Glucocorticoids increase the accumulation of reactive oxygen species and enhance adriamycin-induced toxicity in neuronal culture.
Glucocorticoids (GCs), the adrenal steroids secreted during stress, are known to affect diverse processes involving reactive oxygen species, from exacerbation of ischemic damage to alteration of antioxidant enzyme activities. To determine whether GCs have a direct effect on oxidative processes, we constructed a dose-response curve using adriamycin, an oxygen radical generator, in primary neuronal cultures. In cultures derived from the hippocampus, which has the greatest concentration of corticosteroid receptors in the brain, higher levels of GCs significantly increased adriamycin toxicity, while not being toxic themselves. In cortical cultures, which contain lesser amounts of corticosteroid receptors, GCs had no effect on the adriamycin dose-response. Surprisingly, when tested with dichlorofluorescein for levels of reactive oxygen species (ROS), GCs increased ROS by approximately 10% basally and at all adriamycin doses in both hippocampal and cortical cultures. Thus, greater generation of ROS does not account for the increased susceptibility of the hippocampus to oxidative damage.


[The ancient literature source and flow of the point to point penetration acupuncture method].
It has been the consensus of the academic community that the doctor DOU Han-qing in Jin-Yuan Dynasty was the pioneer of point to point penetration acupuncture method.The contents of several texts in Yuan-Ming-Qing Dynasties were combed on the basis of Dou Taishi Zhenjing(《》).The paradigm,the acupoints,basic elements and the characteristics of the main treatment of diseases were discussed,and the relationship between the point to point penetration acupuncture method with the penetration acupuncture method has been tried to distinguish from the perspective of technical philosophy. It was found that the specifications and quantity of the 28 "penetration and to" cases in Dou Taishi Zhenjing(《》)were sufficiently exemplary for future generations, and were the source documents of Yuan-Ming-Qing's texts,which basically followed its specifications and content and developed.For example,the Yulong Poetries(《》)in the books of Bianque Shenying Zhenjiu Yulong Jing(《》),Zhenjiu Dacheng(《》),Zhenfang Liuji(《》).The 37 cases in Zhenfang Liuji(《》) were the most in several texts.The 31 cases in Xunjing Kaoxue Bian(《》)had the characteristics of DOU Han-qing, YANG Ji-zhou and LING Yun, who developed the opposite direction penetration method with two or more needles on DOU Han-qing's one needle.There were five basic elements in the point to point penetration acupuncture method:the needle pri-cking inch(depth), the needle pricking angle, the needle pricking direction, the starting acupoint, the end acupoint.This method in Dou Taishi Zhenjing(《》)mostly treated local diseases and symptoms,some acupoints below the elbows and knees also treated far-end diseases.The point to point penetration acupuncture method has a specific intention structure, which cannot be confused with the penetration acupuncture method.


Prevalence and factors associated with significant liver fibrosis assessed by transient elastometry in HIV/hepatitis C virus-coinfected patients.
Transient elastometry (TE) could provide a more accurate evaluation of the frequency and risk factors of liver fibrosis in hepatitis C virus (HCV) infection than that based on biopsy. The aim of this study was to assess the prevalence of and factors associated with significant liver fibrosis in a large population of HIV/HCV-coinfected patients. HIV/HCV-coinfected patients, who had participated in a cross-sectional, multicenter, retrospective study of liver fibrosis using noninvasive markers and in whom a determination of liver stiffness (LS) by TE was available, were included in this analysis. Factors potentially associated with significant fibrosis (LS ≥ 9 kPa) were analyzed. One thousand three hundred and ten patients fulfilled the inclusion criteria, 526 (40%) of them showed LS ≥ 9 kPa and 316 (24%) cirrhosis (LS ≥ 14 kPa). The factors independently associated with significant fibrosis [adjusted odds ratio (95% confidence interval, P value) were the following: older age [1.04 (1.01-1.07), 0.002], daily alcohol intake > 50 g/day [1.58 (1.10-2.27), 0.013] and the length of HCV infection [1.03 (1.00-1.06), 0.023]]. A CD4 cell count lower than < 200 per mm(3) [1.67 (0.99-2.81), 0.053] and HCV genotype 4 [0.66 (0.42-1.02), 0.066] were marginally associated with LS ≥ 9 kPa. In conclusion, the prevalence of cirrhosis in HIV/HCV-coinfected patients seems to be higher than previously reported in studies based on liver biopsy. Older age, alcohol consumption and lower CD4 cell counts are related with significant fibrosis. The latter association supports an earlier starting of antiretroviral therapy in this setting.


Brief Communication PD1-related Nephrotoxicity: Optimizing Its Clinical Management Through Histopathologic Features.
Immune-related nephrotoxicity (ir-N) is a rare adverse event of immune-checkpoint(s) inhibitors (ICI) therapy and its clinical management is still debated. Among 501 consecutive ICI-treated patients at our Institution, 6 who developed an ir-N with clinical signs suggestive for an acute kidney injury underwent kidney biopsy. Histology showed an acute tubule-interstitial nephritis, simulating the scenario of acute T-cell-mediated kidney transplant rejection. Thus, the management of allograft kidney rejection routinely utilized at our clinic was implemented, leading to rapid renal function improvement. Histologic features supporting the definition of an immune-mediated acute kidney injury in ICI-treated patients may help optimizing the clinical management of ir-N.


Effect of dietary Quebracho tannin extract on feed intake, digestibility, excretion of urinary purine derivatives and milk production in dairy cows.
The aim of this study was to evaluate the effects of dietary Quebracho tannin extract (QTE) on feed intake, apparent total tract digestibility (ATTD), excretion of urinary purine derivatives (PD) and milk composition and yield in dairy cows. Fifty Holstein cows were divided into two groups. To reach a similar performance of both groups, cows were divided according to their milk yield, body weight, days in milk and number of lactations at the start of the experiment averaging 33.2 ± 8.2 kg/d, 637 ± 58 kg, 114 ± 73 d and 2.3 ± 1.6 lactations, respectively. The cows were fed a basal diet as total mixed ration containing on dry matter (DM) basis 34% grass silage, 32% maize silage and 34% concentrate feeds. Three dietary treatments were tested, the control (CON, basal diet without QTE), QTE15 (basal diet with QTE at 15 g/kg DM) and QTE30 (basal diet with QTE at 30 g/kg DM). Two treatments were arranged along six periods each 21 d (13 d adaptation phase and 8 d sampling phase). The ATTD of DM and organic matter were reduced only in Diet QTE30, whereas both QTE treatments reduced ATTD of fibre and nitrogen (N), indicating that QTE impaired rumen fermentation. Nevertheless, feed intake was unaffected by QTE. In Diet CON, urinary N excretion accounted for 29.8% of N intake and decreased in treatments QTE15 and QTE30 to 27.5% and 17.9%, respectively. Daily faecal N excretion increased in treatments CON, QTE15 and QTE30 from 211 to 237 and 273 g/d, respectively, which amounted to 39.0%, 42.4% and 51.7% of the N intake, respectively. Hence, QTE shifted N excretion from urine to faeces, whereas the proportion of ingested N appearing in milk was not affected by QTE (average 30.7% of N intake). Daily PD excretion as indicator for microbial crude protein (CP) flow at the duodenum decreased in treatment QTE30 compared with Diet CON from 413 to 280 mmol/d. The ratios of total PD to creatinine suggest that urinary PD excretion was already lower when feeding Diet QTE15. While there was no effect of Diet QTE15, treatment QTE30 reduced milk yield, milk fat and protein. Both QTE treatments reduced milk urea concentration, which suggest that ruminal degradation of dietary CP was reduced. In summary, adding QTE at dosages of 15 and 30 g/kg DM to diets of lactating dairy cows to improve feed and protein use efficiency is not recommended.


Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation.
Mediator is considered an enhancer of RNA-Polymerase II dependent transcription but its function and regulation in pluripotent mouse embryonic stem cells (mESCs) remains unresolved. One means of controlling the function of Mediator is provided by the binding of the Cdk8 module (Med12, Cdk8, Ccnc and Med13) to the core Mediator. Here we report that Med12 operates together with PRC1 to silence key developmental genes in pluripotency. At the molecular level, while PRC1 represses genes it is also required to assemble ncRNA containing Med12-Mediator complexes. In the course of cellular differentiation the H2A ubiquitin binding protein Zrf1 abrogates PRC1-Med12 binding and facilitates the association of Cdk8 with Mediator. This remodeling of Mediator-associated protein complexes converts Mediator from a transcriptional repressor to a transcriptional enhancer, which then mediates ncRNA-dependent activation of Polycomb target genes. Altogether, our data reveal how the interplay of PRC1, ncRNA and Mediator complexes controls pluripotency and cellular differentiation.


Enhanced compatibility and initial stability of Ti6Al4V alloy orthodontic miniscrews subjected to anodization, cyclic precalcification, and heat treatment.
To evaluate the bioactivity, and the biomechanical and bone-regenerative properties of Ti6Al4V miniscrews subjected to anodization, cyclic precalcification, and heat treatment (APH treatment) and their potential clinical use. The surfaces of Ti6Al4V alloys were modified by APH treatment. Bioactivity was assessed after immersion in simulated body fluid for 3 days. The hydrophilicity and the roughness of APH-treated surfaces were compared with those of untreated (UT) and anodized and heat-treated (AH) samples. For in vivo tests, 32 miniscrews (16 UT and 16 APH) were inserted into 16 Wistar rats, one UT and one APH-treated miniscrew in either tibia. The miniscrews were extracted after 3 and 6 weeks and their osseointegration (n = 8 for each time point and group) was investigated by surface and histological analyses and removal torque measurements. APH treatment formed a dense surface array of nanotubular TiO2 layer covered with a compact apatite-like film. APH-treated samples showed better bioactivity and biocompatibility compared with UT and AH samples. In vivo, APH-treated miniscrews showed higher removal torque and bone-to-implant contact than did UT miniscrews, after both 3 and 6 weeks (p < 0.05). Also, early deposition of densely mineralized bone around APH-treated miniscrews was observed, implying good bonding to the treated surface. APH treatment enhanced the bioactivity, and the biomechanical and bone regenerative properties of the Ti6Al4V alloy miniscrews. The enhanced initial stability afforded should be valuable in orthodontic applications.


Purification and characterization of cysteine conjugate transaminases from rat liver.
1. Soluble cysteine-conjugate alpha-ketoglutarate transaminase (CAT-I) was purified about 670-fold from rat liver cytosol using s-(p-bromophenyl)-L-cysteine as amino acid substrate. The enzyme preparation of the final step of purification showed a single band in polyacrylamide gel electrophoresis. CAT-I accounted for 64% of the transaminase activity in cytosol. 2. The mol. wt of the enzyme was about 64,000 as determined by gel filtration. Respective Km values for s-(p-bromophenyl)-L-cysteine and alpha-ketoglutaric acid were 1.0 and 1.3 mM in Tris-acetate buffer (pH 7.0). Aminooxyacetic acid, hydroxylamine, and KCN inhibited the enzyme activity. 3. In addition to CAT-I, two isozymes (CAT-IIA and CAT-IIB) were partially purified from rat liver cytosol. In respect of mol. wt, substrate specificity towards cysteine conjugates, and several other properties, CAT-IIA and CAT-IIB were very similar to CAT-I. However, differences were observed for these enzymes in the rate of reverse reaction (formation reaction of cysteine conjugates and alpha-ketoglutaric acid) and substrate specificity towards L-aspartic acid and L-cysteinesulphinic acid.


Short-term results and intermediate-term follow-up of laser wire recanalization of chronic coronary artery occlusions: a single-center experience.
This study sought to elucidate the short-term efficacy and intermediate-term outcome of excimer laser recanalization of chronic coronary artery occlusions in patients in whom attempts at mechanical revascularization had failed. Recanalization of chronic coronary occlusions with the use of a mechanical guide wire fails in 30% to 50% of cases, mostly because of inability to pass the wire through the lesion. The value of using excimer laser energy in this setting has not yet been determined. The study group comprised 66 consecutive patients with 68 chronic coronary occlusions. Patients were eligible for inclusion in the study if a previous attempt at mechanical revascularization had failed and if their angiographic status was such that 1) the vessel segment distal to the occlusion could be visualized by way of collateral vessels, 2) the entry point of the occlusion was clearly outlined, and 3) not more than one anatomic bend was expected within the occlusion. Excimer laser energy was applied to the lesion through a 0.018-in. (0.046 cm) fiber-optic guide wire. Adjunctive balloon angioplasty and stenting were performed in all successfully treated patients but one. Thirty-four occlusions (50%) in 32 patients (48%) could be crossed with the laser wire. Location and age of the occlusion had no adverse influence on the outcome of laser wire recanalization, nor did the presence of bridging collateral vessels, a major side branch at the site of the lesion or a blunt stump of the occlusion. An inverse relation was found between the success rate and the length of the occlusion, such that a 19% reduction of the success rate accompanied each 10-mm increment of the mean occlusion length. Thus, the success rate was 68% for lesions < or = 10 mm but only 25% for lesions > 30 to < or = 40 mm. The presence of a bend in the lesion exceeding 60 degrees was strongly related to procedural failure. During a median angiographic follow-up period of 18 weeks, restenosis > 50% (n = 6) or reocclusion (n = 4) was found in 10 of the 32 successfully treated patients, for an intermediate-term success rate of 33% (22 of 66). Clinical follow-up revealed improved anginal status in 21 patients (66%) after a median of 24 weeks. Major complications (death, myocardial infarction, emergency operation) were not encountered. Successful recanalization of a chronic coronary occlusion by using currently available laser wires can be expected in 50% of selected patients in whom attempts at mechanical revascularization fail. Restenosis or reocclusion accounts for an overall 6-month success rate of 35%.


Analysis of vestibular testing in patients with vestibular schwannoma based on the nerve of origin, the localization, and the size of the tumor.
We aimed to analyze the factors influencing caloric response and vestibular evoked myogenic potential (VEMP) in vestibular schwannoma. The subjects comprised 130 patients with unilateral vestibular schwannoma pathologically diagnosed by surgery. Caloric response and the amplitude and latency of VEMP were measured and analyzed based on the nerve of origin, localization, and size of the tumor. The tumors were classified into 3 types based on localization: intracanalicular, intermediate, and medial; and into 4 grades based on size: 9 mm or less, 10 to 19 mm, 20 to 29 mm, and 30 mm or greater. : Abnormal rates of caloric response and VEMP in patients with tumors arising from the superior vestibular nerve were not significantly different from those in patients with tumors of the inferior vestibular nerve. In the intermediate and medial type-but not in the intracanalicular type-a significant difference in tumor size was observed between patients with normal caloric response and those with canal paresis as also between patients with normal VEMP and those with abnormal VEMP. In patients with tumors that maximally measured 10 to 19 mm or of the intermediate type, the p- and n-wave latencies of VEMP were significantly prolonged compared with those in the normal opposite ear. 1) The nerve of origin of tumors cannot be predicted based on caloric response and VEMP. 2) In the intermediate and medial types, caloric response and the VEMP amplitude are significantly diminished in association with an increase in tumor size. 3) Prolonged VEMP latencies seem to be not only caused by tumor compression to the brainstem or vestibular spinal tract but also by tumor compression isolated to the inferior vestibular nerve.


Neuronal NADPH diaphorase is a nitric oxide synthase.
NADPH diaphorase histochemistry selectively labels a number of discrete populations of neurons throughout the nervous system. This simple and robust technique has been used in a great many experimental and neuropathological studies; however, the function of this enzyme has remained a matter of speculation. We, therefore, undertook to characterize this enzyme biochemically. With biochemical and immunochemical assays, NADPH diaphorase was purified to apparent homogeneity from rat brain by affinity chromatography and anion-exchange HPLC. Western (immunoblot) transfer and immunostaining with an antibody specific for NADPH diaphorase labeled a single protein of 150 kDa. Nitric oxide synthase was recently shown to be a 150-kDa, NADPH-dependent enzyme in brain. It is responsible for the calcium/calmodulin-dependent synthesis of the guanylyl cyclase activator nitric oxide from L-arginine. We have found that nitric oxide synthase activity and NADPH diaphorase copurify to homogeneity and that both activities could be immunoprecipitated with an antibody recognizing neuronal NADPH diaphorase. Furthermore, nitric oxide synthase was competitively inhibited by the NADPH diaphorase substrate, nitro blue tetrazolium. Thus, neuronal NADPH diaphorase is a nitric oxide synthase, and NADPH diaphorase histochemistry, therefore, provides a specific histochemical marker for neurons producing nitric oxide.


The endoplasmic reticulum contributes to lysosomal tubulation/sorting driven by LRRK2.
Lysosomes are dynamic organelles that can remodel their membrane as an adaptive response to various cell signaling events including membrane damage. Recently, we have discovered that damaged lysosomes form and sort tubules into moving vesicles. We named this process LYTL for LYsosomal Tubulation/sorting driven by LRRK2, as the Parkinson's disease protein LRRK2 promotes tubulation by recruiting the motor adaptor protein JIP4 to lysosomes via phosphorylated RAB proteins. Here we use spinning-disk microscopy combined with superresolution to further characterize LYTL after membrane damage with LLOMe (l-leucyl-l-leucine methyl ester). We identified the endoplasmic reticulum (ER) colocalizing with sites of fission of lysosome-derived tubules. In addition, modifying the morphology of the ER by reducing ER tubules leads to a decrease in LYTL sorting, suggesting that contact with tubular ER is necessary for lysosomal membrane sorting. Given the central roles of LRRK2 and lysosomal biology in Parkinson's disease, these discoveries are likely relevant to disease pathology and highlight interactions between organelles in this model.


NiMOF-derived oxygen vacancy rich NiO with excellent capacitance and ORR/OER activities as a cathode material for Zn-based hybrid batteries.
An Ni-Zn battery is a distinguished member in the family of closed Zn-based batteries due to its ideal power density and voltage. However, when it is employed as a power supply for electric vehicles, its defects in terms of specific capacitance and energy density become obvious. Herein, to resolve this problem, a hybrid battery system was created through a combination of Ni-Zn and Zn-air batteries at the cell level. In a hybrid battery system, oxygen vacancy rich NiO with S,N co-modified mesoporous carbon as a matrix was used as the cathode material. This cathode material showed a high specific capacitance of 202.1 mA h g-1 at 1.0 A g-1. When the current density reduces to 20 A g-1, this value decreases to 130.2 mA h g-1, which implies that 64.4% of specific capacitance was retained. It also exhibits excellent OER and ORR activities. For the hybrid battery system, when the discharge process was carried out at 1 mA cm-2, there were two voltage plateaus at 1.72 and 1.12 V, which originated from Ni-Zn and Zn-air, respectively. In this case, its specific capacitance and energy density reaches 800.3 mA h g-1 and 961 W h kg-1, respectively. The hybrid battery also possesses perfect stability during multi-cycle charge-discharge tests. The construction of this hybrid battery system develops a new road to prepare a power supply device with high performance.


Effects and mechanism of downregulation of COX‑2 expression by RNA interference on proliferation and apoptosis of human breast cancer MCF‑7 cells.
The aim of the present study was to investigate the effects of RNA interference with prostaglandin-endoperoxide synthase 2 (COX‑2) gene on the proliferation and apoptosis of breast cancer MCF‑7 cells, as well as the underlying mechanism. The present study constructed the eukaryotic expression vector of the targeted COX‑2 gene, transfected the MCF‑7 cells and screened the stably expressed clone. Changes in the COX‑2 gene expression in breast cancer MCF‑7 cells prior to and following transfection were examined; the proliferation and apoptosis of MCF‑7 cells were analyzed. Furthermore, changes in the protein levels of survivin, B-cell lymphoma 2 (Bcl‑2) and Bcl-2-associated X (Bax) genes were detected. RNA interference mediated by a lentiviral expression vector significantly decreased the protein expression levels of the COX‑2 gene, and therefore, the proliferation and growth of breast cancer MCF‑7 cells was significantly suppressed and the apoptotic rate increased. Of note, the mRNA and protein expression levels of survivin and Bcl‑2 decreased, while those of Bax increased following COX-2 silencing. RNA interference markedly deactivated the COX‑2 gene, suppressed the proliferation of breast cancer MCF‑7 cells, and, to a certain extent, enhanced the induced spontaneous apoptosis, which is regulated by the Bax gene. These results provided evidence for the potential applications of RNA interference of the targeted COX‑2 gene in gene therapy for the treatment of breast cancer.


Monitoring insulin aggregation via capillary electrophoresis.
Early stages of insulin aggregation, which involve the transient formation of oligomeric aggregates, are an important aspect in the progression of Type II diabetes and in the quality control of pharmaceutical insulin production. This study is the first to utilize capillary electrophoresis (CE) with ultraviolet (UV) detection to monitor insulin oligomer formation at pH 8.0 and physiological ionic strength. The lag time to formation of the first detected species in the aggregation process was evaluated by UV-CE and thioflavin T (ThT) binding for salt concentrations from 100 mM to 250 mM. UV-CE had a significantly shorter (5-8 h) lag time than ThT binding (15-19 h). In addition, the lag time to detection of the first aggregated species via UV-CE was unaffected by salt concentration, while a trend toward an increased lag time with increased salt concentration was observed with ThT binding. This result indicates that solution ionic strength impacts early stages of aggregation and β-sheet aggregate formation differently. To observe whether CE may be applied for the analysis of biological samples containing low insulin concentrations, the limit of detection using UV and laser induced fluorescence (LIF) detection modes was determined. The limit of detection using LIF-CE, 48.4 pM, was lower than the physiological insulin concentration, verifying the utility of this technique for monitoring biological samples. LIF-CE was subsequently used to analyze the time course for fluorescein isothiocyanate (FITC)-labeled insulin oligomer formation. This study is the first to report that the FITC label prevented incorporation of insulin into oligomers, cautioning against the use of this fluorescent label as a tag for following early stages of insulin aggregation.


From stress and strain to spikes: mechanotransduction in spider slit sensilla.
This review focuses on the structure and function of a single mechanoreceptor organ in the cuticle of spiders. Knowledge emerging from the study of this organ promises to yield general principles that can be applied to mechanosensation in a wide range of animal systems. The lyriform slit sense organ on the antero-lateral leg patella of the spider Cupiennius salei is unusual in possessing large sensory neurons, whose cell bodies are close to the sites of sensory transduction, and accessible to intracellular recording during mechanotransduction. This situation, combined with recent technical developments, has made it possible to observe and experiment with all the major stages of mechanosensation. Important findings include the approximate size, number and ionic selectivity of the ion channels responsible for mechanotransduction, the types of voltage-activated ion channels responsible for action potential encoding, and the mechanisms controlling the dynamic properties of transduction and encoding. Most recently, a complex efferent system for peripheral modulation of mechanosensation has been discovered and partially characterized. Much remains to be learned about mechanosensation, but the lyriform slit sense organ system continues to offer important opportunities to advance our understanding of this crucial sense.


Myocardial osteopontin expression is associated with left ventricular hypertrophy.
Osteopontin (OP) has been identified in cultured rat cardiac fibroblasts, where it contributes to angiotensin II (AII)-induced remodeling processes; in cultured cardiomyocytes; and in macrophages in cardiac tissues with inflammation. However, the presence of OP has not been reported in histological sections of myocardial tissue. In the present study, we investigated (1) the regulation of OP mRNA expression in cultured rat cardiomyocytes; (2) the localization of OP mRNA in neonatal and adult normal and hypertrophied rat hearts; and (3) the histology of OP expression in myocardial specimens from humans either with myocyte hypertrophy or with no pathological changes. Cultured neonatal cardiomyocytes expressed OP mRNA and were immunoreactive for OP. Endothelin-1 (ET-1) and norepinephrine (NE) increased both OP and atrial natriuretic peptide (ANP) mRNA levels twofold to threefold (P<.01). OP mRNA was prominent in ventricular tissue from neonatal and adult rats with renovascular hypertension and aortic banding, whereas barely detectable levels were observed in normal adult cardiac tissue. ANP and OP mRNA levels in normal and hypertrophied ventricles correlated (r2=.87, P<.001). OP immunoreactivity and mRNA transcripts were predominantly found in cardiomyocytes not associated with inflammatory cells in sections from neonatal and adult hypertrophied hearts. No staining was detectable in normal adult hearts. Human myocardium with extensive fibrosis and cardiomyocyte hypertrophy obtained from explanted hearts with either idiopathic (n=5) or ischemic cardiomyopathy (n=7) demonstrated substantial myocyte immunoreactivity for both OP and ANP in right and left ventricles that was not associated with leukocyte infiltration. In situ hybridization identified cardiomyocytes as the major source of OP mRNA transcripts in these hearts. In contrast, OP immunoreactivity was not detectable in four of five endomyocardial biopsies with normal histology. The present study provides the first evidence that cardiomyocytes are a prominent source of OP in vivo and suggests that induction of OP expression is strongly associated with ventricular hypertrophy.


How and Why to Investigate Multicomponent Reactions Mechanisms? A Critical Review.
We review the most innovative efforts and greatest challenges faced when elucidating multicomponent reactions (MCRs) mechanisms. When compared to traditional reactions, the often two or more concurrent reactions pathways and the greater number of possible intermediates in MCRs turn their mechanistic investigation both a harder and trickier task. The common approaches used to investigate reaction mechanisms are often unable to clarify MCRs mechanisms; hence few but clever approaches are currently used to determine these mechanisms and to depict their key transformations. Their complexity has required most innovative approaches and the use of a number of unique techniques that have shed light over the favored pathway selected from the myriad of alternatives theoretically available for MCRs. This review focuses on the most successful efforts applied by a few leading groups to perform these puzzlingly investigations.


Hyaluronidase is not essential for the lethality of Erysipelothrix rhusiopathiae infection in mice.
To investigate the role of hyaluronidase in the pathogenicity of Erysipelothrix rhusiopathiae, transposon Tn916 was transferred from Enterococcus faecalis CG110 to a virulent strain of E. rhusiopathiae, and hyaluronidase-deficient mutants were isolated. A virulence assay in the mice showed that of the seven hyaluronidase-deficient mutants tested, six mutants were avirulent, but that one mutant, designated AST121, was as virulent as its parental strain. Western immunoblotting with a monoclonal antibody specific to the capsule, a major virulence factor of the organism, revealed that all of the avirulent mutants had lost the capsular antigen, whereas the mutant AST121 did not. These results suggest that the lack of virulence of the six hyaluronidase-negative mutants could be due to a loss of the capsule and that hyaluronidase does not contribute to the lethality of E. rhusiopathiae infection in mice.


Perceptions of breast health practices in Pakistani Muslim women.
Even though breast cancer is the most common form of cancer in females in Pakistan, there is a paucity of evidence on the views of Pakistani Muslim women in relation to breast cancer. This study aimed to investigate the perceptions of Pakistani Muslim women in relation to the aetiology of breast cancer and impressions of breast health. The study took place in Lahore, Pakistan. This survey used a questionnaire and focus group interviews to investigate women's perspectives on breast health. Data was collected over a period of six months, quantitative data was analysed using descriptive statistics and qualitative data was analysed using thematic analysis. 105 women participated in the questionnaire and 48 women contributed to 6 focus group interviews. Women generally were aware of the term breast cancer but were unsure of its aetiology. The questionnaire data revealed that women were aware of both mammography (55%) and breast self-examination (BSE) (77%). Fifty five percent of women had been taught the BSE technique. In comparison, the majority of women attending the focus group interviews had limited exposure to BSE or mammography. Although women had heard of mammograms and BSE they were unaware of BSE technique or breast cancer screening procedures. Even though there is a desire amongst women to engage in BSE by being taught the necessary technique and specific pathological changes to look for, there is a strong cultural opinion that breasts are private organs that should not be discussed publically. In view of this and the frequency of breast cancer in Pakistani Muslim women, it is essential that breast awareness campaigns are implemented by health care professionals such as breast cancer nurses, midwives and medical practitioners to explore the concept of BSE and breast cancer. Selective health education can educate women and lead to changes in health behavior.


Availability of HIV postexposure prophylaxis services in Los Angeles County.
Postexposure prophylaxis after sexual exposure to human immunodeficiency virus (HIV) is recommended by state and national agencies. A cross-sectional survey of 117 Los Angeles County sites found that 17 sites (14.5%) offer postexposure prophylaxis. Ten sites (8.5%) offer postexposure prophylaxis to patients who are uninsured. General availability of postexposure prophylaxis should be a public health priority.


ANALYSIS OF MICROTUBULE STRUCTURE IN EUGLENA GRANULATA.
The microtubules associated with the pellicle, reservoir and locomotory flagellum of Euglena granulata were subjected to rotational analysis using the technique of Markham et al. The results indicate that the microtubules have 11-14 subunits when viewed in transverse section. Rotational analysis of the entire locomotory flagellum was also conducted to better demonstrate the nature of the arms extending from the peripheral microtubules.


Nitrification mainly driven by ammonia-oxidizing bacteria and nitrite-oxidizing bacteria in an anammox-inoculated wastewater treatment system.
Anaerobic ammonium oxidation (anammox) process has been acknowledged as an environmentally friendly and time-saving technique capable of achieving efficient nitrogen removal. However, the community of nitrification process in anammox-inoculated wastewater treatment plants (WWTPs) has not been elucidated. In this study, ammonia oxidation (AO) and nitrite oxidation (NO) rates were analyzed with the incubation of activated sludge from Xinfeng WWTPs (Taiwan, China), and the community composition of nitrification communities were investigated by high-throughput sequencing. Results showed that both AO and NO had strong activity in the activated sludge. The average rates of AO and NO in sample A were 6.51 µmol L-1 h-1 and 6.52 µmol L-1 h-1, respectively, while the rates in sample B were 14.48 µmol L-1 h-1 and 14.59 µmol L-1 h-1, respectively. The abundance of the nitrite-oxidizing bacteria (NOB) Nitrospira was 0.89-4.95 × 1011 copies/g in both samples A and B, the abundance of ammonia-oxidizing bacteria (AOB) was 1.01-9.74 × 109 copies/g. In contrast, the abundance of ammonia-oxidizing archaea (AOA) was much lower than AOB, only with 1.28-1.53 × 105 copies/g in samples A and B. The AOA community was dominated by Nitrosotenuis, Nitrosocosmicus, and Nitrososphaera, while the AOB community mainly consisted of Nitrosomonas and Nitrosococcus. The dominant species of Nitrospira were Candidatus Nitrospira defluvii, Candidatus Nitrospira Ecomare2 and Nitrospira inopinata. In summary, the strong nitrification activity was mainly catalyzed by AOB and Nitrospira, maintaining high efficiency in nitrogen removal in the anammox-inoculated WWTPs by providing the substrates required for denitrification and anammox processes.


Effect of circulating factors on vascular smooth muscle contraction and its calcium uptake in uremia.
Uremia is often associated with alterations in calcium metabolism and vascular smooth muscle function in hypertension and atherosclerosis. The ways in which these conditions inter-relate are not clearly understood. In order to study the possibility that circulating factors might influence smooth muscle function, experiments were performed on rat aortic strips. The serum from both uremic patients and rats enhanced the norepinephrine-induced contraction (NEIC) and net 45-calcium uptake in rat aortic strips. In a similar manner, the serum of parathyroidectomized uremic rats also increased the NEIC, whereas verapamil reduced the aortic response to levels below those of the control, in the presence of uremic serum. These findings suggest that in both chronic (patients) and early (rats) stages of uremia, there is a circulating factor, different from parathyroid hormone, that affects calcium uptake and vascular smooth muscle contraction.


Aggressive Papillary Thyroid Carcinoma Presenting with Metastasis to the Pancreas.
Papillary thyroid cancer is the most common type of thyroid cancer. Aggressive forms tend to metastasize to the lungs and bones, but the abdomen is a rare site of metastasis. We present a 46-year-old male patient who presented with a neck mass associated with shortness of breath and hemoptysis. He was found to have a large thyroid mass on imaging. He underwent a total thyroidectomy with bilateral neck dissection, with pathology showing a multifocal tall cell variant of papillary thyroid carcinoma with lymphovascular invasion in both thyroid lobes. Due to recurrent findings of residual thyroid tissue on whole-body scan imaging, the patient underwent radioactive iodine ablation therapy twice, with poor response to therapy, suggested by persistently elevated thyroglobulin levels. However, the residual tissue responded to external beam radiation. After the initial response to radiation, thyroglobulin was noted to have increased again, prompting a PET-CT after administration of recombinant TSH. PET showed a focal area of increased uptake in the head of the pancreas. The patient underwent the Whipple procedure for resection of the metastasis. Pathology showed papillary thyroid carcinoma with strong and diffuse staining for TTF-1 and thyroglobulin. The patient was started on lenvatinib in the postoperative period and is currently tolerating treatment well with evidence of decreasing thyroglobulin levels. Intra-abdominal metastasis from a thyroid malignancy source is quite rare and can be challenging as far as diagnosis and treatment. Surgical resection can be curative and can be followed by radioactive iodine ablation therapy if cancer cells show avidity. Tyrosine kinase inhibitors can be used in refractory disease. New research is being conducted on new agents that can reverse the resistance to radioactive iodine therapy.


Orbital dermoids: clinical presentation and management.
The authors have reviewed 15 cases of orbital dermoids representing 6% of orbital tumours seen at the University of British Columbia Orbital Clinic. They tended to occur as either asymptomatic superficial lesions in children or as complicated deep lesions in adolescents and adults. The superficial lesions were as frequent medially as laterally and could be dealt with by a direct uncomplicated surgical approach. The deep lesions in contrast, were frequently extensive and difficult to remove, requiring careful preoperative planning. Sites of origin, presentation, differential diagnosis, and management are discussed.


Detection of Influenza C Viruses Among Outpatients and Patients Hospitalized for Severe Acute Respiratory Infection, Minnesota, 2013-2016.
Existing literature suggests that influenza C typically causes mild respiratory tract disease. However, clinical and epidemiological data are limited. Four outpatient clinics and 3 hospitals submitted clinical data and respiratory specimens through a surveillance network for acute respiratory infection (ARI) from May 2013 through December 2016. Specimens were tested using multitarget nucleic acid amplification for 19-22 respiratory pathogens, including influenza C. Influenza C virus was detected among 59 of 10 202 (0.58%) hospitalized severe ARI cases and 11 of 2282 (0.48%) outpatients. Most detections occurred from December to March, 73% during the 2014-2015 season. Influenza C detections occurred among patients of all ages, with rates being similar between inpatients and outpatients. The highest rate of detection occurred among children aged 6-24 months (1.2%). Among hospitalized cases, 7 required intensive care. Medical comorbidities were reported in 58% of hospitalized cases and all who required intensive care. At least 1 other respiratory pathogen was detected in 40 (66%) cases, most commonly rhinovirus/enterovirus (25%) and respiratory syncytial virus (20%). The hemagglutinin-esterase-fusion gene was sequenced in 37 specimens, and both C/Kanagawa and C/Sao Paulo lineages were detected in inpatients and outpatients. We found seasonal circulation of influenza C with year-to-year variability. Detection was most frequent among young children but occurred in all ages. Some cases that were positive for influenza C, particularly those with comorbid conditions, had severe disease, suggesting a need for further study of the role of influenza C virus in the pathogenesis of respiratory disease.


Benchmarks for outcome indicators in pediatric cataract surgery.
PurposeThe purpose of this study was to establish benchmarks for outcome indicators that may help ascertain the quality of pediatric cataract surgery with primary intraocular lens (IOL) implantation.Patients and methodsA retrospective chart review of patients older than 2 years undergoing cataract surgery with primary IOL implantation, by multiple surgeons in a tertiary-care center, from November 2005 to February 2016 was conducted. Patients with ocular comorbidities that would affect the outcomes were excluded. The outcome measures chosen were as follows: (1) final best corrected Snellen visual acuity (BCVA) in patients who had bilateral cataract surgery analyzed at the last clinic visit; (2) prediction error (PE)=expected refraction-actual refraction. Mean PE and mean absolute PE were assessed 1 month postoperatively, irrespective of age or laterality.ResultsMean age at surgery was 8.3±4.6 years and mean follow-up duration was 3.7±2.7 years. The results of outcome measures were as follows: (1) BCVA was 20/40 or better in 96% (n=124 eyes, mean patient age: 8.3±4.6 years). Remaining five eyes had amblyopia with two eyes having BCVA worse than 20/100 that did not respond to amblyopia treatment. (2) Mean PE was 0.3±1.1 D and mean absolute PE was 0.9±0.7 D. PE was within ±0.5 D in 43.0%, ±1.0 D in 66%, and ±2.0 D in 95% (n=235 eyes).ConclusionGood visual acuity after cataract surgery should be expected for children with bilateral cataracts, setting a high benchmark similar to that recommended in adult cataract surgery. Prediction error is greater in pediatric eyes than in adult eyes, setting a lower benchmark. This study establishes benchmark for outcome indicators in pediatric patients older than 2 years undergoing cataract surgery with primary IOL implantation.


Evaluation of a selective prostaglandin E receptor EP1 antagonist for potential properties in colon carcinogenesis.
Cyclooxygenases (COXs) and prostanoids play pivotal roles in colon carcinogenesis. This study was designed to determine the chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP1 antagonist, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats and to compare its potential with that of nimesulide, a well-documented selective COX-2 inhibitor. Five-week-old male F344 rats received s.c. injections of AOM (15 mg/kg body weight) or the saline vehicle once weekly for two weeks and were fed the control diet (AIN-76A) or the experimental diets containing 400 or 800 ppm of ONO-8711 or 400 ppm nimesulide for 5 weeks. Administration of ONO-8711 at 800 ppm significantly reduced the total number of ACF/colon and 5-bromodeoxyuridine (BrdUrd) labeling index as compared to the control diet group (by 31% and 66%, respectively). As expected, dietary administration of nimesulide also suppressed the development of ACF and BrdUrd labeling index in the colon, by about 39% and 54%, respectively. Our finding that ONO-8711 significantly suppresses colonic ACF formation and cell proliferation strengthens the hypothesis that the selective prostaglandin E receptor EP1 antagonists possesses chemopreventive activity against colon cancer development.


Hidden-symmetry-enforced nexus points of nodal lines in layer-stacked dielectric photonic crystals.
It was recently demonstrated that the connectivities of bands emerging from zero frequency in dielectric photonic crystals are distinct from their electronic counterparts with the same space groups. We discover that in an AB-layer-stacked photonic crystal composed of anisotropic dielectrics, the unique photonic band connectivity leads to a new kind of symmetry-enforced triply degenerate points at the nexuses of two nodal rings and a Kramers-like nodal line. The emergence and intersection of the line nodes are guaranteed by a generalized 1/4-period screw rotation symmetry of Maxwell's equations. The bands with a constant k z and iso-frequency surfaces near a nexus point both disperse as a spin-1 Dirac-like cone, giving rise to exotic transport features of light at the nexus point. We show that spin-1 conical diffraction occurs at the nexus point, which can be used to manipulate the charges of optical vortices. Our work reveals that Maxwell's equations can have hidden symmetries induced by the fractional periodicity of the material tensor components and hence paves the way to finding novel topological nodal structures unique to photonic systems.


Insulin-like growth factor binding protein-1 inhibits the DNA amplification induced by insulin-like growth factor I in human granulosa-luteal cells.
In order to study the effects of insulin-like growth factor (IGF-I) and insulin-like growth factor binding protein (IGFBP-1) on human granulosa cell proliferation after in vitro fertilization, cells were obtained after oocyte retrieval and cultured in the presence or absence of graded amounts of recombinant IGF-I, purified IGFBP-1 and [3H]thymidine. Physiological concentrations of IGF-I (2-200 ng/ml) were found to stimulate [3H]thymidine incorporation into the cells in a concentration-dependent manner. Half-maximal stimulation of [3H]thymidine incorporation was obtained with 10 ng/ml exogenous IGF-I, which was chosen for suppression experiments with graded amounts of purified IGFBP-1. Suppression of IGF-stimulated thymidine incorporation was observed when 200 ng/ml or more of IGFBP-1 was added to the culture medium. The same concentration of IGFBP-1 also markedly inhibited binding of [125I]iodotyrosyl IGF-I to the cells. It is concluded that: (i) after a refractory period, granulosa cells from hyperstimulated follicles retained their mitogenic activity; (ii) IGF-I is capable of stimulating DNA amplification in granulosa cells; and (iii) IGFBP-1 inhibits the IGF-I stimulated proliferation in these cells. In view of our previous studies showing that IGFBP-1 is synthesized by the granulosa cells as they luteinize, the present results suggest that IGFBP-1 is one of the endogenous factors locally regulating the growth and differentiation of granulosa cells.


Neuropeptide Y gene expression in the arcuate nucleus: sexual dimorphism and modulation by testosterone.
Neuropeptide Y (NPY) peptide concentrations in the arcuate nucleus have recently been shown to be modulated by gonadal steroids in the male rat. The present study was designed to determine whether NPY messenger RNA (mRNA)-synthesizing cells in the arcuate nucleus (Arc) of the male rat are regulated by testosterone (T) and whether there is a sexual dimorphism in the expression of the NPY gene in this region. In situ hybridization and quantitative autoradiography were used to assess the level of NPY gene expression in the Arc. In the first experiment, NPY mRNA levels were measured in the Arc of intact, castrated, and castrated male rats treated with T to maintain physiological (1.3 +/- 0.1 ng/ml) and supraphysiological (5.3 +/- 0.4 ng/ml) plasma levels of T. A 2-week castration produced a modest but significant decrease in NPY mRNA levels in the Arc (P < 0.05). Replacement with either physiological or supraphysiological levels of T prevented the effect of castration on NPY gene expression, and there was no further potentiation of NPY gene expression in those animals that received high levels of T. In the second experiment, NPY gene expression was compared throughout the Arc between intact male and female rats at 1800 h on the afternoon of proestrus. Comparison of NPY gene expression throughout the rostro-caudal extent of the Arc showed that male rats had significantly more NPY mRNA-containing cells than female rats (P < 0.01). This difference was most strikingly observed in the caudal portions of the nucleus (3.80 mm caudal to bregma). No difference was detected in the mean levels of NPY gene expression in the Arc between male and female rats. These data demonstrate that 1) NPY gene expression throughout the arcuate nucleus is modulated by T in male rats, and 2) a marked regional sex difference exists in the distribution of NPY mRNA-containing cells in the caudal extremity of the Arc. It is hypothesized that gonadal hormones may exert both organizational and activational effects upon NPY neurons in the Arc.


Vascular incorporation of endothelial colony-forming cells is essential for functional recovery of murine ischemic tissue following cell therapy.
Cord blood-derived human endothelial colony-forming cells (ECFCs) bear a high proliferative capacity and potently enhance tissue neovascularization in vivo. Here, we investigated whether the leading mechanism for the functional improvement relates to their physical vascular incorporation or perivascular paracrine effects and whether the effects can be further enhanced by dual-cell-based therapy, including mesenchymal stem cells (MSCs). ECFCs or MSCs were lentivirally transduced with thymidine kinase suicide gene driven by the endothelial-specific vascular endothelial growth factor 2 (kinase insert domain receptor) promoter and evaluated in a hindlimb ischemia model. ECFCs and MSCs enhanced neovascularization after ischemic events to a similar extent. Dual therapy using ECFCs and MSCs further enhanced neovascularization. Mechanistically, 3 weeks after induction of ischemia followed by cell therapy, ganciclovir-mediated elimination of kinase insert domain receptor(+) cells completely reversed the therapeutic effect of ECFCs but not that of MSCs. Histological analysis revealed that ganciclovir effectively eliminated ECFCs incorporated into the vasculature. Endothelial-specific suicide gene technology demonstrates distinct mechanisms for ECFCs and MSCs, with complete abolishment of ECFC-mediated effects, whereas MSC-mediated effects remained unaffected. These data strengthen the notion that a dual-cell-based therapy represents a promising approach for vascular regeneration of ischemic tissue.


Depressive delusion.
In this study of 160 consecutively admitted inpatients who met ICD-9 criteria of endogenous depression, mood-congruent depressive delusions were ascertained in 14.4% (n = 23). The total HRSD score was significantly higher in the delusional than in the nondelusional group. Delusions of guilt were recorded by far the most frequently. There was a correlation between delusions of guilt in the current depressive episode and suicide attempts in the past. In the delusional patients the individual courses of the illness were characterized by marked symptomatological differences from one depressive episode to another. In all but one of the patients, depressive delusions coincided with a thematically identical experience of anxiety. How often anxiety occurs in delusional form depends substantially on the respective theme of anxiety. In accordance with earlier psychopathological literature the findings confirm that depressive delusion is closely linked to the experience of anxiety.


Synchronized On/Off Switching of Four Binding Sites for Water in a Molecular Solomon Link.
A molecular Solomon link adopts different conformations in acetonitrile (1) and in water (2). Contrary to expectations, the main driving force of the transformation is not the change in medium polarity, but the cooperative binding of about four molecules of water, forming a tiny droplet in the central cavity of 2. Mechanistic studies reveal that the four binding sites can simultaneously switch between an inactive state (unable to bind water) and an active state (able to bind water) during the transformation. Spatial and temporal coordination of switching events is commonly observed in biological systems but has been rarely achieved in artificial systems. Here, the concerted activation of the four switchable sites is controlled by the topology of the whole molecule.


Global university performance. Bibliometric analysis of the ARWU platform (2003-2020).
Describe the 2020 report of the ARWU "Academic Ranking World Universities" classification and identify, accordingly, the roadmap of academic excellence, particularly in the countries of the Greater Maghreb. This is an in-depth reading of the 2020 results of the ARWU bibliometric platform (launched in 2003) from top 1000 world-class universities. Six criteria were used in this ranking: 1. Alumni (10%): students who received Nobel / Fields prizes; 2. Award (15%): professors who have won the Nobel / Fields prizes; 3. HiCi (20%): Most cited scientists; 4. PUB (20%): number of publications 5. TOP (20%): proportion of publications in the most influential periodicals; 6. PCP (10%): Per Capita Performance. The 2020 ARWU ranking was characterized by the domination of the "Top 10" ranking by the United States, particularly the "Harvard University", the Asian boom of 55% of the "Top 1000" ranking (Chinese universities evolved from 16 in 2004 to 81 in 2020 in the "Top 500" list) and finally an African incubation of academic excellence, manifested by the selection of nine South African institutions (including the "University of Cape Town ", world rank between 201-300), and the re-entry for the first time of a Maghreb university in the" Top 1000 "list, Tunis El Manar (rank between 901-1000), with the following scores: N&S: 1 , 4; Pub: 26.1 and PCP: 10.3, for a total score of 37.8 points. This report proves once again, the promising academic perspectives of Asia and Africa in the inclusion of the "Top 1000" list of the ARWU ranking. The roadmap for academic excellence would thus be based on the triad of centering scientific publications, in prestigious journals and by national author networks.


Comparative genomic hybridization in clinical cytogenetics.
We report the results of applying comparative genomic hybridization (CGH) in a cytogenetic service laboratory for (1) determination of the origin of extra and missing chromosomal material in intricate cases of unbalanced aberrations and (2) detection of common prenatal numerical chromosome aberrations. A total of 11 fetal samples were analyzed. Seven cases of complex unbalanced aberrations that could not be identified reliably by conventional cytogenetics were successfully resolved by CGH analysis. CGH results were validated by using FISH with chromosome-specific probes. Four cases representing common prenatal numerical aberrations (trisomy 21, 18, and 13 and monosomy X) were also successfully diagnosed by CGH. We conclude that CGH is a powerful adjunct to traditional cytogenetic techniques that makes it possible to solve clinical cases of intricate unbalanced aberrations in a single hybridization. CGH may also be a useful adjunct to screen for euchromatic involvement in marker chromosomes. Further technical development may render CGH applicable for routine aberration screening.


Nonlinear refractive-index changes induced by carrier injection in an InSb étalon.
We report the bistable switching of an InSb étalon in a novel mode of operation where the necessary changes in refractive index are induced by minority carrier injection through a p-n junction. Refractive-index changes of approximately 10(-5) are achieved using 3-V pulses. Switch ON and switch OFF characteristics and projected performance are discussed.


A supra-photoswitch involving sandwiched DNA base pairs and azobenzenes for light-driven nanostructures and nanodevices.
A supra-photoswitch is designed for complete ON/OFF switching of DNA hybridization by light irradiation for the purpose of using DNA as a material for building nanostructures. Azobenzenes, attached to D-threoninols that function as scaffolds, are introduced into each DNA strand after every two natural nucleotides (in the form (NNX)n where N and X represent the natural nucleotide and the azobenzene moiety, respectively). Hybridization of these two modified strands forms a supra-photoswitch consisting of alternating natural base pairs and azobenzene moieties. In this newly designed sequence, each base pair is sandwiched between two azobenzene moieties and all the azobenzene moieties are separated by base pairs. When the duplex is irradiated by visible light, the azobenzene moieties take the trans form and this duplex is surprisingly stable compared to the corresponding native duplex composed of only natural oligonucleotides. On the other hand, when the azobenzene moieties are isomerized to the cis form by UV light irradiation, the duplex is completely dissociated. Based on this design, a DNA hairpin structure is synthesized that should be closed by visible light irradiation and opened by UV light irradiation at the level of a single molecule. Indeed, perfect ON/OFF photoregulation is attained. This is a promising strategy for the design of supra-photoswitches such as photoresponsive sticky ends on DNA nanodevices and other nanostructures.


Histone acetylation and deacetylation of nuclei from sea urchin Hemicentrotus pulcherrimus embryos during early stages of development.
Nuclei were isolated from sea urchin (Hemicentrotus pulcherrimus) embryos during early stages of development, and the rates of histone acetylation and deacetylation were examined. Histone acetylation was measured in the presence of 6 mM sodium n-butyrate, a potent inhibitor of deacetylase, and in the absence of the inhibitor. The deacetylation activity was estimated from the difference between the rates with and without the inhibitor. The activities of the acetylation and the deacetylation, and the ratio of deacetylation to acetylation were unchanged during the stages between early blastula and gastrula. Autoradiographic analysis of acetylated histones showed that all of the internal histones of the nucleosomes were acetylated and that no apparent difference was found in the pattern of the acetylated fractions during the stages compared.


Octave-spanning mid-infrared pulses by plasma generation in air pumped with an Yb:KGW source.
Femtosecond mid-infrared (IR) supercontinuum generation in gas media provides a broadband source suited for time-domain spectroscopies and microscopies. This technology has largely utilized <100 fs Ti:sapphire pump lasers. In this Letter, we describe the first plasma generation mid-IR source based on a 1030 nm, 171 fs Yb:KGW laser system; when its first three harmonics are focused in air, a conical mode supercontinuum is generated that spans <1000 to 2700 cm-1 with a 190 pJ pulse energy and 0.5% RMS stability.


Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran.
The objective of the present study was to assess the suitability of an accurate, sensitive, standardized, chronometric blood coagulation test to determine the anticoagulation activity of dabigatran and to quantify concentrations of dabigatran in plasma. Dabigatran was spiked at increasing concentrations in pooled citrated normal human plasma to measure diluted thrombin time with the HEMOCLOT THROMBIN INHIBITOR assay. Calibration curve linearity, inter-assay and intra-assay precision, and assay accuracy were investigated. Dabigatran stability in plasma and the feasibility of lyophilized dabigatran standards for assay calibration were assessed. Data are presented as back-calculated plasma concentrations of dabigatran using regression analysis. Dabigatran's calibration curve for thrombin clotting time was linear over the concentration range 0-4000 nmol/l (0-1886 ng/ml). The R was 0.99. Total assay imprecision for dabigatran was 4.7-12.0% coefficient of variation, with 1.2-3.1% for intra-run imprecision, 4.0-10.0% for inter-run precision and 0.3-8.3% for between-day imprecision. Assay accuracy was determined at three dabigatran concentrations; deviation from sample target concentrations ranged from -20.7% (100 nmol/l; 47.15 ng/ml) to 5.6% (1500 nmol/l; 707.3 ng/ml). Assay robustness was determined by analysing identical dabigatran samples in two independent laboratories. The mean bias of dabigatran coagulation times between laboratories was 6.6%. The HEMOCLOT Thrombin Inhibitors assay is suitable for determining the anticoagulant activity and calculating plasma concentrations of dabigatran using simple and widely available chronometric coagulation devices. The use of this rapid, established, standardized and calibrated assay should provide accurate and consistent results when assessing the anticoagulant activity of dabigatran.


MutT Homolog1 has multifaceted role in glioma and is under the apparent orchestration by Hypoxia Inducible factor1 alpha.
The study focused on the expression and role of a recent potential cancer therapeutic target protein, MutT Homolog1 (MTH1). MTH1 gets activated in an increased reactive oxygen species (ROS) environment and removes the oxidized nucleotides from the cell. The study aimed to check the role of MTH1 in DNA damage and apoptosis, migration and angiogenesis and also to examine its regulation in glioma. The experiments were carried out in human glioma tissue samples and brain tissues of epilepsy patients (non-tumor control). We used two human glioblastomas cell lines, U87MG and U251MG cells. In order to study the role of MTH1 in glioma and to analyze the relation of MTH1 with Hif1α, we have used MTH1 siRNA and Hif1α siRNA respectively. We found an increased expression of MTH1 in glioma tissues compared to the non-tumor brain tissues. Correlation analysis revealed that those samples showing reduced expression of MTH1 also had high levels of DNA damage and apoptotic markers, while diminished expression of angiogenesis regulators and levels of migration. MTH1 knockdown in vitro by siRNA in tumor cell lines corroborates the above observation. This justifies the emergence of MTH1 inhibitors as potential first-in-class drugs. Mechanistically, our observations suggest that Hif1α may modulate MTH1 expression. We found elevated MTH1 expression in glioma irrespective of their grades, while its inhibition affects multiple tumor progression pathways, and that targeting Hif1α could simulate the same.


A molecular blueprint for the pore-forming structure of voltage-gated calcium channels.
A protein that imitates the sequence of a highly conserved segment predicted to line the pore of dihydropyridine-sensitive L-type calcium channels was designed and synthesized. Single-channel conductance properties were studied in planar lipid bilayers. The synthetic protein emulates the ionic conductance, ionic selectivity, and pharmacological properties of the authentic calcium channel, including the stereospecific action of agonist and antagonist enantiomers of the dihydropyridine BayK 8644. The identified sequence is identical in L-type calcium channels from skeletal muscle and isoforms of cardiac muscle, brain, and aorta. It is plausible that this structural motif represents the molecular blueprint for the pore-forming structure of voltage-gated calcium channels.


Effects of cold-treatment on protein synthesis and mRNA levels in rice leaves.
The effects of cold on protein and RNA metabolism in leaves of rice (Oryza sativa L.) seedlings were investigated. Treatment with a diurnal cycle of 15/10 degrees C or 11/6 degrees C for up to 1 week resulted in progressive changes in the protein synthesis pattern after in vivo labeling of intact rice leaves with [(35)S]methionine. These changes were reversed when the seedlings were returned to normal growth temperatures. While de novo accumulation of several abundant proteins was suppressed, some polypeptides were consistently found to be cold-induced. Synthesis of ribulose 1,5-bisphosphate carboxylase (Rubisco) was drastically reduced after 7 days of cold. Using immunoprecipitation of Rubisco, evidence was obtained that the suppression was greater for the small subunit (over 90%) than for the large subunit (80%), indicating a partial loss of coordination in their synthesis. Preformed Rubisco as well as other cold-suppressed proteins were stable for up to 7 days at 11/6 degrees C. Cold-sensitive rice cultivars responded with similar but more drastic changes in the protein synthesis pattern when compared to cold-tolerant varieties. The suppression of Rubisco synthesis by cold was shown to result from reduced levels of the mRNAs encoding both subunits; their decrease paralleled the lower protein synthesis of each. The levels of other chloroplast-encoded mRNAs, especially psaB, and of the nuclear encoded chlorophyll a/b binding protein, also strongly decreased in the cold, whereas the transcripts of the mitochondrial genes apt9, coxIII, and most nuclear genes analyzed were unaffected or only slightly reduced. These data indicate that some chloroplast functions are disturbed during cold stress. One nuclear gene known to be induced by water stress and ABA (Rab21) was also found to be induced by cold treatment.


Ketoconazole--an effective treatment for disseminated pityriasis versicolor.
Long-standing disseminated lesions of pityriasis versicolor (PV) were found in 101 patients. As they had failed to respond to various topical agents, we treated them with 200 mg/day of ketoconazole. All of them were under clinical and mycological surveillance at weekly intervals. In successive mycological examinations during the course of therapy, an increased ratio of filaments/spores was observed, and the last positive examinations invariably showed the presence of only a few filaments and no spores. The mean duration of therapy, until a negative mycological smear was obtained, was 2.2 weeks. Side effects were insignificant, and did not necessitate interrupting treatment except in one patient, who developed an allergic eruption after a single 200-mg dose of the drug. The transient minor disturbances in liver function tests noted in six patients were considered drug related, but ketoconazole administration was continued in all these patients, and the values normalized gradually during treatment. We conclude that ketoconazole is a well-tolerated and highly effective drug in the systemic therapy of disseminated PV.


Presence of ACTH and its receptor on a B lymphocytic cell line: a possible autocrine function for a neuroendocrine hormone.
A mouse B lymphocytic cell line, designated BCL1, was found to produce immunoreactive ACTH and to secrete this molecule into culture supernates. The BCL1-derived ACTH induced Y-1 adrenal cells to undergo a steroidogeneic response and was eluted from gel filtration columns at a molecular weight similar to that expected for pituitary-derived ACTH. Furthermore, ACTH receptors were detected on the surface of BCL1 cells using indirect immunofluorescence and 125I-ACTH binding studies. Scatchard analysis demonstrated the presence of high and low affinity binding sites with dissociation constants of 4.5 x 10(-12) M and 2.8 x 10(-9) M, respectively. The production of both ACTH and its receptor by this B lymphocyte cell line suggests that an autocrine mechanism might be important for the maintenance of the transformed phenotype.


Intercellular Correlations: Relation between DNA Synthesis and Cell Division in Early Stages of in Vitro Bud Neoformation.
As well as showing the existence, during the first stages of in vitro bud neoformation, of cell populations in a tissue composed of a single cell layer (stem epidermis of Torenia fournieri Lind), some new physiological characteristics of mitosis are defined. Most of the cells which divide during organogenesis synthesize their DNA between 20 and 48 hours of culture. On an epidermal strip (10 x 2.5 millimeters composed of about 5,500 cells) 20% of the original cells enter the S-phase. The first division takes place at the 20-hour stage after the entry into the S-phase of a cell population of about 25 cells. Almost none of the cells of this population divide. The greatest percentage of divisions occurs in cells which synthesize DNA near the 48-hour stage. The relation [Formula: see text] has a value of about 25 at the beginning of cell division (20 hours) and falls to a value of about 1.4 for cells which synthesize DNA near the 48-hour stage. A hypothesis of the existence of a mitotic stimulant in the epidermis is put forward; this stimulant, at first weak, increases progressively.


Clinical implications of the smear layer in endodontics: a review.
It has been recognized for many years that root canal instrumentation produces a smear layer that covers the surfaces of prepared canal walls. This layer contains inorganic and organic substances such as fragments of odontoblastic processes and necrotic debris. There is a lack of agreement regarding the effect of the smear layer on the quality of instrumentation and obturation, but the smear layer itself may be infected and may protect the bacteria within the dentinal tubules. Various methods have been used to remove the smear layer. Conflicting results have been obtained from numerous in vitro studies regarding the significance of the presence or the removal of the smear layer.


Causes of immunosuppression in squamous cell carcinoma of the head and neck.
Numerous dysfunctions of the immune system with prognostic relevance can be found in patients with SCCHN. The role of the different factors affecting the immune system has to be investigated in the future with particular consideration being given to the specific therapy indicated. Varying therapies modifying the immune system are available. It is necessary to clarify whether and how SCCHN patients can benefit from these forms of treatment and how dysfunctions of the immune system can be corrected without causing excessive reactions. From a surgical point of view one has to consider whether immune stimulation or reconstructive measures are indicated in patients with decreased immunity and whether less traumatic procedures with smaller blood loss may have a beneficial effect on the tumor's immunological situation, and therefore on the overall survival of the patient. The terms minimal-invasive or functional surgery may take on a new meaning as biologically-adjusted surgery, biologic preservative reconstructive surgery or biologically functional surgery. In SCCHN not only the radical removal of the primary tumor is of concern, but also the regional lymph nodes and their importance for other lymph nodes, the primary tumor and the immunity of the patient as a whole. These factors have to be taken into consideration in the therapeutic planning for the patient. Therapeutic efforts in SCCHN patients should therefore not only aim at the functional preservation of organs and at plastic reconstructive procedures but also preserve and, by biological immunotherapy, restore the tumor-specific immunity. This may result in better survival rates with better quality of life, even in complicated cases.


A Study of Formate Production and Oxidation in Leaf Peroxisomes during Photorespiration.
When glycolate was metabolized in peroxisomes isolated from leaves of spinach beet (Beta vulgaris L., var. vulgaris) formate was produced. Although the reaction mixture contained glutamate to facilitate conversion of glycolate to glycine, the rate at which H(2)O(2) became "available" during the oxidation of [1-(14)C]glycolate was sufficient to account for the breakdown of the intermediate [1-(14)C]glyoxylate to formate (C(1) unit) and (14)CO(2). Under aerobic conditions formate production closely paralleled (14)CO(2) release from [1-(14)C]glycolate which was optimal between pH 8.0 and pH 9.0 and was increased 3-fold when the temperature was raised from 25 to 35 C, or when the rate of H(2)O(2) production was increased artificially by addition of an active preparation of fungal glucose oxidase.When [(14)C]formate was added to these preparations it was oxidized directly to (14)CO(2) by the peroxidatic action of peroxisomal catalase; however, the breakdown of formate was slow relative to the rate of formate production. For example, when [(14)C]formate was generated from [2-(14)C]glycolate it was not readily oxidized to (14)CO(2) in these organelles. Because the activity of formate-NAD(+) dehydrogenase in cell-free leaf extracts was low compared with that of formyl tetrahydrofolate synthetase it is suggested that most of the formate produced during glycolate oxidation could be metabolized via the one carbon pool and not oxidized directly to CO(2).At 25 C the rate of release of (14)CO(2) from [2-(14)C]glycolate in leaf discs was 40 to 50% of the rate from [1-(14)C]glycolate. Isonicotinyl hydrazide inhibited (14)CO(2) release from both [1-(14)C]- and [2-(14)C]glycolate; but this inhibitor was more effective in blocking (14)CO(2) release from [2-(14)C]glycolate. It is argued that the oxidation of the methylene carbon group of glycolate does not occur as a direct consequence of formate (C(1) unit) breakdown, but is a product of the further metabolism of formate and glycine, possibly, via serine.


The effect of Ge incorporation on the Brønsted acidity of ZSM-5.
The effect of the isomorphous substitution of some of the Si atoms in ZSM-5 by Ge atoms on the Brønsted acid strength has been investigated by i) DFT calculations on cluster models of the formula ((HO)3SiO)3-Al-O(H)-T-(OSi(OH)3)3, with T=Si or Ge, and ((HO)3SiO)3-Al-O(H)-Si-(OGe(OH)3)(OSi(OH)3)2, ii) a 31P NMR study of zeolite samples contacted with trimethyl phosphine oxide probe molecules and iii) a X-ray photoelectron spectroscopy (XPS) study of ZSM-5 and Ge-ZSM-5 samples. The calculations reveal that the effect of Ge incorporation on the framework acidity strongly depends on the degree of substitution and on the exact T-atom positions that are occupied by Ge. High Ge concentrations allow for enhanced stabilisation of the deprotonated Ge-ZSM-5 through structural relaxation, resulting in a slightly higher acidity as compared to ZSM-5. This structural relaxation is not achievable in Ge-ZSM-5 with a low Ge content, which therefore has a slightly lower acidity than ZSM-5. The NMR study indicates no difference between the Brønsted acidity of ZSM-5(47) and Ge(0.09)ZSM-5(36). Instead, evidence for the presence of a substantial amount of Ge-OH groups in the Ge-containing samples was obtained from the NMR results, which is consistent with earlier FTIR studies. The XPS results do not point to an effect of Ge on the framework acidity of ZSM-5(47), instead, the results can be best interpreted by assuming the presence of additional Ge-OH and Si-OH groups near the surface of the Ge(0.08)ZSM-5(47) sample.


Examining co-based nanocrystals on graphene using low-voltage aberration-corrected transmission electron microscopy.
We present a method to produce graphene and few layer graphene sheets using solution phase chemistry, which are used as ultrathin support membranes for enhanced imaging of nanomaterials using transmission electron microscopy. We demonstrate this by decorating the surface of the graphene sheets with Co-based nanocrystals (CoCl(2) and hcp Co). Low-voltage aberration-corrected high resolution transmission electron microscopy at 80 kV is used to image the nanocrystals on the thin graphene supports. We show that electron beam irradiation causes the CoCl(2) nanocrystals to become mobile on the graphene surface and exhibit both rotational and translational motion. We provide real-time in situ monitoring with atomic resolution of the coalescence of two CoCl(2) nanocrystals on the graphene surface, driven by electron beam irradiation. The CoCl(2) nanocrystals are then annealed in vacuum and transform into Co nanocrystals with hcp crystal structure. We show that these Co nanocrystals are catalytic and electron beam irradiation leads to the etching of the graphene surface, not observed for the CoCl(2) nanocrystals.


A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells.
The propagation of Toxoplasma gondii is accomplished by repeated lytic cycles of parasite attachment to a host cell, invasion, replication within a parasitophorous vacuole, and egress from the cell. This lytic cycle is delicately regulated by calcium-dependent reversible phosphorylation of the molecular machinery that drives invasion and egress. While much progress has been made elucidating the protein kinases and substrates central to parasite propagation, little is known about the relevant protein phosphatases. In this study, we focused on the five protein phosphatases that are predicted to be membrane-associated either integrally or peripherally. We have determined that of these only PPM5C, a PP2C family member, localizes to the plasma membrane of Toxoplasma. Disruption of PPM5C results in a slow propagation phenotype in tissue culture. Interestingly, parasites lacking PPM5C divide and undergo egress at a normal rate, but have a deficiency in attaching to host cells. Both membrane localization and phosphatase activity are required for PPM5C's role in attachment. Phosphoproteomic analysis show relatively few phosphorylation sites being affected by PPM5C deletion in extracellular parasites of which several are found on proteins involved in signaling cascades. This implies that PPM5C is part of a wider regulatory network important for attachment to host cells.


Age at first marriage and age at first birth.
This paper presents findings on patterns of age of 1st marriage and age of 1st birth for 41 countries participating in the World Fertility Survey program. The age distribution of 1st marriage and 1st birth is summarized with 3 statistics: the mean, the standard deviation, and the proportion ever experiencing the event. The particular method of estimation is based on a model that ensures that estimates for all cohorts are comparable, even though some women have completed their reproductive experience while others have not. The analysis provides insights into sources of error in the reporting of age at 1st birth. In addition, trends and cross-country patterns are documented and conclusions are drawn about the adequacy of these statistics for the description of patterns of age at 1st birth and age at 1st marriage.


[Human herpesvirus 8].
Human herpesvirus 8 (HHV-8, KSHV) was discovered in 1994 by means of a molecular biology approach which permitted to characterize fragments of its genomic sequence. The partial analysis of nucleotide sequence showed that HHV-8 was closely related to herpesvirus saimiri and Epstein-Barr virus, two members of Gammaherpesvirinae sub-family. So far, the virus has been neither isolated nor observed using electron microscopy. It is only detected by means of polymerase chain reaction (PCR) and molecular hybridization. HHV-8 detection in human tissues is strongly associated with three diseases: Kaposi's sarcoma, body-cavity-based lymphomas and Castleman's disease. This association raises the question of the causative role of HHV-8 in the occurrence of these three disease.


Usefulness of hyperventilation thallium-201 single photon emission computed tomography for the diagnosis of vasospastic angina.
To establish a safe and sensitive diagnostic procedure for detecting coronary vasospasm, we utilized 201-thallium myocardial SPECT combined with hyperventilation (HV-SPECT) in 29 patients with vasospastic angina (VAP) and 11 controls. Twenty-five of 29 patients with VAP and 5 of 11 controls developed transient perfusion defects on HV-SPECT, resulting in a sensitivity and specificity calculated at 86% and 55%, respectively. Overall accuracy in identifying corresponding vessels with coronary vasospasm, respectively. Coronary vasospasm tended to be identified more accurately in the left anterior descending branch and the right coronary artery than in the circumflex branch (75%, 71% and 50%, respectively). The hyperventilation test induced ischemic ECG changes in 11 of 29 patients with VAP, yielding a sensitivity of 38%. Analyzing the washout rate of HV-SPECT in patients with VAP, both the extent and severity scores of patients with ischemic ECG changes were larger than those of patients without. No serious complications occurred during HV-SPECT. In conclusion, HV-SPECT was a safe and sensitive procedure as a primary diagnostic approach for VAP. From the results of washout analysis, HV-SPECT could detect more mild myocardial ischemia than could the ECG, and seemed quite useful especially for detecting coronary vasospasm accompanied by minimal ischemic ECG changes.


Blood transfusion, alcohol consumption, and cigarette smoking in causation of hepatocellular carcinoma: a case-control study in Fukuoka, Japan.
In the present study, we investigated the association between hepatocellular carcinoma (HCC) and hepatitis B virus infection (HBV), blood transfusion and drinking and smoking habits by comparing 124 HCC cases and 250 controls. We confirmed a very high relative risk (RR), i.e. 31.0 (P less than 0.001), among persons who were positive for serum hepatitis B surface antigen (HBsAg). However, the prevalence of serum HBsAg positives among our cases was only 21%, about half of those reported earlier, indicating a role of other etiological factors. Those who have a history of blood transfusion showed a significantly elevated RR of 3.0 (P less than 0.001) or 4.9 (P less than 0.001), and most of them (85%) were non-carriers of HBV. Thus, the past history of blood transfusion is an important risk factor among the Japanese. Unidentified non-A, non-B hepatitis viruses in transfused blood probably play a significant role in causing HCC. We estimated that 15% of male HCCs were attributable to blood transfusion. A positive relationship between alcohol consumption and HCC was detected, particularly among HBsAg-negative subjects with no history of blood transfusion who had drunk heavily in their younger years. RR estimates were not great (e.g., heavy drinkers: 2.5), but a substantial proportion of HCC may be attributed to drinking because of common drinking habits among Japanese males. Smoking was also found to have a positive association, but the relationship at a young age was less clear, and further investigation is needed to clarify the etiological role of smoking.


[Radioimmunoassay of serum myelin basic protein].
Using purified human brain myelin basic protein (MBP) to raise antiserum in rabbits and to prepare 125I-labelled MBP (chloramine-T method), We have established a high specific, precise and sensitive double-antibody radioimmunoassay for the measurement of human serum MBP. The sensitivity was 0.5 ng/ml. In the present study, the serum samples of thirty patients with various neurological diseases were detected. An important clinical implication is that serum MBP level should serve as an index for the damage degree of central neurological diseases.


The prevalence of osteoporosis in patients with chronic obstructive pulmonary disease: a cross sectional study.
Chronic obstructive pulmonary disease (COPD) is a complex disease, where the initial symptoms are often cough as a result of excessive mucus production and dyspnea. With disease progression several other symptoms may develop, and patients with moderate to severe COPD have often multiorganic disease with severely impaired respiratory dysfunction, decreased physical activity, right ventricular failure of the heart, and a decreased quality of life. In addition osteoporosis might develop possibly due to a number of factors related to the disease. We wanted to investigate the prevalence of osteoporosis in a population of patients with severe COPD as well as to correlate the use of glucocorticoid treatment to the occurrence of osteoporosis in this population. Outpatients from the respiratory unit with COPD, a history of forced expiratory volume in 1s (FEV1) less than 1.3 L, with FEV1% pred. ranging from 17.3% to 45.3% (mean 31.4%, standard deviation (sd) 7.3%). Patients between 50 and 70 years were included. Other causes of osteoporosis were excluded before inclusion. At study entry spirometry, X-ray of the spine (to evaluate presence of vertebral fractures), and bone mineral density of lumbar spine and hip were performed. Of 181 patients invited by mail, 62 patients were included (46 females and 16 males). All had symptoms of COPD such as exertional dyspnea, productive cough, limitations in physical activity etc. The mean FEV1 was 0.90 L (sd: 0.43 L) and the mean FEV1% pred. of 32.6% (sd: 14.1%). All had sufficient daily intake of calcium and vitamin D. In 15 patients, X-ray revealed compression fractures previously not diagnosed. Bone density measurements showed osteoporosis in 22 patients and osteopenia in 16. In total, 26 of the COPD patients were osteoporotic as evaluated from both X-ray and bone density determinations. Thus 68% of the participants had osteoporosis or osteopenia, but glucocorticoid use alone could not explain the increased prevalence of osteoporosis. A large fraction of these needed treatment for severe osteoporosis in order to prevent further bone loss and to reduce future risk of osteoporotic fractures. Thus, there is a significant need to screen patients with COPD to select the individuals in risk of fracture and to initiate prophylaxis or treatment for the disease.


Interfacial forces between silica surfaces measured by atomic force microscopy.
Colloidal particle stability and some other interfacial phenomena are governed by interfacial force interactions. The two well known forces are van der Waals force and electrostatic force, as documented by the classical Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory. Moreover, advances in modern instrumentation and colloid science suggested that some short-ranged forces or structure forces are important for relevant colloidal systems. The interfacial and/or molecular forces can be measured as a resultant force as function of separation distance by atomic force microscopy (AFM) colloid probe. This article presents a discussion on AFM colloid probe measurement of silica particle and silica wafer surfaces in solutions with some technical notifications in measurement and data convolution mechanisms. The measured forces are then analyzed and discussed based on the 'constant charge' and 'constant potential' models of DLVO theory. The difference between the prediction of DLVO theory and the measured results indicates that there is a strong short-range structure force between the two hydrophilic surfaces, even at extremely low ionic concentration, such as Milli-Q water purity solution.


Impact of Dim Light at Night on Urinary 6-Sulphatoxymelatonin Concentrations and Sleep in Healthy Humans.
Artificial light at night can have negative effects on human wellbeing and health. It can disrupt circadian rhythms, interfere with sleep, and participate in the progress of civilisation diseases. The aim of the present study was to explore if dim artificial light during the entire night (ALAN) can affect melatonin production and sleep quality in young volunteers. We performed two experiments in real-life home-based conditions. Young volunteers (n = 33) were exposed to four nights of one lux ALAN or two nights of five lux ALAN. Melatonin production, based on 6-sulphatoxymelatonin/creatinine concentrations in urine, and sleep quality, based on actimetry, were evaluated. Exposure to ALAN one lux during the entire night did not suppress aMT6s/creatinine concentrations but did aggravate sleep quality by increasing sleep fragmentation and one-minute immobility. ALAN up to five lux reduced melatonin biosynthesis significantly and interfered with sleep quality, as evidenced by an increased percentage of one-minute immobility and a tendency of increased fragmentation index. Our results show that people are more sensitive to low illuminance during the entire night, as previously expected. ALAN can interfere with melatonin production and sleep quality in young, healthy individuals, and both processes have different sensitivities to light.


Intrapersonal and maternal correlates of aggression, conflict, and externalizing problems in toddlers.
Research has shown that 2-year-olds engage in peer-directed aggression and initiation of conflict. However, there has been little consideration of the factors associated with variability in toddlers' aggression. One hundred and four toddlers (52 females) were observed for 35 min of free play with a same-sex peer, with both mothers present. Experience in early out-of-home care was not related to aggression. Toddlers' observed and mother-rated dysregulated temperament, and mothers' use of warmth and negative dominance during interactions with their children, were used to predict toddlers' aggression and maternal ratings of externalizing difficulties. Boys were observed to be more aggressive than girls. Regression analyses showed that, after controlling for main effects, the interaction of child gender, temperament, and maternal negative dominance predicted both outcomes. Observed aggression and mother-reported externalizing problems were associated significantly with dysregulated temperament only for boys with mothers who demonstrated relatively high levels of negative dominance.


[Management of hypoparathyroidism].
The aim of therapy in all hypoparathyroid states is to restore serum calcium to levels sufficient enough to alleviate symptoms of acute hypocalcemia and to prevent the complications of chronic hypocalcemia and hypercalcemia. The main pharmacologic agents available are calcium and vitamin D preparations. In this review, we comment on the usage and management of these agents. Furthermore, prospective therapeutics are discussed.


Polymyalgia rheumatica and systemic giant cell arteritis. Bioptic findings of the subclavian arteries in a case of aortic arch syndrome.
A 64 year old woman complained of aches and stiffness of the neck and the shoulders with fever and E.S.R. increase. A nonsteroid anti-inflammatory treatment was unsuccessful. A clinical examination revealed absence of both radial pulses and presence of murmurs at level of the carotids. The angiographic findings confirmed an aortic arch syndrome with severe stenosis of the subclavian and axillary arteries. The diagnostic approach, in spite of a negativity of the temporal artery biopsy, was for systemic giant cell arteries with general manifestations of polymyalgia rheumatica. The biopsies of both subclavian arteries, performed during a surgery revascularization, showed a typical giant cell arteries in acute stage. The histopathological pattern of extratemporal giant cell arteries obtained by means of a surgical biopsy is really uncommon, being the previous reports performed on necroscopic findings only. In addition this case confirms that polymyalgia rheumatica implies a systemic arteries even if the clinical and histopathological signs of temporal arteritis are lacking. Therefore the temporal artery should be only considered as a particular and inconstant localization of this vasculitis.


Serodiagnostics of Toxoplasma gondii invasions.
Diagnosis of T. gondii invasions is based mainly on serological tests, because of their relative simplicity and availability. In the present work we examined efficiency of immunoblot and two inhouse ELISA assays in anti-Toxoplasma antibody detection, comparing our results with those obtained using commercial ELISA kit of Organon Teknika. We found that inhouse ELISAs and immunoblot can be helpful in diagnosing toxoplasmosis.


Correlation of the Voice Handicap Index (VHI) and the Voice-Related Quality of Life Measure (V-RQOL).
The purpose of this study was to investigate the correlation between the Voice Handicap Index (VHI) and the Voice-Related Quality of Life Measure (V-RQOL), and to test conversion of scores between the two instruments. Understanding the relationship between instruments will facilitate comparison of voice outcome studies using different measures. A retrospective medical chart review of 140 consecutive patients with a chief complaint related to their voice presenting for speech pathology voice evaluation following laryngology evaluation and diagnosis was adopted. Each patient who filled out the VHI and V-RQOL within a 2-week period with no intervening treatment was included in the study. Correlation analysis for total scores was performed for the patients meeting inclusion criteria (n=132). Correlations were also performed as a function of diagnosis. Calculated VHI score based on measured V-RQOL score was compared to measured VHI score. Pearson correlation between scores on the VHI and V-RQOL was -0.82. There was no significant difference between the mean measured and mean calculated VHI scores. For individual scores, however, regression analysis did reveal a significant difference between calculated and measured VHI. The VHI and V-RQOL are highly correlated; however, this study suggests that the two instruments are not interchangeable for individuals.


Association between polymorphisms in the promoter region of pri-miR-34b/c and risk of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. MicroRNA-34 (miR-34) gene plays a key role in altering the apoptotic cycle and pathways of downstream cells, and therefore influences carcinogenesis. In this case-control study, we assessed the role of the pri-miR-34b/c rs4938723 polymorphism in HCC risk. The pri-miR-34b/c polymorphic genotype was determined in 286 patients with HCC and 572 controls using polymerase chain reaction-restriction fragment length polymorphism. The male gender (X2 = 12.95, P < 0.001), regular alcohol consumption (X2 = 16.81, P < 0.001), and a family history of cancer (X2 = 11.88, P = 0.001) were associated with HCC risk. However, the age (t = 1.19, P = 0.12) and tobacco smoking habit (X2 = 0.64, P = 0.42) of HCC patients were comparable to those of the controls. The TC (adjusted OR = 1.46, 95%CI = 1.06-2.01) and CC (adjusted OR = 3.07, 95%CI = 1.77-5.34) genotypes of pri-miR-34b/c rs4938723 were correlated with a higher risk of HCC compared to the TT genotype. Moreover, the TC+CC genotype was correlated with an increased risk of HCC compared to the TT genotype (adjusted OR = 1.64, 95%CI = 1.21-2.22). In the recessive model, the CC genotype of pri-miR-34b/c rs4938723 was significantly correlated with an elevated risk of HCC compared to the TT+TC genotype (adjusted OR = 2.50, 95%CI = 1.49-4.22). Further large-scale and multi-center studies are required to confirm these results.


Decitabine potentiates efficacy of doxorubicin in a preclinical trastuzumab-resistant HER2-positive breast cancer models.
Acquired drug resistance and metastasis in breast cancer (BC) are coupled with epigenetic deregulation of gene expression. Epigenetic drugs, aiming to reverse these aberrant transcriptional patterns and sensitize cancer cells to other therapies, provide a new treatment strategy for drug-resistant tumors. Here we investigated the ability of DNA methyltransferase (DNMT) inhibitor decitabine (DAC) to increase the sensitivity of BC cells to anthracycline antibiotic doxorubicin (DOX). Three cell lines representing different molecular BC subtypes, JIMT-1, MDA-MB-231 and T-47D, were used to evaluate the synergy of sequential DAC + DOX treatment in vitro. The cytotoxicity, genotoxicity, apoptosis, and migration capacity were tested in 2D and 3D cultures. Moreover, genome-wide DNA methylation and transcriptomic analyses were employed to understand the differences underlying DAC responsiveness. The ability of DAC to sensitize trastuzumab-resistant HER2-positive JIMT-1 cells to DOX was examined in vivo in an orthotopic xenograft mouse model. DAC and DOX synergistic effect was identified in all tested cell lines, with JIMT-1 cells being most sensitive to DAC. Based on the whole-genome data, we assume that the aggressive behavior of JIMT-1 cells can be related to the enrichment of epithelial-to-mesenchymal transition and stemness-associated pathways in this cell line. The four-week DAC + DOX sequential administration significantly reduced the tumor growth, DNMT1 expression, and global DNA methylation in xenograft tissues. The efficacy of combination therapy was comparable to effect of pegylated liposomal DOX, used exclusively for the treatment of metastatic BC. This work demonstrates the potential of epigenetic drugs to modulate cancer cells' sensitivity to other forms of anticancer therapy.


Influence of thoracic drainage fluid on proliferation, migration, apoptosis, and drug resistance in lung cancer cell lines.
This study aimed to clarify the effect of thoracic drainage fluid (DF) on lung cancer cells in vitro. We assessed the influence of DF on the proliferation and migration of lung cancer cells (LTEP-a-2 and A549) using the MTT cell proliferation assay and scratch wound assay. Cell apoptosis was determined by flow cytometric analysis. We also investigated the effect of DF on drug chemosensitivity, assessing viability of LTEP-a-2 and A549 cells. The proliferative rates of cancer cells in the DF-treated group were significantly higher than those of the control group. Similar results were obtained for cell migration of lung cancer cells. Cells in the DF-treated groups showed a lower percentage of apoptosis than those of the control groups. Chemosensitivity of lung cancer cells to doxycycline and cisplatin (DDP) was lowered by DF. These findings suggest that DF affects lung cancer cells by promoting proliferation and migration, inhibiting apoptosis, and increasing drug resistance.


Are mathematics disabilities due to a domain-general or a domain-specific working memory deficit?
The relationship between verbal and visual-spatial working memory and mathematical computation skill was examined in children and adults with and without disabilities in mathematics. A hierarchical regression analysis showed that, when partialing for the influence of reading ability, age, and gender, mathematical computation was better predicted by verbal than by visual-spatial working memory. Furthermore, the results showed that the relationship between mathematics ability and working memory were not significantly moderated by age but were stable across a broad age span. We concluded that, regardless of age, deficits in mathematics are mediated by both a domain-general and a domain-specific working memory system.


Nd:YAIG Laser Cavity Loss due to an Internal Brewster Polarizer.
When an internal Brewster plate is used to polarize a Nd:YAIG laser, its output power generally decreases. This is shown to be largely due to the thermally induced birefringence in the laser rod, which causes a polarization rotation inside the optical cavity and hence a reflection loss at the polarizer. Calculation of this loss for a typical laser has been made and is compared to observed decreases in output power.