[Acute alcoholic hepatitis].
Acute alcoholic hepatitis is an anatomical (fatty liver with sclerosing hyaline necrosis) and a clinical (hepatomegaly with a variety of symptoms of hepatic failure) entity arising out of chronic alcoholism, and of a typically 'pre-cirrhotic' state. Although fatal in 25% of acute cases due to failure of homeostasis, it often leaves a centrilobular scarring necrosis which in more than 60% of cases progresses to nodular cirrhosis. Continued alcoholism worsens the prognosis. Alcoholic hepatitis may be confused with acute abdominal catastrophes or with a hepatoma. The characteristic Mallory bodies found on liver biopsy are found rarely in non-alcoholic hepatitis. There is no effective treatment for this disease except reduction of alcohol intake; indeed, the disease may become self-perpetuating.


Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli.
A constitutively active mutant of histidine kinase sensor EvgS was found to confer multi-drug resistance (MDR) to an acrA-deficient Escherichia coli, indicating the relationship between the two-component system EvgAS and the expression of the MDR system. The observed MDR also depended on an outer-membrane channel, TolC. Microarray and S1 mapping assays indicated that, in the presence of this constitutive mutant EvgS, the level of transcription increased for some MDR genes, including the drug efflux genes emrKY, yhiUV, acrAB, mdfA and tolC. Transcription in vitro of emrK increased by the addition of phosphorylated EvgA. Transcription activation of tolC by the activated EvgS was, however, dependent on both EvgAS and PhoPQ (Mg(2+)-responsive two-component system), in agreement with the presence of the binding site (PhoP box) for the regulator PhoP in the tolC promoter region. Transcription in vitro of yhiUV also appears to require an as-yet-unidentified additional transcriptional factor besides EvgA. Taken together we propose that the expression of the MDR system is under a complex regulatory network, including the phosphorylated EvgA serving as the master regulator.


Genomic and biological characterization of a new cypovirus isolated from Dendrolimus punctatus.
A novel cypovirus (designated DpCPV-MC) was isolated from the pine moth Dendrolimus punctatus using serial in vivo cloning procedures. DpCPV-MC occurs in typical polyhedral occlusion bodies, containing a number of spherical virions. Laboratory bioassays indicated that the infectivity of DpCPV-MC against second-instar Spodoptera exigua larvae does not differ significantly from that of Dendrolimus punctatus cypovirus 1. Full-length amplification of the DpCPV-MC cDNAs identified 16 dsRNA genome segments. Each segment encodes one open reading frame with unique conserved terminal sequences at the 5' and 3' ends, which differ from those of all previously reported cypoviruses. On a phylogenetic tree based on the amino acid sequences of the polyhedrin of 19 cypovirus species, DpCPV-MC was closest to the type-4 cypoviruses. Homology searches showed that ten segments of DpCPV-MC (S1, S2, S3, S4, S5, S7, S8, S9, S12, and S13) encode putative CPV structural and nonstructural proteins, three segments (S6, S10 and S14) encode putative insect proteins or other viral proteins, and the other three segments (S11, S15, and S16) encode proteins that have no obvious sequence similarity to any known protein. Based on RNA secondary structures analysis, two segments of them (S11 and S16) were predicted to possibly transcript less efficiently than the other segments. We speculate that DpCPV-MC is composed of several genotypes. The ten CPV-related segments constantly exist in all genotypes, and one or two of the six CPV-unrelated segments co-exist with the ten CPV-related segments in one DpCPV-MC genotype, thus each virion contains no more than 12 segments. Based on our results and the literature, DpCPV-MC is a new cypovirus (Cypovirus 22, strain DpCPV-22).


[Inner pyelovesical splinting in pyeloplasties (author's transl)].
A total of 112 cases of pyeloplasty were analyzed and the advantages of inner pyelovesical splinting as opposed to external drainage are outlined. Long-term results especially favor the former procedure. Scanning electron microscopic studies were done on the splinting material.


Modulation by steroid hormones of a "sexy" acoustic signal in an Oscine species, the Common Canary Serinus canaria.
The respective influence of testosterone and estradiol on the structure of the Common Canary Serinus canaria song was studied by experimentally controlling blood levels of steroid hormones in males and analyzing the consequent effects on acoustic parameters. A detailed acoustic analysis of the songs produced before and after hormonal manipulation revealed that testosterone and estradiol seem to control distinct song parameters independently. The presence of receptors for testosterone and estradiol in the brain neural pathway controlling song production strongly suggests that the observed effects are mediated by a steroid action at the neuronal level.


Randomized trial of postpartum care after hospital discharge.
Harmful effects of short postpartum hospital stays include dehydration and malnutrition of breastfed infants. These may be prevented by adequate breastfeeding frequency; however, rigorous research to determine the relative effectiveness of various follow-up strategies in supporting breastfeeding frequency is absent. This study addressed the question, "Is there a difference in breastfeeding frequency or infant weight gain for singleton infants discharged within 36 hours' postpartum who received either community nurse (home visit) or hospital nurse (clinic) follow-up?" A randomized, controlled trial was conducted at a university teaching hospital (3700 births/y) and affiliated community health centers. A consecutive sample of 586 healthy mother-infant pairs were recruited from January 1997 to September 1998 before discharge; 513 (87.5%) contributed data on 1 or more outcomes. Forty-eight-hour postpartum telephone contact and day 3 nurse contact in the home (experimental) or at the hospital (control) were provided. The main outcomes measured were breastfeeding frequency and infant weight gain assessed at 2 weeks' postpartum by maternal diary and weight at home by research assistants, masked to group allocation. No clinically important or statistically significant group differences were found in daily breastfeeding frequency (mean difference experimental minus control = 0.1 feeds [95% confidence interval: -0.1-0.3]) or daily rate of infant weight gain (-1.1 g [-2.5-0.3]) based on intention-to-treat analyses. Follow-up by nurses after short postpartum hospital stays, in either the home or a hospital-based clinic, of healthy infants discharged at <36 hours seems associated with satisfactory infant breastfeeding outcomes.


[Pharmacokinetics of cardiovascular drugs in the elderly].
Adverse drug effects are more frequent in elderly patients, especially with drugs that have small safety margins. This is the case of many cardiovascular drugs. Patients who are frail, owing to their age and their psychomotor, nutritional and social stratus, are particularly at risk. Two pharmacokinetic factors appear to be of major concern, namely the age-related decrease renal function and changes in drug metabolism and distribution. Renal function is probably the single factor most responsible for altered drug levels in the elderly. The normal age-related decrease in creatinine clearance can lead to the accumulation of drugs that are normally excreted by the kidneys without being inactivated Dose adjustment of such drugs is usually based on the Cockcroft-Gault formula of creatinine clearance. Changes in hepatic metabolism and drug distribution are less commonly taken into account. The avoidance of drug toxicity requires familiarity with the medications prescribed and particular vigilance for signs of adverse effects.


Clinical Findings and Autopsy of a Preterm Infant with Breast Milk-Acquired Cytomegalovirus Infection.
Background Nonpasteurized, nonfrozen, fresh breast milk from mothers with positive cytomegalovirus (CMV) serology was initially contraindicated to very low-birth-weight infants because of the risk of milk-acquired CMV infection. Recently, the severity of this infection was increasingly discussed and the international guidelines now differ. Since 2012, the American Academy of Pediatrics has recommended nutrition through raw breast milk for all preterm infants. Case We report the case of an infant born prematurely at 27 weeks and 4 days and fed with raw breastmilk from day 12 of life (D12). He presented with a late-onset of CMV infection from D39. The CMV polymerase chain reaction (PCR), negative on D3, was strongly positive on D49, as well as the PCR on breast milk. He had CMV-specific immunoglobulin (Ig) M while his mother had only CMV-specific IgG. On D52, he deteriorated further with septic shock, and a fatal cardiac arrest on D54. His twin presented an asymptomatic CMV infection. The autopsy and histological examination showed evidence of numerous organ damage caused by CMV (with differences compared with congenital infection) but no evidence of bacterial infection. Conclusion Although rare, postnatal CMV infections transmitted by raw breast milk given to very low-birthweight infants can have dramatic consequences.


Development of Poly(lactic acid)/Chitosan Fibers Loaded with Essential Oil for Antimicrobial Applications.
Cinnamon essential oil (CEO) was successfully encapsulated into chitosan (CS) nanoparticles at different loading amounts (1%, 1.5%, 2%, and 2.5% v/v) using oil-in-water (o/w) emulsion and ionic-gelation methods. In order to form active packaging, poly(lactic acid) (PLA) was used to fabricate PLA/CS-CEO composite fibers using a simple electrospinning method. The shape, size, zeta potential, and encapsulation efficacy of the CS-CEO nanoparticles were investigated. The composition, morphology, and release behavior of the composite fibers were investigated. PLA/CS-CEO-1.5 showed good stability and favorable sustained release of CEO, resulting in improved antimicrobial activity compared to the other blends. The PLA/CS-CEO fibers showed high long-term inactivation rates against Escherichia coli and Staphylococcus aureus due to the sustained release of CEO, indicating that the developed PLA/CS-CEO fibers have great potential for active food packaging applications.


Targeting Ku protein for sensitizing of breast cancer cells to DNA-damage.
Targeting molecular components that are critically involved in the maintenance of genome stability is a promising approach for overcoming intrinsic tumor cell resistance to DNA-damaging treatments. In mammalian cells, the Ku-dependent non-homologous end-joining repair pathway is the predominant process for the repair of double-strand breaks (DSBs) in DNA. Previously, RNA aptamers were selected to efficiently block DNA-binding activity of the Ku protein in vitro. In the present study, we have tested the efficacy of RNA aptamers against the Ku protein as molecular sensitizer of MCF-7 breast carcinoma cells to DNA-damage. Toward this end, we established MCF-7 cell sublines stably expressing SC4 aptamer RNAs under the control of the human 7SL small nuclear RNA gene promoter. Vector-transfected (MCF/7SL) cells and cells stably expressing SC4 aptamers (MCF/SC4) were exposed to the anticancer drug etoposide and cellular responses to DNA-damage were evaluated. We found that the presence of RNA aptamers against Ku protein enhanced etoposide-induced growth inhibition of MCF-7 breast cancer. The SC4 aptamer-mediated sensitization of MCF-7 cells to the anticancer drug is attributable to an increased susceptibility of these cells to apoptosis. The observed effects cannot be accounted for by the differential expression levels of Ku protein in control and SC4 aptamer-expressing cells, but are rather due to augmented DNA binding-capacity of Ku protein, as demonstrated in in vitro studies. Thus, RNA aptamers against Ku protein show potential to sensitize MCF-7 breast carcinoma cells to DNA-damaging agents.


Iminocyclohexadienylidenes: Carbenes or Diradicals? The Hetero-Wolff Rearrangement of Benzotriazoles to Cyanocyclopentadienes and 1H-Benzo[b]azirines.
The thermal rearrangements of benzotriazole 1 to fulvenimine 4 and 1H-benzazirine 7 are investigated at DFT and CASPT2 levels of theory. Ring opening of benzotriazole 1 to 2-diazo-cyclohexadienimine 2 followed by N2 elimination affords Z- and E-2-iminocyclohexadienylidenes 3, which have triplet ground states (3A″). The open-shell singlet (OSS) (1A″) and closed-shell singlet (CSS) (1A') of 3 lie ∼15 and 40 kcal/mol higher in free energy, respectively. The OSS 3 (1A″) is best described as a 1,3-diradical, whereas the CSS (1A') has the character of a carbene. A hetero-Wolff rearrangement of OSS 3 yields fulvenimine 4, which is a precursor of cyanocyclopentadiene 5, with a calculated activation barrier of 38 kcal/mol at the CASPT2(8,8) level, whereby there is a surface crossing from the OSS to the CSS near the transition state. The barrier for cyclization to 1H-benzo[b]azirine 7 is only ∼13 kcal/mol. Therefore, reaction paths involving the singlet iminocyclohexadienylidene diradicals 3 will necessarily cause equilibration with 1H-benzazirine 7 prior to ring contraction to iminofulvene 4 and cyanocyclopentadiene 5, in agreement with experimental observations based on 13C labeling. The thermolysis of 1-acetylbenzotriazole 7 leads to the analogous N-acetyl-diazocyclohexadienimines 8, N-acetyliminocyclohexadienylidene diradicals 9, and N-acetylfulvenimine 10. The E-N-acetyliminocyclohexadienylidene E9 ring closes to the N-acetyl-1H-benzazirine 11 prior to ring contraction to N-acetylfulvenimine 10, and the Z-N-acetyl-2-diazocyclohexadienimine Z8 ring closes to 2-methylbenzoxazole 12. 1H-benzazirines are predicted to be spectroscopically observable species.


Selection and Characterization of DNA Aptamers for Electrochemical Biosensing of Carbendazim.
This article reports a novel aptamer-based impedimetric detection of carbendazim, a commonly used benzimidazole fungicide in agriculture. High affinity and specificity DNA aptamers against carbendazim were successfully selected using systematic evolution of ligand by exponential enrichment (SELEX). The dissociation constants (Kds) of the selected DNA aptamers after 10 in vitro selection cycles were characterized using fluorescence-based assays showing values in the nanomolar range. The aptamer which showed the highest degree of affinity and conformation change was used to fabricate an electrochemical aptasensor via self-assembly of thiol-modified aptamer on gold electrodes. The aptasensor exploits the specific recognition of carbendazim by the aptamer immobilized on the gold surface which leads to conformational changes in the aptamer structure. This conformational change alters the access of a ferrocyanide/ferricyanide redox couple to the aptasensor surface. The aptasensor response is thus measured by following the increase in the electron transfer resistance of the redox couple using Faradaic electrochemical impedance spectroscopy. This method allowed a selective and sensitive label-free detection of carbendazim within a range of 10 pg/mL-10 ng/mL with a limit of detection of 8.2 pg/mL. The aptasensor did not show cross reactivity with other commonly used pesticides such as fenamiphos, isoproturon, atrazine, linuron, thiamethoxam, trifluralin, carbaryl, and methyl parathion. Moreover, the aptasensor has been applied in different spiked food matrixes showing high recovery percentages. We believe that the proposed aptasensor is a promising alternative to the currently used methods for carbendazim monitoring.


Self-perception of swallowing by patients with benign nonsurgical thyroid disease.
To verify the frequency of swallowing complaints in patients with benign nonsurgical thyroid disease and compare the self-perception of swallowing disorder intensity between different types of thyroid disease. The study sample comprised 39 women aged 19-58 years (38.54 ± 10.74) with hypothyroidism (n=22; 56.4%) or thyroid nodules (n=17; 43.6%). Presence and type of swallowing complaint and self-perception of swallowing disorder intensity were investigated by means of self-ratings recorded on a 100-millimeter visual analog scale. The data were analyzed by descriptive measures and the Mann-Whitney nonparametric test was used to compare the self-perception of swallowing disorder intensity between both clinical diagnoses of thyroid disease. The level of 5% was adopted for statistical significance. Twenty-six (66.7%) individuals reported the following swallowing complaints: pharyngolaryngeal stasis sensation (37.15%), chocking (34.29%), and odynophagia (28.57%). The mean value of self-perception of swallowing disorder intensity by the visual analog scale was 59.35 (± 27.38) millimeters. No difference in self-perception was reported between the clinical diagnoses of thyroid disease. In this sample, swallowing complaint was frequently observed in patients with benign nonsurgical thyroid disease. Moderate self-perception of swallowing disorder intensity was reported regardless of the clinical diagnosis of thyroid disease.


Rabbit skeletal muscle glycogen synthase expressed in COS cells. Identification of regulatory phosphorylation sites.
Rabbit skeletal muscle glycogen synthase contains multiple sites for phosphorylation. To investigate the relative importance of these sites, the enzyme was overexpressed in COS M9 cells, and Ser-->Ala mutations were introduced singly, or in combinations, at nine known phosphorylation sites. Overexpressed wild-type enzyme had a very low +/- glucose-6-P activity ratio of approximately 0.01, indicative that the glycogen synthase is in a highly phosphorylated state. No single Ser-->Ala mutation was able to cause a substantial increase in activity ratio; rather, simultaneous mutation at both NH2- and COOH-terminal sites was needed. The most effective combinations were mutations at site 3a (Ser-640) or site 3b (Ser-644) together with site 2 (Ser-7). The results were consistent with site 2 phosphorylation being a prerequisite for phosphorylation of site 2a (Ser-10). Mutation of site 5 (Ser-656) perturbed COOH-terminal phosphorylation but did not prevent inactivation. Expression of the most active mutants correlated with increased glycogen accumulation in the COS M9 cells. In summary, we conclude that (i) the sites most important for activating the enzyme are sites 2, 2a, 3a, and 3b; (ii) removal of phosphate from both NH2- and COOH-terminal sites is required for activation; and (iii) sites 3a and/or 3b can be phosphorylated in COS cells by mechanisms that do not depend on phosphorylation of site 5.


Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study.
To assess the evolution of triglyceride (TG) levels in HIV-infected patients receiving stable potent antiretroviral therapy treated with N-3 polyunsaturated fatty acids (PUFAs), a prospective double-blind randomized design for a reliable assessment of TG evolution was performed. One hundred twenty-two patients with TG levels >2 g/L and < or =10 g/L after a 4-week diet (baseline TG: 4.5 +/- 1.9 g/L) were randomized for 8 weeks to N-3 PUFAs (2 capsules containing 1 g of fish oil 3 times daily, n = 60), or placebo (1 g of paraffin oil capsules, n = 62). An 8-week open-label phase of N-3 PUFAs followed. Evaluation criteria were TG percent change at week 8, percentage of responders (normalization or > or =20% TG decrease), and safety issues. Ten patients with baseline TG levels >10 g/L were not randomized and received N-3 PUFAs as open treatment. The difference (PUFA - placebo) in TG percent change at week 8 was -24.6% (range: -40.9% to -8.4%; P = 0.0033), the median was -25.5% in the PUFA group versus 1% in the placebo group, and mean TG levels at week 8 were 3.4 +/- 1.8 g/L and 4.8 +/- 3.1 g/L, respectively. TG levels were normalized in 22.4% (PUFA) versus 6.5% (placebo) of patients (P = 0.013) with a > or =20% reduction in 58.6% (PUFA) versus 33.9% (placebo) of patients (P = 0.007). Under the open-label phase of N-3 PUFAs, the decrease in TG levels was sustained at week 16 for patients in the PUFA group (mean TG: 3.4 +/- 1.7 g/L), whereas a 21.2% decrease in TG levels occurred for patients in the placebo group (mean TG: 3.3 +/- 1.4 g/L). No significant differences were observed between groups in the occurrence of adverse events. The median TG change at week 8 was -43.6% (range: Q1-Q3; 95% CI: -66.5% to -4.6%) for patients with baseline TG levels >10 g/L. The difference in mean total cholesterol between groups (PUFA - placebo) at week 8 was -8.5% (P = 0.0117). This study demonstrated the efficacy of PUFAs to lower elevated TG levels in treated HIV-infected hypertriglyceridemic patients. N-3 PUFAs have a good safety profile.


The supraorbital craniotomy for access to the skull base and intraaxial lesions: a technique in evolution.
The supraorbital craniotomy was initially described as a minimally invasive means to target extra-axial lesions in the anterior cranial fossa and sellar/parasellar region. Since its initial description, various modifications have been described. We report our recent experience with this approach (and its modifications) for not only extra-axial but also intra-axial neoplastic pathology. Based on patient pathology and anatomic considerations, one of two approaches was performed: supraorbital craniotomy through an eyebrow incision or a combined orbital osteotomy and supraorbital craniotomy through an eyelid incision. This technique was performed on twenty-eight consecutive patients. Intra-axial pathology ranged from anaplastic astrocytoma to metastasis while extra-axial lesions included meningiomas and skull-based metastases. Excellent lesion resection was achieved in the majority of patients. Complications were infection (2 patients) and CSF leak. The supraorbital craniotomy and its modifications provide an ideal anterior subfrontal approach through which a wide variety of pathology can be approached. This technique has particular considerations in comparison to traditional cranial base approaches that must be taken into account before it is utilized.


Activator-dependent hydrolysis of myelin cerebroside sulfate by arylsulfatase A.
A purified myelin preparation containing [35S]-labeled cerebroside sulfate (CS) was biosynthesized in developing rat brain and tested as a model of a physiological substrate for CS hydrolysis by arylsulfatase A. Particular attention was directed to the involvement of the CS sulfatase activator protein in facilitating the catabolic process. Although arylsulfatase A alone was incapable of desulfating CS in either purified CS suspensions or the physiological membrane, activator-induced hydrolysis of myelin CS exhibited concentration dependency, pH optimum, and relative insensitivity to salts in a manner similar to purified lipid suspensions. Exogenous protein demonstrated concentration-dependent inhibition. Slower rates of hydrolysis observed for the myelin membrane substrate are proposed to be a consequence of myelin membrane configuration and competition for activator by other lipoidal constituents.


Quantum chemistry study of H+(H2O)8: a global search for its isomers by the scaled hypersphere search method, and its thermal behavior.
The structures of the protonated water cluster H+(H2O)8 have been globally explored by the scaled hypersphere search method. On the Hartree-Fock potential energy surface 174 isomers were found, among which 168 were computed to be minima at the B3LYP/6-31+G** level, and their energies were further refined at the level of MP2/6-311++G(3df,2p). The global minimum on the potential energy surface computed at the B3LYP/6-31+G** level shows a cagelike structure with the "Eigen" motif, while the lowest-free-energy isomer has a five-membered-ring structure at 170 K and a chain form at 273 K. The present results are well in line with previous experimental findings. In addition, the ADMP (atom-centered density matrix propagation) simulation indicates that the extra proton in the lowest-free-energy isomer (170 K), which has a five-membered ring and the "Zundel" feature, is often in an asymmetrical hydrogen bond.


A 68Ga-FAPI-46 PET/CT Imaging Pitfall in Assessing Residual Gastric Cancer Early After Chemotherapy.
After neoadjuvant chemotherapy, preoperative imaging with 68Ga-FAPI-46 PET/CT showed a similar level of tracer uptake at the location of the primary tumors in 2 patients with gastric cancer. Postoperative histopathology revealed residual malignant cells only in one of the patients, whereas the elevated FAPI uptake in the other patient correlated to an inflammatory reaction and fibrosis. With this case, we would like to highlight that an increased FAPI uptake in inflammatory and fibrotic tissue early after chemotherapy may represent a potential interpretation pitfall. Further studies evaluating the clinical application of FAPI-PET in assessing residual cancer tissue are warranted.


Computational study and validation of a novel passive hand tremor attenuator.
Tremors are a prevalent movement disorder due to a nervous system condition that leads to involuntary muscle movements observed in patients. This paper converts the tremorous anatomical human arm model to a single degree of freedom (SDOF) forced vibration problem. The mathematical modelling with Euler-Lagrange's equation is performed for the SDOF human arm model with two different potential vibration absorbers. A computational study is conducted on MATLAB Simulink by MathWorks Inc. (Natick, MA) to compare two absorbers, and the results are verified on the multibody dynamics simulation solution software, MSC Adams by Hexagon AB. It is concluded that the T beam-shaped vibration absorber represented a higher amplitude reduction, up to 80%, compared to the inertial mass absorber, which had an amplitude reduction of 65% over the range of frequencies. Experiments conducted with the T beam absorber prototype also support the computational findings. Future research focuses on designing an ergonomic wearable device with a proposed T-beam absorber that can passively attenuate the tremor at various frequencies.


Second-Generation Antipsychotic-Induced Hypoglycemia.
Complaints of hypoglycemia resemble the sedative effect of antipsychotics. As such, clinicians may overlook hypoglycemia in patients with psychiatric disorders. Here, a case of hypoglycemia associated with hyperinsulinemia induced by quetiapine in a female patient with bipolar disorder is reported. The case suggests that clinicians should be aware of the potential for hypoglycemia induced by second-generation antipsychotics.


[Comparison of preoperative retinometer values with postoperative visual acuity after surgery of epiretinal membranes].
We report about our clinical experience when comparing the preoperative retinometer values with the postoperative visual acuity after microsurgical excision of epiretinal membranes (ERM). Pars plana vitrectomy with membrane peeling was performed in 56 eyes of 53 patients. Preoperatively, we obtained the distant and near visual acuity and the retinometer value. Postoperatively, we compared the preoperative retinometer value to the best postoperative visual acuity. The preoperative retinometer value was in 39 eyes (70 %) equal to the best postoperative distant visual acuity (+/- 1 line) and in 34 eyes (61 %) equal to the best near visual acuity (+/- 1 line). A difference of + 2 or - 2 lines or more from the retinometer value was found in 17 eyes (30 %) for the best postoperative distant visual acuity and in 22 eyes (39 %) for the best near visual acuity. 49 eyes (87.5 %) had a better visual acuity after pars plana vitrectomy, 6 eyes (10.7 %) had equal visual acuities and one eye (1,8 %) was worse than the preoperative visual acuity. The average improvement of vision after the operation was + 2.5 lines for the distant and + 2.4 lines for the near visual acuity. The preoperative retinometer examination is a precise method for obtaining the visual acuity of patients selected for pars plana vitrectomy with membrane peeling. Uncertain results can be achieved in eyes with very opaque ERM and ERM with macular edema.


The reverse fistula for vascular access.
A new technique for vascualr access in the patient requiring chronic hemodialysis and who has had multiple failures of forearm fistulas involves the formation of a side-to-side anastomosis between the brachial artery and the basilic vein and creates reverse flow into the antecubital venous system. Attention to technical considerations will prevent edema of the arm and allow for future use of graft procedures, if necessary.


Value of CT-Angiography in the Emergency Management of Severe Hemoptysis.
Objective To depict imaging anatomy of bronchial artery (BA) using multidetector CT-angiography (MDCTA) and evaluate the value of MDCTA for management of hemoptysis patients requiring admission to emergency room. Methods We retrospectively studied the clinical and radiological data of patients with severe hemoptysis (≥100 ml of expectorated blood in a 24-hour period) requiring admission to emergency room from Jan 1, 2013 to Dec 31, 2015. Patients' images of MDCTA, treatment modalities, and outcome were discussed. Results A total of 108 patients underwent MDCTA scans. Etiology of hemoptysis was mainly bronchiectasis (44%), tuberculosis sequelae (26%) and tumor (18%). MDCTA visualized 197 traceable BAs and also suggested the involvement of 35 nonbronchial systemic arteries. The mean diameter of BAs, measured at the level of the bronchial bifurcation in the mediastinum, was 2.8±1.2 mm. The mean diameter of BAs, for 52 patients who only received conservative treatment, was 2.9±1.1 mm, and was not significantly larger than that of BAs for 56 patients who underwent bronchial artery embolization (BAE) for continued bleeding which did not resolve after conservative treatment (2.7±1.1 mm, P = 0.94). The technical success rate of embolization was 95% (53/56). Clinical success rate during follow-up was achieved in 50 (94%) of 53 patients who had undergone embolization. Conclusions MDCTA provides useful information for identifying the anatomical characteristics of bleeding-related BAs and nonbronchial systemic arteries for the management of patients with severe hemoptysis. However, MDCTA could not determine the individuals who need BAE through measuring diameter of BAs.


Comparison of protein expression profiles between monolayer and spheroid cell culture of HT-29 cells revealed fragmentation of CK18 in three-dimensional cell culture.
The use of three-dimensional cell culture models, so-called multicellular tumor spheroids, is a special approach in experimental cancer research, because spheroids are similar to in vivo tumors in structural as well as functional sense. Cells grown in spheroids exhibit alterations of cell cycle regulation, induction of apoptosis and differentiation and can acquire multidrug resistance. In this study we investigated the protein expression in human colorectal cancer cells grown in monolayer and in spheroid cultures using proteomics. Evaluation by computer-assisted image analysis revealed overexpression of three cytokeratin 18 fragments that were generated in vivo. Cytokeratin 18 has previously been described as a target for caspase-mediated cleavage during apoptosis and our results indicate that apoptosis may take place in spheroids. Other proteins upregulated in spheroids include calreticulin precursor, a rho GDP dissociation inhibitor variant, several cytokeratins and peroxiredoxin 4. Some of these proteins have already been linked to chemoresistance and apoptotic phenomena.


Treatment of febrile neutropenia and prophylaxis in hematologic malignancies: a critical review and update.
Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis.


Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex.
We investigated the interaction of phospholipase C-gamma (PLC-gamma) with wild-type and mutant forms of the platelet-derived growth factor (PDGF) beta-receptor both in vivo and in vitro. After PDGF treatment of CHO cell lines expressing wild-type or either of two mutant (delta Ki and Y825F) PDGF receptors, PLC-gamma became tyrosine phosphorylated and associated with the receptor proteins. The receptor association and tyrosine phosphorylation of PLC-gamma correlated with the ability of these receptors to mediate ligand-induced phosphatidylinositol turnover. However, both the delta Ki and Y825F mutant receptors were deficient in transmitting mitogenic signals, suggesting that the PDGF-induced tyrosine phosphorylation and receptor association of PLC-gamma are not sufficient to account for the growth-stimulatory activity of PDGF. Wild-type and delta Ki mutant PDGF receptor proteins expressed with recombinant baculovirus vectors also associated in vitro with mammalian PLC-gamma. However, baculovirus-expressed c-fms, v-fms, c-src, and Raf-1 proteins failed to associate with PLC-gamma under similar conditions. Phosphatase treatment of the baculovirus-expressed PDGF receptor greatly decreased its association with PLC-gamma. This requirement for receptor phosphorylation was also observed in vivo, where PLC-gamma could not associate with a mutant PDGF receptor (K602A) defective in autophosphorylation. PLC-gamma also coimmunoprecipitated with two other putative receptor substrates, the serine-threonine kinase Raf-1 and the 85-kilodalton phosphatidylinositol-3' kinase, presumably through its association with the ligand-activated receptor. Furthermore, baculovirus-expressed Raf-1 phosphorylated purified PLC-gamma in vitro at sites which showed increased serine phosphorylation in vivo in response to PDGF. These results suggest that PDGF directly influences PLC activity by inducing the association of PLC-gamma with a receptor signaling complex, resulting in increased tyrosine and serine phosphorylation of PLC-gamma.


Risk factors associated with cesarean section and adverse fetal outcomes in intrahepatic cholestasis of pregnancy.
To determine the risk factors for cesarean section (CS) and adverse fetal outcomes (AFOs) in patients with intrahepatic cholestasis of pregnancy (ICP) based on the severity of maternal hypercholanemia. A hospital-based retrospective cohort study was performed between January 1, 2015, and December 31, 2019. A total of 227 nulliparous women with a singleton fetus complicated by ICP were included. The patients were divided into two groups according to the levels of total bile acids, that is, mild (10 μmol/L < total bile acids < 40 μmol/L) and severe (≥40 μmol/L). The patients' clinical characteristics and fetal outcomes were assessed. Among the 227 eligible women, 177 (78.0%) were allocated to the mild group and 50 (22.0%) were in the severe group. Women with severe ICP also had a significantly higher incidence of planned and unplanned CS compared with mild ICP subjects (52.0% vs. 23.7% and 22.0% vs. 6.8%, respectively; p < 0.001). The indications for CS showed that fetal intolerance (65.4% vs. 14.3%) was higher in severe ICP compared with mild ICP (p < 0.001). Severe ICP was associated with an increased risk of preterm delivery (p < 0.001), low birthweight (p = 0.001), and neonatal intensive care unit (NICU) admission (p < 0.001). Women with severe ICP (OR 6.397, 95%CI 3.041-13.455, p < 0.001) or preeclampsia (OR 12.434, 95%CI 5.166-29.928, p < 0.001) had increased risks of AFOs compared to controls. Severe ICP and preeclampsia are associated with a higher incidence of AFOs.


Investigation of fine nanoparticles syngas catalyst (POM) considering their various morphology.
Ni/SiO2 fine nanoparticles were prepared by coprecipitation method using various nonionic surfactants as templates with Tylose as a binder dispersant. Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD) have been used to study the templates influence on the morphology of the produced samples. Although the phase structure remained as a tetrahedron amorphous cristobalite-sin-SiO2 (101,100), rhombohedron and cubic NiO, but samples with different morphology (homogeneous nano spherical, nano rose flower and nano cubic shapes) have been achieved. These fine nanoparticles as syngas catalysts in Partial Oxidation of Methane to Hydrogen and Carbon Monoxide (POM) have been studied. Because of high Hydrogen production, it is a candidate to be a green fuel. A fixed-bed reactor at P = 1 atm, T = 800 degrees C, H2/CO = 1.8, GHSV (CH4) = 6000/hr and BET = 25, 63.5 and 87.1 m2/gr have been used as POM catalyst. From other hand these fine compounds could be converted to metallic nanotube (nanofiber) at above 850 degrees C and also bamboo shape tip mode carbon nanotube by thermal chemical vapor deposition at 800 degrees C. Transmission Electron Microscopy confirmed the metallic nanotube or single nano crystal growth. The Raman spectroscopy of all samples has been studied to confirm the different formation of Ni-Si. Choosing different templates for production of these nanoparticles could create width range of medical and industrial applications.


Perspectives on passive antibody therapy and peptide-based vaccines against emerging pathogens like SARS-CoV-2.
The current epidemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is raising awareness of the need to act faster when dealing with new pathogens. Exposure to an emerging pathogen generates an antibody response that can be used for preventing and treating the infection. These antibodies might have a high specificity to a target, few side effects, and are useful in the absence of an effective vaccine for treating immunocompromised individuals. The approved antibodies against the receptor-binding domain (RBD) of the viral spike protein of SARS-CoV-2 (e.g., regdanvimab, bamlanivimab, etesevimab, and casirivimab/imdevimab) have been selected from the antibody repertoire of B cells from convalescent patients using flow cytometry, next-generation sequencing, and phage display. This encourages use of these techniques especially phage display, because it does not require expensive types of equipment and can be performed on the lab bench, thereby making it suitable for labs with limited resources. Also, the antibodies in blood samples from convalescent patients can be used to screen pre-made peptide libraries to identify epitopes for vaccine development. Different types of vaccines against SARS-CoV-2 have been developed, including inactivated virus vaccines, mRNA-based vaccines, non-replicating vector vaccines, and protein subunits. mRNA vaccines have numerous advantages over existing vaccines, such as efficacy, ease of manufacture, safety, and cost-effectiveness. Additionally, epitope vaccination may constitute an attractive strategy to induce high levels of antibodies against a pathogen and phages might be used as immunogenic carriers of such peptides. This is a point worth considering further, as phage-based vaccines have been shown to be safe in clinical trials and phages are easy to produce and tolerate high temperatures. In conclusion, identification of the antibody repertoire of recovering patients, and the epitopes they recognize, should be an attractive alternative option for developing therapeutic and prophylactic antibodies and vaccines against emerging pathogens.


THz absorption spectroscopy of solvated β-lactoglobulin.
The influence of β-lactoglobulin (βLG) on the fast sub-picosecond collective hydration dynamics in the solvent was investigated by THz absorption spectroscopy as a function of pH. It is well-known that a change in pH from pH 6 to pH 8 reversibly opens or closes the binding cavity by a transition of the E-F loop. Furthermore, the aggregation of the protein into dimers is affected, which is thought to be triggered by changes in the enzyme's electrostatic potential. Our data reveal that pH has a clear influence on the THz absorption of βLG. We discuss this influence in light of the changes observed in the sub-psec solute/solvent dynamics when probed by THz spectroscopy, which are, in turn, seen to correlate with changes in the pH value.


Consequence of evolutionary loss of seasonal breeding by humans for prostate cancer chemoprevention.
During mammalian evolution, circulating levels of gonadotropins [i.e., luteinizing hormone (LH) and follicle-stimulating hormone (FSH)] acquired regulation by environmental (e.g., light, temperature, water, food, predators, etc.), and social (e.g., sound, sight, aggression, crowding, etc.) inputs that determine the level of testosterone production and secretion by the testis and systemic levels in the blood. This regulation became coordinated by interaction between the retinohypothalamic-pineal and the hypothalamic-pituitary neural axes, which resulted in androgen levels and its ligand-dependent transducing receptor being the master downstream determinant of male reproduction. A major factor in this selection of androgen levels relates to the unique danger of mammalian reproduction for survival of the individual. During mammalian evolution, breeding needed for survival of the species became episodically (i.e., seasonally) timed by androgen levels. Seasonal breeding has great reproductive advantage in restricting energy requirements for reproduction and limiting dangers associated with procreation (i.e., survival of the species) at the expense of suppression of the flight instinct (i.e., survival of the individual) to the minimal time frame of the breeding season. Human males evolved away from strict seasonal breeding by chronically maintaining androgen levels, enabling human males to reproduce year-round and worldwide, rather than "locking" them into specific indigenous breeding ranges, like other mammals. The price for the reproductive "freedom" that arises from the loss of seasonal breeding is an increased probability of developing prostate cancer as a result of chronically maintaining a hyperplastic state in the prostate. In human males, this results in the loss of episodic pruning of genetically-mutated prostate cancer precursors that normally occurs during seasonal breeding. Instead, the continuous androgen-dependent stimulation of the growth of such precursors occurs during prostate carcinogenesis. This review provides the rationale for the development of a therapeutic approach using PSA-activated prodrugs to selectively deplete prostate-specific AR protein for chemoprevention of prostate cancer.


Blood flow in rat gastrocnemius muscle and Achilles tendon after Achilles tenotomy.
The effect of Achilles tenotomy on resting blood flow of rat gastrocnemius muscle and Achilles tendon was studied by radioactive microspheres. Tenotomy produced an immediate, marked decrease in both intramuscular and intratendinous blood flow and it remained significantly lowered at both sites till the end of the observation period, i.e., day 18 after tenotomy. The decrease in the resting blood flow was more rapid and pronounced in the Achilles tendon than in the gastrocnemius muscle. Although the blood flow of the Achilles tendon started to recover after the 4th postoperative day, it was still 33% (statistically not significant) lower than that in the controls 18 days after tenotomy. In the gastrocnemius muscle, the 18-day deficit was 38% (p < 0.001), respectively. The results indicate that after division of a rat Achilles tendon the resting blood flow to the gastrocnemius muscle and Achilles tendon is not adequately restored, remaining at a significantly lowered level even 18 days after tenotomy.


Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats.
Vascular endothelial dysfunction (VED) plays an important role in the initiation of cardiovascular diseases. Roselle, enriched with antioxidants, demonstrates high potential in alleviating hypertension. This study was undertaken to investigate the effects of roselle supplementation of VED and remodelling in a rodent model with prolonged nicotine administration. Male Sprague-Dawley rats (n = 6 per group) were administered with 0.6 mg/kg nicotine for 28 days to induce VED. The rats were given either aqueous roselle (100 mg/kg) or normal saline orally 30 min prior to nicotine injection daily. One additional group of rats served as control. Thoracic aorta was isolated from rats to measure vascular reactivity, vascular remodelling and oxidative stress. Roselle significantly lowered aortic sensitivity to phenylephrine-induced vasoconstriction (Endo-(+) Cmax = 234.5 ± 3.9%, Endo-(-) Cmax = 247.6 ± 5.2%) compared with untreated nicotine group (Endo-(+) Cmax = 264.5 ± 6.9%, Endo-(-) Cmax = 276.5 ± 6.8%). Roselle also improved aortic response to endothelium-dependent vasodilator, acetylcholine (Endo-(+) Rmax = 73.2 ± 2.1%, Endo-(-) Rmax = 26.2 ± 0.8%) compared to nicotine group (Endo-(+) Rmax = 57.8 ± 1.7%, Endo-(-) Rmax = 20.9 ± 0.8%). In addition, roselle prevented an increase in intimal media thickness and elastic lamellae proliferation to preserve vascular architecture. Moreover, we also observed a significantly lowered degree of oxidative stress in parallel with increased antioxidant enzymes in aortic tissues of the roselle-treated group. This study demonstrated that roselle prevents VED and remodelling, and as such it has high nutraceutical value as supplement to prevent cardiovascular diseases.


Environmental and Biological Impact of Fly Ash and Metakaolin-Based Alkali-Activated Foams Obtained at 70°C and Fired at 1,000°C.
Alkali-activated foams (AAFs) are inorganic porous materials that can be obtained at temperatures well below 100°C with the use of inorganic wastes as aluminosilicate precursors. In this case, fly ash derived from a Slovenian power plant has been investigated. Despite the environmental benefits per se, due to saving of energy and virgin materials, when using waste materials, it is of extreme importance to also evaluate the potential leaching of heavy metal cations from the alkali-activated foams. This article presents an environmental study of a porous geopolymer derived from this particular fly ash, with respect to the leachability of potentially hazardous elements, its environmental toxicity as determined by biological testing, and the environmental impact of its production. In particular, attention was focused to investigate whether or not 1,000°C-fired alkali-activated fly ash and metakaolin-based foams, cured at 70°C, are environmentally friendlier options compared to unfired ones, and attempts to explain the rationale of the results were done. Eventually, the firing process at 1,000°C, apart from improving technical performance, could reinforce heavy metal cation entrapment within the aluminosilicate matrix. Since technical performance was also modified by addition of different types of activators (K-based or Na-based), as well as by partial replacement of fly ash with metakaolin, a life cycle assessment (LCA) analysis was performed to quantify the effect of these additions and processes (curing at 70°C and firing at 1,000°C) in terms of global warming potential. Selected samples were also evaluated in terms of leaching of potentially deleterious elements as well as for the immobilization effect of firing. The leaching test indicated that none of the alkali-activated material is classified as hazardous, not even the as-received fly ash as component of new AAF. All of the alkali-activated foams do meet the requirements for an inertness. The highest impact on bacterial colonies was found in samples that did not undergo firing procedures, i.e., those that were cured at 70°C, which induced the reduction of bacterial Enterococcus faecalis viability. The second family of bacteria tested, Escherichia coli, appeared more resistant to the alkaline environment (pH = 10-12) generated by the unfired AAMs. Cell viability recorded the lowest value for unfired alkali-activated materials produced from fly ash and K-based activators. Its reticulation is only partial, with the leachate solution appearing to be characterized with the most alkaline pH and with the highest ionic conductivity, i.e., highest number of soluble ions. By LCA, it has been shown that 1) changing K-based activators to Na-based activators increases environmental impact of the alkali-activated foams by 1%-4% in terms of most of the impact categories (taking into account the production stage). However, in terms of impact on abiotic depletion of elements and impact on ozone layer depletion, the increase is relatively more significant (11% and 18%, respectively); 2) replacing some parts of fly ash with metakaolin also results in relatively higher environmental footprint (increase of around 1%-4%, while the impact on abiotic depletion of elements increases by 14%); and finally, 3) firing at 1,000°C contributes significantly to the environmental footprint of alkali-activated foams. In such a case, the footprint increases by around one third, compared to the footprint of alkali-activated foams produced at 70°C. A combination of LCA and leaching/toxicity behavior analysis presents relevant combinations, which can provide information about long-term environmental impact of newly developed waste-based materials.


[Primary vasospastic angina pectoris: relations between manifestations of ischemia and presence of ventricular arrhythmia].
24-hour ECG monitoring was performed in 12 patients with primary vasospastic angina (PVA). Angiography revealed a predominant lesion to a single coronary vessel (83%). There were 64 episodes of ST-segment changes (46 elevations and 18 depressions) during the monitoring that lasted 388 hours and 54 minutes. Ventricular arrhythmias were concomitant in 34% of the episodes. Ventricular arrhythmia significantly more frequently occurred when an ischemic episode lasted more than 5 minutes. No significant relation was established between the presence of ventricular arrhythmia and other indicators of ischemic manifestation.


Implications of intensification of pastoral animal production on animal welfare.
The intensification of pastoral animal production results from several major developments including increased forage production and utilisation, diet supplementation, breeding animals to increase milk, meat or wool production, and changes in management. The impact of increased intensification on welfare will differ across species and systems. More intensive-grazing systems and the feeding of novel forages will underpin all moves to intensification. More intensive grazing generally reduces opportunities for shade and shelter. Improved nutrition will generally benefit welfare but competition for available feed may cause increased social pressure. Increased flock and herd size will be associated with a reduction in the human:animal ratio and less time to observe individual animals. Remote monitoring of activity and health might counter this impact. Intensification of dairy production will result in larger herds, more year-round milking, robotic milking, use of housing and yards year round, and total mixed-ration feeding. Larger herds mean longer distances to walk to and from the dairy shed, and more lameness and less time to spend on self-maintenance activities such as grooming. Holding and feeding dairy cows on yards will cause an increase in lameness and mastitis and perhaps an increase in agonistic behaviour but will reduce time spent walking. Intensification of sheep production will involve increased flock size, increased fecundity, breeding from hoggets, and breeding ewes all year round. Housing during lambing might be considered appropriate, as would feeding to lift milk yields. Increased fecundity with an increase in triplets will increase lamb mortality rates, but housing ewes, when managed well, will result in reduced lamb mortality. Intensification of lamb finishing will be by improved nutrition. Intensification of beef production will include more breeding of heifers at 15 months, and more problems with dystocia. Intensification of pastoral production will have positive and negative effects on animal welfare. The balance will be determined by the quality of management and stockmanship, and the pressure on businesses to be profitable.


Spatial visual function in anomalous trichromats: Is less more?
Color deficiency is a common inherited disorder affecting 8% of Caucasian males with anomalous trichromacy (AT); it is the most common type of inherited color vision deficiency. Anomalous trichromacy is caused by alteration of one of the three cone-opsins' spectral sensitivity; it is usually considered to impose marked limitations for daily life as well as for choice of occupation. Nevertheless, we show here that anomalous trichromat subjects have superior basic visual functions such as visual acuity (VA), contrast sensitivity (CS), and stereo acuity, compared with participants with normal color vision. Both contrast sensitivity and stereo acuity performance were correlated with the severity of color deficiency. We further show that subjects with anomalous trichromacy exhibit a better ability to detect objects camouflaged in natural gray scale figures. The advantages of color-deficient subjects in spatial vision performance could explain the relatively high prevalence of color-vision polymorphism in humans.


Serum Endocan Levels are Associated With Paraoxonase 1 Concentration in Patients With Chronic Kidney Disease.
Endocan is a soluble proteoglycan released by the vascular endothelium. The increase of its serum levels is associated with inflammation, endothelial dysfunction and cardiovascular events in patients with chronic kidney disease (CKD). We studied the association of serum endocan with the lipid profile of 105 CKD patients with dyslipidemia, divided in two groups, non-dialyzed (CKD, N = 57) and hemodialysis (HD, N = 48) in comparison with 30 normal controls (NC). We also analyzed endocan in relation with the concentration of two serum HDL-linked members of the paraoxonase (PON) family, PON1 and PON3, which have been previously found to have antiatherogenic properties. The results showed that endocan levels were significantly higher in HD patients than in CKD patients (P < 0.001) and NC (P < 0.001). PON1 was significantly decreased only in HD patients compared to NC (P < 0.001), whereas PON3 was significantly increased in both patient groups (P < 0.001). Endocan levels were significantly and positively correlated with total cholesterol and LDL-C in CKD and additionally were negatively correlated with HDL-C in HD group. PON1 levels were significantly correlated with endocan in both groups, while no correlation was observed for PON3 in either group. Multiple regression analysis between endocan and the above lipid parameters in the total of patients revealed that endocan was independently associated only with PON1 (β = -0.513, P = 0.002). It is concluded that the increase of serum endocan levels in patients with CKD may be associated with the decrease of PON1 concentration, irrespective of lipid alterations produced by atherosclerosis development.


Characterizing the community use of an ultralight wheelchair with "on the fly" adjustable seating functions: A pilot study.
An ultralight manual wheelchair that allows users to independently adjust rear seat height and backrest angle during normal everyday usage was recently commercialized. Prior research has been performed on wheelchair tilt, recline, and seat elevation use in the community, however no such research has been done on this new class of manual ultralight wheelchair with "on the fly" adjustments. The objective of this pilot study was to investigate and characterize the use of the two adjustable seating functions available on the Elevation™ ultralight dynamic wheelchair during its use in the community. Eight participants had data loggers installed onto their own wheelchair for seven days to measure rear seat height, backrest angle position, occupied sitting time, and distance traveled. Analysis of rear seat height and backrest adjustment data revealed considerable variability in the frequency of use and positions used by participants. There was a wide spread of mean daily rear seat heights among participants, from 34.1 cm to 46.7 cm. Two sub-groups of users were further identified: those who sat habitually at a single typical rear seat height, and those who varied their rear seat height more continuously. Findings also showed that participants used the rear seat height adjustment feature significantly more often than the backrest adjustment feature. This obvious contrast in feature use may indicate that new users of this class of wheelchair may benefit from specific training. While the small sample size and exploratory nature of this study limit the generalizability of our results, our findings offer a first look at how active wheelchairs users are using a new class of ultralight wheelchair with "on the fly" seating adjustments in their communities. Further studies are recommended to better understand the impact of dynamic seating and positioning on activity, participation and quality of life.


Mast cell sensitizing antibodies in experimental candidiasis.
Inoculation into foot-pads of guinea-pigs of a living suspension of Candida albicans together with Complete Freund's Adjuvant, provoked a hypersensitive state, characterized by: 1) positive skin tests; 2) direct degranulation of peritoneal mast cells when exposed in vitro to the antigen; and 3) homologous "mast cell sensitizing antibodies" detected by the "indirect mast cell degranulation test". The mast cell sensitizing antibodies were heat labile, and their activity could not be restored by complement.


PEG-induced fusion of phosphatidylcholine-liposomes with protoplasts and post-fusion evaluation of plating efficiency and enrichment in plasmamembrane phosphatidylcholine of protoplasts in Datura innoxia Mill.
Liposomes entrapping fluorescein diacetate were fused with protoplasts of Datura innoxia Mill by employing polyethylene glycol (PEG) as the fusogen. Factors that influence liposome-protoplast fusion were optimized as a function of PEG-concentration and incubation duration, liposome composition and surface charge and liposome:protoplast ratio. Phosphatidylcholine-liposomes were found ideal for the objectives of the study. Fusion index based on per cent fluorescing protoplasts varied among the protoplast types. PEG-incubation duration in the fusion assay and growth ability of protoplasts to form microcalli subsequent to liposome-protoplast fusion was determined based on protoplast plating-efficiency. Plating efficiency of post-fusion protoplasts increased due to incorporation of liposome-phosphatidylcholine in the plasmamembrane of protoplasts. Results are discussed in relation to the application of liposome-protoplast fusion system in selective modification of plasmamembrane phospholipids of protoplasts.


Selenium nanoparticles trigger alterations in ovarian cancer cell biomechanics.
High dose selenium acts as a cytotoxic agent, with potential applications in cancer treatment. However, clinical trials have failed to show any chemotherapeutic value of selenium at safe and tolerated doses (<90 μg/day). To enable the successful exploitation of selenium for cancer treatment, we evaluated inorganic selenium nanoparticles (SeNP), and found them effective in inhibiting ovarian cancer cell growth. In both SKOV-3 and OVCAR-3 ovarian cancer cell types SeNP treatment resulted in significant cytotoxicity. The two cell types displayed contrasting nanomechanical responses to SeNPs, with decreased surface roughness and membrane stiffness, characteristics of OVCAR-3 cell death. In SKOV-3, cell membrane surface roughness and stiffness increased, both properties associated with decreased metastatic potential. The beneficial effects of SeNPs on ovarian cancer cell death appear cell type dependent, and due to their low in vivo toxicity offer an exciting opportunity for future cancer treatment.


Relaxant effects of carvacrol on guinea pig tracheal chains and its possible mechanisms.
The bronchodilatory effects of three cumulative volumes (0.02, 0.04, and 0.08 ml) of 1/100 diluted carvacrol were examined by their relaxant effects on tracheal chains of guinea pigs precontracted by 60 mM KCl (group 1) and 10 microM methacholine in two different conditions including: non-incubated tissues (group 2) and incubated tissues with 1 microM propranolol and 1 microM chlorpheniramine (group 3), (for each group, n = 5). The relaxant effects of all three volumes of carvacrol were significantly higher than those of ethanol and even theophylline in all three groups of experiments (p < 0.05 to p < 0.001). There were positive correlations between the relaxant effect of carvacrol and incremental volume (p < 0.05 to p < 0.001). These results indicated that carvacrol has a potent relaxant effect on tracheal chains of guinea pigs which is not due to beta2-adrenergic stimulatory, histamine H1, and muscarinic blocking effect.


A joint modeling approach for uncovering associations between gene expression, bioactivity and chemical structure in early drug discovery to guide lead selection and genomic biomarker development.
The modern drug discovery process involves multiple sources of high-dimensional data. This imposes the challenge of data integration. A typical example is the integration of chemical structure (fingerprint features), phenotypic bioactivity (bioassay read-outs) data for targets of interest, and transcriptomic (gene expression) data in early drug discovery to better understand the chemical and biological mechanisms of candidate drugs, and to facilitate early detection of safety issues prior to later and expensive phases of drug development cycles. In this paper, we discuss a joint model for the transcriptomic and the phenotypic variables conditioned on the chemical structure. This modeling approach can be used to uncover, for a given set of compounds, the association between gene expression and biological activity taking into account the influence of the chemical structure of the compound on both variables. The model allows to detect genes that are associated with the bioactivity data facilitating the identification of potential genomic biomarkers for compounds efficacy. In addition, the effect of every structural feature on both genes and pIC50 and their associations can be simultaneously investigated. Two oncology projects are used to illustrate the applicability and usefulness of the joint model to integrate multi-source high-dimensional information to aid drug discovery.


A sensitive one-step method for quantitative detection of α-amylase in serum and urine using a personal glucose meter.
Assays of α-amylase (AMS) activity in serum and urine constitute the important indicator for the diagnosis of acute pancreatitis, mumps, renal disease and abdominal disorders. Since these diseases confer a heavy financial burden on the health care system, AMS detection in point-of-care is fundamental. Here, a one-step assay for direct determination of the AMS activity was developed using a portable personal glucose meter (PGM). In this assay, maltopentaose was used as a substrate for sensitive detection of AMS with the assistance of α-glucosidase. In the presence of AMS, maltopentaose can be readily hydrolyzed to form maltotriose and maltose quickly. With the enzymatic hydrolysis of α-glucosidase, maltotriose and maltose can be turned into glucose rapidly, which can be quantitatively measured using a portable PGM. This assay did not require any cumbersome and time consuming operations, such as surface modification, synthesis of invertase conjugate, washing and centrifugation. Detection of AMS can be achieved using only a one-step mixture, and the limit of detection was 20 U L(-1) which was lower than the clinical cutoff for AMS. More importantly, this sensitive and selective assay was also used for the detection of AMS in human serum/urine samples. The results showed that the recovery of AMS from human serum/urine samples was 91-107%. The rapid and easy-to-operate assay may have potential application in the fields of point-of-care (POC) clinical diagnosis, particularly in rural and remote areas where lab equipment may be limited.


A second corticotropin-releasing hormone gene (CRH2) is conserved across vertebrate classes and expressed in the hindbrain of a basal neopterygian fish, the spotted gar (Lepisosteus oculatus).
To investigate the origins of the vertebrate stress-response system, we searched sequenced vertebrate genomes for genes resembling corticotropin-releasing hormone (CRH). We found that vertebrate genomes possess, in addition to CRH, another gene that resembles CRH in sequence and syntenic environment. This paralogous gene was previously identified only in the elephant shark (a holocephalan), but we find it also in marsupials, monotremes, lizards, turtles, birds, and fishes. We examined the relationship of this second vertebrate CRH gene, which we name CRH2, to CRH1 (previously known as CRH) and urocortin1/urotensin1 (UCN1/UTS1) in primitive fishes, teleosts, and tetrapods. The paralogs CRH1 and CRH2 likely evolved via duplication of CRH during a whole-genome duplication early in the vertebrate lineage. CRH2 was subsequently lost in both teleost fishes and eutherian mammals but retained in other lineages. To determine where CRH2 is expressed relative to CRH1 and UTS1, we used in situ hybridization on brain tissue from spotted gar (Lepisosteus oculatus), a neopterygian fish closely related to teleosts. In situ hybridization revealed widespread distribution of both crh1 and uts1 in the brain. Expression of crh2 was restricted to the putative secondary gustatory/secondary visceral nucleus, which also expressed calcitonin-related polypeptide alpha (calca), a marker of parabrachial nucleus in mammals. Thus, the evolutionary history of CRH2 includes restricted expression in the brain, sequence changes, and gene loss, likely reflecting release of selective constraints following whole-genome duplication. The discovery of CRH2 opens many new possibilities for understanding the diverse functions of the CRH family of peptides across vertebrates.


Total energy intake and intake of three major nutrients by body mass index in Japan: NIPPON DATA80 and NIPPON DATA90.
This paper investigated the relationship between body mass index (BMI) and total energy intake as well as intake of three major nutrients in representative Japanese populations enrolled in the National Nutrition Surveys of Japan in 1980 and 1990. A total of 10,422 participants (4585 men and 5837 women) and 8342 participants (3488 men and 4854 women) aged 30 or older from 300 randomly selected districts participated in the National Survey of Circulatory Disorders and the National Nutrition Survey in Japan in 1980 and 1990, respectively. The nutrition surveys were performed with weighing record method for three consecutive days to each household. Individually estimated total energy intake and intakes of three major nutrients (carbohydrate, protein, and fat) were compared by the categories of BMI and by 10-year age groups. In men, total energy intake (kcal/day), intakes of three major nutrients (g/day) and energy intake ratio from protein and fat (%) increased as BMI increased in each age group, whereas energy intake ratio from carbohydrate (%) decreased. In women, total energy intake, intakes of three major nutrients, and energy intake ratio from protein increased as BMI increased. Energy intake ratio from carbohydrate and fat decreased as BMI increased in women in 1990. When participants were categorized into quartiles according to total energy intake in each sex group, BMI increased as total energy intake increased in men in both 1980 and 1990. A positive relationship was observed between body mass index and total energy intake in Japanese men. The relationship was weaker in Japanese women.


Sex, shoulder pain, and range of motion in manual wheelchair users.
Upwards of 70% of manual wheelchair users (MWUs) experience shoulder pain. Pain is more prevalent among females than males. The causes of this sex discrepancy are not understood. Decreased range of motion (ROM) has been suggested as a major contributor, but the interaction of sex, ROM, and shoulder pain has not been investigated, thus the purpose of this investigation. We divided 30 MWUs (18 males, 12 females; 21.93 +/- 3.77 yr) into two groups based on self-reported shoulder pain: pain group (n = 14; 9 males, 5 females) and no pain group (n = 16; 9 males, 7 females). We used a digital goniometer to assess ROM. Participants' shoulder active and passive ROMs were tested bilaterally on the following joint motions: flexion, extension, abduction, adduction, internal rotation, and external rotation. We used a visual analog scale to assess shoulder pain. Of the participants, 47% reported shoulder pain. Overall, the no pain group had greater ROM than the pain group, with further analysis revealing this association was only significant in females during extension (p < 0.05). ROM impairments were only present in extension in females with shoulder pain. The mechanism underlying this sex difference is not clear.


Gluteal gunshot wounds: who warrants exploration?
It is difficult to determine which stable patients with gluteal gunshot wounds warrant exploration since 22% to 36% will have injuries requiring operative intervention. The ability of preoperative studies to identify major injuries was evaluated to determine which studies could accurately triage patients into a high-risk group that would warrant laparotomy and a low-risk group that could be managed with observation. The findings of abdominal tenderness or gross blood in the urine or rectum were each highly predictive of major injury. The determination of an extrapelvic versus transpelvic bullet trajectory allowed accurate triage of 94% of patients. Nearly 85% of patients with a transpelvic trajectory had injuries that required operative intervention. No patients with an extrapelvic trajectory required laparotomy. Given the density of vital structures above and below the peritoneum in the pelvis, we conclude that any patient with a transpelvic bullet trajectory warrants exploration.


Epithelial cell differentiation of human mesenchymal stromal cells in decellularized lung scaffolds.
Identification of appropriate donor cell types is important for lung cell therapy and for lung regeneration. Previous studies have indicated that mesenchymal stromal cells derived from human bone marrow (hBM-MSCs) and from human adipose tissue (hAT-MSCs) may have the ability to trans-differentiate into lung epithelial cells. However, these data remain controversial. Herein, the ability of hBM-MSCs and hAT-MSCs to repopulate acellular rodent lung tissue was evaluated. hBM-MSCs and hAT-MSCs were isolated from bone marrow aspirate and lipoaspirate, respectively. Rat lungs were decellularized with CHAPS detergent, followed by seeding the matrix with hBM-MSCs and hAT-MSCs. Under appropriate culture conditions, both human MSC populations attached to and proliferated within the lung tissue scaffold. In addition, cells were capable of type 2 pneumocyte differentiation, as assessed by marker expression of surfactant protein C (pro-SPC) at the protein and the RNA level, and by the presence of lamellar bodies by transmission electron microscopy. Additionally, hAT-MSCs contributed to Clara-like cells that lined the airways in the lung scaffolds, whereas the hBM-MSCs did not. We also tested the differentiation potential of MSCs on different extracellular matrix components in vitro, and found that protein substrate influences MSC epithelial differentiation. Together our data show the capacity for human MSCs to differentiate toward lung epithelial phenotypes, and the possibility of using these cells for lung cell therapies and tissue engineering.


Identifying vulnerable older adult populations by contextualizing geriatric syndrome information in clinical notes of electronic health records.
Geriatric syndromes such as functional disability and lack of social support are often not encoded in electronic health records (EHRs), thus obscuring the identification of vulnerable older adults in need of additional medical and social services. In this study, we automatically identify vulnerable older adult patients with geriatric syndrome based on clinical notes extracted from an EHR system, and demonstrate how contextual information can improve the process. We propose a novel end-to-end neural architecture to identify sentences that contain geriatric syndromes. Our model learns a representation of the sentence and augments it with contextual information: surrounding sentences, the entire clinical document, and the diagnosis codes associated with the document. We trained our system on annotated notes from 85 patients, tuned the model on another 50 patients, and evaluated its performance on the rest, 50 patients. Contextual information improved classification, with the most effective context coming from the surrounding sentences. At sentence level, our best performing model achieved a micro-F1 of 0.605, significantly outperforming context-free baselines. At patient level, our best model achieved a micro-F1 of 0.843. Our solution can be used to expand the identification of vulnerable older adults with geriatric syndromes. Since functional and social factors are often not captured by diagnosis codes in EHRs, the automatic identification of the geriatric syndrome can reduce disparities by ensuring consistent care across the older adult population. EHR free-text can be used to identify vulnerable older adults with a range of geriatric syndromes.


Thirty-five years of the Department of Plastic Surgery and Burns Treatment at the University Hospital in Hradec Králové.
The Department of Plastic Surgery and Burns Treatment was established as a part of the newly created 2nd Department of Surgery of Charles University, Medical Faculty and the University Hospital in Hradec Králové in 1985. Through modest beginnings, activities of the Department expanded up to full coverage of specialized care in plastic surgery within the region with almost one million inhabitants. In this article, the most important events of several historical phases related to almost four decades are described. The aspects of medical personnel, technological and space equipment are especially emphasized. The Department has always been working on the principles of interdisciplinary co-operation within the department itself and other departments within the hospital as well. Over the past 35 years, the Department of Plastic Surgery and Burns Treatment has been firmly entrenched in the spectrum of specialized activities of the University Hospital in Hradec Králové.


Clinical Feasibility of Multi-Acquisition Variable-Resonance Image Combination-Based T2 Mapping near Hip Arthroplasty.
Background: Hip arthroplasty is increasingly prevalent, and early detection of complications can improve outcomes. Quantitative magnetic resonance imaging (qMRI) methods using multi-acquisition variable-resonance image combination (MAVRIC) may allow for the assessment of soft tissues in close proximity to hip arthroplasty devices. Question/Purposes: We sought to determine the clinical feasibility of MAVRIC-based T2 mapping as a qMRI approach for assessing synovial reactions in patients with a hip arthroplasty device. We hypothesized that there would be differences in T2 metrics by synovial type, clinical impression, and clinical findings related to synovitis. Methods: We conducted a cross-sectional study of 141 subjects with 171 hip arthroplasties with greater than 1 year post-implantation. We enrolled subjects who had had a primary total hip arthroplasty or hip resurfacing arthroplasty between May 2019 and March 2020, excluding those with a revision hip arthroplasty and those with standard safety contraindications for receiving an MRI. Institutional standard 2D fast spin echo (FSE), short-tau inversion recovery (STIR), and susceptibility-reduced MAVRIC morphological MR images were acquired for each hip and followed by a dual-echo acquisition MAVRIC T2 mapping sequence. Results: While 131 subjects (81%) were classified as having a "normal" synovial reaction, significantly longer T2 values were found for fluid synovial reactions compared with mixed reactions. In addition, subjects with synovial dehiscence and decompression present had T2 prolongation. Larger synovial volumes were found in subjects with low-signal intensity deposits. Conclusions: MAVRIC-based T2 mapping is clinically feasible and there are significant quantitative differences based on type of synovial reaction. Patients undergoing hip arthroscopy revision surgery will warrant comparison of T2 values with direct histologic assessment of a tissue sample obtained intraoperatively. The approach used in this study may be used for a quantitative evaluation and monitoring of soft tissues around metal implants.


Application and Resistance Mechanisms of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma.
Lenvatinib, a multitargeted tyrosine kinase inhibitor (TKI), is one of the preferred targeted drugs for the treatment of advanced hepatocellular carcinoma (aHCC). Since the REFLECT study showed that lenvatinib was noninferior to sorafenib in overall survival (OS), lenvatinib monotherapy has been widely used for aHCC. Moreover, lenvatinib combination therapy, especially lenvatinib combined with immune checkpoint inhibitors (ICIs), has shown more encouraging clinical results. However, drug development and comprehensive treatment have not significantly improved the prognosis, and lenvatinib resistance is often encountered in treatment. The underlying molecular mechanism of lenvatinib resistance is still unclear, and studies to solve drug resistance are ongoing. The molecular mechanisms of lenvatinib resistance in patients with aHCC include the regulation of signaling pathways, the regulation of noncoding RNAs, the impact of the immune microenvironment, tumor stem cell activation and other mechanisms. This review aims to (1) summarize the progress of lenvatinib in treating aHCC, (2) delineate the known lenvatinib resistance mechanisms of current therapy, and (3) describe the development of therapeutic methods intended to overcome these resistance mechanisms.


An Incision-less Ultrasound-guided Carpal Tunnel Release Technique.
Ultrasound guidance in the operative treatment of carpal tunnel syndrome is gaining in popularity as it noninvasively provides the surgeon with a real-time high-resolution overview of anatomic structures. A new incision-less approach to achieve a division of the transverse carpal ligament has been developed that combines ultrasound guidance with cannulated needles and a thread. Conceptually, an abrasive thread is looped percutaneously around the ligament while avoiding injury to neurovascular structures, the palmar aponeurosis, and skin. The thread is positioned using 2 puncture sites and a contoured Tuohy needle under ultrasound visualization. With a minimal injury to surrounding structures, this approach is designed to minimize recovery time and decrease pillar pain. This article will provide a step-by-step overview of the technique and includes a review of clinical outcomes published so far.


Antcin C from Antrodia cinnamomea Protects Liver Cells Against Free Radical-Induced Oxidative Stress and Apoptosis In Vitro and In Vivo through Nrf2-Dependent Mechanism.
In this study, we investigated the cytoprotective effects of antcin C, a steroid-like compound isolated from Antrodia cinnamaomea against AAPH-induced oxidative stress and apoptosis in human hepatic HepG2 cells. Pretreatment with antcin C significantly protects hepatic cells from AAPH-induced cell death through the inhibition of ROS generation. Furthermore, AAPH-induced lipid peroxidation, ALT/AST secretion and GSH depletion was significantly inhibited by antcin C. The antioxidant potential of antcin C was correlated with induction of antioxidant genes including, HO-1, NQO-1, γ -GCLC, and SOD via transcriptional activation of Nrf2. The Nrf2 activation by antcin C is mediated by JNK1/2 and PI3K activation, whereas pharmacologic inhibition of JNK1/2 and PI3K abolished antcin C-induced Nrf2 activity. In addition, AAPH-induced apoptosis was significantly inhibited by antcin C through the down-regulation of pro-apoptotic factors including, Bax, cytochrome c, capase 9, -4, -12, -3, and PARP. In vivo studies also show that antcin C significantly protected mice liver from AAPH-induced hepatic injury as evidenced by reduction in hepatic enzymes in circulation. Further, immunocytochemistry analyses showed that antcin C significantly increased HO-1 and Nrf2 expression in mice liver tissues. These results strongly suggest that antcin C could protect liver cells from oxidative stress and cell death via Nrf2/ARE activation.


Strategies for Biofilm Inhibition and Virulence Attenuation of Foodborne Pathogen-Escherichia coli O157:H7.
Enterohemorrhagic Escherichia coli (E. coli) O157:H7, a gram-negative bacteria identified as a foodborne pathogen causing severe disease is of great concern worldwide. The pathogenicity of E. coli O157:H7 is due to the presence of some virulence factors and its ability to form biofilm which resist antimicrobial compounds, withstand harsh environmental condition and protects from the host immune responses. Formation of biofilm is a multistep process such as adhesion, cellular aggregation and productions of extracellular matrix in which colonies are embedded. There are high numbers of research in the discovery of natural and synthetic compounds which can attenuate the E. coli O157:H7 biofilm formation as well as suppress virulence-related genes. The present review article focuses on the steps involved in E. coli O157:H7 biofilm formation, factors associated with virulence and attenuation.


Neocytolysis: physiological down-regulator of red-cell mass.
It is usually considered that red-cell mass is controlled by erythropoietin-driven bone marrow red-cell production, and no physiological mechanisms can shorten survival of circulating red cells. In adapting to acute plethora in microgravity, astronauts' red-cell mass falls too rapidly to be explained by diminished red-cell production. Ferrokinetics show no early decline in erythropolesis, but red cells radiolabelled 12 days before launch survive normally. Selective destruction of the youngest circulating red cells-a process we call neocytolysis-is the only plausible explanation. A fall in erythropoietin below a threshold is likely to initiate neocytolysis, probably by influencing surface-adhesion molecules. Recognition of neocytolysis will require re-examination of the pathophysiology and treatment of several blood disorders, including the anaemia of renal disease.


Oral immunization with simian immunodeficiency virus p55gag and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates.
Rhesus macaques were orally immunized with a mucosal vaccine consisting of two different concentrations (1 mg vs 250 microg) of recombinant SIV p55gag (p55) with or without cholera toxin (CT, 50 microg) as a mucosal adjuvant. The plasma from macaques receiving the higher dose of p55 (1 mg) and CT had higher p55-specific IgG and IgA Ab titers compared with macaques that received the lower dose of p55 (250 microg) and CT. Further, high levels of p55-specific IgG and IgA Abs were present in external secretions from both groups. The level of p55-induced T cell responses was elevated in PBMCs isolated from the high dose group compared with the low dose group. When culture supernatants from these p55-stimulated PBMCs were examined for Th1 (IFN-gamma) and Th2 (IL-4 and IL-10) cytokines, both IFN-gamma and IL-10 were present, but IL-4 was absent. CD4+ T cells isolated from these p55-stimulated PBMCs contained IFN-gamma spot-forming cells (SFCs) but not IL-4 SFCs. These results were further confirmed by cytokine-specific reverse transcriptase PCR analysis, where p55-specific CD4+ T cells expressed mRNA for IFN-gamma, IL-6, and IL-10, but not IL-4. These findings suggest that oral immunization of nonhuman primates induced both IFN-gamma-secreting Th1 and select Th2 cytokine (e.g., IL-6 and IL-10)-producing CD4+ Th cells, which accounted for the generation of p55-specific systemic and mucosal Ab responses.


[Antibacterial effect of Nd:YAG laser in periodontal pockets decontamination: a in vivo study].
Tha aim of this paper is to assess the effects in vivo of the Nd: Yag laser on gingival microflora in patients periodontally at risk. An investigation has been carried out on 5 patients suffering from serious periodontal disease, with a sub-gingival check-up a week after the treatment. The selected patients presented either a relapse after the raising of a traditional flap, or showed acute phenomena and were, therefore, treated with a laser with the propedeutic intention of surgery; or they refused traditional surgical therapy or presented systematic pathologies that could not be included in the appropriate protocol. Pockets were chosen that had a probe depth of between 5-8 mm, an optic fibre probe was pushed as far as possible into the probe depth, for about 1 minute per site, 5 times, at 30 second intervals. The samples, taken in order to calculate bacteria colonies, were carried out before using the laser, immediately after and, again, 1 week later. All the sites showed a slight reduction in the quantity of colonies forming immediately after the Nd:Yag laser application, while a week later, only if clinical inflammation appeared to be resolved, the bacteria forming colonies seemed to be reduced. From this study it can be concluded that the use of the Nd:Yad laser represents, in mild and average periodontitis, a therapeutic aid to scaling and root planing and, in the same way, in serious periodontitis for traditional surgical therapy.


Neutrophil gelatinase-associated lipocalin as a screening test in prostate cancer.
Prostate specific antigen (PSA) with digital rectal examination is used for diagnosis of prostate cancer (PCa), where definite diagnosis can only be made by prostate biopsy. Recently neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin family member glycoprotein, come into prominence as a cancer biomarker. This study is aimed to test serum NGAL as a diagnostic biomarker for PCa and discriminate PCa from benign prostatic hyperplasia (BPH). In this prospective study, 90 patients who underwent transrectal ultrasound-guided 12-core prostate biopsy between May 2015 and September 2015, were evaluated. Histopathologically diagnosed 45 PCa and 45 BPH patients were enrolled in this study. Serum NGAL and PSA levels of all participants were measured, then these data were evaluated by statistical programs. When sensitivity fixed to 80% specificity of NGAL was better than PSA (49%, 31% respectively). Receiver operating characteristic (ROC) curve analysis showed that NGAL alone or its combined use with PSA have better area under curve (AUC) results than PSA alone (0.662, 0.693, and 0.623 respectively). In conclusion NGAL gave promising results such as increased sensitivity and a better AUC values in order to distinguish PCa from BPH. NGAL showed a potential to be a non-invasive biomarker which may decrease the number of unnecessary biopsies.


Environmental correlates of intercity variation in age-adjusted cancer mortality rates.
Factors contributing to urban differences in cancer mortality rates are difficult to specify because of migration and the delay between exposure to carcinogens and manifestations of the disease. Proxy measures for prior migration, motor vehicle emissions, industrial pollution, factors in the water supplies, and climate, explain more than half the intercity variation in age-adjusted cancer mortality rates among 98 cities in the U.S. in 1970. The potential importance of these environmental factors as the "urban factor" in cancer is discussed.


XbaI-RFLP of the APOB gene in a sample group from southern Italy.
The XbaI Restriction Fragment Length Polymorphism (RFLP) of the APOB gene at codon 2488 was investigated in a sample group from Southern Italy (165 subjects), taken from a population characterized by a low average level of cholesterolemia. The X2 allele (presence of XbaI cutting site), that in several groups was found to be associated with increased cholesterolemia, showed in Southern Italians a frequency of 39% which is significantly (P much less than 0.001) lower than that found in the majority of the Caucasoid groups so far tested (50%). However, an analysis of both cholesterol and APOB serum levels performed in a sample of 82 subjects, homogeneous for sex and age did not reveal any significant association between lipidemic parameters and APOB-XbaI genotypes.


Three-dimensional structure of apical vesicles of tuft cells in the main excretory duct of the rat submandibular gland.
Tuft cells are present in the mucosal epithelium of a number of hollow organs including the main excretory duct (MED). Despite their distinctive features such as the long, thick, blunt microvilli with prominent rootlets and the large number of vesicles in the apical cytoplasm, the hypolemmal terminal-tuft cell relationship and the true form of the various vesicles and tubules are still controversial. The present study investigated the above mentioned features of tuft cells in the MED of rat submandibular gland by computer three-dimensional (3-D) reconstruction with focus on their function. Computer 3-D reconstruction revealed that nerve endings are present at both sides of the basal portion of the lateral cytoplasmic branch of tufts cells and that the apical tubulovesicular system of these cells consists of two separate components: the complex and coherent vesicles and the small network of tubules. We suggest that such a system may be involved in the rapid changes of surface area observed in tuft cells. Furthermore, our findings demonstrate that the images seen in thin sections and formerly regarded as evidence for the presence of variations in the shape of the tubules and of the vesicles are in reality the product of the different angles at which the tubulovesicular system was sectioned. Finally, a few vesicles and tubules that were not part either of the complex or of the network, also were found.


Parallel-stranded DNA with mixed sequence. Evidence for conformational transition in solution at low water activity.
Parallel-stranded deoxyoligonucleotide 5'd(CTATAGGGAT)3'/5'd(GATATCCCTA)3' (I-II) was shown to be stable in solution at 3 degrees-5 degrees C, 0.1-0.25 M NaCl, 10(-2) M phosphate buffer, pH 7.0 by means of a set of fluorescent techniques as well as of conventional optical methods. A cooperative change in the CD spectra is observed in trifluoroethanol (TFE) solutions at decreased water activity (relative humidity, r.h.). This distinctive change is supposed to stem from a cooperative conformational transition of parallel double helix from a B-like form with C2' endo sugar conformation to an A-like form designated as Ap. The free energy difference between the Ap and B-like conformation for the parallel duplex is 7.35 kcal/mol which is close to the value 7.40 kcal/mol for the antiparallel 5'd(CTATAGGGAT)3'/3'd(GATATCCCTA)5' (I-III). The ability of parallel helix to transit into Ap form is important for DNA-RNA parallel double helix formation.


Development and implementation of an independence rating scale and evaluation process for nursing orientation of new graduates.
A wide variety of evaluation formats are available for new graduate nurses, but most of them are single-point evaluation tools that do not provide a clear picture of progress for orientee or educator. This article describes the development of a Web-based evaluation tool that combines learning taxonomies with the Synergy model into a rating scale based on independent performance. The evaluation tool and process provides open 24/7 access to evaluation documentation for members of the orientation team, demystifying the process and clarifying expectations. The implementation of the tool has proven to be transformative in the perceptions of evaluation and performance expectations of new graduates. This tool has been successful at monitoring progress, altering education, and opening dialogue about performance for over 125 new graduate nurses since inception.


Qualitative research on suicide in East Asia: a scoping review.
Suicide is a serious problem in East Asia. Yet, there is a significant lack of research on the topic, particularly using qualitative methodology. This scoping review reports on findings drawn from 11 qualitative studies, providing up-to-date knowledge and understandings about suicide in East Asian populations. A web-based literature search was performed to identify empirical qualitative research articles addressing suicide in East Asia, published from January 2002 to December 2011. Three themes were identified within the reviewed studies; (1) influence of cultural beliefs; (2) the role of caregivers; and (3) specific sociological contexts. These themes are interrelated rather than mutually exclusive. The findings drawn from this scoping review reveal specific as well as broad contexts where suicidal ideation and behaviours occur among East Asians. To advance understandings, future studies should focus on comparative and longitudinal research to distil prevailing trends as well as the specificities that reside among particular East Asian subgroups (i.e. gender, sexual identity and generational) as a means to developing culturally sensitive and targeted suicide prevention programs.


Histiocytoid Sweet syndrome treated with azathioprine: a case report.
Histiocytoid Sweet syndrome (HSS) is a rare histologic variation of Sweet syndrome (SS) predominantly exhibiting mononuclear histiocytoid cells instead of neutrophils. We report a 22-year-old woman with HSS, who, after minimal improvement with colchicine and dapsone, had significant improvement of her cutaneous eruption and systemic symptoms following empiric treatment with azathioprine. Since azathioprine has historically been known to cause SS, this case highlights a previously unreported treatment response for the histiocytoid variant.


Huntingtin Plays a Role in the Physiological Response to Ethanol in Drosophila.
Huntingtin (htt) protein is an essential regulator of nervous system function through its various neuroprotective and pro-survival functions, and loss of wild-type htt function is implicated in the etiology of Huntington's disease. While its pathological role is typically understood as a toxic gain-of-function, some neuronal phenotypes also result from htt loss. Therefore, it is important to understand possible roles for htt in other physiological circumstances. To elucidate the role of htt in the context of ethanol exposure, we investigated how loss of htt impacts behavioral and physiological responses to ethanol in Drosophila. We tested flies lacking htt for ethanol sensitivity and tolerance, preference for ethanol using capillary feeder assays, and recovery of mobility after intoxication. Levels of dopamine neurotransmitter and numbers of dopaminergic cells in brains lacking dhtt were also measured. We found that dhtt-null flies are both less sensitive and more tolerant to ethanol exposure in adulthood. Moreover, flies lacking dhtt are more averse to alcohol than controls, and they recover mobility faster following acute ethanol intoxication. We showed that dhtt mediates these effects at least in part through the dopaminergic system, as dhtt is required to maintain normal levels of dopamine in the brain and normal numbers of dopaminergic cells in the adult protocerebrum. Our results demonstrate that htt regulates the physiological response to ethanol and indicate a novel neuroprotective role for htt in the dopaminergic system, raising the possibility that it may be involved more generally in the response to toxic stimuli.


Urinary cysteinyl leukotriene E4 level and therapeutic response to montelukast in children with mild obstructive sleep apnea.
Antileukotriene has been used for alleviating disease severity in children with adenotonsillar hypertrophy (ATH) and mild obstructive sleep apnea (OSA). Previous study showed the relationship between urinary cysteinyl leukotriene E₄ (uLTE₄) level and therapeutic response to montelukast in asthmatic adults. However, this relationship has never been investigated in pediatric OSA. To determine the relationship between uLTE₄ level and therapeutic response to montelukast in children with ATH and mild OSA. Children aged 3-15 yrs who had ATH and mild OSA were enrolled. All had quality of life (assessed by Thai version OSA-18 QoL questionnaire) and uLTE₄ levels measured prior to start a 6-week course of montelukast treatment. Overnight polysomnography (PSG) and QoL reassessment were performed after completing the treatment. Those who demonstrated a large improvement of mean total QoL score or ≥ 50% decrease of obstructive apnea-hypopnea index (OAHI) after the treatment were defined as responders. Twenty-six children were enrolled (mean age 7.5 ± 2.9 yrs, 38.5% male). After 6-week course of montelukast, nine (34.6%) children showed significant improvement. The mean uLTE₄ level from the responders was higher comparing to the non-responders (2,952.56 ± 966.9 vs. 978.6 ± 460.8 pg/mg creatinine; p < 0.001). uLTE₄ level of ≥ 1,457 pg/mg creatinine had 100% sensitivity and 88.2% specificity in identifying the responders. We found the association between ULTE4 and therapeutic response to monteleukast. The uLTE₄ level of ≥ 1,457 pg/mg creatinine could predict the therapeutic response to montelukast in children who had ATH and mild OSA.


Mucinous cystadenoma of the renal pelvis with malignant transformation: a case report.
A mucinous cystadenoma of the renal pelvis with malignant transformation is an extremely rare entity. We discuss one such rare occurrence in a 62 year old female who developed mucinous nephrosis due to marked retention of mucin produced by the tumor.