Computational Studies of the Effect of Shock Waves on the Binding of Model Complexes.
We have simulated effects of a shock wave in water that would result from the collapse of a cavitation bubble on binding in model complexes. We have considered a benzene dimer, a pair of uracil molecules, a complex of fragments of the X-linked inhibitor of apoptosis and caspase-9, and a fragment of c-Myc oncoprotein in binding with its dimerization partner Max. The effect of the shock waves was simulated by adding a momentum to a slab of solvent water molecules and observing the system as the slab moved and caused changes. In the cases of the small molecular pairs, the passage of the shock waves lead to dissociation of the complexes. The behavior of the protein systems was more complex, yet significant disruption of the binding and geometry was also observed. In all the cases, the effects did not occur during the immediate impact of the high-momentum solvent molecules, but rather during the expansion of the compressed system that followed the passage of the waves. The rationale of the studies was in attempting to understand the strong effects that irradiation with a low-intensity ultrasound can have on biomolecular systems, because such ultrasound irradiation can cause cavitation bubbles to be produced and collapse, thus leading to local shock wave generation. The long-term objective is to contribute to future design of synergetic ultrasound and chemical drug strategy of protein inhibition.


Identification and functional characterization of a novel monotreme- specific antibacterial protein expressed during lactation.
Monotremes are the only oviparous mammals and exhibit a fascinating combination of reptilian and mammalian characters. They represent a component of synapsidal reproduction by laying shelled eggs which are incubated outside the mother's body. This is accompanied by a prototherian lactation process, marking them as representatives of early mammals. The only extant monotremes are the platypus, and the short- and long- beaked echidnas, and their distributions are limited to Australia and New Guinea. Apart for a short weaning period, milk is the sole source of nutrition and protection for the hatchlings which are altricial and immunologically naive. The duration of lactation in these mammals is prolonged relative to the gestational length and period of incubation of eggs. Much of the development of monotreme young occurs in the non-sterile ex-utero environment. Therefore the role of milk in the growth, development and disease protection of the young is of significant interest. By sequencing the cDNA of cells harvested from monotreme milk, we have identified a novel monotreme- specific transcript, and the corresponding gene was designated as the EchAMP. The expression profile of this gene in various tissues revealed that it is highly expressed in milk cells. The peptides corresponding to the EchAMP protein have been identified in a sample of echidna milk In silico analysis indicated putative antimicrobial potential for the cognate protein of EchAMP. This was further confirmed by in vitro assays using a host of bacteria. Interestingly, EchAMP did not display any activity against a commensal gut floral species. These results support the hypothesis of enhancement of survival of the young by antimicrobial bioactives of mammary gland origin and thus emphasize the protective, non- nutritional role of milk in mammals.


A Systematic Review of therapeutic agents for the treatment of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV).
The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first described in 2012 and attracted a great international attention due to multiple healthcare associated outbreaks. The disease carries a high case fatality rate of 34.5%, and there is no internationally or nationally recommended therapy. We searched MEDLINE, Science Direct, Embase and Scopus databases for relevant papers published till March 2019 describing in vitro, in vivo or human therapy of MERS. Initial search identified 62 articles: 52 articles were from Medline, 6 from Embase, and 4 from Science Direct. Based on the inclusions and exclusions criteria, 30 articles were included in the final review and comprised: 22 in vitro studies, 8 studies utilizing animal models, 13 studies in humans, and one study included both in vitro and animal model. There are a few promising therapeutic agents on the horizon. The combination of lopinavir/ritonavir and interferon-beta- 1b showed excellent results in common marmosets and currently is in a randomized control trial. Ribavirin and interferon were the most widely used combination and experience comes from a number of observational studies. Although, the data are heterogenous, this combination might be of potential benefit and deserve further investigation. There were no randomized clinical trials to recommend specific therapy for the treatment of MERS-CoV infection. Only one such study is planned for randomization and is pending completion. The study is based on a combination of lopinavir/ritonavir and interferon-beta- 1b. A fully human polyclonal IgG antibody (SAB-301) was safe and well tolerated in healthy individuals and this agent may deserve further testing for efficacy. Despite multiple studies in humans there is no consensus on the optimal therapy for MERS-CoV. Randomized clinical trials are needed and potential therapies should be evaluated only in such clinical trials. In order to further enhance the therapeutic aroma for MERS-CoV infection, repurposing old drugs against MERS-CoV is an interesting strategy and deserves further consideration and use in clinical settings.


p53 and Cell Fate: Sensitizing Head and Neck Cancer Stem Cells to Chemotherapy.
Head and neck cancers are deadly diseases that are diagnosed annually in approximately half a million individuals worldwide. Growing evidence supporting a role for cancer stem cells (CSCs) in the pathobiology of head and neck cancers has led to increasing interest in identifying therapeutics to target these cells. Apart from the canonical tumor-suppressor functions of p53, emerging research supports a significant role for this protein in physiological stem cell and CSC maintenance and reprogramming. Therefore, p53 has become a promising target to sensitize head and neck CSCs to chemotherapy. In this review, we highlight the role of p53 in stem cell maintenance and discuss potential implications of targeting p53 to treat patients with head and neck cancers.


Addition of grape pomace extract to probiotic fermented goat milk: the effect on phenolic content, probiotic viability and sensory acceptability.
Grape pomace is a source of phenolic compounds, which are associated with health benefits in humans. Additionally, fermented dairy foods with probiotics can be good vehicles to deliver these bioactive compounds. The effects of the addition of grape pomace extract (GPE) on the total phenolic (TP) content, physico-chemical characteristics and viability of Lactobacillus acidophilus LA-5 or Lactobacillus rhamnosus HN001 in fermented goat milks prepared with grape juice were investigated. The TP concentration increased significantly in fermented milks with the addition of GPE. A protective effect of GPE on the viability of L. acidophilus was observed. However, after 14 days of storage, the populations of L. acidophilus were significantly lower when compared with those of L. rhamnosus, and only the last probiotic maintained its viability above 7 log CFU mL-1 throughout the period investigated. The sensory scores of flavor, color and overall acceptability of the fermented milk containing L. rhamnosus HN001 were significantly increased when GPE was added. The use of GPE might increase the functionality of probiotic fermented goat milk processed with L. rhamnosus HN001 and grape juice because grape polyphenols are known for their antioxidant properties and positive effect on the modulation of gut microbiota. © 2016 Society of Chemical Industry.


Quantitation of clovamide-type phenylpropenoic acid amides in cells and plasma using high-performance liquid chromatography with a coulometric electrochemical detector.
A high-performance liquid chromatography (HPLC) method was developed for measuring the concentrations of clovamide-type phenylpropenoic acid amides (N-caffeoyldopamine and N-caffeoyltyramine) in cell and plasma samples. The separation was performed on a Nova-Pak C18 column using an isocratic buffer with a coulometric electrochemical detector with four electrode channels. Using the HPLC method, N-caffeoyldopamine and N-caffeoyltyramine could be detected with good peak resolutions at respective retention times (4 and 6.4 min). The calibration curves were linear over the ranges (0.1 and 100 microM), and their lower limit of detection was as little as 100 fmol. For quantifying N-caffeoyldopamine and N-caffeoyltyramine in cell and plasma samples, the samples were extracted by extraction methods with more than 95% recoveries. After extraction, the amides were detected with the same sensitivity, peak resolutions, and retention times. Using this method, plasma concentrations of N-caffeoyltyramine were determined in blood samples collected at 12, 24, 30, 36, 48, 60, and 75 min after the oral administrations of N-caffeoyltyramine (0.5 mg and 2 mg/30 g body weight). This HPLC method with an electrochemical detector is the first reported method able to quantify N-caffeoyldopamine and N-caffeoyltyramine in biological samples with excellent detection limits, peak resolutions, discrete retention times, and consistent reproducibility.


Rotavirus contains integrin ligand sequences and a disintegrin-like domain that are implicated in virus entry into cells.
Rotavirus contains two outer capsid viral proteins, the spike protein VP4 and major capsid component VP7, both of which are implicated in cell entry. We show that VP4 and VP7 contain tripeptide sequences previously shown to act as recognition sites for integrins in extracellular matrix proteins. VP4 contains the alpha2beta1 integrin ligand site DGE. In VP7, the alphaxbeta2 integrin ligand site GPR and the alpha4beta1 integrin ligand site LDV are embedded in a novel disintegrin-like domain that also shows sequence similarity to fibronectin and the tie receptor tyrosine kinase. Microorganism sequence homology to these ligand motifs and to disintegrins has not been reported previously. In our experiments, peptides including these rotaviral tripeptides and mAbs directed to these integrins specifically blocked rotavirus infection of cells shown to express alpha2beta1 and beta2 integrins. Rotavirus VP4-mediated cell entry may involve the alpha2beta1 integrin, whereas VP7 appears to interact with alphaxbeta2 and alpha4beta1 integrins.


The observation of the formation of splenic artery pseudoaneurysms.
Pseudoaneurysms are infrequent, potentially fatal angiopathies. Because of a high mortality rate, pseudoaneurysms must be handled urgently, regardless of the size and symptoms at presentation. We report a case of chronic pancreatitis and a pseudocyst of the pancreas complicated with a splenic artery pseudoaneurysm. Endoscopic ultrasonography (EUS) was chosen as the device to observe the forming of a splenic artery pseudoaneurysm, which could provide timely, minimally invasive, precise lesion information. Early diagnosis and urgent measure are important when there is a high probability of splenic artery psedoaneurysm. In recent years, EUS has been extensively studied in the detection, diagnosis and treatment of pancreatic disease. The color-Doppler flow imaging (CDFI) can dynamically reflect the peripheral blood flow signal. EUS with a CDFI function can play an important role in the initial detection of pseudoaneurysms, especially when complicated with chronic pancreatitis with or without a pseudocyst. We recommend that EUS should be carried out if a pseudoaneurysm near the digestive tract is considered, then effective and timely measures can produce a favorable prognosis.


Controlled growth of iron oxide nanoparticles in the aqueous microdroplets.
Magnetite nanoparticles were synthesized by chemical coprecipitation of ferric and ferrous aqueous solutions via regulation of the microenvironment at ambient conditions. Nanocrystals having an average diameter of 6 to 12 nm were obtained by picoliter droplets, whereas only 9 nm diameter nanocrystals were prepared by microliter droplets. The size of the nanocrystals was controlled by a precise balance of reactions of hydroxide ions with positive ions at the surface layer and inner layers of the droplets. The crystal structure and average size were analyzed by X-ray diffraction pattern and transmission electron microscope images. The field dependence and temperature dependence on magnetization measured by a superconducting quantum interference device demonstrate that the as-synthesized particles are superparamagnetic at room temperature and have a size-dependent magnetic property. The anisotropy constant calculated by the blocking temperature and particle size was found to decrease with increasing particle size.


Reference intervals data mining: no longer a probability paper method.
To describe the application of a data-mining statistical algorithm for calculation of clinical laboratory tests reference intervals. Reference intervals for eight different analytes and different age and sex groups (a total of 11 separate reference intervals) for tests that are unlikely to be ordered during routine screening of disease-free populations were calculated using the modified algorithm for data mining of test results stored in the laboratory database and compared with published peer-reviewed studies that used direct sampling. The selection of analytes was based on the predefined criteria that include comparability of analytical methods with a statistically significant number of observations. Of the 11 calculated reference intervals, having upper and lower limits for each, 21 of 22 reference interval limits were not statistically different from the reference studies. The presented statistical algorithm is shown to be an accurate and practical tool for reference interval calculations.


Mitochondrial DNA Copy Number Variations and Serum Pepsinogen Levels for Risk Assessment in Gastric Cancer
Variations in mitochondrial DNA copy number (mtDNA-CN) of peripheral blood leukocytes (PBLs), as a potential biomarker for gastric cancer (GC) screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with serum pepsinogen (sPG) I/II ratio, as an established indicator of gastric atrophy. The study population included GC (n = 53) and non-GC (n = 207) dyspeptic patients. The non-GC group was histologically categorized into CG (n = 104) and NM (n = 103) subgroups. The MtDNA-CN of PBLs was measured by quantitative real-time PCR. The sPG I and II levels and anti-H. pylori serum IgG were measured by ELISA. The mtDNA-CN was found significantly higher in GC vs. non-GC (OR = 3.0; 95% CI = 1.4, 6.4) subjects. Conversely, GC patients had significantly lower sPG I/II ratio than the non-GC (OR = 3.2; CI = 1.4, 7.2) subjects. The combination of these two biomarkers yielded a dramatic amplification of the odds of GC risk in double-positive (high mtDNA-CN-low sPGI/II) subjects, in reference to double-negatives (low mtDNA-CN-high sPGI/II), when assessed against non-GC (OR = 27.1; CI = 5.0, 147.3), CG (OR = 13.1; CI = 2.4, 72.6), or NM (OR = 49.5; CI = 7.9, 311.6) groups. The combination of these two biomarkers, namely mtDNA-CN in PBLs and serum PG I/II ratio, drastically enhanced the efficiency of GC risk assessment, which calls for further validations.


Comparison of the effects of the new orally active antiestrogen EM-800 with ICI 182 780 and toremifene on estrogen-sensitive parameters in the ovariectomized mouse.
The nonsteroidal antiestrogen EM-800 is approximately 10-fold more potent than ICI 182 780, the most potent known steroidal antiestrogen, at inhibiting estrone-stimulated uterine weight in ovariectomized mice (half-maximal inhibitory daily s.c. doses of 0.2 and 2.0 microg, respectively). At maximal doses, however, both compounds lead to a similar maximal 90% inhibition of estrone-stimulated uterine weight. A 10-fold higher activity of EM-800 compared with ICI 182 780 was also observed on estrone-stimulated vaginal weight, with maximal inhibitions of 96% and 90%, respectively, achieved by the two compounds. In addition, EM-800 injected s.c. or administered orally led to a marked loss of uterine and vaginal estrogen receptor levels measured by binding assay, whereas ICI 182 780 exerted no inhibitory effect on this parameter under the experimental conditions used. Comparable effects were observed when estrogen receptor protein levels were measured by enzyme immunoassay. After oral administration, EM-800 exerted maximal 83% and 88% inhibitions of uterine and vaginal weight, respectively, whereas maximal inhibitions limited to 51% and 67% were achieved with toremifene. This limited inhibition by toremifene of the stimulatory effect of estrone on uterine and vaginal weight is probably due to the intrinsic estrogenic activity of the compound. The present data also show that the steroidal antiestrogen ICI 182 780 has less than 3% the activity of EM-800 when administered by the oral route. In fact, EM-800 administered orally is 2- to 3-fold more potent than ICI 182 780 injected s.c.


Cutting edge: antigen-specific TGF beta-induced regulatory T cells suppress Th17-mediated autoimmune disease.
CD4(+) T cells from the TCR transgenic TxA23 mouse recognize a peptide from the H/K-ATPase alpha-chain. When TxA23 CD4(+) thymocytes are differentiated into Th1, Th2, and Th17 lines, all three subpopulations induced autoimmune gastritis (AIG) upon transfer into nu/nu recipients. The induction of AIG by naive T cells or by Th1 or Th2 cell lines could be prevented by the cotransfer of polyclonal Foxp3(+) T regulatory cells (nTreg), whereas Th17-induced AIG was resistant to suppression. We compared the capacity of different types of Treg to suppress Th17-mediated AIG. Cotransfer of either nTreg or polyclonal TGFbeta-induced Treg (iTreg) did not prevent AIG, while cotransfer of TGFbeta-induced Ag-specific TxA23 iTreg completely prevented the development of disease. Ag-specific iTreg were able to suppress Th17-mediated disease when injected 6 days after the Th17 effectors. The implications of these results for the use of Treg for the cellular biotherapy of autoimmune disease are discussed.


SEXUAL SIZE DIMORPHISM AND SELECTION IN THE WILD IN THE WATERSTRIDER AQUARIUS REMIGIS: LIFETIME FECUNDITY SELECTION ON FEMALE TOTAL LENGTH AND ITS COMPONENTS.
Darwin's fecundity advantage model is often cited as the cause of female biased size dimorphism, however, the empirical studies of lifetime selection on male and female body size that would be required to demonstrate this are few. As a component of a study relating sexual size dimorphism to lifetime selection in natural populations of the female size-biased waterstrider Aquarius remigis (Hemiptera: Gerridae), we estimated coefficients for daily fecundity selection, longevity selection, and lifetime fecundity selection acting on female body size and components of body size for two consecutive generations. Daily fecundity was estimated using females confined in field enclosures and reproductive survival was estimated by twice-weekly recaptures. We found that daily fecundity selection favored females with longer total length through direct selection acting on abdomen length. Longevity selection favored females with smaller total length. When daily fecundity and reproductive longevity were combined to estimate lifetime fecundity we found significant balancing selection acting on total length in both years. The relationship between daily fecundity and reproductive longevity also reveals a significant cost of reproduction in one of two years. We relate these selection estimates to previous estimates of sexual selection on male body size and consider the relationship between contemporary selection and sexual size dimorphism.


Theoretical model of internally cooled interstitial ultrasound applicators for thermal therapy.
Interstitial ultrasound applicators for high-temperature thermal therapy are currently being developed for treating cancerous and benign disease. Internally cooled, direct-coupled (ICDC) applicators, composed of a segmented array of cylindrical ultrasound transducers, have demonstrated capabilities of producing controllable and conformal heating distributions along the applicator length and angular orientation. In this study, 2D transient acoustic and biothermal models of ICDC applicators were developed using a mixed implicit and explicit finite difference solution with variable node spacing in cylindrical coordinates for enhanced speed, stability and accuracy. The model incorporates dynamic behaviour of acoustic parameters and blood perfusion as a function of temperature and thermal dose. Acoustic intensity distributions were modelled as a composite of measured and theoretical intensity distributions. The shape and time evolution of temperature contours and thermal lesions for 90 degrees, 200 and 360 degrees angularly directional applicators and multi-transducer applicators were modelled for heating durations between 1 and 5 min. Model parameters were selected to match previously reported ex vivo and in vivo studies of 2.2 mm diameter ICDC devices in thigh muscle and liver (15-30 W cm(-2) applied power density, 0.5-5 min treatment times, 2.8-3.6 cm diameter thermal lesions). The temperatures and lethal thermal dose (600 EM43 degrees C) contours calculated using the models were in excellent agreement with temperatures and thermal lesion dimensions (visible coagulation) determined experimentally. The differences between maximum radial depths of coagulation calculated using the r-z and r-theta models were small, less than approximately 2 mm for 10-15 mm lesions. There was a strong correlation between the calculated 50 degrees C contour and the radial, angular and axial lesion dimensions obtained for 3-5 min heating protocols. The models developed in this study have significant application in design studies and potential future use in treatment planning of ICDC interstitial ultrasound thermal therapy.


[Parallel structures in multidimensional networks].
What restrictions does the space dimension impose on a variety of multidimensional regular networks? The parallel representation method is used to answer this question. An analytical relation of regular network dimension with the connectivity of vertices and the perimeter of elementary contours has been established. It has also been shown that a infinite dimensional network is equivalent to an infinite tree. In addition, the problem of closed regular polytops inside networks is discussed.


Mitral valve prolapse with pulmonary haemosiderosis and severe anaemia: cause or association?
A 12 years boy presented with the history of pallor for one month. Two days before hospitalisation he developed fever, cough, shortness of breath. He had past history of such episode. On examination, his heart rate was found to be 120/minute, respiratory rate 40/minute and moderate anaemia was detected. Scattered creptus was audible over mid and lower lung fields and a soft systolic murmur was auscultated at apex. On investigations, Hb was found as 4.6 g/dl and HbF was less than 2%. Plasma Hb was 5 g/dl. Straight x-ray chest showed bilateral patchy opacities over mid and lower zones. His sputum was found to be blood stained and prompted the possibility of blood loss occurring in the lungs, which was confirmed by demonstrating haemosiderin laden macrophages on three consecutive sputum specimens. Echocardiography revealed a systolic displacement of mitral valve leaflets into the left atrium with co-optation superior to the plane of mitral annulus. Doppler study showed a minimal late systolic regurgitation. It was decided to treat the case as idiopathic pulmonary haemosiderosis. Oxygen inhalation, hypertonic saline nebulisation, i.v. hydrocortisone, packed cell transfusion followed by oral prednisolone improved the patient's condition. After 3 months of discontinuing prednisolone, he remained asymptomatic. Here one case of pulmonary haemosiderosis characterised by abnormal accumulation of haemosiderin in the lungs following repeated alveolar haemorrhages with the presence of mitral valve prolapse is reported.


Three-dimensional culture of hepatocytes for prediction of drug-induced hepatotoxicity.
Hepatotoxicity is the most frequent reason for the withdrawal of an approved drug from the market. Monolayer culture of hepatocyte in two-dimension, which is relatively inexpensive, convenient and easy to use, serves a traditional hepatocyte-based high-content screening for identifying hepatotoxic side effects of tested drugs. However, two-dimensional methods have their limitations in lack of insensitivity on reflection of drug hepatotoxicity. Three-dimensional (3D) cultures of hepatocytes in sandwich, spheroid and gel entrapment provide a microenvironment for high expression of liver-specific functions and are being proposed for prediction of drug hepatotoxicity. This review addressed the reliability of 3D culture models on screening hepatotoxic drugs with particular emphasis on gel entrapment culture model due to its more systematic data on drug testing. The reader will gain a comprehensive understanding of the improved prediction efficacy of 3D culture models. Hepatocytes in 3D cultures, although in need of further standardization required by the throughput operation, show great potential in attempts to ensure the efficacy on prediction of drug hepatotoxicity.


Normative characteristics of ipsilateral acoustic reflex adaptation.
Contralateral and ipsilateral acoustic reflex adaptation (decay) were examined using 500-, 1000-, and 2000-Hz tonal activators for stimulation periods of 30 seconds in 30 normal subjects. For these normal subjects, ipsilateral adaptation always exceeded contralateral adaptation, although differences between the two conditions were not significant. In addition, contralateral and ipsilateral acoustic reflex adaptation of four subjects with varying degrees of sensorineural hearing loss were compared to the normative data. Results for these impaired ears indicated that a longer period of activation may be necessary to distinguish between normal reflex adaptation and adaptation which may occur in cochlear pathology. Further, in three normal ears and two ears with cochlear pathology, ipsilateral adaptation equaled or exceeded 50% of the initial value within 10 seconds of activation. This finding suggests that the same criterion which is used for establishing abnormal contralateral adaptation cannot be used for abnormal ipsilateral adaptation.


Incarceration of a pedunculated uterine fibroid in an umbilical hernia.
Uterine fibroids are common benign tumors that may cause an umbilical hernia in patients with increased intra-abdominal pressure due to pregnancy, obesity, ascites, and intra-abdominal tumors. However, the simultaneous occurrence of uterine fibroids and umbilical hernias, or fibroids and an associated umbilical hernia, during pregnancy has rarely been reported. Here, we present the case of a fibroid presenting as an incarcerated umbilical hernia in a menopausal patient.


Angiotensin II blockade limits tubular protein overreabsorption and the consequent upregulation of endothelin 1 gene in experimental membranous nephropathy.
Proteinuric renal diseases are associated with excessive renal synthesis of endothelin 1 (ET-1) either in experimental animals or humans. This has been interpreted as an upregulation of ET-1 gene in proximal tubular cells secondary to overreabsorption of an unusual amount of filtered proteins. Here we used a model of chronic proteinuria, passive Heymann nephritis (PHN), to localize the structure of the kidney responsible for excessive ET-1 expression and synthesis and to clarify whether drugs that reduce glomerular protein trafficking modified the distribution of ET-1 mRNA and the corresponding peptide in the kidney. PHN was induced in Sprague-Dawley rats after injection of rabbit anti-Fx1A antibody. Group 1 (n = 5) was untreated, group 2 (n = 5) was given daily the angiotensin-converting enzyme inhibitor lisinopril (40 mg/l) plus the angiotensin II receptor antagonist L-158,809 (50 mg/l) from day 7--when rats were already proteinuric--to month 12. An additional group of normal rats (n = 5) was used as controls. Urinary excretion of ET-1 was significantly increased in PHN rats as compared with controls and normalized by the treatment. By in situ hybridization a weak signal for ET-1 mRNA was detectable in glomeruli, distal tubular segments, and proximal tubules of control kidneys. By contrast, a strong labeling was found in the kidneys of rats with PHN which was mainly localized to proximal tubules and renal interstitium. The pattern of renal ET-1-like immunoreactivity was remarkably consistent with ET-1 mRNA expression. In animals with PHN given the angiotensin II blocking therapy, the urinary excretion of proteins normalized, and the structural integrity of the kidney was well preserved. In the kidney tissue taken from these animals, both ET-1 mRNA and protein staining were quite comparable to controls. These data suggest a link between excessive protein tubular reabsorption and enhanced renal ET-1 in chronic nephropathies and provide a novel explanation for the renoprotective effect in vivo of drugs that, by blocking the biological activity of angiotensin II, reduce glomerular protein traffic and possible deleterious effects of excessive tubular protein overloading.


Charge tunable zwitterionic polyampholyte layers formed in cyclic olefin copolymer microchannels through photochemical graft polymerization.
Zwitterionic layers immobilized on various surfaces exhibit ideal biocompatibility and antifouling capability, but direct immobilization of zwitterionic molecules provides limited choice of surface charges. In this paper, the formation of charge tunable zwitterionic polyampholyte layers onto the surface of microfluidic channels of cyclic olefin copolymer by photochemical graft polymerization of mixed acrylic monomers, [2-(acryloyloxy) ethyl] trimethyl ammonium chloride and 2-acrylamido-2-methyl-1-propanesulfonic, under UV illumination was reported. With this method, surface charge of the resulting modification layers could be tailored through the initial monomer ratio and reaction conditions. The incorporation of both monomers into the grafted layers was confirmed by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FTIR). The results indicate that the modified layers are hydrophilic with contact angles of 33.0-44.3°, and the isoelectric points of the modified layers can be tuned from <3 to >9 simply by adjusting the monomer ratios. Elimination of the nonspecific adsorption of proteins on the zwitterionic layers thus formed was proved by fluorescent microscopy and streaming potential measurement. The uniformity of the modified layers was verified through a comparison of electrophoresis inside the modified and native microchannels. A whole blood coagulation time measurement was performed to show its applicability.


Interpreting laser Doppler recordings from free flaps.
Although the transfer of free flaps is nowadays accomplished with an increasing degree of safety, thrombosis of the microvascular anastomoses is still a problem. In order to avoid delay in re-operating, various methods for objective blood flow monitoring have been tried, among them Laser Doppler Flowmetry (LDF). When one reviews the literature, it is apparent that opinions differ about whether or not LDF is a reliable technique for this purpose. To focus on the need to interpret continuous recordings, this paper reports our findings in six latissimus dorsi free flaps chosen from our series of LDF monitoring procedures. One uneventful flap, no. 1, had an immediate postoperative LDF value of 4.5 perfusion units (PU). LDF values improved during the recovery period and the graphic recording showed fluctuations due to normal physiological variations of the blood flow in the flap. Another uneventful flap, no. 4, showed the same pattern, though at an appreciably lower level, 2 PU, on average. Flap no. 2 had an acceptably high value of 3.5 PU despite suffering a venous thrombosis. However, the LDF recording showed no fluctuations and the value declined gradually. Another flap, no. 3, showed fluctuations and blood flow was normal although the value decreased to 2.5 PU. In flap no. 5, any value between 2 and 3.5 PU could be obtained merely by adjusting the position of the probe in the holder. In no. 6, the LDF value suddenly dropped, accompanied by a decrease in the total amount of backscattered light, indicating venous obstruction which was confirmed at re-operation.(ABSTRACT TRUNCATED AT 250 WORDS)


Keeping up with the Wangs: individual and contextual influences on mental wellbeing and depressive symptoms in China.
In recent decades, China has experienced dramatic changes to its social and economic environment, which has affected the distribution of wellbeing across its citizens. While several studies have investigated individual level predictors of wellbeing in the Chinese population, less research has been done looking at contextual effects. This cross-sectional study looks at the individual and contextual effects of (regional) education, unemployment and marriage (rate) on individual happiness, life satisfaction and depressive symptomatology. Data were collected from over 29,000 individuals (aged 18 to 110, 51.91% female) in the China Family Panel Studies, and merged with county level census data obtained from the 2010 China Population Census and Statistical Yearbook. To explore contextual effects, we used multilevel models accounting for the hierarchical structure of the data. We found that a one-year increase in education was associated with a 0.17% increase in happiness and a 0.16% decrease in depressive symptoms. Unemployed men were 1% less happy, 1% less satisfied with life and reported 0.84% more depressive symptoms than employed men while minimal effects were seen for women. Single, divorced and widowed individuals had worse outcomes than married individuals (ranging from 2.96 to 21% differences). We found interaction effects for education and employment. Less educated individuals had greater happiness and less depressive symptoms in counties with higher average education compared to counterparts in less educated counties. In contrast, more educated individuals were less satisfied with life in more educated counties, an effect that is possibly due to social comparison. Employed individuals had lower life satisfaction in areas of high unemployment, while levels were constant for the unemployed. A 1% increase in county marriage rate was associated with 0.33 and 0.24% increases in happiness and life satisfaction respectively, with no interactions. We speculate that this effect could be due to greater social cohesion in the neighbourhood. Our results show that policies designed to improve employment and marriage rates will be beneficial for all, while interventions to encourage positive social comparison strategies may help to offset the negative effects of increasing neighbourhood average education on the highly educated.


GPU-based streaming architectures for fast cone-beam CT image reconstruction and demons deformable registration.
This paper shows how to significantly accelerate cone-beam CT reconstruction and 3D deformable image registration using the stream-processing model. We describe data-parallel designs for the Feldkamp, Davis and Kress (FDK) reconstruction algorithm, and the demons deformable registration algorithm, suitable for use on a commodity graphics processing unit. The streaming versions of these algorithms are implemented using the Brook programming environment and executed on an NVidia 8800 GPU. Performance results using CT data of a preserved swine lung indicate that the GPU-based implementations of the FDK and demons algorithms achieve a substantial speedup--up to 80 times for FDK and 70 times for demons when compared to an optimized reference implementation on a 2.8 GHz Intel processor. In addition, the accuracy of the GPU-based implementations was found to be excellent. Compared with CPU-based implementations, the RMS differences were less than 0.1 Hounsfield unit for reconstruction and less than 0.1 mm for deformable registration.


Closed-system anaesthesia for laparoscopic surgery: is there a risk for carbon monoxide intoxication?
One of the complications of laparoscopic surgery is carbon monoxide production during electrocautery. The aim of our study was to ascertain the relationship between intraperitoneal and alveolar concentrations of carbon monoxide and systemic carboxyhaemoglobin in patients undergoing laparoscopic cholecystectomy and anaesthetized with a closed system, where the carbon monoxide excreted through the lungs is accumulated in the circuit and thus re-inhaled. Nine consecutive patients undergoing laparoscopic cholecystectomy were studied. Patients' lungs were ventilated with a closed anaesthesia breathing system (Physioflex). Measurements were taken after establishing pneumoperitoneum (baseline) and at 5, 15 and 30 min after starting electrocautery. Mean duration of pneumoperitoneum was 42 +/- 13 min with cumulative electrocautery time of 2.4 +/- 1.8 min. Intraperitoneal carbon monoxide concentrations increased significantly at 5, 15 and 30 min reaching peak values of 481 +/- 151 ppm at 15 min. No significant differences were found in alveolar carbon monoxide and carboxyhaemoglobin concentrations with respect to baseline. No significant increase in carboxyhaemoglobin is produced during laparoscopic surgery, even under closed-system anaesthesia without pulmonary carbon monoxide elimination. This is most likely due to a low peritoneal absorption of carbon monoxide. We conclude that in adult patients, no carbon monoxide intoxication is caused if reasonable periods of electrocautery are used and the intraperitoneal gas is regularly renewed.


Significance of fluid flow for morphology of acute hypoxic-ischaemic brain cell injury.
It has been suggested that the presence or absence of hypoxic fluid flow during ischaemia determines the structural character of the ischaemic nerve cell injury. It is hypothesised that if a flow of fluid irrigates the injured neurons, there will be major shifts of ions and water, with consequent volumetric changes in the tissue and the 'dark' type of neuronal injury will result; otherwise, the structural changes are less striking and are designated as the 'pale' type. To test this hypothesis, rats were subjected to a global cerebral insult by filling the vasculature with a plasma substitute, which was either left stagnant or was flowing, and was either oxygenated (hypoxic flow) or nitrogenated (anoxic flow). Light and electron microscopy of the brain following 10 to 60 min of hypoxic or anoxic ischaemia disclosed that, under all three circumstances, the predominant nerve cell injury was of the pale type. The results indicate that some additional factors present in whole blood (but not in the plasma substitute) are needed during or after the insult to induce in quantity the dark type of ischaemic nerve cell injury.


The management of valvular heart disease in children.
The child with significant valvular heart disease may present in any single instance both the most difficult of management decisions or a surprisingly simple one. Thus, if a direct surgical approach on the valve is feasible, the problems may very well be quite simple and straightforward; conversely, if valve replacement is indicated such may not be the case. We have recently reported our experience with one type of valvular heart condition, congenital aortic stenosis, in respect to determination of surgical approach based upon the ability to predict the orifice area and valvular anatomy. This report reviews our current experience with this technique. As well, the experience concerning the approach to each of the valvular conditions will also be reviewed with emphasis in respect to the left heart valves and particularly their long term postoperative management.


Vitamin E deficiency and aging effect on expression levels of GAP-43 and MAP-2 in selected areas of the brain.
The expression levels of GAP-43 and MAP-2, two proteins involved, respectively, in axonal and dendritic remodeling, in control adult (11 months), old (24 months), and vitamin E-deficient (11 months) rats were evaluated. mRNA levels were determined by means of a quantitative in situ hybridization procedure in subregions of hippocampus and cerebellum. Though a general trend can be observed indicating a reduction in GAP-43 expression in aging as compared to adult animals and an increase in vitamin E-deprived rats in comparison with adult animals, no statistically significant change was found in any region analyzed. In the same way, MAP-2 mRNA levels show an increase in vitamin E-deprived rats in comparison with other groups tested; only one variation was statistically significant, namely the increase in cerebellar cortex MAP-2 nRNA levels in vitamin E-deficient versus adult rats. These results suggest that oxidative stress and aging negatively affect neuroplasticity, showing different characteristics at the dendritic and axonal levels.


Gender and income in pharmacy: human capital and gender stratification theories revisited.
This is a case study of gender and earnings in pharmacy--a profession characterized by its rapid recruitment of female practitioners. We try to account for disparities in earnings between male and female pharmacists in Ontario with the aid of human capital theory and gender stratification theory. Data is drawn from a random sample of 463 Ontario pharmacists. We find a consistent sex gap in earnings regardless of occupational level of practitioners (i.e. owner, manager or employee) and net of such factors as hours worked, commitment to work, hours devoted to childcare, absences from the labour market, and years since graduation. Instead, the main reason why women in pharmacy earn less than males is because they remain employees throughout their careers. However, we are less successful at identifying the additional factors responsible for the depressed earnings of female practitioners. We discuss our findings in light of the claims of gender stratification and human capital theory.


Early management of prostate cancer.
Prostate cancer is now the commonest cancer diagnosed in Australia. In 2005 there were 5913 men diagnosed with prostate cancer in New South Wales alone (31% of male cancers; 17% of all cancers). However, that year there were only 980 deaths from prostate cancer in NSW, and so prostate cancer dropped to be the fourth commonest cause of cancer death, ahead of breast cancer with 877 deaths. This discrepancy is a major cause of the angst experienced in the detection and management of prostate cancer. What is needed is a way to separate the significant prostate cancers from the insignificant ones, and accept that identifying them is a very different issue to managing them aggressively.


1 kW 1 mJ eight-channel ultrafast fiber laser.
An ultrafast fiber chirped-pulse amplifier comprising eight coherently combined amplifier channels is presented. The laser delivers 1 kW average power at 1 mJ pulse energy and 260 fs pulse duration. Excellent beam quality and low-noise performance are confirmed. The laser has proven suitable for demanding scientific applications. Further power scaling is possible right away using even more amplifier channels.


A Simple Novel Method to Elevate the Sternum in Thoracoscopic Thymectomy.
The right-chest thoracoscopic surgery approach has become the preferred operation for the treatment of thymic disease. Due to the limited space in the anterior mediastinum, achieving en bloc resection of the tumor is a common difficulty. Here, we report a simple method to lift the sternum by single hook. This method has a lot of advantages, including providing a wide view of the anterior mediastinum for clear vision and being an easy operation.


Effects of thermal mass, window size, and night-time ventilation on peak indoor air temperature in the warm-humid climate of Ghana.
Most office buildings in the warm-humid sub-Saharan countries experience high cooling load because of the predominant use of sandcrete blocks which are of low thermal mass in construction and extensive use of glazing. Relatively, low night-time temperatures are not harnessed in cooling buildings because office openings remain closed after work hours. An optimization was performed through a sensitivity analysis-based simulation, using the Energy Plus (E+) simulation software to assess the effects of thermal mass, window size, and night ventilation on peak indoor air temperature (PIAT). An experimental system was designed based on the features of the most promising simulation model, constructed and monitored, and the experimental data used to validate the simulation model. The results show that an optimization of thermal mass and window size coupled with activation of night-time ventilation provides a synergistic effect to obtain reduced peak indoor air temperature. An expression that predicts, indoor maximum temperature has been derived for models of various thermal masses.


Evaluation of an alternative care provider clinic for severe sleep-disordered breathing: a study protocol for a randomised controlled trial.
Despite the high prevalence of sleep-disordered breathing (SDB) and the significant health consequences associated with untreated disease, access to diagnosis and treatment remains a challenge. Even patients with severe SDB (severe obstructive sleep apnoea or hypoventilation), who are at particularly high risk of adverse health effects, are subject to long delays. Previous research has demonstrated that, within a sleep clinic, management by alternative care providers (ACPs) is effective for patients with milder forms of SDB. The purpose of this study is to compare an ACP-led clinic (ACP Clinic) for patients with severe SDB to physician-led care, from the perspective of clinical outcomes, health system efficiency and cost. The study is a randomised, controlled, non-inferiority study in which patients who are referred with severe SDB are randomised to management by a sleep physician or by an ACP. ACPs will be supervised by sleep physicians for safety. The primary outcome is positive airway pressure (PAP) adherence after 3 months of therapy. Secondary outcomes include: long-term PAP adherence; clinical response to therapy; health-related quality of life; patient satisfaction; healthcare usage; wait times from referral to treatment initiation and cost-effectiveness. The economic analysis will be performed using the perspective of a publicly funded healthcare system. Ethics approval was obtained from the Conjoint Health Research Ethics Board (ID: REB13-1280) at the University of Calgary. Results from this study will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals. NCT02191085; Pre-results.


Acute and long-term response of the meniscus to partial meniscectomy using the holmium: YAG laser.
The purpose of this study was to evaluate the histological effects of holmium:YAG laser partial meniscectomy in an in vivo rabbit model and compare it with scalpel partial meniscectomy at selected time intervals. Twenty-four adult male New Zealand rabbits underwent bilateral partial medial meniscectomies through the avascular zone. In the right knee, partial medial meniscectomy was performed using a standard surgical blade; in the left knee, an anatomically similar partial medial meniscectomy was performed using a Ho:YAG laser (Coherent, Santa Clara, CA). All animals were randomized and three animals were killed at postoperative days I and 3, and postoperative weeks 1, 2, 3, 4, 6, and 10. Samples of all medial and lateral menisci, with attached synovium and vascular rim, from both knees were harvested and submitted for histological and/or ultrastructural examination. The results indicate that (1) at all time periods, laser cut menisci had more cell loss and matrix degradation; (2) synovial necrosis was more common in laser-treated knees; (3) the Ho:YAG laser creates three zones of damage in the meniscal fibrocartilage: a zone of fibrin and debris at the incision site, a zone of necrosis characterized by degeneration of the collagen and loss of viable cells, and a zone of thermal change characterized by collagen degeneration. The zone of thermal change, with its histological injury was thought at the time of surgery to be the viable border. The zone of thermal change may act as a barrier to delay healing, and the scalpel produced a consistently straighter cut.


Predictive Value of Retinal Morphology for Visual Acuity Outcomes of Different Ranibizumab Treatment Regimens for Neovascular AMD.
To establish the predictive value of defined retinal morphologic parameters on visual outcomes and re-treatment needs in patients with neovascular age-related macular degeneration (nAMD) receiving ranibizumab treatment. Post hoc analysis of a prospective, 12-month, multicenter, phase IIIb trial. Three hundred fifty-three treatment-naïve patients with nAMD. Available data from 319 treatment-naïve patients receiving ranibizumab 0.3 mg monthly (frequent regimen; n = 102) or ranibizumab 0.3 or 0.5 mg quarterly (pooled 0.3/0.5 mg = infrequent regimen; n = 217) were analyzed to assess the correlations between baseline retinal morphologic parameters and best-corrected visual acuity (BCVA) change (structure-function correlations). The BCVA was measured at monthly visits. Optical coherence tomography scans were acquired monthly for quantitative measures of the central retinal thickness and qualitative assessment of retinal morphologic features. Assessed morphologic parameters included intraretinal cystoid fluid (IRC), subretinal fluid (SRF), pigment epithelial detachment, and vitreomacular interface configuration classification comprising vitreomacular adhesion and posterior vitreous detachment (PVD). An analysis of covariance was conducted to evaluate the impact of retinal morphologic features on BCVA change at month 12. Change in BCVA from baseline to month 12 compared between frequent and infrequent treatment arms. Relevant predictive factors for BCVA change at month 12 were baseline SRF (P = 0.05), PVD (P = 0.03), IRC (P = 0.05), treatment frequency (P < 0.01), and BCVA (P < 0.01). The presence of both SRF and PVD at baseline was associated with similar BCVA gains regardless of treatment frequency (mean difference in BCVA gains at month 12 of +2.6 letters in favor of infrequent treatment). Subretinal fluid was present in 71% of patients, and PVD was present in 64% of patients. In patients with both SRF and PVD at baseline, similar BCVA outcomes were observed regardless of treatment frequency. These patients may require less frequent treatments compared with patients without SRF, without PVD, or without either who may require more frequent injections for maintenance of vision. This finding may have implications in clinical practice by helping to tailor an individualized re-treatment interval in nAMD patients.


Neurosteroids dehydroepiandrosterone and its sulfate in individuals with personality disorders convicted of serious violent crimes.
We studied blood serum levels of neurosteroids, dehydroepiandrosterone and its sulfate, in individuals with personality disorders convicted of serious violent crimes. The data were compared with that of a group of mentally and physically healthy persons convicted of acquisitive crimes, and with that of the control group. Significant increase in DHEA in both groups of convicts in comparison with the control was shown. The level of dehydroepiandrosterone sulfate remained unchanged. Increased dehydroepiandrosterone level in the convicted individuals with personality disorders is probably more associated with detention stress than directly with psychopathology or criminal aggression.


Cementless, modular, distally fixed stem in hip revision arthroplasty: a single-center study of 132 consecutive hips.
The use of cementless, modular, distally fixed stem in hip revision arthroplasty has increased during the last decades. We aimed to analyze the early and late postoperative complications, re-operation rate, and survival rate of the MP stem operated at our county hospital with relatively limited caseload. In this retrospective study, we included 132 hips operated with MP stem between January 2007-2014. An independent observer reviewed patients' medical records in July 2015 (18-102 months postoperatively, median 52.5) to collect the following data: age, sex, American Society of Anesthesiologists (ASA) class, body mass index, indication of revision, type of operation, early and late complications, re-operation rate, and mortality during study period. The commonest indication for MP stem operation was aseptic loosening (72%). We found early and late postoperative complications in 29% of cases. The most common complication was prosthetic dislocation (8%), followed by intra-operative peri-prosthetic fracture (5%). The commonest indication for MP re-operation was soft tissue revision for infection (7%) followed by closed reduction for prosthetic dislocation (6%). We found no correlation between the age, sex, ASA class, and type of operation and the re-operation risk. Only one prosthesis was extracted giving a survival rate for 99% for the study period. This study showed good results of the MP prosthesis with reasonable complication and re-operation rates and negligible extraction rate, indicating the good performance of this implant even when used in the setting of a county hospital with limited caseload.


Androgen receptor modulation: lessons learned from beyond the prostate.
Androgen receptor (AR) is an important transcription factor in prostatic diseases, such as prostate cancer and benign prostatic hyperplasia (BPH). AR regulates the growth and survival of both benign and cancerous prostate epithelial cells. Therefore, modulation of AR function is an important means of treating prostatic diseases. Modern pharmacotherapy for these diseases includes, for example, medical castration and AR antagonists for prostate cancer and 5-alpha-reductase inhibitors for BPH. However, these treatments have limitations and are illustrated by AR reactivation after medical castration for prostate cancer, commonly termed castrate-resistant prostate cancer. A novel method of AR modulation has been demonstrated in spinal and bulbar muscular atrophy, a disease defined by a polyglutamine repeat expansion which leads to gain-of-function changes in AR and neuromuscular pathology. Here, we examine recent findings from the description of a compound that degrades AR and induces dissociation of AR from an AR coactivator. The biochemistry of this compound may have implications for prostate cancer.


Short-term effects of physiotherapy combining repetitive facilitation exercises and orthotic treatment in chronic post-stroke patients.
[Purpose] This study investigated the short-term effects of a combination therapy consisting of repetitive facilitative exercises and orthotic treatment. [Subjects and Methods] The subjects were chronic post-stroke patients (n=27; 24 males and 3 females; 59.3 ± 12.4 years old; duration after onset: 35.7 ± 28.9 months) with limited mobility and motor function. Each subject received combination therapy consisting of repetitive facilitative exercises for the hemiplegic lower limb and gait training with an ankle-foot orthosis for 4 weeks. The Fugl-Meyer assessment of the lower extremity, the Stroke Impairment Assessment Set as a measure of motor performance, the Timed Up & Go test, and the 10-m walk test as a measure of functional ambulation were evaluated before and after the combination therapy intervention. [Results] The findings of the Fugl-Meyer assessment, Stroke Impairment Assessment Set, Timed Up & Go test, and 10-m walk test significantly improved after the intervention. Moreover, the results of the 10-m walk test at a fast speed reached the minimal detectible change threshold (0.13 m/s). [Conclusion] Short-term physiotherapy combining repetitive facilitative exercises and orthotic treatment may be more effective than the conventional neurofacilitation therapy, to improve the lower-limb motor performance and functional ambulation of chronic post-stroke patients.


Supervised selection of single nucleotide polymorphisms in chronic fatigue syndrome.
The different ways for selecting single nucleotide polymorphisms have been related to paradoxical conclusions about their usefulness in predicting chronic fatigue syndrome even when using the same dataset. To evaluate the efficacy in predicting this syndrome by using polymorphisms selected by a supervised approach that is claimed to be a method that helps identifying their optimal profile. We eliminated those polymorphisms that did not meet the Hardy-Weinberg equilibrium. Next, the profile of polymorphisms was obtained through the supervised approach and three aspects were evaluated: comparison of prediction accuracy with the accuracy of a profile that was based on linkage disequilibrium, assessment of the efficacy in determining a higher risk stratum, and estimating the algorithm influence on accuracy. A valid profile (p<0.01) was obtained with a higher accuracy than the one based on linkage disequilibrium, 72.8 vs. 62.2% (p<0.01). This profile included two known polymorphisms associated with chronic fatigue syndrome, the NR3C1_11159943 major allele and the 5HTT_7911132 minor allele. Muscular pain or sinus nasal symptoms in the stratum with the profile predicted V with a higher accuracy than those symptoms in the entire dataset, 87.1 vs. 70.4% (p<0.01) and 92.5 vs. 71.8% (p<0.01) respectively. The profile led to similar accuracies with different algorithms. The supervised approach made it possible to discover a reliable profile of polymorphisms associated with this syndrome. Using this profile, accuracy for this dataset was the highest reported and it increased when the profile was combined with clinical data.


The use of microfluidics in hemostasis: clinical diagnostics and biomimetic models of vascular injury.
This article reviews the application of microfluidic technologies in hemostasis. The emphasis is on promising developments in devices for clinical applications and novel approaches to modeling complex hemodynamics. Microfluidics combined with micropatterning of prothrombotic substrates provides devices for measuring platelet function and coagulation with low blood volumes (∼100 μl) over a wide range of shear stresses. This technology has been applied to the diagnosis of bleeding and thrombotic disorders, as well as to dosing and monitoring of anticoagulation and antiplatelet agents. Microfluidic devices that mimic vascular geometries such as bifurcations, stenosis, and complex interconnected networks yield complex flow fields that have revealed new mechanisms of platelet adhesion and aggregation. Applying techniques from tissue engineering by endothelializing these networks is beginning to close the gap between in-vitro and in-vivo models of vascular injury. Microfluidic technology enables researchers to create in-vitro models of vascular disease with unprecedented control of the biochemical and biophysical conditions. Two promising directions are flow-dependent clinical assays and biomimetic vascular networks. These approaches are particularly well suited for modeling the microvasculature. However, caution should be used when extrapolating results from microfluidic channels to the pathophysiology of thrombosis in large arteries and veins.


Improvement of table grapes quality and safety by the combination of modified atmosphere packaging (MAP) and eugenol, menthol, or thymol.
Table grape is a nonclimacteric fruit that shows a rapid loss of quality during storage and is very susceptible to colonization by fungi, especially Botrytis cinerea, which is considered the most important disease of this commodity. To solve this problem, synthetic fungicides have been used, although legal restrictions and consumer's concern demand the search of other safe means. In the present paper, and as an alternative of synthetic fungicides, an active packaging to improve MAP effectiveness on preserving table grape (cv. Crimson Seedless) quality and safety was developed by the addition of 0.5 mL of eugenol, thymol, or menthol inside the packages. Packages were stored at 1 degree C for 35 days. The final gas composition inside the packages was 1.4-2.0 and 10.0-14.5 kPa of CO(2) and O(2), respectively, with no significant slight differences among treatments. Results showed that the addition of eugenol, thymol, or menthol improved the beneficial effect of MAP in terms of delaying weight loss and color changes, retarding degrees Brix/acidity ratio evolution, and maintaining of firmness. Thereafter, these treatments showed additional benefit in terms of delayed rates of rachis deterioration and berry decay. Finally, the total viable counts for both mesophilic aerobics and especially yeast and molds were significantly reduced in the grapes packaged with the natural antimicrobial compounds. All of the above effects led to maintenance of table grape quality and safety for longer storage periods (3 additional weeks as compared to controls under MAP only).


Brief versus standard hospitalization: the families.
A total of 175 newly admitted inpatients who lived with families were randomly assigned to three treatment groups: standard inpatient care (discharge at the therapist's discretion), brief hospitalization (one week or less) with transitional day care available, and brief hospitalization without day care. Outpatient aftercare was offered to all patients. There was no major differential family burden as a function of length of hospitalization. Generally, brief hospitalization had several positive effects on family functioning, primarily earlier resumtption of occupational roles and less financial burden, with few significant deleterious effects.


Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in KRAS-Mutant Cancers.
It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in rewiring of signal transduction. We aimed to study differences in dynamic signaling changes within mutant KRAS (KRAS MT), non-small cell lung cancer (NSCLC), colorectal cancer, and pancreatic ductal adenocarcinoma (PDAC) cells. We used an antibody-based phosphoproteomic platform to study changes in 50 phosphoproteins caused by seven targeted anticancer drugs in a panel of 30 KRAS MT cell lines and cancer cells isolated from 10 patients with KRAS MT cancers. We report for the first time significant differences in dynamic signaling between colorectal cancer and NSCLC cell lines exposed to clinically relevant equimolar concentrations of the pan-PI3K inhibitor pictilisib including a lack of reduction of p-AKTser473 in colorectal cancer cell lines (P = 0.037) and lack of compensatory increase in p-MEK in NSCLC cell lines (P = 0.036). Differences in rewiring of signal transduction between tumor types driven by KRAS MT cancers exist and influence response to combination therapy using targeted agents.


Maintenance treatment of combination with bevacizumab vs single agent for advanced non-squamous non-small cell lung cancer: A systematic review and meta-analysis.
When the patients of advanced non-squamous non-small cell lung cancer (NSCLC) have achieved remission by induction therapy, it is controversial that combination with bevacizumab is used as maintenance therapy. Pemetrexed is a classic drug for maintenance therapy, is bevacizumab the superiority to pemetrexed is also unclear. This meta-analysis aims to evaluate the effectiveness and safety of advanced non-squamous NSCLC in the maintenance treatment. From the establishment as of December 6, 2020, PubMed, Embase, and Cochrane electronic databases were searched and the American Society of Clinical Oncology, European Society of Medical Oncology, and National Comprehensive Cancer Network databases in the past 10 years. The application of combination with bevacizumab, pemetrexed was studied in clinical trials of maintenance treatment for advanced NSCLC. The extracted data include progression-free survival (PFS), overall survival (OS), and grade 3-4 adverse events (AE). Seven clinical trials we screened, 6 were phase III RCTs, and a cohort trial, including 3298 patients. Compared with bevacizumab and pemetrexed, PFS of combination with bevacizumab was significantly improved (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.65-0.77, P < .00001), but OS was not improved (HR = 0.93, 95% CI = 0.85-1.01, P = .10). Compared with bevacizumab and pemetrexed, no significant difference of PFS (HR = 0.87, 95% CI = 0.69-1.09, P = .21), and OS (HR = 0.87, 95% CI = 0.72-1.05, P = .15) was found. A higher incidence of grade 3-4 AE occurred in combination with bevacizumab (odds ratio = 1.63, 95% CI = 1.35-1.97, P < .00001). PFS was significantly improved in patients with advanced non-squamous NSCLC who use bevacizumab combination with single-agent as maintenance treatment, but it does not translate into the advantages of OS; compared with bevacizumab, no PFS and OS benefits were found. A higher incidence of grade 3-4 AE occurred in combination with bevacizumab than pemetrexed and bevacizumab.


[Life expectancy and disability in Parkinson disease].
Idiopathic Parkinson's disease is a chronic progressive neurodegenerative disease with no possibility of curative treatment up until now. The natural course leads to severe handicap or death within 10-15 years, but due to the development of dopaminergic drug therapy life expectancy of parkinsonian patients has normalized and productivity remains good for a longer period during the course of disease.


Head-down bed rest reduces the breathing rate short-term variability in subjects with orthostatic intolerance.
Orthostatic intolerance is the most serious symptom of cardiovascular deconditioning induced by microgravity. We have showed that in symptomatic subjects the baroreflex control of sinus node is affected by short term simulated microgravity. At present the influence of the respiration on the cardiovascular system in this condition is not clear. The aim of the present study was to examine the behaviour of the Breathing Rate (BR) in 5 Non-Symptomatic (NS) and 3 Symptomatic (S) subjects before and after 4 hours of head-down bed rest (HD).


Differential gene expression of human adipose-derived stem cells in osteogenic induction.
Human adipose-derived stem cells (HADSC) have demonstrated the capacity of differentiating into bone depending on the specific induction stimuli and growth factors. However, investigation on stem cell characteristic after osteogenic differentiation is still lacking. The goal of this study was to investigate the differential expression of sternness and osteogenic genes in non-induced HADSC compared with HADSC after osteogenic induction using quantitative Real Time RT-PCR. Our results showed that OCT-4, REX-1, FZD9, OSC, RUNX, and ALP were up regulated after osteogenic induction. This may indicated that HADSCs after osteogenic induction still possessed some stemness properties.


Focal cryotherapy: step by step technique description.
Focal cryotherapy emerged as an efficient option to treat favorable and localized prostate cancer (PCa). The purpose of this video is to describe the procedure step by step. We present the case of a 68 year-old man with localized PCa in the anterior aspect of the prostate. The procedure is performed under general anesthesia, with the patient in lithotomy position. Briefly, the equipament utilized includes the cryotherapy console coupled with an ultrasound system, argon and helium gas bottles, cryoprobes, temperature probes and an urethral warming catheter. The procedure starts with a real-time trans-rectal prostate ultrasound, which is used to outline the prostate, the urethra and the rectal wall. The cryoprobes are pretested and placed in to the prostate through the perineum, following a grid template, along with the temperature sensors under ultrasound guidance. A cystoscopy confirms the right positioning of the needles and the urethral warming catheter is installed. Thereafter, the freeze sequence with argon gas is started, achieving extremely low temperatures (-40ºC) to induce tumor cell lysis. Sequentially, the thawing cycle is performed using helium gas. This process is repeated one time. Results among several series showed a biochemical disease-free survival between 71-93% at 9-70 month- follow-up, incontinence rates between 0-3.6% and erectile dysfunction between 0-42% (1-5). Focal cryotherapy is a feasible procedure to treat anterior PCa that may offer minimal morbidity, allowing good cancer control and better functional outcomes when compared to whole-gland treatment.


Effect of light irradiation on anthocyanin production by suspended culture of Perilla frutescens.
After a series of experiments on photoperiodicity and light intensity under daylight supplied by an ordinary fluorescent lamp in cultivations using a flask and a roux bottle, it was found that irradiation at 27.2 W/m(2) for the whole period was effective for anthocyanin production by a suspended culture of Perilla frutescens (shiso). A high amount of anthocyanin pigments, 3.0 g/L, was obtained in a bubble column bioreactor after 10 days of cultivation at an aeration rate of 0.1 vvm with light irradiation at 27.2 W/m(2), while 2 g/L was obtained at 13.6 W/m(2) and very little at 54.4 W/m(2). A high amount of anthocyanin pigments, 2.9 g/L, was also produced using an aerated and agitated bioreactor at an agitation speed of 130 rpm, an aeration rate of 0.1 vvm and light irradiation intensity of 27.2 W/m(2). The amount of anthocyanin produced was more than twice that without light irradiation, Keeping the other cultivation conditions the same. The results obtained also showed that the amount of anthocyanin pigment accumulated in a shake flask could be rather well reproduced in bioreactors for both aerated culture, and aerated and agitated culture, by improving the conditions of light irradiation, which conspicuously affects metabolite formation.


Barriers, facilitators and implementation strategies for guideline-adherence in physiotherapy: a scoping review protocol.
Guideline-adherent physiotherapy can improve patient outcomes and reduce costs in the healthcare system. However, although there are numerous guidelines for physiotherapy practice, services are not consistently based on clinical practice guidelines. While various systematic and scoping reviews have highlighted barriers, facilitators and implementation strategies for guideline-adherent practice in other health professions, this scoping review aims to explore the barriers and facilitators for guideline-adherent physiotherapy and summarises the strategies used to implement such practice. This scoping review will be based on Arksey and O'Malley's scoping review methodology and the methodological guidance for conducting scoping reviews published by Joanna Briggs Institute. Relevant publications will be first searched from the beginning of June 2023 on the MEDLINE and CINAHL databases before we expand the search to other databases such as EMBASE, the Cochrane Library and PEDro at the end of June 2023. Two reviewers will independently screen the titles and abstracts of all retrieved citations for inclusion against the eligibility criteria before conducting an independent full-text screening. The criteria will be tested on a sample of abstracts before beginning the abstract review to ensure that they are robust enough to capture any articles that may relate. The extracted data will finally be collated and charted to summarise key findings regarding our research question. This scoping review will provide an extensive overview of the barriers, facilitators and implementation strategies for guideline-adherent physiotherapy. As scoping reviews are a form of secondary data analysis, ethical review is not required. Results will be disseminated through a peer-reviewed publication and stakeholder meetings. This scoping review has been registered on 3 April 2023 on the Open Science Framework under https://doi.org/10.17605/OSF.IO/SEUW6.


Comparative analysis of CpG islands among HBV genotypes.
DNA methylation is being increasingly recognized to play a role in regulation of hepatitis B virus (HBV) gene expression. The aim of this study was to compare the CpG island distribution among different HBV genotypes. We analyzed 176 full-length HBV genomic sequences obtained from the GenBank database, belonging to genotypes A through J, to identify the CpG islands in the HBV genomes. Our results showed that while 79 out of 176 sequences contained three conventional CpG islands (I-III) as previously described, 83 HBV sequences harbored only two of the three known islands. Novel CpG islands were identified in the remaining 14 HBV isolates and named as CpG island IV, V, and VI. Among the eight known HBV genotypes and two putative genotypes, while HBV genomes containing three CpG islands were predominant in genotypes A, B, D, E, and I; genotypes C, F, G, and H tended to contain only two CpG islands (II and III). In conclusion, the CpG islands, which are potential targets for DNA methylation mediated by the host functions, differ among HBV genotypes, and these genotype-specific differences in CpG island distribution could provide new insights into the understanding of epigenetic regulation of HBV gene expression and hepatitis B disease outcome.


HLA compatibility and different features of liver allograft rejection.
The influence of human leukocyte antigen (HLA) on acute liver allograft rejection was investigated in 48 adult patients. The diagnosis of rejection was always based on the full triad of histological findings, clinical signs, and the required antirejection treatment. Sixty-two percent of the patients closely observed for 6 months postoperatively revealed acute rejection within the first 3 weeks, mostly on days 7-11. HLA compatibility was not observed to have any significant influence on the incidence of acute rejection. However, different histological and clinical features were revealed in conjunction with DR compatibility. Patients without DR compatibility showed a type of rejection with fever and increase of bilirubin, frequently associated with cholestasis and cholangitis, which sometimes persisted for weeks. Patients with 1 DR compatibility showed a predominant increase of transaminases, which was never associated with cholangitis. The conjunction of different DR compatibilities and various clinical signs may indicate possible pathways from immunological assault to the clinical appearance of acute rejection. A knowledge of a patient's individual compatibility and an expectation of certain rejection patterns may lead to earlier and more reliable diagnosis and treatment.


Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate.
Huperzine a, a potential therapeutic agent for Alzheimer's disease, inhibits acetylcholinesterase in primary cultures derived from forebrain, hippocampus, cortex and cerebellum of embryonic rat brain. Glutamate induces cell death in cultures from all these brain regions. Maximum cell toxicity was observed in cerebellar cultures. Pretreatment of cell cultures with Huperzine A reduced cell toxicity, as evidenced by cytotoxicity assay and general morphology. Huperzine A pretreatment also reduced glutamate-induced calcium mobilization, but did not affect elevations in intraneuronal free Ca2+ ([Ca]i) caused by KCl or (-)Bay K 8644. The data suggest that Huperzine A could be a potent neuroprotective agent not only where cholinergic neurons are impaired, but also under conditions in which glutamatergic functions are compromised.


Physical activity in European adolescents and associations with anxiety, depression and well-being.
In this cross-sectional study, physical activity, sport participation and associations with well-being, anxiety and depressive symptoms were examined in a large representative sample of European adolescents. A school-based survey was completed by 11,110 adolescents from ten European countries who took part in the SEYLE (Saving and Empowering Young Lives in Europe) study. The questionnaire included items assessing physical activity, sport participation and validated instruments assessing well-being (WHO-5), depressive symptoms (BDI-II) and anxiety (SAS). Multi-level mixed effects linear regression was used to examine associations between physical activity/sport participation and mental health measures. A minority of the sample (17.9 % of boys and 10.7 % of girls; p < 0.0005) reported sufficient activity based on WHO guidelines (60 min + daily). The mean number of days of at least 60 min of moderate-to-vigorous activity in the past 2 weeks was 7.5 ± 4.4 among boys and 5.9 days ± 4.3 among girls. Frequency of activity was positively correlated with well-being and negatively correlated with both anxiety and depressive symptoms, up to a threshold of moderate frequency of activity. In a multi-level mixed effects model more frequent physical activity and participation in sport were both found to independently contribute to greater well-being and lower levels of anxiety and depressive symptoms in both sexes. Increasing activity levels and sports participation among the least active young people should be a target of community and school-based interventions to promote well-being. There does not appear to be an additional benefit to mental health associated with meeting the WHO-recommended levels of activity.


Evolution of a Surgical Philosophy in Orthognathic Surgery.
A surgical philosophy of orthognathic surgery is presented. It has evolved over an entire surgical career as orthognathic surgical goals have evolved to become primarily aesthetic. In this context, the occlusal result serves as a means of achieving the aesthetic ends. It relies on the physical examination, using qualitative concepts of facial appearance, to be the most important determinant of treatment plans. It makes a distinction between a quantitatively normal face and one that is visually well proportioned and emphasizes the attributes of the soft tissue. The emotional expression of the patient is also considered in treatment planning. By using surgical tactics that provide control of facial projection and height, this philosophy affords the surgeon an opportunity to manipulate the skeletal elements to the extent that one can simultaneously achieve a well-proportioned face and favorably influence the appearance of the soft tissues and facial countenance.


Extracellular peptidase activity tunes motor pattern modulation.
We are examining how extracellular peptidase activity sculpts the peptidergic actions of modulatory projection neurons on rhythmically active neuronal circuits, using the pyloric circuit in the stomatogastric ganglion (STG) of the crab Cancer borealis. Neurally released peptides can diffuse long distances to bind to their receptors. Hence, different neurons releasing the same neuropeptide into the same neuropil may reach the same receptor complement. However, extracellular peptidases can limit neuropeptide diffusion and terminate its actions. Distinct versions of the pyloric rhythm are elicited by selective activation of different projection neurons, including those with overlapping sets of cotransmitters. Two of these projection neurons, modulatory commissural neuron 1 (MCN1) and the modulatory proctolin neuron (MPN), contain the neuropeptide proctolin plus GABA. MCN1 also contains Cancer borealis tachykinin-related peptide Ia (CabTRP Ia). CabTRP Ia is not fully responsible for the distinct actions of MCN1 and MPN. Because there is aminopeptidase activity in the STG that terminates proctolin actions, we tested the hypothesis that the differences in the actions of MCN1 and MPN that are not mediated by CabTRP Ia result from the differential actions of aminopeptidase activity on proctolin released from these two projection neurons. We found that the pyloric circuit response to these two projection neurons becomes more similar when this aminopeptidase activity is blocked. This result supports the hypothesis that extracellular peptidase activity enables different projection neurons to use the same neuropeptide transmitter for eliciting distinct outputs from the same neuronal circuit.


Depletion of Csk preferentially reduces the protein level of LynA in a Cbl-dependent manner in cancer cells.
There are eight human Src-family tyrosine kinases (SFKs). SFK members c-Src, c-Yes, Fyn, and Lyn are expressed in various cancer cells. SFK kinase activity is negatively regulated by Csk tyrosine kinase. Reduced activity of Csk causes aberrant activation of SFKs, which can be degraded by a compensatory mechanism depending on Cbl-family ubiquitin ligases. We herein investigated whether all SFK members are similarly downregulated by Cbl-family ubiquitin ligases in cancer cells lacking Csk activity. We performed Western blotting of multiple cancer cells knocked down for Csk and found that the protein levels of the 56 kDa isoform of Lyn (LynA), 53 kDa isoform of Lyn (LynB), c-Src, and Fyn, but not of c-Yes, were reduced by Csk depletion. Induction of c-Cbl protein levels was also observed in Csk-depleted cells. The reduction of LynA accompanying the depletion of Csk was significantly reversed by the knockdown for Cbls, whereas such significant recovery of LynB, c-Src, and Fyn was not observed. These results suggested that LynA is selectively downregulated by Cbls in cancer cells lacking Csk activity.


Augmenter of liver regeneration-mediated mitophagy protects against hepatic ischemia/reperfusion injury.
Augmenter of liver regeneration (ALR) is an anti-apoptotic protein found mainly in mitochondria. It protects hepatocytes from ischemia-reperfusion (I/R) injury, but the underlying mechanism is not clear. We found that in rats, delivery of the ALR gene alleviated hepatic I/R injury during orthotopic liver transplantation as evidenced by reduced serum aminotransferase, oxidative stress and apoptosis, and increased expression of autophagy markers. In an in vitro hypoxia/reoxygenation (H/R) model, overexpression of the ALR gene activated autophagy and relieved defective mitophagy via the PINK1/Parkin pathway. Mechanistically, ALR transfection induced the expression of mitofusin 2 (Mfn2) in the H/R model, which led to PINK1 accumulation and mitochondrial translocation of Parkin. Deletion of Mfn2 abolished mitophagy activation induced by ALR transfection, promoted mitochondrial dysfunction, and eventually increased cell apoptosis. Mfn2 administration prevented the inhibition of mitophagy in ALR-knockout (KO) cells, thus attenuated mitochondrial dysfunction and cell apoptosis. In heterozygous ALR-knockout mice treated with a warm I/R injury, marked aggravation of liver injury was associated with mitophagy inhibition and reduction in Mfn2 expression. Taken together, our results confirm that ALR accelerated Parkin translocation and mitophagy via Mfn2, and protected hepatocytes from I/R-induced injury. Our findings provide a novel rationale for the treatment of hepatic I/R injury.


[Life-threatening complications and death in anorexia nervosa].
The medical complications of anorexia nervosa may endanger the patient in several ways; the severity of somatic complications may be underestimated; medical findings may be assigned to other diagnoses than anorexia nervosa or complications may indicate an emergency, leading to therapeutic activities which may result in a life-threatening situation for the patient. There are some indications that phosphate depletion is involved in medical complications in anorexia nervosa, even in those cases with fatal outcome. Acute hypophosphatemia may be induced by hyperalimentation.


Energy Metabolism and the Burden of Multimorbidity in Older Adults: Results From the Baltimore Longitudinal Study of Aging.
Excessively elevated resting metabolic rate (RMR) for persons of a certain age, sex, and body composition is a mortality risk factor. Whether elevated RMR constitutes an early marker of health deterioration in older adult has not been fully investigated. Using data from the Baltimore Longitudinal Study of Aging, we hypothesized that higher RMR (i) was cross-sectionally associated with higher multimorbidity and (ii) predicted higher multimorbidity in subsequent follow-ups. The analysis included 695 Baltimore Longitudinal Study of Aging participants, aged 60 or older at baseline, of whom 248 had follow-up data available 2 years later and 109 four years later. Multimorbidity was assessed as number of chronic diseases. RMR was measured by indirect calorimetry and was tested in regression analyses adjusted for covariates age, sex, and dual-energy x-ray absorptiometry-measured total body fat mass and lean mass. Baseline RMR and multimorbidity were positively associated, independent of covariates (p = .002). Moreover, in a three-wave bivariate autoregressive cross-lagged model adjusted for covariates, higher prior RMR predicted greater future multimorbidity above and beyond the cross-sectional and autoregressive associations (p = .034). RMR higher than expected, given age, sex, and body composition, predicts future higher multimorbidity in older adults and may be used as early biomarker of impending health deterioration. Replication and the development of normative data are required for clinical translation.


Prospective study of extractable latex allergen contents of disposable medical gloves.
Exposure to natural rubber latex medical gloves poses risks to latex-sensitive patients and medical workers. Preliminary studies have shown that the latex allergen contents of these gloves vary widely. To study long-term trends in latex allergen levels of disposable medical gloves prospectively, and to identify lower allergen gloves for purchase by our medical center. Extractable total latex allergen was measured by solid-phase inhibition immunoassay. Allergen contents of gloves were expressed in allergy units (AU)/mL relative to a raw latex standard assigned an arbitrary potency of 100,000 AU/mL. For gloves in use during July, 1993, extractable allergen levels ranged from < 10 to 5,500 AU/mL among nine lots of examination gloves, from < 10 to 2,300 AU/mL among 13 lots of surgical gloves, and from < 10 to 1,000 AU/mL among five lots of chemotherapy, autopsy, or utility gloves. Among ten lots of examination gloves purchased on two occasions between July, 1993 and January, 1994, the allergen levels in two of the three private label brands were more variable (6- to 40-fold) than in the other eight brands tested (0- to 2-fold). Extractable allergen levels in latex medical gloves remain highly variable, particularly among some private label brands. Use of synthetic gloves or lower allergen latex gloves should lessen exposure of latex-sensitized patients and health care workers to latex aeroallergens.


Novel lipophilic analogues from 2,4-D and Propanil herbicides: Biological activity and kinetic studies.
This work describes the synthesis of new lipophilic amides and esters analogues of classical organochlorides herbicides by incorporation of long-chains from fatty acids and derivatives. The new fatty esters and amides were synthesized in 96-99% and 80-89% yields, respectively. In general, all compounds tested showed superior in vitro activity than commercial herbicides against growth L. sativa and A. cepa, in ranges 86-100% of germinative inhibition. The target compounds showed, significantly more susceptible towards acid hydrolysis than 2,4-dichlorophenoxyacetic acid (2,4-D). The kinetic and NMR studies showed that the incorporation of lipophilic chains resulted in a decrease in half-life time of new herbicides compounds (1.5 h) than 2,4-D (3 h). These findings suggest the synthesis of new lipophilic herbicides as potential alternative to traditional formulations, by incorporation of long fatty alkyl chains in the molecular structure of 2,4-D, resulting in superior in vitro herbicidal activity, best degradation behavior and more hydrophobic derivatives.


Hematological values for adult eastern Hermann's tortoise (Testudo hermanni boettgeri) in semi-natural conditions.
Hermann's tortoise (Testudo hermanni) is considered near threatened in the wild but, by contrast, it is one of the most popular pet tortoises in Europe. Scant data is reported in the veterinary literature on hematological values for T. hermanni and, to our knowledge, none focused on the subspecies boettgeri (eastern Hermann's tortoise). Published reports are based on small sample populations, and confusion arises when comparing the sampling sites, the anticoagulants, and the counting methods used. The purpose of the current study was to establish the normal mean values and reference intervals for the main hematological parameters for captive adult T. hermanni boettgeri and to evaluate the reliability of a semiautomated blood analyzer for red blood cell count and hematocrit determination. Blood values were determined in 23 adult tortoises using a Neubauer chamber with Natt and Herrick solution; red blood cells and hematocrit were also measured using a semiautomated blood analyzer. Statistical analysis included descriptive statistics, differences between sexes, and agreement between the counting methods. Reference intervals were calculated with the robust method. Wilcoxon signed rank test with continuity correction was used to investigate differences between sexes, and Bland-Altman analysis was performed to compare manual versus semiautomated values. Red blood cells, hematocrit, and hemoglobin determinations were significantly higher in males than in females. White blood cell counts did not show any sex variability. The agreement of manual versus semiautomated determination was considered acceptable for clinical use.


The face-lift incision.
Numerous variations of the "standard" face-lift incision are used to achieve adequate exposure, skin redraping , and minimal scar deformity. Our incision technique is based on careful study of over 1,000 of our patients who underwent rhytidectomies . We believe that our technique allows the goals of rhytidectomy to be achieved with minimal morbidity.


Pericyte Loss Leads to Capillary Stalling Through Increased Leukocyte-Endothelial Cell Interaction in the Brain.
The neurovascular unit is a functional unit composed of neurons, glial cells, pericytes, and endothelial cells which sustain brain activity. While pericyte is a key component of the neurovascular unit, its role in cerebral blood flow regulation remains elusive. Recently, capillary stalling, which means the transient interruption of microcirculation in capillaries, has been shown to have an outsized impact on microcirculatory changes in several neurological diseases. In this study, we investigated capillary stalling and its possible causes, such as the cerebral endothelial glycocalyx and leukocyte adhesion molecules after depleting pericytes postnatally in mice. Moreover, we investigated hypoxia and gliosis as consequences of capillary stalling. Although there were no differences in the capillary structure and RBC flow, longitudinal optical coherence tomography angiography showed an increased number of stalled segments in capillaries after pericyte loss. Furthermore, the extent of the cerebral endothelial glycocalyx was decreased with increased expression of leukocyte adhesion molecules, suggesting enhanced interaction between leukocytes and endothelial cells. Finally, pericyte loss induced cerebral hypoxia and gliosis. Cumulatively, the results suggest that pericyte loss induces capillary stalling through increased interaction between leukocytes and endothelial cells in the brain.


Gene expression mediated by dendrimer/DNA complexes encapsulated in biodegradable polymer microspheres.
A convenient and effective 'ultrasonic dispersion method' was used to fabricate vector/DNA complexes encapsulated microspheres. Polyamidoamine (PAMAM) dendrimer/DNA complexes protected by a water-soluble polymer, poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA), were encapsulated in a polymer film mainly composed of cholic acid functionalized star poly(DL-lactide), which degraded through surface erosion mechanism with a fast degradation rate. The PAMAM/DNA complexes encapsulated polymer film was then immersed in ethanol and ultrasonicated to afford the microspheres. The in vitro gene transfections showed PAMAM/DNA complexes protected by PHEA exhibited a much higher transfection activity compared with PAMAM/DNA complexes without the protection by PHEA. The expressions of pGL3-Luc in HEK293 cells could be effectively mediated by the polymer film and microspheres with the presence of PHEA. The ultrasonic dispersion method, which did not involve toxic organic solvents, could keep the bioactivity of DNA and offer good control over the size of microspheres.


Mesenchymal Stem Cell Therapy for Doxorubicin-Induced Cardiomyopathy: Potential Mechanisms, Governing Factors, and Implications of the Heart Stem Cell Debate.
Over the past decades, researchers have reported several mechanisms for doxorubicin (DOX)-induced cardiomyopathy, including oxidative stress, inflammation, and apoptosis. Another mechanism that has been suggested is that DOX interferes with the cell cycle and induces oxidative stress in C-kit+ cells (commonly known as cardiac progenitor cells), reducing their regenerative capacity. Cardiac regeneration through enhancing the regenerative capacity of these cells or administration of other stem cells types has been the axis of several studies over the past 20 years. Several experiments revealed that local or systemic injections with mesenchymal stem cells (MSCs) were associated with significantly improved cardiac function, ameliorated inflammatory response, and reduced myocardial fibrosis. They also showed that several factors can affect the outcome of MSC treatment for DOX cardiomyopathy, including the MSC type, dose, route, and timing of administration. However, there is growing evidence that the C-kit+ cells do not have a cardiac regenerative potential in the adult mammalian heart. Similarly, the protective mechanisms of MSCs against DOX-induced cardiomyopathy are not likely to include direct differentiation into cardiomyocytes and probably occur through paracrine secretion, antioxidant and anti-inflammatory effects. Better understanding of the involved mechanisms and the factors governing the outcomes of MSCs therapy are essential before moving to clinical application in patients with DOX-induced cardiomyopathy.


Can we improve the management of chronic obstructive respiratory disease? The example of asthma in adults.
Zeralda health district, Algeria. To analyse the impact of asthma refresher courses on the knowledge, attitudes and practice of general practitioners (GPs) working in primary health centres (PHC); to improve the system of referral between the PHCs and the district reference centre; and to measure the impact of the intervention on the management of asthma patients. Before and after study: situation analysis with an epidemiological survey in the general population and a study of the demand for care in three PHCs and an emergency department, three refresher training workshops for voluntary GPs and adoption of new consensual methods of collaboration. Despite a district asthma prevalence of 1.6%, patients were usually seen in emergency situations and sent to the district reference centre for follow-up. The refresher courses were attended by 56 GPs. Apart from improvements in knowledge, their practices and prescribing habits changed, with more beta-agonists (68.5% after vs. 12% before) and inhaled anti-inflammatories (52% vs. 0%), and less theophylline (2% vs. 55%), antibiotics (13% vs. 59%) and mucolytics (9% vs. 73.5%). The referral system was improved as follows: 69 health personnel were trained by GPs, recording and reporting forms designed during the workshops were implemented, essential emergency drugs were identified and collaboration between GPs and specialists at the reference centre was enhanced.


Metabolic syndrome and chronic kidney disease: a Japanese perspective on a worldwide problem.
Metabolic syndrome and obesity have causative roles in the development of chronic kidney disease (CKD). CKD leads to end-stage renal disease (ESRD), cardiovascular disease and death. The prevalence of metabolic syndrome is increasing worldwide in both developing and developed countries. Early detection and treatment of metabolic syndrome would be a cost-effective strategy to target the increasing prevalence of ESRD. Therefore, subjects with metabolic syndrome are candidates for CKD screening via dipstick proteinuria testing and serum creatinine measurements. The international community is beginning to share information on CKD through World Kidney Day, Kidney Disease Improving Global Outcomes, Commission for the Global Advancement of Nephrology, International Society of Nephrology and other scientific societies. The Japanese Society of Nephrology initiated the Asian Forum of CKD Initiative 2007 to discuss regional issues related to CKD in Asian countries. The clinical effects of metabolic syndrome vary among ethnic groups. A fundamental scientific question is the ethnic factor for calculating the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease Study equation. The incidence and prevalence of CKD are closely related with lifestyle factors such as diet, exercise, tobacco use, as well as other cultural differences. Research on the relationship between CKD and metabolic syndrome may provide clues to better understand the role of lifestyle-related factors and the age-related decline in GFR.