangioma retrovirus is density dependent.
Hemangiomas are localized tumors of vascular cells which appear frequently in humans and animals, and their mode of induction is unknown. Recently, a new field strain of avian retrovirus, avian hemangioma virus (AHV), was isolated from spontaneous hemangiomas in layer hens. Sequence analysis of the AHV genome revealed the presence of three prototypic retroviral genes, gag, pol, and env, but no oncogenes. AHV was capable of inducing hemangiomas in hens in vivo, but it induced a strong cytopathic effect in cultured endothelial cells. The AHV envelope glycoprotein, gp85, was found to be responsible for the cell-killing effect. Four independent lines of experimental evidence indicated that AHV induces a cytopathic effect through a typical programmed cell death, apoptosis: (i) morphological changes in cells visualized by light microscopy, (ii) nuclear condensation and fragmentation indicated by 4',6-diamidino-2- phenylindole staining, (iii) intranucleosomal degradation of DNA demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining, and (iv) flow cytometry analysis of the DNA content of the infected cells. Quiescent endothelial G0/G1 cells were much more sensitive to AHV-induced apoptosis than actively dividing cells, suggesting that the AHV ability to induce apoptosis is dependent on the proliferative state of the infected cells.


A case control study to assess risk factors for hepatitis C among a general population in a highly endemic area of northwest Tunisia.
A matched case-control study was undertaken in 2004 in Béja, north-western Tunisia, to evaluate potential risk factors for hepatitis C infection. Cases were anti-HCV positive subjects screened in 1996 serosurvey. HCV seronegative controls (5 per case) were selected in the proximity of cases and matched for age and gender. A standardized questionnaire was used to collect demographic, socioeconomic, social behavior, medical and surgical history information. Matched odds ratios (OR) and adjusted OR (AOR) and their 95% CI were calculated in multivariate analysis using logistic regression. 57 HCV positive cases (mean age 61.63 +/- 14,84; 68.4 % female) and 285 HCV negative controls (mean age 60.95 +/- 14.66; 68.4 % female) were enrolled. Multivariate analysis revealed that intravenous drug injections (AOR=1.96; 95%CI[1.02-3.8] p=0.045), past history of invasive procedures (AOR=2.53; 95%CI[1.21-5.29] p=0.0014) and medical history of hypertension (AOR=2.31; 95%CI [1.17-4.56]p=0.015) were significantly associated to HCV infection. These results suggest that nosocomial transmission of HCV infection in north-west Tunisia is common.