Combined calcium carbimide and ethanol treatment induces high blood acetaldehyde levels, myocardial apoptosis and altered expression of apoptosis-regulating genes in rat.
The effects of ethanol and ethanol-derived acetaldehyde on rat myocardial apoptosis and expression of genes involved in the regulation of apoptosis and cell cycle arrest were studied. Combined ethanol and calcium carbimide treatment for 2, 5 or 8 days (E + CC) markedly increased blood acetaldehyde levels. Cytosolic DNA fragmentation was quantified in the 5-day treatment group. Increased amount of DNA-fragmentation, reflecting increased apoptosis, was evident in the E + CC group (23% increase compared to controls). mRNA levels of genes regulating apoptosis were measured by using quantitative PCR in the 2- and 8-day treatment groups. In the 2-day treatment group, p21 gene expression was increased by 25% and bax/bcl-2 mRNA ratio by 57% in E + CC, compared to the control, group. In the 8-day treatment group, p21 mRNA level was 24% lower, p53 mRNA level was 15% higher (P < 0.005), and bcl-2 mRNA level 36% higher in E + CC-treated, compared to the control, group. Interestingly, both ethanol and calcium carbimide treatments alone increased bax mRNA levels, as compared to the control group at 2 and 8 days. These results indicate that acetaldehyde might regulate the expression of apoptosis-linked genes and that apoptosis of myocardial cells may be involved in the development of alcoholic heart disease.


CD38 and ADP-ribosyl cyclase catalyze the synthesis of a dimeric ADP-ribose that potentiates the calcium-mobilizing activity of cyclic ADP-ribose.
CD38, a lymphocyte differentiation antigen, is also a bifunctional enzyme catalyzing the synthesis of cyclic ADP-ribose (cADPR) from NAD+ and its hydrolysis to ADP-ribose (ADPR). An additional enzymatic activity of CD38 shared by monofunctional ADP-ribosyl cyclase from Aplysia californica is the exchange of the base group of NAD+ (nicotinamide) with various nucleophiles. Both human CD38 (either recombinant or purified from erythrocyte membranes) and Aplysia cyclase were found to catalyze the exchange of ADPR with the nicotinamide group of NAD+ leading to the formation of a dimeric ADPR ((ADPR)2). The dimeric structure of the enzymatic product, which was generated by recombinant CD38 and by CD38(+) Namalwa cells from as low as 10 microM NAD+, was demonstrated using specific enzyme treatments (dinucleotide pyrophosphatase and 5'-nucleotidase) and mass spectrometry analyses of the resulting products. The linkage between the two ADPR units of (ADPR)2 was identified as that between the N1 of the adenine nucleus of one ADPR unit and the anomeric carbon of the terminal ribose of the second ADPR molecule by enzymatic analyses and by comparison with patterns of cADPR cleavage with Me2SO:tert-butoxide. Although (ADPR)2 itself did not release Ca2+ from sea urchin egg microsomal vesicles, it specifically potentiated the Ca2+-releasing activity of subthreshold concentrations of cADPR. Therefore, (ADPR)2 is a new product of CD38 that amplifies the Ca2+-mobilizing activity of cADPR.


Roles of microRNA-140 in stem cell-associated early stage breast cancer.
An increasing body of evidence supports a stepwise model for progression of breast cancer from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Due to the high level of DCIS heterogeneity, we cannot currently predict which patients are at highest risk for disease recurrence or progression. The mechanisms of progression are still largely unknown, however cancer stem cell populations in DCIS lesions may serve as malignant precursor cells intimately involved in progression. While genetic and epigenetic alterations found in DCIS are often shared by IDC, mRNA and miRNA expression profiles are significantly altered. Therapeutic targeting of cancer stem cell pathways and differentially expressed miRNA could have significant clinical benefit. As tumor grade increases, miRNA-140 is progressively downregulated. miR-140 plays an important tumor suppressive role in the Wnt, SOX2 and SOX9 stem cell regulator pathways. Downregulation of miR-140 removes inhibition of these pathways, leading to higher cancer stem cell populations and breast cancer progression. miR-140 downregulation is mediated through both an estrogen response element in the miR-140 promoter region and differential methylation of CpG islands. These mechanisms are novel targets for epigenetic therapy to activate tumor suppressor signaling via miR-140. Additionally, we briefly explored the emerging role of exosomes in mediating intercellular miR-140 signaling. The purpose of this review is to examine the cancer stem cell signaling pathways involved in breast cancer progression, and the role of dysregulation of miR-140 in regulating DCIS to IDC transition.


Effect of different traversal schemes in integral image coding.
Integral imaging (InIm) is a highly promising technique for the delivery of three-dimensional (3D) image content. During capturing, different views of an object are recorded as an array of elemental images (EIs), which form the integral image. High-resolution InIm requires sensors with increased resolution and produces huge amounts of highly correlated data. In an efficient encoding scheme for InIm compression both inter-EI and intra-EI correlations have to be properly exploited. We present an EI traversal scheme that maximizes the performance of InIm encoders by properly rearranging EIs to increase the intra-EI correlation of jointly coded EIs. This technique can be used to augment performance of both InIm specific and properly adapted general use encoder setups, used in InIm compression. An objective quality metric is also introduced for evaluating the effects of different traversal schemes on the encoder performance.


Probing low-energy hyperbolic polaritons in van der Waals crystals with an electron microscope.
Van der Waals materials exhibit intriguing structural, electronic, and photonic properties. Electron energy loss spectroscopy within scanning transmission electron microscopy allows for nanoscale mapping of such properties. However, its detection is typically limited to energy losses in the eV range-too large for probing low-energy excitations such as phonons or mid-infrared plasmons. Here, we adapt a conventional instrument to probe energy loss down to 100 meV, and map phononic states in hexagonal boron nitride, a representative van der Waals material. The boron nitride spectra depend on the flake thickness and on the distance of the electron beam to the flake edges. To explain these observations, we developed a classical response theory that describes the interaction of fast electrons with (anisotropic) van der Waals slabs, revealing that the electron energy loss is dominated by excitation of hyperbolic phonon polaritons, and not of bulk phonons as often reported. Thus, our work is of fundamental importance for interpreting future low-energy loss spectra of van der Waals materials.Here the authors adapt a STEM-EELS system to probe energy loss down to 100 meV, and apply it to map phononic states in hexagonal boron nitride, revealing that the electron loss is dominated by hyperbolic phonon polaritons.


Results of typhoid perforation management: our experience in Bir Hospital, Nepal.
To determine the demographic characteristics, clinical features, operative findings and postoperative complications in patients operated for typhoid enteric perforation. A retrospective study was carried out in the Department of General Surgery, Bir Hospital since 2002 to April 2004. Among 189 patients who underwent laparotomy for hollow viscus perforation in two years, ileal perforation was found in 102 patients. The sex ratio of the patients was 4.66:1, in favor of male, with age range of 14-78 years and mean age 28.35 years. Most of the patients (80.39 %) presented with history of fever for two weeks. Half of the patients presented within 24 hours of onset of generalized abdominal pain. Majority (65.67%) had a solitary perforation on the antimesenteric border of terminal ileum. Eighty one percent of patients had trimming of the ulcer margins and primary closure. Complications included wound infection (35.3%), wound dehiscence (17.6%), fecal fistula (7.84%) and hospital mortality (6.86%). Typhoid ulcer perforation is common among developing nations, including Nepal. Postoperative complications following surgical management of perforation are high and increases mortality.


Clinical staging for youth at-risk for serious mental illness.
The first aim of this project was to identify a sample of youth who met different stages of risk for the development of a serious mental illness (SMI) based on a published clinical staging model. The second aim was to determine whether participants allocated to the different stages were a good fit to the model by comparing these groups on a range of clinical measures. This two-site longitudinal study recruited 243 youth, ages 12 to 25. The sample included (a) 42 healthy controls, (b) 43 non-help seeking individuals with no mental illness but with some risk of SMI, such as having a first-degree relative with a SMI (stage 0), (c) 52 help-seeking youth experiencing distress and possibly mild symptoms of anxiety or depression (stage 1a) and (d) 108 youth with attenuated symptoms of SMI, such as bipolar disorder or psychosis (stage 1b). Participants completed a range of measures assessing depression, anxiety, mania, suicide ideation, attenuated psychotic symptoms, negative symptoms, anhedonia and beliefs about oneself. There were no clinical differences between HCs and participants in stage 0. For most of the clinical measures, participants in stage 1b had more severe ratings than participants in stages 1a and 0 and HCs; those in stage 1a had more severe ratings than HCs and stage 0 participants. These results suggest that the staging process used to allocate participants to various stages is a good fit. That is, the clinical ratings followed an ordering effect consistent with that hypothesized in the staging model.


Optical path difference microscopy with a Shack-Hartmann wavefront sensor.
In this Letter, we show that a Shack-Hartmann wavefront sensor can be used for the quantitative measurement of the specimen optical path difference (OPD) in an ordinary incoherent optical microscope, if the spatial coherence of the illumination light in the plane of the specimen is larger than the microscope resolution. To satisfy this condition, the illumination numerical aperture should be smaller than the numerical aperture of the imaging lens. This principle has been successfully applied to build a high-resolution reference-free instrument for the characterization of the OPD of micro-optical components and microscopic biological samples.


Peroxynitrite elicits dysfunction of stereoselective s-nitrosocysteine recognition sites.
The aim of this study was to determine whether induction of tachyphylaxis to peroxynitrite (induced by giving 10 intravenous injections of a 10-micromol/kg dose) differentially affects the vasodilator responses elicited by systemic injections of the L- and D-isomers of S-nitrosocysteine (L-SNC and D-SNC), in pentobarbital-anesthetized rats. L- and D-SNC (12.5-200 nmol/kg, iv) elicited dose-dependent reductions in hindquarter, mesenteric, and renal vascular resistances. The L-SNC-induced vasodilator responses in the hindquarter and renal vascular beds were virtually abolished whereas the vasodilator responses in mesenteric bed were markedly diminished after administration of peroxynitrite. The D-SNC-induced vasodilator responses in the hindquarter and renal beds were slightly attenuated whereas the vasodilator responses in the mesenteric bed were not diminished after administration of peroxynitrite. The vasodilator responses elicited by the nitric oxide donor, MAHMA NONOate (5-50 nmol/kg, iv), were not attenuated by peroxynitrite. The finding that induction of tachyphylaxis to peroxynitrite diminishes the effects of L- and D-SNC but not MAHMA NONOate suggests that the stereoisomers exert their vasodilator effects by mechanisms other than their decomposition to nitric oxide. Moreover, the finding that induction of tachyphylaxis to peroxynitrite causes a more pronounced attenuation of the vasodilator effects of L- than D-SNC supports evidence that the stereoisomers differentially interact with stereoselective S-nitrosothiol recognition sites in the vasculature. Taken together, these novel results support the possibility that peroxynitrite diminishes the vasodilator potencies of L- and D-SNC by oxidation and/or nitration of amino acids in these recognition sites.


Knowledge and Behavior in Rational Drug Use Among College Students in Zunyi City.
To investigate the current status of knowledge and behavior about rational drug use in college students in different colleges and universities in a city in southwest China, providing reference for students' education of rational drug use in colleges and universities. A questionnaire survey on knowledge and behavior in rational drug use was carried out on the students recruited by occasional sampling method in 6 colleges and universities in Zunyi, China. Statistical analyses on demographic information and answers to questionnaire questions were carried out with SPSS 18.0. A total of 865 valid questionnaires were recovered from 923 questionnaires sent out. Some knowledge and behaviors of the students on drug use were irrational. There was statistically significant difference in some specific questions of the knowledge in rational drug use between medical and non-medical students (P<0.05); the average score of rational drug use behavior of medical students was lower than that of non-medical students (P<0.05); the average score of the rational drug use behavior of female students was lower than that of male (P<0.05); the students' major types had significantly different influence on their behavior in rational drug use (P<0.05). The school-carried pharmacy education can effectively improve students' rational medication; the majority of college students believed that it is necessary to popularize the knowledge of rational drug use on campus; and students' favorite way to acquire knowledge about rational drug use was to attend related lectures or elective courses. The knowledge and behavior of rational drug use among college students need to be improved. Professional medical education may exert a positive impact on rational drug use among college students. Thus, it is necessary to popularize the knowledge of rational drug use among college students, especially in non-medical colleges and universities.


Rho kinase inhibitor Y27632 affects initial heart myofibrillogenesis in cultured chick blastoderm.
During early vertebrate development, Rho-associated kinases (ROCKs) are involved in various developmental processes. Here, we investigated spatiotemporal expression patterns of ROCK1 protein and examined the role of ROCK during initial heart myofibrillogenesis in cultured chick blastoderm. Immunohistochemistry showed that ROCK1 protein was distributed in migrating mesendoderm cells, visceral mesoderm of the pericardial coelom (from which cardiomyocytes will later develop), and cardiomyocytes of the primitive heart tube. Pharmacological inhibition of ROCK by Y27632 did not alter the myocardial specification process in cultured posterior blastoderm. However, Y27632 disturbed the formation of striated heart myofibrils in cultured posterior blastoderm. Furthermore, Y27632 affected the formation of costamere, a vinculin/integrin-based rib-like cell adhesion site. In such cardiomyocytes, cell-cell adhesion was disrupted and N-cadherin was distributed in the perinuclear region. Pharmacological inactivation of myosin light chain kinase, a downstream of ROCK, by ML-9 perturbed the formation of striated myofibrils as well as costameres, but not cell-cell adhesion. These results suggest that ROCK plays a role in the formation of initial heart myofibrillogenesis by means of actin-myosin assembly, and focal adhesion/costamere and cell-cell adhesion.


Helicobacter pylori Secreted Protein HP1286 Triggers Apoptosis in Macrophages via TNF-Independent and ERK MAPK-Dependent Pathways.
Macrophages constitute a powerful line of defense against H. pylori. The final disease outcome is highly dependent on the bacterial ability to modulate the effector functions of activated macrophages. Here, we report that H. pylori secreted protein HP1286 is a novel regulator of macrophage responses. Differential expression and release of HP1286 homologues were observed among H. pylori strains. Recombinant purified HP1286 (rHP1286) had the ability to bind to primary human monocyte-derived macrophages (MDM) and macrophage cell lines. Exposure to rHP1286 induced apoptosis in macrophages in a dose- and time-dependent manner. Although interaction of rHP1286 was observed for several other cell types, such as human monocytes, differentiated neutrophil-like HL60 cells, and the T lymphocyte Jurkat cell line, rHP1286 failed to induce apoptosis under similar conditions, indicating a macrophage-specific effect of the protein. A mutant strain of H. pylori lacking HP1286 protein expression was significantly impaired in its ability to induce apoptosis in macrophages. Significantly higher caspase 3 activity was detected in rHP1286-challenged macrophages. Furthermore, rHP1286-induced macrophages apoptosis was not inhibited in the presence of neutralizing antibodies against TNF. These observations indicate that rHP1286 induced a caspase-dependent and TNF-independent macrophage apoptosis. Pre-treatment of macrophages with U0126, an inhibitor of the ERK MAPK signaling pathway significantly reduced rHP1286-induced apoptosis. Furthermore, nuclear translocation of ERK and phosphorylation of c-Fos was detected in rHP1286-treated macrophages. These results provide functional insight into the potential role of HP1286 during H. pylori infection. Considering the ability of HP1286 to induce macrophage apoptosis, the protein could possibly help in the bacterial escape from the activated macrophages and persistence in the stomach.


Phase transition in the Ising model on a small-world network with distance-dependent interactions.
We study the collective behavior of an Ising system on a small-world network with the interaction J(r) proportional to r(-alpha), where r represents the Euclidean distance between two nodes. In the case of alpha=0 corresponding to the uniform interaction, the system is known to possess a phase transition of the mean-field nature, while the system with the short-range interaction (alpha-->infinity) does not exhibit long-range order at any finite temperature. The Monte Carlo simulations are performed at various values of alpha, and the critical value alpha(c) beyond which the long-range order does not emerge is estimated to be 0. Thus, concluded is the absence of a phase transition in the system with the algebraically decaying interaction r(-alpha) for any nonzero positive value of alpha.


Estimating the probability of dengue virus introduction and secondary autochthonous cases in Europe.
Given the speed of air travel, diseases even with a short viremia such as dengue can be easily exported to dengue naïve areas within 24 hours. We set out to estimate the risk of dengue virus introductions via travelers into Europe and number of secondary autochthonous cases as a result of the introduction. We applied mathematical modeling to estimate the number of dengue-viremic air passengers from 16 dengue-endemic countries to 27 European countries, taking into account the incidence of dengue in the exporting countries, travel volume and the probability of being viremic at the time of travel. Our models estimate a range from zero to 167 air passengers who are dengue-viremic at the time of travel from dengue endemic countries to each of the 27 receiving countries in one year. Germany receives the highest number of imported dengue-viremic air passengers followed by France and the United Kingdom. Our findings estimate 10 autochthonous secondary asymptomatic and symptomatic dengue infections, caused by the expected 124 infected travelers who arrived in Italy in 2012. The risk of onward transmission in Europe is reassuringly low, except where Aedes aegypti is present.


A Novel and Validated Inflammation-Based Prognosis Score (IBPS) Predicts Outcomes in Patients with Diffuse Large B-Cell Lymphoma.
We aimed to create a novel prognostic score, the inflammation-based prognosis score (IBPS). In addition, we attempted to establish and validate a nomogram to predict the overall survival (OS) of patients with DLBCL. We retrospectively investigated the data of 213 patients with DLBCL diagnosed and treated in the Affiliated Hospital of Jiangnan University and used these data to develop nomograms. At the same time, 89 patients diagnosed and treated in Wuxi People's Hospital Affiliated with Nanjing Medical University from January 2015 to June 2021 were collected as an external validation cohort. We developed IBPS through the least absolute shrinkage and selection operator (LASSO) Cox regression. The univariate and multivariate Cox regression method was used to develop the nomogram. We used the concordance index (C-index), calibration chart, time-dependent receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and the Kaplan-Meier curve were used to assess the nomogram. The systemic immune inflammation index (SII), prognostic nutrition index (PNI), and modified Glasgow prognostic score (mGPS) were used to construct IBPS. The Eastern Cooperative Oncology Group performance status (ECOG PS), IBPS, response to treatment, and whether accept surgery were used to construct the nomogram to predict the OS of DLBCL patients. The C-index in the training and validation cohorts were 0.844 and 0.828, respectively. According to the time-dependent ROC curve and DCA, the nomogram has good predictive accuracy and clinical net benefit. The Kaplan-Meier curve showed that according to the nomogram score, patients in the training and validation cohorts could be classified into three risk groups. In patients with DLBCL, baseline IBPS was a reliable predictor of OS. The survival probability of DLBCL patients can be precisely predicted using the prognosis nomogram based on IBPS.


Pharmaceutical Co-Crystallization: Regulatory Aspects, Design, Characterization, and Applications.
Pharmaceutical co-crystals are novel class of pharmaceutical substances, which possess an apparent probability of advancement of polished physical properties offering stable and patentable solid forms. These multi-component crystalline forms influence pertinent physicochemical parameters like solubility, dissolution rate, chemical stability, physical stability, etc. which in turn result in the materials with superior properties to those of the free drug. Co-crystallization is a process by which the molecular interactions can be altered to optimize the drug properties. Co-crystals comprise a multicomponent system of active pharmaceutical ingredient (API) with a stoichiometric amount of a pharmaceutically acceptable coformer incorporated in the crystal lattice. By manufacturing pharmaceutical co-crystals, the physicochemical properties of a drug can be improved thus multicomponent crystalline materials have received renewed interest in the current scenario due to the easy administration in the pharmaceutical industry. There is an immense amount of literature available on co-crystals. However, there is a lack of an exhaustive review on a selection of coformers and regulations on co-crystals. The review has made an attempt to bridge this gap. The review also describes the methods used to prepare co-crystals with their characterization. Brief description on the pharmaceutical applications of co-crystals has also been incorporated here. Efforts are made to include reported works on co-crystals, which further help to understand the concept of co-crystals in depth.


Acetazolamide improves cerebral oxygenation during exercise at high altitude.
Vuyk, Jaap, Jan Van Den Bos, Kees Terhell, Rene De Bos, Ad Vletter, Pierre Valk, Martie Van Beuzekom, Jack Van Kleef, and Albert Dahan. Acetazolamide improves cerebral oxygenation during exercise at high altitude. High Alt. Med. Biol. 7:290-301, 2006.--Acute mountain sickness is thought to be triggered by cerebral hypoxemia and be prevented by acetazolamide (Actz). The effect of Actz on cerebral oxygenation at altitude remains unknown. In 16 members of the 2005 Dutch Cho Oyu (8201 m, Tibet) expedition, the influence of Actz and exercise (750 mg PO daily) on heart rate, peripheral and regional cerebral oxygen saturation (Sa(O(2) ) and rS(O(2) )), the Lake Louise score (LLS), and psychomotor function were studied at 0 m 14 days prior to the expedition, after arrival at 3700 m on day 3, after arrival at 5700 m on day 29, and again at 5700 m before the end of the expedition on day 51. After arrival at 3700 m, the LLS of the climbers taking Actz (n = 8) was significantly lower compared to those who did not take Actz (n = 8): 0.75 +/- 1.0 versus 2.9 +/- 2.0, p < 0.05 (ANOVA). High LLSs were associated with low rS(O(2) ) values in rest and exercise (p < 0.01 and p < 0.001). With altitude, resting Sa(O(2) ) and resting rS(O(2) ) decreased significantly (p < 0.001), irrespective of Actz use. Exercise at 3700 m and 5700 m reduced Sa(O(2) ) and rS(O(2) ) even further compared to rest (p < 0.001), although at 3700 m the rS(O(2) ) was preserved better in those who took Actz (55.3 +/- 4.3% versus 47.9 +/- 5.7%, p < 0.05). Irrespective of Actz use, with altitude, the percentage of omissions in the vigilance and tracking test increased while the climbers' scores on vigor decreased (p < 0.05). In conclusion, at altitude, exercise-induced reduction in cerebral oxygenation is less in climbers on Actz compared to climbers not taking Actz. This effect is nullified after several weeks at altitude due to acclimatization in climbers not taking Actz.


Small molecule therapeutics for inflammation-associated chronic musculoskeletal degenerative diseases: Past, present and future.
Inflammation-associated chronic musculoskeletal degenerative diseases (ICMDDs) like osteoarthritis and tendinopathy often results in morbidity and disability, with consequent heavy socio-economic burden. Current available therapies such as NSAIDs and glucocorticoid are palliative rather than disease-modifying. Insufficient systematic research data on disease molecular mechanism also makes it difficult to exploit valid therapeutic targets. Small molecules are designed to act on specific signaling pathways and/or mechanisms of cellular physiology and function, and have gradually shown potential for treating ICMDDs. In this review, we would examine and analyze recent developments in small molecule drugs for ICMDDs, suggest possible feasible improvements in treatment modalities, and discuss future research directions.


Automated social skills training with audiovisual information.
People with social communication difficulties tend to have superior skills using computers, and as a result computer-based social skills training systems are flourishing. Social skills training, performed by human trainers, is a well-established method to obtain appropriate skills in social interaction. Previous works have attempted to automate one or several parts of social skills training through human-computer interaction. However, while previous work on simulating social skills training considered only acoustic and linguistic features, human social skills trainers take into account visual features (e.g. facial expression, posture). In this paper, we create and evaluate a social skills training system that closes this gap by considering audiovisual features regarding ratio of smiling, yaw, and pitch. An experimental evaluation measures the difference in effectiveness of social skill training when using audio features and audiovisual features. Results showed that the visual features were effective to improve users' social skills.


Secular changes in standards of bodily attractiveness in women: tests of a reproductive model.
Since success at work is favored by a more slender body build while reproduction is favored by curvaceousness, standards of women's bodily attractiveness should be predictable from economic and reproductive variables. This hypothesis was tested in a replication and extension of a study by Silverstein, Perdue, Peterson, Vogel, and Fantini (1986) which looked at correlates of curvaceousness of Vogue models over time. As economic prosperity increased, and as women's participation in the economy, and higher education, increased, curvaceousness of the standards declined. As the proportion of single women to men, both aged 20-24 years, increased, and as the birth rate declined, curvaceousness was reduced. Results suggest that cultural standards of attractiveness are influenced by an evolved psychology of mate selection.


[Effect of okadaic acid on differentiation of NB4 and MR2 cells induced by all-trans retinoic acid].
To study the changes in expression and activity of protein phosphatases type 2A (PP2A ) during differentiation of NB4 and NB4-MR2 cells induced by all-trans retinoic acid (ATRA), and evaluate the role of PP2A in MR2 resistance to ATRA. ATRA, okadaic acid (OKA) and ATRA + OKA at the same dosage were incubated with NB4 and MR2 cells respectively. Wright's staining and NBT reduction test were employed to evaluate the change in the cells. The CD11b expression was measured by flow cytometry. The activity of PP2A was evaluated by serine/threonine phosphatase assay system, and the level of PP2A subunits was detected by Western blot. 1) Wright's staining, NBT reduction test and flow cytometry results showed OKA could augment the differentiation of NB4 induced by ATRA, and OKA + ATRA induced slight differentiation of MR2 cells. 2) Phosphatase assay showed a decrease in PP2A phosphatase activity [(534 +/- 43) pmol x min(-1) x microg protein(-1)] in NB4 after ATRA treatment, accompanied with that activity [(959 +/- 83) pmol x min(-1) x microg protein(-1)] in untreated NB4 cells. OKA enhanced the inhibitory effect of ATRA on the activity in NB4. When OKA + ATRA was incubated with MR2, PP2A in the cells was significantly decreased [(229 +/- 23) pmol x min(-1) x microg protein(-1)]. 3) Western blot analysis showed that the level of PP2A catalytic subunit (PP2A/C) was decreased during the course of ATRA-induced NB4 cell differentiation, whereas expressions of every subunits of PP2A in MR2 cells were somewhat unaltered. Expression of PP2A/C and activity of PP2A is decreased during differentiation of NB4 induced by ATRA, and no repression of the PP2 activity maybe related to MR2 resistance to ATRA.


[Parkinsonism and postoperative complications in the elderly].
The risk factors for postoperative morbidity and mortality in elderly patients with Parkinsonism after gastrointestinal surgery were evaluated by univariate and multivariate analyses in comparison to those of patients with cerebrovascular disease and to those of patients with no comorbid condition. Data were obtained on 36 patients with Parkinsonism (PK), 77 with cerebrovascular disease (CVD) and 120 with no comorbid condition (ND). All data were adjusted for age, sex and operative procedure. The postoperative morbidity rate was highest in the PK group (77.8%), followed by the CVD group (70.1%), and both differed significantly from the rate of the ND group (32.5%). Gastrointestinal and pulmonary complications and delirium were the major postoperative complications, and were significantly more common in the PK group than in the ND group. Patients in the PK group had the longest postoperative hospital stay, followed by those in the CVD and ND groups; the differences were significant between the PK and ND groups and between CVD and ND groups. The PK group had the highest operative and hospital mortality rates, and they differed significantly from the ND group. Hayashi's second method of quantification was used to assess the risk factors for postoperative death. The highest partial correlation coefficient was that found for postoperative pulmonary complication. We conclude that we should pay close attention to postoperative respiratory management, particularly in elderly patients with Parkinsonism, to prevent pulmonary complications and reduce postoperative mortality.


Affect and Cognition in Managerial Decision Making: A Systematic Literature Review of Neuroscience Evidence.
How do affect and cognition interact in managerial decision making? Over the last decades, scholars have investigated how managers make decisions. However, what remains largely unknown is the interplay of affective states and cognition during the decision-making process. We offer a systematization of the contributions produced on the role of affect and cognition in managerial decision making by considering the recent cross-fertilization of management studies with the neuroscience domain. We implement a Systematic Literature Review of 23 selected contributions dealing with the role of affect and cognition in managerial decisions that adopted neuroscience techniques/points of view. Collected papers have been analyzed by considering the so-called reflexive (X-) and reflective (C-) systems in social cognitive neuroscience and the type of decisions investigated in the literature. Results obtained help to support an emerging "unified" mind processing theory for which the two systems of our mind are not in conflict and for which affective states have a driving role toward cognition. A research agenda for future studies is provided to scholars who are interested in advancing the investigation of affect and cognition in managerial decision making, also through neuroscience techniques - with the consideration that these works should be at the service of the behavioral strategy field.


Health lifestyle education in high schools. A three-year follow-up study.
An experimental "healthy lifestyle programme" was initiated in Year 7 (first year of high school) in selected high schools in 1980 and was conducted over a three-year period. The programme had two main objectives: to influence attitudes and increase knowledge about health matters, in order to improve lifestyle; and to strengthen the general case for the more organized instruction of schoolchildren in this field. As part of the programme, children were given lessons on nutrition, physical activity and fitness, and on alcohol, tobacco and drugs. The programme was reasonably implemented in three of the four schools which took part in the experiment. Significant improvements, over three years, in attitudes and knowledge about health and nutrition and a reduction in cigarette smoking, were noted among children in schools where the programme had been implemented reasonably. The reasons for the partial success of the programme are discussed.


Arabidopsis thaliana Somatic Embryogenesis Receptor Kinase 1 protein is present in sporophytic and gametophytic cells and undergoes endocytosis.
Arabidopsis thaliana plants expressing AtSERK1 fused to yellow-fluorescent protein were generated. Fluorescence was detected predominantly at the cell periphery, most likely the plasma membrane, of cells in ovules, embryo sacs, anthers, and embryos and in seedlings. The AtSERK1 protein was detected in diverse cell types including the epidermis and the vascular bundles. In some cells, fluorescent receptors were seen in small vesicle-like compartments. After application of the fungal toxin Brefeldin A, the fluorescent receptors were rapidly internalized in the root meristem and root vascular tissue. We conclude that the AtSERK1 receptor functions in a common signalling pathway employed in both sporophytic and gametophytic cells.


Effectiveness of Saphenous Vein Y-Grafts in Patients Undergoing Off-Pump Complete Myocardial Revascularization.
BACKGROUND To evaluate perioperative and mid-term outcomes of saphenous vein Y-grafts in patients with multi-vessel coronary artery disease. MATERIAL AND METHODS Sixty patients who underwent off-pump coronary surgery with Y-graft between 2005 and 2016 were enrolled, including 38 patients with natural Y-graft. Sixty patients with multi-vessel lesions in the same period were randomly selected as a control group. RESULTS A total of 484 conduits were employed. The intraoperative variables were insignificantly different between groups, but Y-graft group compared with control group had more grafts (4.2±0.84 vs. 3.87±0.85) and anastomoses (6.30±1.39 vs. 5.62±1.15). No patient died during coronary artery bypass grafting and no episode of perioperative myocardial infarction was found. Follow-up duration lasted from 1 to 137 (40.0±27.7) months. No significant difference between Y-graft group and control group was found in Kaplan-Meier 3-year survival rate (93.4% vs. 88.0%) or 5-year survival rate (81.4% vs. 88.0%). CONCLUSIONS Saphenous vein Y-graft is a feasible and safe revascularization strategy for multi-vessel coronary artery disease patients and brings about satisfactory outcomes.


Ex Vivo Evaluation of Intravaginal Progesterone and Testosterone to Treat the Luteal-phase Deficiency and Vaginal Atrophy.
The purpose of this study was to evaluate the transmucosal permeation of progesterone and testosterone using Pentravan as its vehicle for vaginal delivery. Progesterone deficiency is a hormone imbalance that could lead to luteal-phase deficiency, which is a common problem in assisted reproductive technologies. Testosterone has been explored for treating postmenopausal symptoms, such as vaginal atrophy. The ex vivo experiments were performed using porcine vaginal mucosa and phosphate buffered saline + 0.5% 2-hydroxypropyl-ß-cyclodextrin as the receptor media, which was later quantified through high-performance liquid chromatography. The percentage of the permeated drug was 0.4% and 20.3% for progesterone and testosterone, respectively. The permeation studies revealed that testosterone formulated with Pentravan is potentially effective in reaching the bloodstream and acts locally, whereas progesterone was mostly retained in the mucosa.


5,10-Methylenetetrahydrofolate reductase (MTHFR) assay in the forward direction: residual activity in MTHFR deficiency.
Assay of methylenetetrahydrofolate reductase (MTHFR), a key enzyme in homocysteine metabolism, is important for the study of severe and mild deficiency states. Because the conventional assay measures in the reverse direction, lacks sensitivity, and uses nonphysiologic substrates, the exact measurement and characterization of residual activity in easily accessible tissues have been difficult. To measure MTHFR in the physiologic direction, we determined the NADPH-dependent conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate by use of HPLC with fluorescence detection. MTHFR activity in control fibroblast in the presence of FAD was maximal between pH 6.3 and 6.9, increased linearly up to 40 min and 80 microg protein/assay, and showed K(m)s of 30 micromol/L for NADPH and 26 micromol/L for 5,10-methylenetetrahydrofolate. Intraassay variation (CV) was 10%, interassay variation was 7.2%, and variation among 10 subcultures of the same cell line was 18%. Mean (SD) control activity was 431 (150) microU/mg protein (range, 242-910; n = 75), which is 2.5-fold higher than that with the reverse assay. After heat treatment (46 degrees C for 5 min), the activity showed a trimodal distribution corresponding to the 677TT (thermolabile; 15%), 677CT (35%), and 677CC (51%) genotypes. We found clearly measurable activity ranging from 2.6% to 25.6% of the mean control value in 15 patients with MTHFR deficiency, including 11 cell lines with zero activity in the reverse assay. Ten patients had complete enzyme deficiency. This assay allows reliable determination of residual activity in mutant fibroblasts and characterization of kinetic parameters for natural substrates.


Lead extractions: the Zwolle experience with the Evolution mechanical sheath.
The Evolution sheath (Cook, USA) is a power sheath with a cutting screw tip operated by mechanical rotation. It has been reported to be an effective tool for chronic lead extraction. We evaluated the safety and efficacy of this system. From 2009 to 2014, all lead extractions requiring the use of an Evolution sheath were prospectively examined. In 77 patients, 111 leads were extracted. The first 57 leads were extracted with the original unidirectional sheath, and since 2013, 54 leads were extracted with the bidirectional R/L type. According to the current guidelines, complete procedural success was defined as the removal of all targeted lead material. Clinical success was the retention of a small portion of the lead, and failure was the inability to achieve either complete procedural or clinical success or the development of any permanently disabling complication. The Evolution sheath was used to extract 111 leads in 77 patients. The median age of the lead at time of extraction was 8.0 years (median 6.9, interquartile range 6.4, minimum: 0.6 and maximum: 34.4), with a clinical success rate of 98% and a complete procedural success of 88%. Complete procedural success was higher for the R/L type Evolution sheath (96 vs. 80%, P = 0.006). There were 21 (19%) implantable cardioverter defibrillator leads, 22 (20%) right ventricular pacing leads, 60 (54%) right atrial leads, and 8 (7%) left ventricular leads. There were no major complications and six (8%) minor complications. There was no need for the usage of a femoral tool or snares. Use of Evolution for lead extractions seems to be safe and effective, with a high clinical success rate.


Direct competitive enzyme-linked immunosorbent assay (ELISA) for rapid screening of anisakid larvae in seafood.
Anisakid larvae are one of the most important pathogenic parasites in marine products; however, simple and rapid analytical techniques for them are still very limited. In this research, based on specific rabbit polyclonal antibodies which were raised against crude extracts of Anisakis larvae, purified by protein A affinity chromatography and labeled with horseradish peroxidase, a direct competitive enzyme-linked immunosorbent assay (ELISA) was developed and validated for detection of anisakid larvae in seafood. The established method exhibited a broad selectivity to Anisakis larvae and Pseudoterranova larvae, and the lowest detection limit to them was estimated to be about 5 parasites kg(-1) in food matrix. Using Pseudopleuronectes yokohamae, Scomberomorus niphonius and Ommastrephes bartrami as samples and within spiking concentrations from 20 to 100 larvae kg(-1), the determination recovery for Anisakis larvae and Pseudoterranova larvae ranged from 77.8% to 107.0%, with relative standard deviations all less than 20%. The results allowed us to suggest the established direct competitive ELISA as an effective analytical tool for fast screening of anisakid larvae in sea foods.


Receptor conversion in metastatic breast cancer: analysis of 390 cases from a single institution.
Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status provide clinical utility in guiding therapeutic decision-making in metastatic breast cancer (BC). Increasing data have shown substantial differences between the receptor profiles of primary BCs and their paired metastases. In this study, we provide a large single center cohort to assess the frequency of receptor conversion in metastatic BC. The overall discordant rates were 18.3%, 40.3%, and 13.7% for ER, PR, and HER2, respectively. The discordance was significantly higher for PR when compared with ER and HER2. The conversion occurred significantly as a switch from positive to negative receptor status when compared with that from negative to positive for all three receptors. Semiquantitative analyses revealed a significantly decreased expression of both ER (25%) and PR (57%) in the metastases. There was a higher rate of PR discordance in bone metastases when comparing to other common organs of relapse. Furthermore, in the subset of patients with a single primary and multiple distant metastases, the discordant rates among the distant sites were 27.5%, 39.4%, and 14.3% for ER, PR, and HER2, respectively. A positive ER status, be it in primary or metastatic BC, was associated with a prolonged metastasis-free survival when compared with ER-negative primary tumors without conversion. Furthermore, a positive ER status in metastatic BC regardless of primary was associated with a superior overall survival when compared with an ER-negative tumor without conversion. Thus, receptor conversion is a frequent event in the course of BC progression, and can also be seen between different metastatic sites. Moreover, some conversions are of prognostic significance. The findings may reflect tumor heterogeneity, sampling or treatment effect, but may also indicate alteration in tumor biology. Repeat biomarker testing is warranted in making appropriate treatment plans in the pursuit of precision medicine.


Atrazine removal from water by polycation-clay composites: effect of dissolved organic matter and comparison to activated carbon.
Atrazine removal from water by two polycations pre-adsorbed on montmorillonite was studied. Batch experiments demonstrated that the most suitable composite poly (4-vinylpyridine-co-styrene)-montmorillonite (PVP-co-S90%-mont.) removed 90-99% of atrazine (0.5-28 ppm) within 20-40 min at 0.367% w/w. Calculations employing Langmuir's equation could simulate and predict the kinetics and final extents of atrazine adsorption. Column filter experiments (columns 20x1.6 cm) which included 2g of the PVP-co-S90%-mont. composite mixed with excess sand removed 93-96% of atrazine (800 ppb) for the first 800 pore volumes, whereas the same amount of granular activated carbon (GAC) removed 83-75%. In the presence of dissolved organic matter (DOM; 3.7 ppm) the efficiency of the GAC filter to remove atrazine decreased significantly (68-52% removal), whereas the corresponding efficiency of the PVP-co-S90%-mont. filter was only slightly influenced by DOM. At lower atrazine concentration (7 ppb) the PVP-co-S90%-mont. filter reduced even after 3000 pore volumes the emerging atrazine concentration below 3 ppb (USEPA standard). In the case of the GAC filter the emerging atrazine concentration was between 2.4 and 5.3 microg/L even for the first 100 pore volumes. Thus, the PVP-co-S90%-mont. composite is a new efficient material for the removal of atrazine from water.


The effects of livestock grazing on biodiversity are multi-trophic: a meta-analysis.
Anthropogenic disturbance has generated a significant loss of biodiversity worldwide and grazing by domestic herbivores is a contributing disturbance. Although the effects of grazing on plants are commonly explored, here we address the potential multi-trophic effects on animal biodiversity (e.g. herbivores, pollinators and predators). We conducted a meta-analysis on 109 independent studies that tested the response of animals or plants to livestock grazing relative to livestock excluded. Across all animals, livestock exclusion increased abundance and diversity, but these effects were greatest for trophic levels directly dependent on plants, such as herbivores and pollinators. Detritivores were the only trophic level whose abundance decreased with livestock exclusion. We also found that the number of years since livestock was excluded influenced the community and that the effects of grazer exclusion on animal diversity were strongest in temperate climates. These findings synthesise the effects of livestock grazing beyond plants and demonstrate the indirect impacts of livestock grazing on multiple trophic levels in the animal community. We identified the potentially long-term impacts that livestock grazing can have on lower trophic levels and consequences for biological conservation. We also highlight the potentially inevitable cost to global biodiversity from livestock grazing that must be balanced against socio-economic benefits.


Plummer Vinson syndrome: unusual features.
Plummer Vinson syndrome is a constellation of postcricoid esophageal webs, iron deficiency anemia, dysphagia and koilonychia. We describe some unusual manifestations in three patients with this syndrome; these were clubbing instead of koilonychia, tortuous esophagus in addition to presence of esophageal webs, and celiac disease.


Adenovirus-mediated small interfering RNA against matrix metalloproteinase-2 suppresses tumor growth and lung metastasis in mice.
Matrix metalloproteinases (MMP) are a group of proteinases that have normal physiologic roles degrading and remodeling the extracellular matrix. They also have multiple roles in different stages of tumor progression. Elevated levels of MMPs have been observed in many tumors; these increases have a strong association with the invasive phenotype. MMP-2 and MMP-9 are particularly involved in cancer invasion and metastasis. MMP inhibitors are currently being tested as therapeutic agents for a number of cancers in both preclinical models and in clinical trials. To date, clinical trials using this strategy have had limited efficacy. A major concern is the lack of specificity of commercially available MMP inhibitors. An adenoviral vector expressing small interfering RNA against the MMP-2 gene (Ad-MMP-2) was constructed to specifically inhibit MMP-2 expression. The effect of Ad-MMP-2 on invasion, angiogenesis, tumor growth, and metastasis of A549 lung cancer cell was evaluated. Ad-MMP-2 infection of lung cancer cells showed specific down-regulation of MMP-2 protein, activity, and transcription as determined by Western blotting, gelatin zymography, and reverse transcription-PCR. Ad-MMP-2 inhibition also mitigated lung cancer invasion and migration, and reduced tumor cell-induced angiogenesis in vitro. In an experimental metastatic lung tumor model, treatment of established tumors by Ad-MMP-2 inhibited s.c. tumor growth and formation of lung nodules in mice. Adenoviral-mediated RNA interference against MMP-2 has significant therapeutic potential for lung cancer and exerts some of this effect by inhibiting angiogenesis.


The T cell system in rheumatoid arthritis: activated or defective?
Rheumatoid Arthritis (RA) is characterised by the presence of activated lymphocytes in the synovial compartment, which are classically considered to be of particular importance to the pathogenesis of the disease. We have shown that activated lymphocytes are also found in the rheumatoid lymph nodes and peripheral blood, and that their proportions are increased in early or active disease. Double-labelling experiments showed that T cell subsets within the activated circulating lymphocytes resemble closely those found in the synovium, and suggested an important role for circulating activated lymphoid populations in the pathogenesis of RA. In vitro studies indicate that although rheumatoid lymphocytes express activation markers, they are functionally deficient. This is well established in the case of synovial lymphocytes. We have demonstrated that functional defects are also present in circulating rheumatoid lymphocytes, which show a decreased autologous mixed leucocyte response (AMLR), corrected partially by the addition of exogenous IL-2. They also proliferate poorly in response to PHA and produce significantly less IL-2 than normal controls. This is more marked in patients with active or complicated RA. These defects cannot be explained by a lack of CD4+2H4+ cells which we have shown to be the major IL-2-producing circulating lymphocyte subpopulation. These findings suggest an intrinsic-functional rather than a numerical deficiency of the IL-2 producing T cells in RA. In recent experiments we have shown that non-lymphoid populations, such as activated phagocytic cells, are also involved in the deficient rheumatoid T cell function, partly via the production of prostaglandins and reactive oxygen intermediates. We and others have demonstrated that the latter may significantly and selectively affect lymphocyte viability and function. These findings may explain the differences in the functional capacity of lymphocytes frequently observed between cells derived from different sites or at different stages of the disease. We suggest that it is not lymphocyte activation as such, but its defective nature, that is of pathogenetical importance in RA. Furthermore, the T cell system should not be viewed and studied in isolation in this disease, but its interactions with inflammatory cells should be taken into account.


NRAMP1 (SLC11A1) gene polymorphisms that correlate with autoimmune versus infectious disease susceptibility in tuberculosis and rheumatoid arthritis.
NRAMP1 gene has multiple pleiotropic effects on macrophage activation pathways. These pleiotropic effects may increase resistance to infections such as tuberculosis (TB), but may also lead to susceptibility of autoimmune diseases such as rheumatoid arthritis (RA). It has been hypothesized that allele 3 would be associated with autoimmune diseases, whereas allele 2 would be associated with infectious diseases, and genetic factors that enhanced survival in the epidemics of TB might have led to susceptibility for the development of RA. We analysed four NRAMP1 gene polymorphisms including 5' promoter (GT)(n) (rs34448891), INT4 (469 + 14G/C) (rs3731865), 3'UTR (1729 + 55del4) (rs17235416) and D543N (codon 543, Asp to Asn) (rs17235409) in 112 patients with TB, 98 patients with RA, 80 healthy controls for TB and 122 healthy controls for RA using ARMS-PCR and PCR-RFLP. We found a significant association between INT4 and RA (P = 0.004, odds ratio: 2.06, 95% CI: 1.24-3.41), but no significant differences between 5' promoter, D543N, 3'UTR polymorphisms and RA. There were no associations between NRAMP1 gene polymorphisms and TB. Similarly, no significant differences were observed between NRAMP1 polymorphisms and rheumatoid factor positivity and erosive disease in RA and localization of TB. INT4 polymorphism may be associated with RA in Turkish patients.


New serovars of plesiomonas shigelloides--1996.
Eight new 0 (91-98) and H (46-49) antigens are described. Their reference strains come from Czech Republic, Cuba and USA. The majority of reference strains are of human origin. Some of the new antigens have been found in other strains coming mostly from water.


QTL mapping of seedling tolerance to exposure to low temperature in the maize IBM RIL population.
Maize is a cold sensitive crop that exhibits severe retardation of growth and development when exposed to cold spells during and right after germination, including the slowdown in development of new leaves and in formation of the photosynthetic apparatus. Improving cold tolerance in maize would allow early sowing to improve crop yield by prolonging a growing season and by decreasing the negative effects of summer drought, diseases, and pests. Two maize inbreds widely incorporated into American maize germplasm, B73 and Mo17, exhibit different levels of tolerance to low temperature exposure at seedling stage. In addition, thirty seven diverse inbred maize lines showed large variation for seedling response to low temperature exposure with lines with extremely low tolerance to seedling exposure to low temperatures falling into stiff stalk, non-stiff stalk, and tropical clades. We employed the maize intermated B73×Mo17 (IBM) recombinant inbred line population (IBM Syn4 RIL) to investigate the genetic architecture of cold stress tolerance at a young seedling stage and to identify quantitative trait loci (QTLs) controlling this variation. A panel of 97 recombinant inbred lines of IBM Syn4 were used to measure, and score based on several traits related to chlorophyll concentration, leaf color, and tissue damage. Our analysis resulted in detection of two QTLs with high additive impact, one on chromosome 1 (bin 1.02) and second on chromosome 5 (bin 5.05). Further investigation of the QTL regions using gene expression data provided a list of the candidate genes likely contributing to the variation in cold stress response. Among the genes located within QTL regions identified in this study and differentially expressed in response to low temperature exposure are the genes with putative functions related to auxin and gibberellin response, as well as general abiotic stress response, and genes coding for proteins with broad regulatory functions.


Isolation of pancreatic islets from dogs. Semiautomated purification on albumin gradients.
We describe a procedure for the isolation of large numbers of canine pancreatic islets with a high level of purity. The method utilizes enzymatic and mechanical disruption of the pancreas, followed by islet purification on discontinuous density gradients of bovine serum albumin. Purification has been semiautomated through use of the Cobe 2991 cell processor. Islet preparations have a purity of 86.5% and contain 36.8 microliters of endocrine tissue. Islets isolated by this procedure are functionally intact, and restore fasting euglycemia following autotransplantation.


[Experimental study on tissue engineered cartilage complex three-dimensional nano-scaffold with collagen type II and hyaluronic acid in vitro].
To explore the possibility of constructing tissue engineered cartilage complex three-dimensional nano-scaffold with collagen type II and hyaluronic acid (HA) by electrospinning. The three-dimensional porous nano-scaffolds were prepared by electrospinning techniques with collagen type II and HA (8 : 1, W : W), which was dissolved in mixed solvent of 3-trifluoroethanol and water (1 : 1, V : V). The morphology were observed by light microscope and scanning electron microscope (SEM). And the porosity, water absorption rate, contact angle, and degradation rate were detected. Chondrocytes were harvested from 1-week-old Japanese white rabbit, which was disgested by 0.25% trypsin 30 minutes and 1% collagenase overlight. The passage 2 chondrocytes were seeded on the nano-scaffold. The cell adhesion and proliferation were evaluated by cell counting kit 8 (CCK-8). The cell-scaffold composites were cultured for 2 weeks in vitro, and the biological morphology and extracelluar matrix (ECM) secretion were observed by histological analysis. The optimal electrospinning condition of nano-scaffold was 10% electrospinning solution concentration, 10 cm receiver distance, 5 mL/h spinning injection speed. The scaffold had uniform diameter and good porosity through the light microscope and SEM. The diameter was 300-600 nm, and the porosity was 89.5% +/- 25.0%. The contact angle was (35.6 +/- 3.4) degrees, and the water absorption was 1 120% +/- 34% at 24 hours, which indicated excellent hydrophilicity. The degradation rate was 42.24% +/- 1.51% at 48 days. CCK-8 results showed that the adhesive rate of cells with scaffold was 169.14% +/- 11.26% at 12 hours, and the cell survival rate was 126.03% +/- 4.54% at 7 days. The histological and immunohistochemical staining results showed that the chondrocytes could grow well on the scaffold and secreted ECM. And the similar cartilage lacuma structure could be found at 2 weeks after co-culture, which suggested that hyaline cartilage formed. The collage type II and HA complex three-dimensional nano-scaffold has good physicochemical properties and excellent biocompatibility, so it can be used as a tissue engineered cartilage


Associations between serum uric acid concentrations and metabolic syndrome and its components in the PREDIMED study.
Several studies have demonstrated a relationship between increased serum uric acid (SUA) concentrations and the prevalence of metabolic syndrome (MetS) in the oriental population. However, to the best of our knowledge, the association between SUA and MetS has never been investigated in elderly European individuals at high cardiovascular risk. The aim of this study was to conduct a cross-sectional and prospective evaluation of the associations between SUA concentrations and the MetS in elderly individuals at high cardiovascular risk. Men and women (55-80 years of age) from different PREDIMED (Prevención con DIeta MEDiterránea) recruiting centers were studied. Baseline cross-sectional (n = 4417) and prospective assessments (n = 1511) were performed. MetS was defined in accordance with the updated harmonized criteria. Anthropometric measurements and biochemical determinations were assessed at baseline and yearly during follow-up. Unadjusted and adjusted regression models were fitted to assess the risk of MetS and its components according to the levels of baseline SUA. Participants in the highest baseline sex-adjusted SUA quartile showed an increased prevalence of MetS than those in the lowest quartile, even after adjusting for potential confounders (odd ratio (OR): 2.3 (95% confidence interval (CI), 1.8-2.8); P < 0.001). Participants in the highest baseline sex-adjusted SUA quartile presented a higher incidence of new-onset MetS than those in the lowest quartile (hazard ratios (HR): 1.4 (95% CI, 1.1-1.9); P < 0.001). Participants initially free at baseline of hypertriglyceridemia (HR: 1.9 (1.6-2.4); P < 0.001), low high-density lipoprotein (HDL)-cholesterol (HR: 1.4 (1.1-1.7); P = 0.002), and hypertension components of MetS (HR: 2.0 (1.2-3.3); P = 0.008) and who were in the upper quartile of SUA had a significantly higher risk of developing these MetS components during follow-up. Elevated SUA concentrations are significantly associated with the development of MetS.


Pharmacological inhibition of mTORC1 activity protects against inflammation-induced apoptosis of nucleus pulposus cells.
Lumbar disc herniation is a common disease characterized by the degeneration of intervertebral discs (IVDs), accompanied by imbalance of metabolic and inflammatory homeostasis. Current studies establish that IVD degeneration is induced by increased apoptosis of nucleus pulposus (NP) cells. However, the underlying mechanisms of NP cell survival/apoptosis are not well elucidated. Here, we reveal a novel mechanism by which mTORC1 signaling controls NP cell survival through regulating metabolic homeostasis. We demonstrated that hyperactivated mTORC1 activity induced by inflammatory cytokines engenders the apoptosis of NP cells, whereas pharmacological inhibition of mTORC1 activity promotes NP cell survival. Using an integrative approach spanning metabolomics and biochemical approaches, we showed that mTORC1 activation enhanced glucose metabolism and lactic acid production, and therefore caused NP cell apoptosis. Our study identified mTORC1 in NP cells as a novel target for IVD degeneration, and provided potential strategies for clinical intervention of lumbar disc herniation.


High-performance liquid chromatographic determination of components of bleomycin preparations.
A fast and sensitive method was developed for the quantitative determination of at least 10 components of pharmaceutical bleomycin sulfate preparations. The method is based on the reversed-phase high-performance liquid chromatographic (HPLC) separation of the components on a muBondapak C18 column with a mobile phase having a linear gradient of 10--40% methanol in aqueous 0.005 M 1-pentanesulfonic acid at pH 4.3. With this assay, the average standard deviations for components A2 and B2 are 0.92 and 0.87, respectively, for a 7.5--22.5 x 10(-3)-mg sample. Regulatory agencies presently use the official Code of Federal Regulations (CFR) method, which is based on CM-Sephadex column chromatography. It was demonstrated that this CFR method does not separate the bleomycin A2 component from some other minor bleomycin components. After elution from the CM-Sephadex column, the "A2 component" was separated into five components by the HPLC method. Bleomycin A2 is stable under these HPLC conditions.


Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats.
Hypothalamic inflammation is associated with insulin and leptin resistance, hyperphagia, and obesity. In this scenario, hypothalamic protein tyrosine phosphatase 1B (PTP1B) has emerged as the key phosphatase induced by inflammation that is responsible for the central insulin and leptin resistance. Here, we demonstrated that acute exercise reduced inflammation and PTP1B protein level/activity in the hypothalamus of obese rodents. Exercise disrupted the interaction between PTP1B with proteins involved in the early steps of insulin (IRβ and IRS-1) and leptin (JAK2) signaling, increased the tyrosine phosphorylation of these molecules, and restored the anorexigenic effects of insulin and leptin in obese rats. Interestingly, the anti-inflammatory action and the reduction of PTP1B activity mediated by exercise occurred in an interleukin-6 (IL-6)-dependent manner because exercise failed to reduce inflammation and PTP1B protein level after the disruption of hypothalamic-specific IL-6 action in obese rats. Conversely, intracerebroventricular administration of recombinant IL-6 reproduced the effects of exercise, improving hypothalamic insulin and leptin action by reducing the inflammatory signaling and PTP1B activity in obese rats at rest. Taken together, our study reports that physical exercise restores insulin and leptin signaling, at least in part, by reducing hypothalamic PTP1B protein level through the central anti-inflammatory response.


Redesign of soluble fatty acid desaturases from plants for altered substrate specificity and double bond position.
Acyl-acyl carrier protein (ACP) desaturases introduce double bonds at specific positions in fatty acids of defined chain lengths and are one of the major determinants of the monounsaturated fatty acid composition of vegetable oils. Mutagenesis studies were conducted to determine the structural basis for the substrate and double bond positional specificities displayed by acyl-ACP desaturases. By replacement of specific amino acid residues in a Delta6-palmitoyl (16:0)-ACP desaturase with their equivalents from a Delta9-stearoyl (18:0)-ACP desaturase, mutant enzymes were identified that have altered fatty acid chain-length specificities or that can insert double bonds into either the Delta6 or Delta9 positions of 16:0- and 18:0-ACP. Most notably, by replacement of five amino acids (A181T/A200F/S205N/L206T/G207A), the Delta6-16:0-ACP desaturase was converted into an enzyme that functions principally as a Delta9-18:0-ACP desaturase. Many of the determinants of fatty acid chain-length specificity in these mutants are found in residues that line the substrate binding channel as revealed by x-ray crystallography of the Delta9-18:0-ACP desaturase. The crystallographic model of the active site is also consistent with the diverged activities associated with naturally occurring variant acyl-ACP desaturases. In addition, on the basis of the active-site model, a Delta9-18:0-ACP desaturase was converted into an enzyme with substrate preference for 16:0-ACP by replacement of two residues (L118F/P179I). These results demonstrate the ability to rationally modify acyl-ACP desaturase activities through site-directed mutagenesis and represent a first step toward the design of acyl-ACP desaturases for the production of novel monounsaturated fatty acids in transgenic oilseed crops.


[Methods of determining the concentration of total lipids and phosphorus in the bile].
Standard kits of reagents, manufactured in the CSSR, intended for measurements of the blood serum and urinary lipids and phosphorus, were used for measurements of these component' concentrations in the bile. The levels of the total lipids and phosphorus in the bladder bile, measured with the use of this kit in normal subjects, did not essentially differ from those reported in literature.


Systemic Amyloidosis in a Teenage Boy With Inflammatory Bowel Disease.
Systemic amyloidosis is a very rare complication of inflammatory bowel disease (IBD). The reported cases of secondary amyloidosis in children with IBD are much fewer than those reported in adults. Herein, a teenage boy with Crohn's disease is presented who developed nephrotic syndrome due to renal involvement secondary to amyloidosis, whereas the patient was under treatment with corticosteroid and 6-mercaptopurine. To our best knowledge, this is the first reported case of secondary amyloidosis in a teenage Iranian boy with Crohn's disease.


Assessment of a long-range corrected hybrid functional.
Common approximate exchange-correlation functionals suffer from self-interaction error, and as a result, their corresponding potentials have incorrect asymptotic behavior. The exact asymptote can be imposed by introducing range separation into the exchange component and replacing the long-range portion of the approximate exchange by the Hartree-Fock counterpart. The authors show that this long-range correction works particularly well in combination with the short-range variant of the Perdew-Burke-Ernzerhof (PBE) exchange functional. This long-range-corrected hybrid, here denoted LC-omegaPBE, is remarkably accurate for a broad range of molecular properties, such as thermochemistry, barrier heights of chemical reactions, bond lengths, and most notably, description of processes involving long-range charge transfer.


Analysis of recurrent angiotensin converting enzyme inhibitor-induced angioedema.
A known risk for patients taking angiotensin converting enzyme-inhibitors (ACE-Is) is angioedema that can involve the face, lips, oral cavity, and larynx. Such upper airway obstruction may be severe enough to require an emergency department visit or even necessitate prompt airway intervention. Once a patient has had an episode of ACE-inhibitor induced angioedema (AIIA), certainly a thrust of continuing case management would be to avoid the occurrence of subsequent episodes of AIIA that potentially can be life-threatening. Nevertheless, recurrent episodes of AIIA do occur. This study aims to characterize a patient's risk for recurrent AIIA, determine the cause for repeat episodes of AIIA and recommend steps to be taken to minimize the recurrence of AIIA. Retrospective study. A retrospective chart review of all patient encounters at our medical center between January 1, 1991 and December 30, 2005 with a diagnosis of angioedema was performed. The documented etiology of the angioedema, comorbidities, and documentation of an "allergy" to ACE-I were noted. Observations regarding risk factors for recurrent AIIA were made. Recurrent AIIA occurred in 23 patients with a recurrence rate of 6.2%. Risk factors for recurrence were categorized as patient factors, physician factors, or systems factors. Physician error with failure to document in the medical record, the suspicion of AIIA, and failure to consider risk in prescribing ACE-I after an episode of angioedema had occurred were the most common causes of recurrent AIIA. Angioedema can cause life-threatening airway compromise yet patients with a history of one episode of AIIA are at risk for a subsequent episode. Physicians can modify clinical practices to avert the potentially life-threatening side effects of ACE-inhibitors in patients with a prior episode of AIIA.


Improvement of sound source localization abilities in patients bilaterally supplied with active middle ear implants.
Patients, who are bilaterally supplied with active middle ear implants, perform slightly better in sound localization tasks than when unilaterally aided or unaided. To investigate the impact of bilateral use of active middle ear implants on sound source localization in the horizontal plane in patients with a sloping moderate-to-severe hearing loss. Ten adults supplied with Med-EL Vibrant Soundbridge systems (VSB) in both ears participated in the study. Four listening conditions were tested: unaided, aided with VSB on left or right ear and on both sides. In each condition the subjects had to judge the direction of broadband noises delivered randomly across a semicircular array of 11 loudspeakers arranged in an anechoic chamber. When unaided or bilaterally aided, the subjects localized on average 40% of the stimuli correct; when unilaterally aided (left or right), this rate dropped to 20-30% in either condition. Precision of sound localization was highest when bilaterally aided, i.e. the mean RMS angular error was 10°, and lowest when unilaterally aided, i.e. 15°. This is in line with bilateral hearing aid users, who show similar performance in sound localization tasks.


Action-Effect Associations in Voluntary and Cued Task-Switching.
The literature of action control claims that humans control their actions in two ways. In the stimulus-based approach, actions are triggered by external stimuli. In the ideomotor approach, actions are elicited endogenously and controlled by the intended goal. In the current study, our purpose was to investigate whether these two action control modes affect task-switching differently. We combined a classical task-switching paradigm with action-effect learning. Both experiments consisted of two experimental phases: an acquisition phase, in which associations between task, response and subsequent action effects were learned and a test phase, in which the effects of these associations were tested on task performance by presenting the former action effects as preceding effects, prior to the task (called practiced effects). Subjects either chose freely between tasks (ideomotor action control mode) or they were cued as to which task to perform (sensorimotor action control mode). We aimed to replicate the consistency effect (i.e., task is chosen according to the practiced task-effect association) and non-reversal advantage (i.e., better task performance when the practiced effect matches the previously learned task-effect association). Our results suggest that participants acquired stable action-effect associations independently of the learning mode. The consistency effect (Experiment 1) could be shown, independent of the learning mode, but only on the response-level. The non-reversal advantage (Experiment 2) was only evident in the error rates and only for participants who had practiced in the ideomotor action control mode.


The use of audiovisual procedures in evaluating oral diagnostic and treatment planning skills of dental students.
In the belief that an examination testing the diagnostic and treatment planning capabilities of junior dental students should involve more than the traditional paper and pencil test, a new test was developed at the University of Mississippi School of Dentistry. Interesting and varied stimuli, such as a videotape, visual aids, and relevant dental data were included as part of this exam. The test was administered, and the degree of student anxiety before, during, and after the examination was measured. In general, students performed well; the majority indicated a preference for this type of examination over the usual paper and pencil test. As expected, anxiety levels increased until the examination was completed and then decreased. Student evaluations were not affected by the degree of anxiety. The inclusion of a variety of materials in a test measuring diagnostic and treatment planning skills resulted in a more challenging examination; the use of a videotaped segment simulating a case history provided consistency in the test material.


In silico vaccine design based on molecular simulations of rhinovirus chimeras presenting HIV-1 gp41 epitopes.
A cluster of promising epitopes for the development of human immunodeficiency virus (HIV) vaccines is located in the membrane-proximal external region (MPER) of the gp41 subunit of the HIV envelope spike structure. The crystal structure of the peptide corresponding to the so-called ELDKWA epitope (HIV-1 HxB2 gp41 residues 662-668), in complex with the corresponding broadly neutralizing human monoclonal antibody 2F5, provides a target for structure-based vaccine design strategies aimed at finding macromolecular carriers that are able to present this MPER-derived epitope with optimal antigenic activity. To this end, a series of replica exchange molecular dynamics computer simulations was conducted to characterize the distributions of conformations of ELDKWA-based epitopes inserted into a rhinovirus carrier and to identify those with the highest fraction of conformations that are able to bind 2F5. The length, hydrophobic character, and precise site of insertion were found to be critical for achieving structural similarity to the target crystal structure. A construct with a high degree of complementarity to the corresponding determinant region of 2F5 was obtained. This construct was employed to build a high-resolution structural model of the complex between the 2F5 antibody and the chimeric human rhinovirus type 14:HIV-1 ELDKWA virus particle. Additional simulations, which were conducted to study the conformational propensities of the ELDKWA region in solution, confirm the hypothesis that the ELDKWA region of gp41 is highly flexible and capable of assuming helical conformations (as in the postfusion helical bundle structure) and beta-turn conformations (as in the complex with the 2F5 antibody). These results also suggest that the ELDKWA epitope can be involved in intramolecular--and likely intermolecular--hydrophobic interactions. This tendency offers an explanation for the observation that mutations decreasing the hydrophobic character of the MPER in many cases result in conformational changes that increase the affinity of this region for the 2F5 antibody.


Critical role for mouse marginal zone B cells in PF4/heparin antibody production.
Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder that can cause fatal arterial or venous thrombosis/thromboembolism. Immune complexes consisting of platelet factor 4 (PF4), heparin, and PF4/heparin-reactive antibodies are central to the pathogenesis of HIT. However, the B-cell origin of HIT antibody production is not known. Here, we show that anti-PF4/heparin antibodies are readily generated in wild-type mice on challenge with PF4/heparin complexes, and that antibody production is severely impaired in B-cell-specific Notch2-deficient mice that lack marginal zone (MZ) B cells. As expected, Notch2-deficient mice responded normally to challenge with T-cell-dependent antigen nitrophenyl-chicken γ globulin but not to the T-cell-independent antigen trinitrophenyl-Ficoll. In addition, wild-type, but not Notch2-deficient, B cells plus B-cell-depleted wild-type splenocytes adoptively transferred into B-cell-deficient μMT mice responded to PF4/heparin complex challenge. PF4/heparin-specific antibodies produced by wild-type mice were IgG2b and IgG3 isotypes. An in vitro class-switching assay showed that MZ B cells were capable of producing antibodies of IgG2b and IgG3 isotypes. Lastly, MZ, but not follicular, B cells adoptively transferred into B-cell-deficient μMT mice responded to PF4/heparin complex challenge by producing PF4/heparin-specific antibodies of IgG2b and IgG3 isotypes. Taken together, these data demonstrate that MZ B cells are critical for PF4/heparin-specific antibody production.


Effect of manipulating positive and negative feedback on goal orientations, perceived motivational climate, satisfaction, task choice, perception of ability, and attitude toward physical education lessons.
This study examined the effect of different types of feedback on goal orientation, perception of motivational climate, satisfaction, and boredom in physical education (PE) classes, pupils' preferences for challenging versus easy tasks, pupils' attitudes towards PE lessons, and perception of gymnastic ability. 95 subjects in three treatment conditions (positive feedback, negative feedback, and both feedback types) participated in 14 lessons and completed pre- and postintervention measures. Results showed that subjects in the positive feedback group had significantly higher scores on learning-oriented motivational climate and enjoyment than the subjects of the negative feedback group. The negative feedback group reported higher scores on performance-oriented motivational climate than the positive feedback group. Results also showed that subjects in the group receiving both types of feedback had lower scores on learning-oriented motivational climate, higher scores on enjoyment than the negative feedback group, and lower scores on boredom than the positive feedback group. The effects of feedback on physical education students' motivation are discussed.


A hereditary case of lipid storage myopathy with carnitine deficiency. Ultrastructural observation of muscle tissue in parents.
A case of lipid storage myopathy with systemic carnitine deficiency is reported. There was lipid storage also in the liver but not in leukocytes or the Schwann cells of peripheral nerves. Carnitine concentration was normal in the father but below normal in the mother's muscle where abnormal accumulations of lipid droplets and mitochondria were present between the myofibrils and beneath the sarcolemmal sheath. Histographic analysis demonstrated type I fiber predominance in the patient and in his parents. Hereditary transmission of the disease through a recessive autosomal mechanism might be admitted in this case.


Cross reactivity of serum antibody responses elicited by DNA vaccines expressing HA antigens from H1N1 subtype influenza vaccines in the past 30 years.
In the past three decades, ten H1 subtype influenza vaccines have been recommended for global seasonal flu vaccination. Some of them were used only for one year before being replaced by another H1 flu vaccine while others may be used for up to seven years. While the selection of a new seasonal flu vaccine was based on the escape of a new emerging virus that was not effectively protected by the existing flu formulation, there is limited information on the magnitude and breadth of cross reactivity among H1 subtype virus circulation over a long period. In the current study, HA-expressing DNA vaccines were constructed to express individual HA antigens from H1 subtype vaccines used in the past 30 y. Rabbits naïve to HA antibody responses were immunized with these HA DNA vaccines and the cross reactivity of these sera against HA antigen and related H1 viruses in the same period was studied. Our data indicate that the level of cross reactivity was different for different viral isolates and the key mutations responsible for the cross reactivity may involve only a limited number of residues. Our results provide useful information for the development of improved seasonal vaccines than can achieve broad protection against viruses within the same H1 subtype.


Cognitive control during sentence generation.
Sentence generation involves selecting the right words out of multiple co-activated representations for the right utterance positions. This selection process is hypothesized to involve cognitive control. Previous research has linked cognitive control during language processing to regions within the frontal lobe, including the anterior cingulate cortex (ACC) and left ventrolateral prefrontal cortex (VLPFC). We examined the neural correlates of word and sentence generation to determine whether these cognitive control regions were activated more for sentences than words. We also manipulated the phonological overlap between nouns in the sentence to determine whether cognitive control recruitment increased under phonological competition. Whole-brain analysis revealed increased activation in the ACC and bilateral frontal cortex for sentences over words. Region of interest analysis revealed an effect of phonological competition within the ACC. Psychophysiological interaction (PPI) analysis further showed that functional connectivity within a task-maintenance network increased under phonological competition. These results suggest a role for conflict detection and monitoring during sentence generation, which is consistent with a theoretical framework incorporating domain-general cognitive control processes into language processing.


From Preassociation to Chelation: A Survey of Cisplatin Interaction with Methionine at Molecular Level by IR Ion Spectroscopy and Computations.
Methionine (Met) plays an important role in the metabolism of cisplatin anticancer drug. Yet, methionine platination in aqueous solution presents a highly complex pattern of interconnected paths and intermediates. This study reports on the reaction of methionine with the active aqua form of cisplatin, cis-[PtCl(NH3)2(H2O)]+, isolating the encounter complex of the reactant pair, {cis-[PtCl(NH3)2(H2O)]+·Met}, by electrospray ionization. In the unsolvated state, charged intermediates are characterized for their structure and photofragmentation behavior by IR ion spectroscopy combined with quantum-chemical calculations, obtaining an outline of the cisplatin-methionine reaction at a molecular level. To summarize the major findings: (i) the {cis-[PtCl(NH3)2(H2O)]+·Met} encounter complex, lying on the reaction coordinate of the Eigen-Wilkins preassociation mechanism for ligand substitution, is delivered in the gas phase and characterized by IR ion spectroscopy; (ii) upon vibrational excitation, ligand exchange occurs within {cis-[PtCl(NH3)2(H2O)]+·Met}, releasing water and cis-[PtCl(NH3)2(Met)]+, along the calculated energy profile; (iii) activated cis-[PtCl(NH3)2(Met)]+ ions undergo NH3 departure, forming a chelate complex, [PtCl(NH3)(Met)]+, whose structure is congruent with overwhelming S-Met ligation as the primary coordination step. The latter process involving ammonia loss marks a difference with the prevailing chloride replacement in protic solvent, pointing to the effect of a low-polarity environment.


[Analysis on the concept and clinical practice of patient-controlled analgesia in the treatment of cancer pain by Chinese medical providers].
Objective: To investigated the concept and clinical practice of patient-controlled analgesia (PCA) in the treatment of cancer pain. Methods: Doctors, nurses, pharmacists from the oncology department, pain department, or hospice department were investigated using an electronic questionnaire from December 1 to December 31, 2021. In addition to the basic information, there were 26 questions were collected, including the current situation of cancer pain treatment, the concept of medical staff on PCA treatment of cancer pain and the clinical practice of PCA. Results: Questionnaires from 2 872 medical staff were collected from 993 hospitals in 30 provincial administrative units. Only 34.8% (955/2 748) of medical staff considered that the satisfaction rate of cancer pain control was over 75%, and 27.9% (548/1 968) of medical staff convinced that the satisfaction rate of breakthrough pain control was less than 50%. 97.1% (2 439/2 513) of medical staff considered that PCA could be effectively used for cancer pain treatment. The proportion of medical staff in secondary and tertiary hospitals who thought that PCA was applicable to cancer pain that could not be effectively alleviated by standardized non-invasive drug administration was 64.6% (319/494) and 69.1% (1 262/1 826) respectively, which was higher than that in primary hospitals [57.0% (110/193)] (P=0.002). In different occupations, the proportion of nurses who convinced PCA treatment of cancer pain increased the risk of addiction and drug overdose was 62.8% (431/686) and 76.1% (522/686), respectively, which was higher than doctors [39.2% (670/1709) and 58.2% (995/1709), respectively] and pharmacists [49.2% (58/118) and 65.3% (77/118), respectively] (all P<0.001). There was no significant difference in type of pump, route of administration, mode of infusion, protocol for PCA administration and selection of common medication in PCA treatment of cancer pain among different hospitals (all P>0.05). The calculation of continuous infusion dose and rescue dose of PCA was not uniform among different hospitals. After initiation of PCA, 71.7% (1 226/1 709) of hospitals had insufficient analgesia and most of them needed to be adjusted for 1-3 times to achieve satisfactory analgesia. Conclusion: Medical staff have insufficient cognition of PCA treatment of cancer pain and there is a lack of unified guidance in clinical practice. Therefore, it is an urgent need to develop an expert consensus on PCA treatment of cancer pain.


Mechanisms underlying volume regulatory decrease by Necturus gallbladder epithelium.
Volume regulatory decrease (VRD) by Necturus gallbladder epithelial cells in Cl Ringer was unaffected by the addition of 5 mM BaCl2 to apical perfusates but was inhibited by the addition of 5 mM BaCl2 and 50 or 3 microM phencyclidine (PCP) to serosal perfusates, suggesting that K channels in the basolateral membrane were activated during VRD. VRD was unaffected by replacement of Cl with NO3 or SCN, suggesting that Cl-dependent Na-K-Cl and K-Cl cotransport were not involved. In SCN Ringer, VRD was inhibited by the addition of 0.1 mM bumetanide to serosal perfusates, suggesting that bumetanide-sensitive anion channels in the basolateral membrane were also activated. A transient 10-mV hyperpolarization of the membrane potential was associated with VRD. The channel blockers that inhibited VRD had little or no effect on the hyperpolarization, suggesting that the changes in membrane potential were unrelated to the changes in cell volume. Perfusion of the apical surface of the epithelium with isotonic solutions containing 10 mM D-glucose resulted in a variable increase in cell volume followed by a variable shrinkage to normal, suggesting that VRD was also activated during organic solute absorption. The increase in cell volume was blocked by the addition of 0.01 or 1 mM phlorizin to mucosal perfusates. The reduction in cell volume was inhibited by the addition of 0.1 mM bumetanide, but not BaCl2 or PCP, to serosal perfusates, indicating the the shrinkage mechanism secondary to glucose addition differed from that seen after exposure to hypotonic perfusates.


Fine-Mapping of the PLCL2 Gene Identifies Candidate Variants Associated With Ischaemic Stroke Risk in Metabolic Syndrome Patients.
A genome-wide association study (GWAS) reported PLCL2 on chromosome 3p24. 3 (rs4618210:A>G) as a novel susceptibility locus for myocardial infarction in the Japanese population. As the most common pathological process, atherosclerosis leads to metabolic syndrome (MetS)-related ischaemic stroke (IS) and myocardial infarction. Hypothesizing that polymorphisms of the PLCL2 gene might be associated with the onset and prognosis of IS in MetS patients, we performed the following study in a Chinese Han population. A total of 709 cases (patients with MetS plus IS) and 711 controls (patients with MetS) were enrolled. A fine-mapping strategy was adopted to identify tagged single nucleotide polymorphisms (SNPs) of the PLCL2 gene, and improved multiplex ligation detection reaction (iMLDR) technology was used to genotype the selected SNPs. Logistic regression was used to analyse the values of the selected SNPs for the risk of IS between the cases and controls, adjusting for sex, age, hypertension, dyslipidaemia, hyperglycaemia, smoking and drinking. To compare the mean age of IS onset among different risk score groups, a genetic risk score was constructed for each case. The cumulative risk of IS events in the case group was presented using a cumulative incidence curve. All cases were followed up for 3 months, and functional outcomes were recorded prospectively. Two SNPs (rs4685423 and rs4618210) were significantly related to the risk of IS in MetS patients. For rs4685423, patients who were AA homozygotes were less likely to suffer from IS than C-allele carriers (OR 0.718; 95% CI 0.567-0.909; multivariate-adjusted, P = 0.006). For rs4618210, A-allele carriers were less likely to develop IS than patients who were GG homozygotes (OR 0.679; 95% CI 0.548-0.841; multivariate-adjusted, P < 0.001). As the genetic risk score increased, the mean age at IS onset decreased (log-rank P = 0.010). There was no statistically significant difference in the distribution of the 90-day modified Rankin Scale (mRS) outcomes across the rs4685423 (P = 0.319) or rs4618210 polymorphisms (P = 0.148). Our findings suggested that genetic polymorphisms of PLCL2 might be associated with the onset of MetS-related IS. Further studies are warranted to validate our findings in other ethnic populations.


MicroMagnify: A Multiplexed Expansion Microscopy Method for Pathogens and Infected Tissues.
Super-resolution optical imaging tools are crucial in microbiology to understand the complex structures and behavior of microorganisms such as bacteria, fungi, and viruses. However, the capabilities of these tools, particularly when it comes to imaging pathogens and infected tissues, remain limited. MicroMagnify (µMagnify) is developed, a nanoscale multiplexed imaging method for pathogens and infected tissues that are derived from an expansion microscopy technique with a universal biomolecular anchor. The combination of heat denaturation and enzyme cocktails essential is found for robust cell wall digestion and expansion of microbial cells and infected tissues without distortion. µMagnify efficiently retains biomolecules suitable for high-plex fluorescence imaging with nanoscale precision. It demonstrates up to eightfold expansion with µMagnify on a broad range of pathogen-containing specimens, including bacterial and fungal biofilms, infected culture cells, fungus-infected mouse tone, and formalin-fixed paraffin-embedded human cornea infected by various pathogens. Additionally, an associated virtual reality tool is developed to facilitate the visualization and navigation of complex 3D images generated by this method in an immersive environment allowing collaborative exploration among researchers worldwide. µMagnify is a valuable imaging platform for studying how microbes interact with their host systems and enables the development of new diagnosis strategies against infectious diseases.


A Novel Microstructural Evolution Model for Growth of Ultra-Fine Al2O3 Oxides from SiO2 Silica Ceramic Decomposition during Self-Propagated High-Temperature Synthesis.
In this paper, experimental verification of the microstructural evolution model during sintering of aluminum, iron and particulate mullite ceramic powders using self-propagated high-temperature synthesis (SHS) was performed. The powder mixture with 20% wt. content of reinforcing ceramic was investigated throughout this research. The mixed powders were cold pressed and sintered in a vacuum at 1030 °C. The SHS reaction between sintered feed powders resulted in a rapid temperature increase from the heat generated. The temperature increase led to the melting of an aluminum-based metallic liquid. The metallic liquid infiltrated the porous SiO2 ceramics. Silicon atoms were transited into the intermetallic iron-aluminum matrix. Subsequently, a ternary matrix from the Fe-Al-Si system was formed, and synthesis of the oxygen and aluminum occurred. Synthesis of both these elements resulted in formation of new, fine Al2O3 precipitates in the volume of matrix. The proposed microstructural evolution model for growth of ultra-fine Al2O3 oxides from SiO2 silica ceramic decomposition during SHS was successfully verified through scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS) analysis and X-ray diffraction (XRD).


[Prostaglandin and cAMP levels in the endometrium of women with a normal menstrual cycle].
The content of prostaglandins and cAMP was determined in the endometrium of healthy women with a regular menstrual cycle in its different phases. It was shown that the PGE2 level in the proliferative (the 7th-10th day of the cycle) and secretory (the 24th-26th day of the cycle) phases was the same. At the same time the level of PGE2 in the secretory phase of the cycle was 3 times higher than in the proliferative phase. The level of cAMP in the secretory phase of the cycle was 2 times higher than in the proliferative phase.


Anatomical study of renal and accessory renal arteries.
In recent years, more conservative methods of surgery of the renal artery are coming up. Hence, a precise knowledge of renal vasculature has become a necessity. Knowledge of the existence of accessory renal arteries is important; otherwise, they may get inadvertently damaged during renal surgery. Furthermore, their presence must be considered while evaluating a donor's kidney for possible renal transplantation. The study may also be useful to clinicians performing invasive techniques, vascular surgeries, other uro-radiological procedures, and in cases of trauma. Keeping this in mind, this study was conducted on 530 adult cadavers. A total of 1060 kidneys obtained from these cadavers were dissected and accessory renal arteries were looked for; 24.99% of the specimens showed the presence of accessory renal arteries. In 20.75%, one accessory renal artery was found, and in 4.24% of specimens, two accessory renal arteries were seen.


Epidermal cyst of temporal bone as a delayed complication of myringoplasty.
Epidermal cysts are benign tumors derived from the epidermis or the epithelial hair follicle filled with keratin and lipid-rich debris, typically occurring in areas with a high-density of sebaceous glands. These cysts commonly occur on the face, scalp, neck and trunk, where the sebaceous glands are more active. Their localization within the bone is extremely uncommon. The current study details the case of a 24-year-old male who presented with right otorrhea and ipsilateral hypoacusia having undergone right overlay myringoplasty for subtotal eardrum perforation. This patient represents a rare case of an epidermal cyst localized in the temporal bone (the fifth described in English-language literature), which may be considered as a complication of myringoplasty.