Induction of polymorphonuclear leukocyte-derived hepatocyte stimulating factor and effects on alpha 2-macroglobulin synthesis.
We investigated the kinetics of production of the hepatocyte stimulating factor (HSF) by peritoneal exudate- and peripheral circulating blood-polymorphonuclear leukocytes (PMNLs). Effects of the HSFs on alpha-2-macroglobulin (a2M) synthesis and a2M specific gene expression in primary cultured adult rat hepatocytes were also examined. Peritoneal exudate-PMNLs were collected 3 hr after the injection of alkaline-denatured casein into the peritoneal cavity of rats. Secretion of HSF into the culture medium began within 15 min after the start of incubation and practically a full secretion was noted within 3 hr. Lipopolysaccharide or other agents were not required to induce HSF from the PMNLs. Inhibitors of protein or DNA synthesis, cycloheximide, actinomycin D or puromycin, did not inhibit the secretion of HSF by rat PMNLs thereby suggesting that preformed and pooled HSF in the PMNLs was secreted during incubation. Peripheral circulating blood-PMNLs collected from a healthy man did not secrete HSF, in the absence of stimulation but did secrete HSF after vigorous agitation during incubation at 37 degrees C. The PMNL-HSF induced the synthesis of a2M and the accumulation of a2M mRNA in primary cultured rat hepatocytes. However, the effect was evident only with dexamethasone present in the culture medium. Furthermore, the effects of the PMNL-HSFs on a2M and albumin protein synthesis were reciprocal: The PMNL-HSF induced a2M synthesis, whereas it suppressed albumin synthesis.


Control of activity through oxidative modification at the conserved residue Cys66 of aryl sulfotransferase IV.
Oxidation at Cys66 of rat liver aryl suflotransferase IV alters the enzyme's catalytic activity, pH optima and substrate specificity. Although this is a cytosolic detoxification enzyme, the pH optimum for the standard assay substrate 4-nitrophenol is at pH 5.5; upon oxidation, the optimum changes to the physiological pH range. The principal effect of the change in pH optimum is activation, which is manifest by an increase in K'cat without any major influence on substrate binding. In contrast, with tyrosine methyl ester as a substrate, the enzyme's optimum activity occurs at pH 8.0; upon oxidation, it ceases to be a substrate at any pH. The presence of Cys66 was essential for activation to occur, thereby providing a putative reason underlying the conserved nature of this cysteine throughout the phenol sulfotransferase family. Mapping of disulfides by mass spectrometry showed the critical event to be the oxidation of Cys66 to form a disulfide with either Cys232 or glutathione, either one is effective. These results point to a mechanism for regulating the activity of a key enzyme in xenobiotic detoxication during cellular oxidative stress.


Nucleotide sequence and chromosomal mapping of the 5S rDNA repeat of the crustacean Proasellus coxalis.
In this investigation we analysed the 5S rRNA genes of the isopod crustacean Proasellus coxalis, 5S rDNA hybridization of digested genomic DNA and amplification by PCR demonstrate that these genes are organized in tandem repeats of 589 bp, 120 of which represent the coding sequence and 469 the spacer sequence. Proasellus coxalis is the first crustacean species in which 5S rRNA genes have been found tandemly arranged without being linked to other repeated genes. The PCR product has been used as a probe in FISH to locate the 5S rRNA genes on two chromosome pairs of the P. coxalis karyotype. Comparison of the 5S rRNA sequence of this species with previously published sequences of six other crustacean species shows the existence of a good correlation between phylogenetic relationships and sequence identity.


Initial Diagnosis of Classic Hodgkin Lymphoma With Skin Biopsy: A Rare Case and Review of Diagnostic Considerations.
Classic Hodgkin lymphoma (CHL) is a B-cell-derived lymphoma that classically displays a bimodal age distribution. CHL typically involves the mediastinum, lymph nodes, and other visceral organs. CHL is characterized histologically by the presence of a relatively paucicellular neoplastic cell population composed of large atypical cells (including Hodgkin and Reed-Sternberg forms) in a reactive mixed inflammatory background, often with prominent necrosis. CHL rarely occurs in the skin, and the associated mixed inflammatory infiltrate or necrotic appearance can create diagnostic uncertainty. Herein, we report the case of a 31-year-old man presenting with a painful dendritic rash of the anterior chest wall with axillary lymphadenopathy. After multiple nondiagnostic biopsies that revealed largely necrotic material, a chest wall skin biopsy was obtained. The skin biopsy was diagnostic of CHL, based on the presence of large atypical dermal cells, including Hodgkin and Reed-Sternberg forms, which expressed CD15, CD30 and Fascin, in a typical mixed inflammatory and necrotic background. Through the lens of this case, we discuss the characteristics and mechanisms of skin involvement of CHL, and the histopathologic and immunohistochemical pitfalls when considering the rare diagnosis of CHL in the skin.


Underreporting of side effects of standard first-line ART in the routine setting in Blantyre, Malawi.
In the Malawi ART programme, 92% of 250,000 patients are using the standard first-line regime of stavudine-lamivudine-nevaripine. National ART reports indicate <4% experience ART side effects, much less than expected from literature. We interviewed adult patients on standard first-line ART for at least one year, after routine visits to an urban clinic in Blantyre, Malawi. We determined the prevalence of symptoms that are common side-effects, described discrepancies between symptoms that patients reported to us and those that had been recorded by attending staff as side-effects in the point-of-care electronic monitoring system, and studied factors associated with such discrepancies. Of 170 participants, 75 (44%) reported at least one symptom, most common were symptoms suggesting peripheral neuropathy (n=57) and lipodystrophy (n=16). Forty-six (66%) symptomatic patients said they reported symptoms to attending ART staff. Side-effects were recorded in the clinic database for just 4 patients. Toxicity recording was too low for meaningful analysis of factors associated with discrepancies between reporting and recording of side-effects. The prevalence of symptoms indicating characteristic side-effects of the standard first-line regimen was 39% based on interviews, and 2% in the electronic monitoring system. There was gross under-recording of side-effects in this setting, mainly due to not recording by ART staff. Pressure of work and insufficient perceived benefit of side-effect recording are suspected causes. Local and national ART reports do not reflect the true toxicity of the standard first line regimen.


Coding of information in limit cycle oscillators.
Starting from a general description of noisy limit cycle oscillators, we derive from the Fokker-Planck equations the linear response of the instantaneous oscillator frequency to a time-varying external force. We consider the time series of zero crossings of the oscillator's phase and compute the mutual information between it and the driving force. A direct link is established between the phase response curve summarizing the oscillator dynamics and the ability of a limit cycle oscillator, such as a heart cell or neuron, to encode information in the timing of peaks in the oscillation.


Evidence conflict measure based on OWA operator in open world.
Dempster-Shafer evidence theory has been extensively used in many information fusion systems since it was proposed by Dempster and extended by Shafer. Many scholars have been conducted on conflict management of Dempster-Shafer evidence theory in past decades. However, how to determine a potent parameter to measure evidence conflict, when the given environment is in an open world, namely the frame of discernment is incomplete, is still an open issue. In this paper, a new method which combines generalized conflict coefficient, generalized evidence distance, and generalized interval correlation coefficient based on ordered weighted averaging (OWA) operator, to measure the conflict of evidence is presented. Through ordered weighted average of these three parameters, the combinatorial coefficient can still measure the conflict effectively when one or two parameters are not valid. Several numerical examples demonstrate the effectiveness of the proposed method.


Behavioural factors related to metabolic control in patients with phenylketonuria.
The objective of this study was to determine the importance of parental factors possibly related to dietary control in early and continuously treated patients with phenylketonuria (PKU). A questionnaire was disseminated among parents of 238 patients with PKU born after the nationwide introduction of newborn screening for PKU (1 September 1974) until 31 December 1995. The questionnaire was based on a behavioural model measuring people's attitudes, subjective norms, and self-efficacy. Dietary control was defined on the basis of mean phenylalanine (Phe) concentration of the PKU patients measured between 1 January 1994 and 31 December 1996. Response rate was 71%. Attitudes: children of parents who believed that their child adheres well to the diet, even if his or her Phe concentrations are sometimes too high, had lower Phe concentrations than children of parents who disagree with this statement (adjusted difference -103 micromol/L, p < 0.001). Subjective norm: Phe concentrations were higher when parents answered that their relatives did not approve when their child deviates from the diet (p = 0.004). Self-efficacy: children of parents who reported difficulties in having their child eat the synthetic protein substitute three times a day had higher Phe concentrations than those of parents who did not have such difficulties (adjusted difference 156 micromol/L, p = 0.007). More attention should be given to parents having their child eat the synthetic protein substitute at least three times a day and to teaching parents to keep strictly to the diet without being too rigid. These factors were strongly associated to dietary control and may be amenable to change.


Differentiation of lumbar disc herniation and lumbar spinal stenosis using natural language processing-based machine learning based on positive symptoms.
The purpose of this study was to develop natural language processing (NLP)-based machine learning algorithms to automatically differentiate lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS) based on positive symptoms in free-text admission notes. The secondary purpose was to compare the performance of the deep learning algorithm with the ensemble model on the current task. In total, 1921 patients whose principal diagnosis was LDH or LSS between June 2013 and June 2020 at Zhongda Hospital, affiliated with Southeast University, were retrospectively analyzed. The data set was randomly divided into a training set and testing set at a 7:3 ratio. Long Short-Term Memory (LSTM) and extreme gradient boosting (XGBoost) models were developed in this study. NLP algorithms were assessed on the testing set by the following metrics: receiver operating characteristic (ROC) curve, area under the curve (AUC), accuracy score, recall score, F1 score, and precision score. In the testing set, the LSTM model achieved an AUC of 0.8487, accuracy score of 0.7818, recall score of 0.9045, F1 score of 0.8108, and precision score of 0.7347. In comparison, the XGBoost model achieved an AUC of 0.7565, accuracy score of 0.6961, recall score of 0.7387, F1 score of 0.7153, and precision score of 0.6934. NLP-based machine learning algorithms were a promising auxiliary to the electronic health record in spine disease diagnosis. LSTM, the deep learning model, showed better capacity compared with the widely used ensemble model, XGBoost, in differentiation of LDH and LSS using positive symptoms. This study presents a proof of concept for the application of NLP in prediagnosis of spine disease.


High glucose enhances the gene expression of interleukin-8 in human endothelial cells, but not in smooth muscle cells: possible role of interleukin-8 in diabetic macroangiopathy.
We examined the effect of high glucose concentrations on the production of interleukin(IL)-8, which seems to be important for the development of atherosclerosis, in cultured human aortic endothelial cells (AoEC) and smooth muscle cells (AoSMC). After incubating these cells with various concentrations of glucose for 2 days or 7 days, the IL-8 concentration in cell lysates was measured by enzyme-linked immunosorbent assay and the IL-8 mRNA expression was examined by Northern analysis. After 2 days' culture, 42.5 mmol/l glucose enhanced IL-8 mRNA expression in AoEC, but not in AoSMC, compared to 4 mmol/l glucose. After 7 days' culture, the IL-8 concentration in AoEC lysate and the expression of IL-8 mRNA were significantly increased by 20.5 mmol/l glucose, or 42.5 mmol/l glucose compared to 4 mmol/l glucose. On the other hand, the IL-8 concentration in AoSMC lysate was not affected by any glucose concentration and the expression of IL-8 mRNA in AoSMC was diminished by high glucose. These results suggest that the chemotactic gradient by IL-8 is established between arterial intima and media in response to high glucose levels in diabetic patients, and that it may be one of the key factors for SMC migration to the intima leading to diabetic macroangiopathy.


Enablers of Candida auris persistence on medical devices and their mode of eradication.
Candida auris is an emerging pathogen predominantly isolated from immunocompromised patients, hospitalized for a long time. It inhabits the skin surfaces of patients causing ear, wound, and systemic infections; if not treated properly, it could lead to severe mortality. Apart from being a skin pathogen, C. auris colonizes the surfaces of medical devices. Medical devices are hospital tools and components often utilized for the diagnosis and treatment of diseases associated with human skin. The mechanism of survival and persistence of C. auris on medical devices has remained unclear and is a serious concern for clinicians. The persistence of C. auris on medical devices has deterred its effective elimination, hindered the treatment of infections, and increased its antifungal resistance. Evidence has shown that a few surface molecules on the cell wall of C. auris and the extracellular matrix of the biofilm are responsible for its persistence and exist as enablers. Due to the increased cases of ear, skin, and systemic infections as well as death resulting from the spread of C. auris in hospitals, there is a need to study these enablers. This review focused on the identification of the enablers and aimed to evaluate them in relation to their ability to induce persistence in C. auris. In order to reduce the spread of or completely eliminate C. auris and its enablers in hospitals, the efficacy of disinfection and sterilization methods were compared.


Conformational sampling of CDR-H3 in antibodies by multicanonical molecular dynamics simulation.
The diversity in the lengths and the amino acid sequences of the third complementarity determining region of the antibody heavy chain (CDR-H3) has made it difficult to establish a relationship between the sequences and the tertiary structures, in contrast to the other CDRs, which are classified by their canonical structures. Enhanced conformational sampling of two different CDR-H3s was performed by multicanonical molecular dynamics (multicanonical MD) simulation while restricting the base structures, with and without the other surrounding CDR segments. The results showed that the multicanonical MD sampled a much larger conformational space than the conventional MD, independent of the initial conformations of the simulations. When the other CDRs surrounding the CDR-H3 segments were included in the calculations, the predominant conformations at 300 K corresponded to the X-ray crystal structures. When only the single CDR-H3 loops were considered with the restricted base structures, a greater number of different conformations were sampled as putative loops, but only a small number of stable conformations appeared at 300 K. Analyses of the resultant conformations revealed a structural role for the glycine, when it is located at position three residues before the last residue of CDR-H3 (Gly-X-X-last residue), coincident with the statistical tendencies of many antibody crystal structures. This reflects the general consistency between the energetically stable conformations and the empirically observed conformations. The current method is expected to be applicable to the structural modeling and the design of antibodies, especially for the inherently flexible loops.


A Ratio Between Infrarenal and Suprarenal Aortic Diameters Corrects for Absolute Aortic Diameter Variations due to Patients' Sex and Body Size.
Aortic diameters may differ significantly between patients with different gender and body size. The aim of this study was to relate absolute aortic diameters to age, sex, height, and weight of the patients and to correct for these factors by calculating the ratio between the infrarenal and the suprarenal aortic diameters. A total of 458 patients who underwent elective endovascular aneurysm repair (EVAR) between 2004 and 2018 were included. The aortic anatomy in this group of elective EVAR patients was compared with a control group of 75 patients without an abdominal aortic aneurysm (AAA). The aortic diameter was measured at 4 suprarenal points and 4 infrarenal points. Ratios were calculated by dividing the mean infrarenal neck diameter by 4 suprarenal measurements. Patients in the aneurysm group had significantly larger suprarenal and infrarenal aortic diameters. The ratios between the mean infrarenal neck diameter and all 4 suprarenal measurements were larger in the AAA group than in the control group. In both groups, there was a significant correlation between the mean infrarenal neck diameter and sex, height, weight, and body surface area (BSA). However, in both groups, all 4 ratios between the mean infrarenal neck diameter and suprarenal aortic diameters were not correlated with age, sex, height, weight, or BSA, except for the ratio between the mean infrarenal neck diameter and the aortic diameter measurement proximal to the upper renal artery, which was correlated to weight and BSA in the control group. The mean infrarenal neck diameter is correlated with sex, height, weight, and BSA. However, when the suprarenal aortic diameter was used as an internal control for the mean infrarenal neck diameter, we were able to correct for these variations in aortic diameters due to sex and body size. The clinical relevance of this ratio in patients treated by EVAR has yet to be assessed in future research. In the assessment for EVAR suitability the absolute diameter of the aneurysm neck is taken into account. We believe that using absolute diameters is not the appropriate way to assess this suitability, but that patient characteristics such as age, gender and body size, should be factored into this assessment. In this paper, we show that suprarenal and infrarenal aortic diameters are both significantly increased in patients with an aneurysm compared with patients without an aneurysm. Besides, we found that mean infrarenal aortic diameter is correlated with sex, height, weight, and body surface area. Finally, we propose a new ratio system, using suprarenal diameters as an internal control, to correct for aortic diameter variations due to sex and body size.


Diagnostic implications of albumin messenger RNA detection and cytokeratin pattern in benign hepatic lesions and biliary cystadenocarcinoma.
Cytokeratin (CK) patterns and albumin messenger RNA (mRNA) are investigated in 24 patients with benign hepatic lesions (7 patients with focal nodular hyperplasia [FNH], 10 with hepatocellular adenomas [HA], 1 with biliary hamartoma, 4 with biliary cysts, 2 with cystadenomas) and in 8 patients with cystadenocarcinoma, a rare liver malignancy. The lesions and surrounding tissue of the hepatocytic components expressed CK 8 and 18 at immunohistochemistry, whereas the biliary elements evidenced CK 8 and 18 and CK 7 and 19. The albumin mRNA, as detected by in situ hybridization (ISH), revealed different distributions in the hepatocytes of FNH and HA. In the benign biliary lesions, the normal hepatocytes surrounding the tumors expressed albumin mRNA, whereas the biliary structures did not. Interestingly, in the cystadenocarcinomas, albumin mRNA was observed not only in the hepatocytes of residual parenchyma, but also in neoplastic bile duct cells lining the carcinomatous cysts; no signal was identified in the nonneoplastic biliary elements. This indicates that cystadenocarcinomas have a mixed biological phenotype and suggests they could arise either from pluripotent cells or from neoplastic cells that reacquire epigenetic features. Our results suggest two possible diagnostic applications for albumin ISH: on routine sections, it could represent an important tool for distinguishing between cystadenoma and cystadenocarcinoma; and on fine needle biopsy specimens, it could reduce uncertainty between FNH and HA.


[Smooth muscle hamartoma or nevus of Becker? Apropos of 4 cases].
Theoretically, Becker's melanosis or hairy epidermal nevus and smooth muscle hamartoma are two quite separate entities. In fact, there are cases which could be considered as intermediate. As a matter of fact, a slight underlying smooth muscle hyperplasia can be seen in Becker's nevus; on the other hand, hypermelanosis of the basal layer and hypertrichosis may be encountered in smooth muscle hamartoma. The 4 here reported cases are examples of diagnostic difficulties for which the sometimes not clear-cut limits of these 2 types of lesion can be responsible.


Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain.
The formation of beta-amyloid in the brains of individuals with Alzheimer disease requires the proteolytic cleavage of a membrane-associated precursor protein. The proteases that may be involved in this process have not yet been identified. Cathepsins are normally intracellular proteolytic enzymes associated with lysosomes; however, when sections from Alzheimer brains were stained by antisera to cathepsin D and cathepsin B, high levels of immunoreactivity were also detected in senile plaques. Extracellular sites of cathepsin immunoreactivity were not seen in control brains from age-matched individuals without neurologic disease or from patients with Huntington disease or Parkinson disease. In situ enzyme histochemistry of cathepsin D and cathepsin B on sections of neocortex using synthetic peptides and protein substrates showed that senile plaques contained the highest levels of enzymatically active cathepsin. At the ultrastructural level, cathepsin immunoreactivity in senile plaques was localized principally to lysosomal dense bodies and lipofuscin granules, which were extracellular. Similar structures were abundant in degenerating neurons of Alzheimer neocortex, and cathepsin-laden neuronal perikarya in various stages of disintegration could be seen within some senile plaques. The high levels of enzymatically competent lysosomal proteases abnormally localized in senile plaques represent evidence for candidate enzymes that may mediate the proteolytic formation of amyloid. We propose that amyloid precursor protein within senile plaques is processed by lysosomal proteases principally derived from degenerating neurons. Escape of cathepsins from the stringently regulated intracellular milieu provides a basis for an abnormal sequence of proteolytic cleavages of accumulating amyloid precursor protein.


Regulation of Vibrio parahaemolyticus T3SS2 gene expression and function of T3SS2 effectors that modulate actin cytoskeleton.
Vibrio parahaemolyticus is a leading causative agent of seafood-borne gastroenteritis worldwide. Most clinical isolates from patients with diarrhoea possess two sets of genes for the type III secretion system (T3SS) on each chromosome (T3SS1 and T3SS2). T3SS is a protein secretion system that delivers effector proteins directly into eukaryotic cells. The injected effectors modify the normal cell functions by altering or disrupting the normal cell signalling pathways. Of the two sets of T3SS genes present in V. parahaemolyticus, T3SS2 is essential for enterotoxicity in several animal models. Recent studies have elucidated the biological activities of several T3SS2 effectors and their roles in virulence. This review focuses on the regulation of T3SS2 gene expression and T3SS2 effectors that specifically target the actin cytoskeleton.


Beta-adrenergic activation and memory for emotional events.
Substantial evidence from animal studies suggests that enhanced memory associated with emotional arousal results from an activation of beta-adrenergic stress hormone systems during and after an emotional experience. To examine this implication in human subjects, we investigated the effect of the beta-adrenergic receptor antagonist propranolol hydrochloride on long-term memory for an emotionally arousing short story, or a closely matched but more emotionally neutral story. We report here that propranolol significantly impaired memory of the emotionally arousing story but did not affect memory of the emotionally neutral story. The impairing effect of propranolol on memory of the emotional story was not due either to reduced emotional responsiveness or to nonspecific sedative or attentional effects. The results support the hypothesis that enhanced memory associated with emotional experiences involves activation of the beta-adrenergic system.


In vivo strain measurements from hardware and lamina during spine fusion.
Currently, spine fusion is determined using radiography and clinical evaluation. There are discrepancies between radiographic evidence and direct measurements of fusion, such as operative exploration and biomechanical or histological measurements. In order to facilitate the rapid return of patients to normal activities, a monitoring technique to accurately detect fusion in vivo and to prevent overload during the postoperative period would be useful. The objectives of this study were to develop an implantable monitoring system consisting of CPC-coated strain gauges and a radio transmitter to detect the onset of fusion and measure strain during postsurgical activities. A patient underwent anterior release and fusion, followed by posterior instrumentation and fusion with segmental spinal instrumentation. Four strain gauges were placed during surgery. One was attached to the left-side rod and one to each of the lamina at T9, T10, and T11. An externally powered implanted radio transmitter attached to the gauges was placed in a subcutaneous pouch. Strains were monitored weekly and tabulated during various activities for 7 months. Peak strains during twisting and bending were tabulated to detect the onset of fusion. Strains were also recorded during activities such as climbing off an examination table, rising from a chair, and climbing stairs. Strains collected from the left rod indicated that, immediately postoperatively, it was loaded at acceptable levels. The largest and most consistent strain changes measured from the lamina were recorded during twisting.


Efficient hydration of alkynes through acid-assisted Brønsted acid catalysis.
The combined acid catalyzed hydration of alkynes is an efficient one-step synthesis of carbonyl compounds. This atom-economical method is effective with a wide range of substrates, and the products are obtained in very good yields with low catalyst loading (0.2%). Furthermore, solid acids like Nafion were also efficient and could be easily recycled multiple times without loss of reactivity.


Comparative study of hydroxyapatite from eggshells and synthetic hydroxyapatite for bone regeneration.
The objective of this study was to evaluate the physical properties of synthetic hydroxyapatite (sHA) and hydroxyapatite from eggshells (eHA) by Fourier-transform infrared (FT-IR) and x-ray diffraction (XRD) and to compare the regenerative ability of the bone using sHA and eHA in a rabbit calvarial defect model. FT-IR and XRD were used to compare the physical properties of sHA and eHA. sHA was purchased from Sigma, and eHA was kindly donated from the Hungarian academy of science. Sixteen New Zealand white rabbits were used for the animal study. After the formation of a bilateral parietal bony defect (diameter 8.0 mm), either sHA or eHA was grafted into the defect. The defect in the control was left unfilled. Bone regeneration was evaluated by histomorphometry at 4 and 8 weeks after the operation. The peak broadening of the XRD experiments were in agreement with scanning electron microscope observation; the sHA had a smaller granule size than the eHA. The eHA had impurities phases of CaO (International Center for Diffraction Data (ICDD) 075-0264) and Ca(OH)(2) (ICDD 072-0156). Total new bone was 17.11 ± 10.24% in the control group, 28.81 ± 12.63% in sHA group, and 25.68 ± 10.89% in eHA group at 4 weeks after the operation. The difference was not statistically significant (P > .05). Total new bone at 8 weeks after the operation was 27.50 ± 10.89% in the control group, 38.62 ± 17.42% in sHA group, and 41.99 ± 8.44% in the eHA group. When comparing the sHA group to the control group, the difference was not statistically significant (P > .05). However, the eHA group was significantly different from the control group (P = .038). When comparing the eHA group to the sHA group, the difference was not statistically significant (P > .05). Both types of HA showed higher bone formation than the unfilled control. However, eHA had significantly higher bone formation than the unfilled control at 8 weeks after operation.


Down-regulation of layilin, a novel hyaluronan receptor, via RNA interference, inhibits invasion and lymphatic metastasis of human lung A549 cells.
Human lung carcinoma is a highly metastatic tumour that leads to a high death rate and in which lymphatic metastasis is an important early event. HYA (hyaluronan) is involved in the invasion of a variety of tumour cells. Layilin, a specific and novel HYA receptor, was detected in the human lung cell line A549 in our preliminary research, and was hypothesized to play an essential role in cell motility and tumour lymphatic metastasis. In the present study we found that, as expected, suppression of layilin expression by RNA interference significantly inhibited A549-cell invasion and migration in vitro and lymphatic metastasis in vivo and thereby resulted in the increased survival of tumour-bearing mice. These findings suggested that layilin might play crucial roles in lymphatic metastasis of lung carcinoma and that suppression of layilin expression might be a promising strategy for treatment of human lung carcinoma.


Resolution considerations in imaging of the cortical layers.
The cortical layers are a finger print of brain development, function, connectivity and pathology. Obviously, the formation of the layers and their composition is essential to cognition and behavior. The layers were traditionally measured by histological means but recent studies utilizing MRI suggested that T1 relaxation imaging consist of enough contrast to separate the layers. Indeed extreme resolution, post mortem, studies demonstrated this phenomenon. Yet, one of the limiting factors of using T1 MRI to visualize the layers in neuroimaging research is partial volume effect. This happen when the image resolution is not high enough and two or more layers resides within the same voxel. In this paper we demonstrate that due to the physical small thickness of the layers it is highly unlikely that high resolution imaging could resolve the layers. By contrast, we suggest that low resolution multi T1 mapping conjugate with composition analysis could provide practical means for measuring the T1 layers. We suggest an acquisition platform that is clinically feasible and could quantify measures of the layers. The key feature of the suggested platform is that separation of the layers is better achieved in the T1 relaxation domain rather than in the spatial image domain.


Validation of Deleterious Mutations in Vorderwald Cattle.
In Montbéliarde cattle two candidate mutations on bovine chromosomes 19 and 29 responsible for embryonic lethality have been detected. Montbéliarde bulls have been introduced into Vorderwald cattle to improve milk and fattening performance. Due to the small population size of Vorderwald cattle and the wide use of a few Montbéliarde bulls through artificial insemination, inbreeding on Montbéliarde bulls in later generations was increasing. Therefore, we genotyped an aborted fetus which was inbred on Montbéliarde as well as Vorderwald x Montbéliarde crossbred bulls for both deleterious mutations. The abortion was observed in an experimental herd of Vorderwald cattle. The objectives of the present study were to prove if one or both lethal mutations may be assumed to have caused this abortion and to show whether these deleterious mutations have been introduced into the Vorderwald cattle population through Montbéliarde bulls. The aborted fetus was homozygous for the SLC37A2:g.28879810C>T mutation (ss2019324563) on BTA29 and both parents as well as the paternal and maternal grandsire were heterozygous for this mutation. In addition, the parents and the paternal grandsire were carriers of the MH2-haplotype linked with the T-allele of the SLC37A2:g.28879810C>T mutation. For the SHBG:g.27956790C>T mutation (rs38377500) on BTA19 (MH1), the aborted fetus and its sire were heterozygous. Among all further 341 Vorderwald cattle genotyped we found 27 SLC37A2:g.28879810C>T heterozygous animals resulting in an allele frequency of 0.0396. Among the 120 male Vorderwald cattle, there were 12 heterozygous with an allele frequency of 0.05. The SLC37A2:g.28879810C>T mutation could not be found in further nine cattle breeds nor in Vorderwald cattle with contributions from Ayrshire bulls. In 69 Vorderwald cattle without genes from Montbéliarde bulls the mutated allele of SLC37A2:g.28879810C>T could not be detected. The SHBG:g.27956790C>T mutation appeared unlikely to be responsible for the present case of abortion and, in addition, we observed this mutation in a homozygous state in a living animal. In conclusion, we could demonstrate the first case of an aborted fetus carrying the deleterious SLC37A2:g.28879810C>T mutation homozygous and show that this deleterious mutation had been introduced through Montbéliarde bulls into Vorderwald cattle.


Suppression of Fatty Acid and Triglyceride Synthesis by the Flavonoid Orientin through Decrease of C/EBPδ Expression and Inhibition of PI3K/Akt-FOXO1 Signaling in Adipocytes.
Plant flavonoids have a variety of biological properties. In a previous study, we found that the tea of the Asian dayflower, Commelina communis L., decreased the body weight gain in high-fat diet-fed mice. In this study, we studied the anti-adipogenic ability of a flavonoid orientin that is found in abundance in C. communis. Orientin repressed the accumulation of intracellular triglyceride (TG) in mouse adipocyte 3T3-L1 cells. The treatment with orientin also decreased the mRNA levels of the genes involved in adipogenesis, lipogenesis, lipolysis, and TG synthesis, and reduced the release of glycerol. Orientin lowered the expression of CCAAT/enhancer binding protein (C/EBP) δ in the early stage of adipogenesis, leading to a decrease in the expression of the adipogenic master transcription factors such as peroxisome proliferator-activated receptor (PPAR) γ and C/EBPα. Moreover, the anti-adipogenic effect of orientin repressed the phosphorylation of Akt and subsequent phosphorylation of forkhead box protein O1 (FOXO1), which inhibits the transcription of the Ppar gene. These results indicate that a plant flavonoid orientin suppressed the expression of the Pparγ gene through repression of C/ebpδ expression and inhibition of the phosphoinositide 3-kinase /Akt-FOXO1 signaling in adipocytes.


Optogenetic Activation of Interneuron Subtypes Modulates Visual Contrast Responses of Mouse V1 Neurons.
Interneurons are critical for information processing in the cortex. In vitro optogenetic studies in mouse primary visual cortex (V1) have sketched the connectivity of a local neural circuit comprising excitatory pyramidal neurons and distinct interneuron subtypes that express parvalbumin (Pvalb+), somatostatin (SOM+), or vasoactive intestinal peptide (VIP+). However, in vivo studies focusing on V1 orientation tuning have ascribed discrepant computational roles to specific interneuron subtypes. Here, we sought to clarify the differences between interneuron subtypes by examining the effects of optogenetic activation of Pvalb+, SOM+, or VIP+ interneurons on contrast tuning of V1 neurons while also accounting for cortical depth and photostimulation intensity. We found that illumination of the cortical surface produced a similar spectrum of saturating additive photostimulation effects in all 3 interneuron subtypes, which varied with cortical depth rather than light intensity in Pvalb+ and SOM+ cells. Pyramidal cell modulation was well explained by a conductance-based model that incorporated these interneuron photostimulation effects.


The diagnostic and predictive validity of the Renfrew Bus Story.
Two studies are presented providing evidence indicating the diagnostic and predictive validity of the American version of The Renfrew Bus Story (J. Cowley & C. Glasgow, 1994). Thirty-two children with specific language impairment (SLI) and 32 children with typical language development participated in the first study to determine identification accuracy of The Renfrew Bus Story. A second study of 12 children with SLI participated in a 3-year longitudinal study that was used to gather evidence of the predictive validity of The Renfrew Bus Story. The combined Information and Length scores of The Renfrew Bus Story yielded adequate (84%) sensitivity but weak (78%) specificity, making it an inappropriate tool for identifying children with language impairment or typical language development. Moderate to high correlations were found between The Renfrew Bus Story scores and nearly all scores from language tests administered 3 years later. The evidence supports the use of The Renfrew Bus Story as an indicator of future language performance for children with SLI. However, its performance as a measure for identifying impairments during the preschool years is somewhat weaker due to overidentification of typically developing children, and in particular minority children, as having poor narrative skills.


Role of computed tomography angiography in detection and staging of small bowel carcinoid tumors.
Small-bowel carcinoid tumors are the most common form (42%) of gastrointestinal carcinoids, which by themselves comprise 70% of neuroendocrine tumors. Although primary small bowel neoplasms are overall rare (3%-6% of all gastrointestinal neoplasms), carcinoids still represent the second most common (20%-30%) primary small-bowel malignancy after small bowel adenocarcinoma. Their imaging evaluation is often challenging. State-of-the-art high-resolution multiphasic computed tomography together with advanced postprocessing methods provides an excellent tool for their depiction. The manifold interactive parameter choices however require knowledge of when to use which technique. Here, we discuss the imaging appearance and evaluation of duodenal, jejunal and ileal carcinoid tumors, including the imaging features of the primary tumor, locoregional mesenteric nodal metastases, and distant metastatic disease. A protocol for optimal lesion detection is presented, including the use of computed tomography enterography, volume acquisition, computed tomography angiography and three-dimensional mapping. Imaging findings are illustrated with a series of challenging cases which illustrate the spectrum of possible disease in the small bowel and mesentery, the range of possible appearances in the bowel itself on multiphase data and extraluminal findings such as the desmoplastic reaction in mesentery and hypervascular liver metastases. Typical imaging pitfalls and pearls are illustrated.


A psychophysiological investigation of emotion regulation in chronic severe posttraumatic stress disorder.
There have been few direct examinations of the volitional control of emotional responses to provocative stimuli in PTSD. To address this gap, an emotion regulation task was administered to 27 Operation Enduring Freedom/Operation Iraqi Freedom combat veterans and 23 healthy controls. Neutral and aversive photographs were presented to participants who did or did not employ emotion regulation strategies. Objective indices included corrugator electromyogram, the late positive potential, and the electrocardiogram. On uninstructed trials, participants with PTSD exhibited blunted cardiac reactivity rather than the exaggerated cardioacceleratory responses seen in trauma cue reactivity studies. On interleaved regulation trials, no measure evidenced group differences in voluntary emotion regulation. Persons with PTSD may not differ from normals in their capacity to voluntarily regulate normative emotional responses to provocative stimuli in the laboratory, though they may nevertheless respond differentially on uninstructed trials and endorse symptoms of dyscontrol pathognomonic of the disorder outside of the laboratory.


Experience of switching from a traditional sitting workstation to a sit-stand workstation in sedentary office workers.
Prolonged sedentary time (ST) is associated with adverse health outcomes, while decreasing ST improves health outcomes. The use of sit-stand desks (SSDs) in workplaces has been proposed as a means of reducing ST. The purpose of this study was to gain knowledge about participants' experience and perceptions of a workplace intervention involving the introduction of SSDs. Focus groups and interviews were conducted with 28 study participants who used SSDs for 4 weeks. Data were analyzed using a grounded theory approach. Participants reported a high level of satisfaction with the SSDs and 96% chose to use them permanently. Participants experienced greater energy and alertness at work and reported increased face-to-face interaction with coworkers. Lack of work-surface space was the most significant problem with the use of SSDs. There was no perception of decreased productivity or reduced workplace privacy among participants.


Impact evaluation of the routine hepatitis B vaccination program of infants in China.
To evaluate the impact of the routine hepatitis B vaccination program of infants in China. The incidence of new hepatitis B infection and coverage with three doses of the vaccines by age groups and provinces were derived from the National Network Direct Report System of Infectious Disease during 2004-10. Chi square test and Pearson correlation analysis were used to analyze differences in incidence according to vaccination coverage and the relationship between the coverage with three doses and the incidence in different provinces. The incidence of new infection was 8.96/100 000 among children with complete coverage (0-15 years old), which was significantly lower than that with partial or no coverage. Among 0-9-year-old children in 2010, the incidence of new infection was 6.36/100 000, which was significantly lower than 2004. Considering the impact of vaccination on cumulative incidence among 0-5-year-old children, a 2.2-fold greater incidence of new infection was observed in provinces with the lowest to the highest vaccination rate. The impact of the routine hepatitis B vaccination program of infants in China has become more apparent over time. Program implementation and regional disequilibrium should be payed attention to as well as the expanded program.


Lattice sum for a hexagonal close-packed structure and its dependence on the c/a ratio of the hexagonal cell parameters.
We continue the work by Lennard-Jones and Ingham, and later by Kane and Goeppert-Mayer, and present a general lattice sum formula for the hexagonal close packed (hcp) structure with different c/a ratios for the two lattice parameters a and c of the hexagonal unit cell. The lattice sum is expressed in terms of fast converging series of Bessel functions. This allows us to analytically examine the behavior of a Lennard-Jones potential as a function of the c/a ratio. In contrast to the hard-sphere model, where we have the ideal ratio of c/a=sqrt[8/3] with 12 kissing spheres around a central atom, we observe the occurrence of a slight symmetry-breaking effect and the appearance of a second metastable minimum for the (12,6) Lennard-Jones potential around the ratio c/a=2/3. We also show that the analytical continuation of the (n,m) Lennard-Jones potential to the domain n,m<3 such as the Kratzer potential (n=2,m=1) gives unphysical results.


Production of ethanol by Clostridium thermosaccharolyticum: I. Effect of cell recycle and environmental parameters.
The direct microbial conversion (DMC) process for the production of ethanol from lignocellulosic biomass is limited by low volumetric ethanol production rates due to the low cell densities of Clostridium thermosaccharolyticum which is a key organism for ethanol production in this process. Hence, this study focuses on the use of a continuous- culture cell recycle system to improve the volumetric ethanol productivity and yield of the fermentation of xylose by C. thermosaccharolyticum. Early experiments with the continuous-culture cell recycle system showed a two-fold improvement in volumetric ethanol productivity. However, the ethanol yield at the higher dilution rates suffered because of the large amount of lactate produced. The manipulation of two environmental parameters--iron concentration in the nutrient medium and the N(2) purge rate of the fermentor headspace--allowed a dramatic reduction in the lactate production and a simultaneous improvement in the ethanol titer and yield. Under the improved conditions of increased iron concentration (12.5 mg/L FeSO(4) x 7H(2)O) and decreased N(2) purge rate (0.1 L/min), a continuous culture of C. thermosaccharolyticum operating at a dilution rate of 0.24 h(-1) and 50% cell recycle produced 8.6 g/L ethanol and less than 1 g/L each of acetate and lactate. The volumetric ethanol productivity was 2.2 g/L/h, which is 8 times larger than obtained for a continuous culture operated with no cell recycle and the same specific growth rate.


Safety and Efficacy of Immediate Rotational Atherectomy in Nondilatable Calcified Coronary Lesions Complicated by Coronary Artery Dissection (RAISE).
To examine the safety and efficacy of immediate rotational atherectomy (RA) in nondilatable calcified coronary lesions complicated by coronary dissection during percutaneous coronary intervention (PCI). In the presence of coronary dissection in nondilatable calcified coronary lesions, conservative management is suggested to permit the dissection to heal prior to treatment with RA. However, many patients have frequent angina attacks and some patients develop serious complications during this period. One hundred and nighty-eight patients with severe coronary calcification underwent PCI, and were randomized into immediate (n = 105) or delayed RA group (n = 93) when coronary dissections occur. The primary endpoint of the present study was all-cause death including cardiac and non-cardiac death in 4 years follow-up. Non-fatal myocardial infarction, stent thrombosis, cardiac tamponade, stroke, target lesion revascularization, New York Heart Association (NYHA) class IV heart failure were analyzed as secondary end points. At a follow-up of 4 years, event-free survival rates were not statistically different between the immediate and delayed RA group (81.9% vs 80.6%, P = 0.820). Rates of PCI- and RA-related major adverse cardiac events (MACE) and severe RA-related complications were not statistically different between groups. Luminal loss was not significantly different between the immediate and delayed RA group as evaluated by Intravascular ultrasound (IVUS). Two cases in the delayed RA group experienced myocardial infarction during the 4-week waiting. This study indicates that immediate RA during PCI is safe and effective in patients with coronary artery dissection.


Factors influencing parent reports on quality of life for children with asthma.
Children and parents often differ in their perceptions of a complex disease such as asthma. This ancillary study of children with mild to moderate asthma that was conducted at four of the eight clinics in the Childhood Asthma Management Program had two aims: (1) to relate quality of life to asthma symptoms, sociodemographic characteristics, child psychosocial adjustment and family social support and (2) to relate agreement between child- and parent-reported quality of life to child age. For this study participants completed the Caregiver's Pediatric Asthma Quality of Life Questionnaire (C-PAQLQ), Pediatric Asthma Quality of Life Questionnaire, and a battery of psychosocial health outcomes questionnaires at the 12-month follow-up. The average asthma symptom score from diary cards for the 2 weeks before the visit was also collected. Parent-reported family burden was the strongest correlate of C-PAQLQ scores. Although the average asthma symptom score was not associated with parent-reported quality of life, the study had low power to detect a relationship because of the few episodes of asthma reported during the assessment period. The correlation between child and parent reported quality of life improved with increasing age of the child, suggesting increased child-parent agreement about quality of life outcomes was associated with increasing age of the child. Family characteristics, such as degree of cohesion among family members, are not associated with quality of life ratings.


The positioning of the asymmetric septum during sporulation in Bacillus subtilis.
Probably one of the most controversial questions about the cell division of Bacillus subtilis, a rod-shaped bacterium, concerns the mechanism that ensures correct division septum placement-at mid-cell during vegetative growth but closer to one end during sporulation. In general, bacteria multiply by binary fission, in which the division septum forms almost exactly at the cell centre. How the division machinery achieves such accuracy is a question of continuing interest. We understand in some detail how this is achieved during vegetative growth in Escherichia coli and B. subtilis, where two main negative regulators, nucleoid occlusion and the Min system, help to determine the division site, but we still do not know exactly how the asymmetric septation site is determined during sporulation in B. subtilis. Clearly, the inhibitory effects of the nucleoid occlusion and Min system on polar division have to be overcome. We evaluated the positioning of the asymmetric septum and its accuracy by statistical analysis of the site of septation. We also clarified the role of SpoIIE, RefZ and MinCD on the accuracy of this process. We determined that the sporulation septum forms approximately 1/6 of a cell length from one of the cell poles with high precision and that SpoIIE, RefZ and MinCD have a crucial role in precisely localizing the sporulation septum. Our results strongly support the idea that asymmetric septum formation is a very precise and highly controlled process regulated by a still unknown mechanism.


Performance of a hybrid MC dose algorithm for IMRT optimization dose evaluation.
This paper presents a hybrid intensity modulated radiation therapy (IMRT) optimization strategy which combines the speed of pencil beam (PB) and the accuracy of Monte Carlo (MC) dose calculations. After an initial deliverable-based optimization using a PB algorithm, doses are recomputed using the VMC++ MC code to determine dose correction factors, which are then utilized during further PB-based optimization. The hybrid method is benchmarked with respect to full MC deliverable-based optimization for ten prostate and ten head-and-neck IMRT plans. Final optimized plans are compared in terms of dose-volume indices used for the plan optimization. Dose prediction errors (DPEs) and optimization convergence errors (OCEs) at intermediate steps of the hybrid sequence are evaluated. The hybrid method is found to produce optimized plans that are clinically equivalent to full MC-based optimization, yet requires only 40% of the number of MC dose calculations. With the hybrid strategy presented here, MC-based optimization results are achieved in 35 min or less on a modest computing cluster. While the initial PB-deliverable-based optimization is found to have DPEs and OCEs of up to 3 Gy relative to the 65-73 Gy prescription doses, application of the first MC correction reduces the average DPEs to less than 0.3 Gy for the prostate plans and less than 0.06 Gy for the head and neck plans. The maximum observed DPE or OCE is 0.7 Gy after 1 MC dose correction, indicating that a single MC dose calculation correction might be sufficient for IMRT optimization.


[Alcohol intoxicated female drivers in Schleswig-Holstein between 1977 and 1987].
This paper reports data on frequency of blood alcohol analyses of female drivers between the years 1977-1987 in Schleswig-Holstein, Germany, West. A comparison between the male and female drivers during the same period is made. Since the year 1980 the increase of traffic offences as well as general rise of other offences by alcoholized females was observed. Statistical data refering to day, hour, reason for the taking of blood sample, possible influence of taking medicaments and illness have been evaluated.


[Principal component analysis on ultrasound indexes of schistosomiasis and the assessment on prevalence rate].
To explore the synthetical index for diagnosing schistosomiasis with ultrasound and to assess the prevalence rate with the index. Ultrasound indexes of schistosomiasis Japonicum were analyzed by principal component analysis, and the synthetical indexes were assessed by ROC curve. Among the abnormal rates of the 6 indexes, the lowest was 1.6% comparing with the highest of 59.5%. Significant difference was noficed among the abnormal rates (chi(2) = 631.1, P < 0.01). The individual correlation of the six indexes to each other as will as with age distribution was significant (P < 0.05). The three principal components reflected the degree of pathological changes on liver and spleen. The first principal component was the factor reflecting the degree of liver pathological changes, and the second and third principal components reflected the degree of pathological changes on spleen. The synthetical index D(1) = 0.047X(1) + 0.428X(2) + 1.247X(3) + 0.095X(4) + 0.002X(5) + 0.213X(6) - 12.837 was found by adding the three weight principal components, and it's area under the ROC curve was 0.957. When -1.70 was taken as the critical value, the abnormal rate of population was 66.3%, close to the resident's actual prevalence rate 66.9%. Ultrasonography was considered as a method which could rapidly assessing the resident's prevalence rate in the endemic areas of schisitosomiasis Japonicum, and could also provide powerful information for development of strategy on chemotherapy.


Against the odds: unlikely COVID-19 recovery.
We present a 67-year-old male, with palliative hypopharyngeal squamous cell carcinoma, who contracted COVID-19 infection while in hospital. Cancer diagnosis, among other clinical features, increases the risk of poor outcome of COVID-19 infection. A recently validated risk calculator (COVID-GRAM) can help to guide prognosis. COVID-19 infection caused significant clinical deterioration in this patient. A Treatment Escalation Plan of ward-based care was put in place and the palliative care team involved. The goal of care was comfort. The patient improved clinically and retested negative for COVID-19. He was discharged to a nursing home for ongoing supportive care of his malignancy. The validated COVID-GRAM calculator predicted a greater than 99% risk that this patient would require intensive therapy unit admission or die. This patient overcame significant physiological challenges to survive COVID-19, highlighting the challenges of prognostication and suggesting that palliation of COVID-19 is not detrimental to survival.


Future directions: anti-hormones in reproductive medicine.
Anti-hormones are important in reproductive medicine because they are useful tools that teach us about the normal physiological actions of hormones. They also provide effective therapies to control or treat a variety of pathogenic processes. We expect that the future repertoire of anti-hormones will include the paracrine and autocrine regulators of specific cell functions, in addition to the endocrine systems described here. The availability of recombinant DNA expression systems for an ever larger portion of the human genome will surely accelerate the development of novel anti-hormones.


TcR-α recombinations in renal cell carcinoma exome files correlate with an intermediate level of T-cell exhaustion biomarkers.
Renal cell carcinoma exome-derived, V(D)J recombination reads had an elevated presence and variability, for both TcR-α and -β, when compared to marginal tissue, reflecting an opportunity to assess tumor immunogenicity by comparison with marginal tissue T cells. PD-1, PD-L2, CTLA4 and FOXP3, all of which are implicated in the evasion of an anti-tumor immune response, had a significantly higher expression for samples representing co-detection of productive TcR-α and -β recombination reads. Samples representing tumors with productive TcR-α recombination reads but no detectable, productive TcR-β recombination reads, reflected a 20% survival advantage, and RNASeq data indicated an intermediate level of immune checkpoint gene expression for those samples. These results raise the question of whether relatively high levels of detection of productive TcR-α recombination reads, in comparison with detection of reads representing the TcR-β gene, identify a microenvironment that has not yet entered a T-cell exhaustion phase and may thereby represent conditions for immune enhancements that do not require anti-immune checkpoint therapies.


Isolation and characterization of a cold-active, alkaline, detergent stable α-amylase from a novel bacterium Bacillus subtilis N8.
A cold-active alkaline amylase producer Bacillus subtilis N8 was isolated from soil samples. Amylase synthesis optimally occurred at 15°C and pH 10.0 on agar plates containing starch. The molecular weight of the enzyme was found to be 205 kDa by performing SDS-PAGE. While the enzyme exhibited the highest activity at 25°C and pH 8.0, it was highly stable in alkaline media (pH 8.0-12.0) and retained 96% of its original activity at low temperatures (10-40°C) for 24 hr. While the amylase activity increased in the presence of β-mercaptoethanol (103%); Ba2+, Ca2+, Na+, Zn2+, Mn2+, H2O2, and Triton X-100 slightly inhibited the activity. The enzyme showed resistance to some denaturants: such as SDS, EDTA, and urea (52, 65, and 42%, respectively). N8 α-amylase displayed the maximum remaining activity of 56% with 3% NaCl. The major final products of starch were glucose, maltose, and maltose-derived oligosaccharides. This novel cold-active α-amylase has the potential to be used in the industries of detergent and food, bioremediation process and production of prebiotics.


An outbreak of food-borne gastroenteritis due to sapovirus among junior high school students.
The human sapovirus (SaV) causes acute gastroenteritis mainly in infants and young children. A food-borne outbreak of gastroenteritis associated with SaV occurred among junior high school students in Yokohama, Japan, during and after a study trip. The nucleotide sequences of the partial capsid gene derived from the students exhibited 98% homology to a SaV genogroup IV strain, Hu/Angelholm/SW278/2004/SE, which was isolated from an adult with gastroenteritis in Solna, Sweden. An identical nucleotide sequence was detected from a food handler at the hotel restaurant, suggesting that the causative agent of the outbreak was transmitted from the food handler. This is the first description of a food-borne outbreak associated with the SaV genogroup IV strain in Japan.


Yeast can accommodate phosphotyrosine: v-Src toxicity in yeast arises from a single disrupted pathway.
Tyrosine phosphorylation is a key biochemical signal that controls growth and differentiation in multicellular organisms. Saccharomyces cerevisiae and nearly all other unicellular eukaryotes lack intact phosphotyrosine signaling pathways. However, many of these organisms have primitive phosphotyrosine-binding proteins and tyrosine phosphatases, leading to the assumption that the major barrier for emergence of phosphotyrosine signaling was the negative consequences of promiscuous tyrosine kinase activity. In this work, we reveal that the classic oncogene v-Src, which phosphorylates many dozens of proteins in yeast, is toxic because it disrupts a specific spore wall remodeling pathway. Using genetic selections, we find that expression of a specific cyclic peptide, or overexpression of SMK1, a MAP kinase that controls spore wall assembly, both lead to robust growth despite a continuous high level of phosphotyrosine in the yeast proteome. Thus, minimal genetic manipulations allow yeast to tolerate high levels of phosphotyrosine. These results indicate that the introduction of tyrosine kinases within single-celled organisms may not have been a major obstacle to the evolution of phosphotyrosine signaling.


[The cytokine network in multiple myeloma].
The authors review contemporary findings on the role of different components of the cytokine network from the aspect of development, prognosis and treatment of multiple myeloma. Greatest attention was devoted to the main growth factor of myeloma elements IL-6, but also to the real or so far sparsely elucidated role of other cytokines (IL-1, IL-2, GM-CSF, G-CSF, IL-3, IL-4, IL-5, IL-10, TNF, interferon alpha and gamma) under conditions in vitro and in vivo. For completeness sake the authors did not omit the problem of the soluble receptor of IL-2 and the role of TNF, TNF beta and in particular IL-1 beta in the pathogenesis of osteolytic lesions and the potential therapeutic role of antibodies against IL-6 (anti IL-6 mab) and interferon alpha and gamma.


Light stimulation of active transport in Hydrodictyon africanum.
The mechanism of light stimulation of active K and Cl influx and active Na efflux, in Hydrodictyon africanum has been investigated using different wavelengths of red light and different gas mixtures, and the inhibitors DCMU and CCCP. The active Cl influx requires photosystem 2, since its relative quantal efficiency falls with increasing wavelength of red light, and it is as sensitive to the inhibitor DCMU as is photosynthesis; it is relatively insensitive to the uncoupler CCCP. The active K influx and active Na efflux are inhibited by CCCP, but the relative quantal efficiency of these processes increases with increasing wavelength of red light, and they are relatively insensitive to DCMU. These cation fluxes can be supported by cyclic photophosphorylation, whereas Cl influx needs photosystem 2 but probably not ATP.


Performance evaluation of transcriptomics data normalization for survival risk prediction.
One pivotal feature of transcriptomics data is the unwanted variations caused by disparate experimental handling, known as handling effects. Various data normalization methods were developed to alleviate the adverse impact of handling effects in the setting of differential expression analysis. However, little research has been done to evaluate their performance in the setting of survival outcome prediction, an important analysis goal for transcriptomics data in biomedical research. Leveraging a unique pair of datasets for the same set of tumor samples-one with handling effects and the other without, we developed a benchmarking tool for conducting such an evaluation in microRNA microarrays. We applied this tool to evaluate the performance of three popular normalization methods-quantile normalization, median normalization and variance stabilizing normalization-in survival prediction using various approaches for model building and designs for sample assignment. We showed that handling effects can have a strong impact on survival prediction and that quantile normalization, a most popular method in current practice, tends to underperform median normalization and variance stabilizing normalization. We demonstrated with a small example the reason for quantile normalization's poor performance in this setting. Our finding highlights the importance of putting normalization evaluation in the context of the downstream analysis setting and the potential of improving the development of survival predictors by applying median normalization. We make available our benchmarking tool for performing such evaluation on additional normalization methods in connection with prediction modeling approaches.


Synthesis, anti-HIV activity, and metabolic stability of new alkenyldiarylmethane HIV-1 non-nucleoside reverse transcriptase inhibitors.
Non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) are part of the combination therapy currently used to treat HIV infection. Based on analogy with known HIV-1 NNRT inhibitors, 18 novel alkenyldiarylmethanes (ADAMs) containing 5-chloro-2-methoxyphenyl, 3-cyanophenyl, or 3-fluoro-5-trifluoromethylphenyl groups were synthesized and evaluated as HIV inhibitors. Their stabilities in rat plasma have also been investigated. Although introducing 5-chloro-2-methoxyphenyl or 3-fluoro-5-trifluoromethylphenyl groups into alkenyldiarylmethanes does not maintain the antiviral potency, the structural modification of alkenyldiarylmethanes with a 3-cyanophenyl substituent can be made without a large decrease in activity. The oxazolidinonyl group was introduced into the alkenyldiarylmethane framework and found to confer enhanced metabolic stability in rat plasma.


Variation in passing standards for graduation-level knowledge items at UK medical schools.
Given the absence of a common passing standard for students at UK medical schools, this paper compares independently set standards for common 'one from five' single-best-answer (multiple-choice) items used in graduation-level applied knowledge examinations and explores potential reasons for any differences. A repeated cross-sectional study was conducted. Participating schools were sent a common set of graduation-level items (55 in 2013-2014; 60 in 2014-2015). Items were selected against a blueprint and subjected to a quality review process. Each school employed its own standard-setting process for the common items. The primary outcome was the passing standard for the common items by each medical school set using the Angoff or Ebel methods. Of 31 invited medical schools, 22 participated in 2013-2014 (71%) and 30 (97%) in 2014-2015. Schools used a mean of 49 and 53 common items in 2013-2014 and 2014-2015, respectively, representing around one-third of the items in the examinations in which they were embedded. Data from 19 (61%) and 26 (84%) schools, respectively, met the inclusion criteria for comparison of standards. There were statistically significant differences in the passing standards set by schools in both years (effect sizes (f2 ): 0.041 in 2013-2014 and 0.218 in 2014-2015; both p < 0.001). The interquartile range of standards was 5.7 percentage points in 2013-2014 and 6.5 percentage points in 2014-2015. There was a positive correlation between the relative standards set by schools in the 2 years (Pearson's r = 0.57, n = 18, p = 0.014). Time allowed per item, method of standard setting and timing of examination in the curriculum did not have a statistically significant impact on standards. Independently set standards for common single-best-answer items used in graduation-level examinations vary across UK medical schools. Further work to examine standard-setting processes in more detail is needed to help explain this variability and develop methods to reduce it.


Estrogen and estrogen receptor signaling promotes allergic immune responses: Effects on immune cells, cytokines, and inflammatory factors involved in allergy.
Hypersensitivity occurs when the body is stimulated by an antigen, resulting in an immune response, and leads to a physiological disorder or abnormal tissue trauma. Various immune cells, cytokines, and inflammatory mediators are involved in the immune responses related to allergic diseases, which are the core of anaphylaxis. Estrogen receptors are widely distributed in immune cells, which combine with estrogen and participate in allergic responses by affecting immune cells, cytokines, and inflammatory factors. We aimed to summarize the association between estrogen and allergic reactions to provide a scientific basis for understanding and studying the mechanisms of allergic diseases.


Baculovirus display strategies: Emerging tools for eukaryotic libraries and gene delivery.
Recombinant baculoviruses have been extensively used as vectors for abundant expression of a large variety of foreign proteins in insect cell cultures. The appeal of the system lies essentially in easy cloning techniques and virus propagation combined with the eukaryotic post-translational modification machinery of the insect cell. Recently, a novel molecular biology tool was established by the development of baculovirus surface display, using different strategies for presentation of foreign peptides and proteins on the surface of budded virions. This eukaryotic display system enables presentation of large complex proteins on the surface of baculovirus particles and has thereby become a versatile system in molecular biology. Surface display strategies play an important role, as they may be used to enhance the efficiency and specificity of viral binding and entry to mammalian cells. In addition, baculovirus surface display vectors have been engineered to contain mammalian promoter elements designed for gene delivery both in vitro and in vivo. Moreover, baculovirus capsid display has recently been developed; this holds promise for intracellular targeting of the viral capsid and subsequent cytosolic delivery of desired protein moieties. Finally, the viruses can accommodate large insertions of foreign DNA and replicate only in insect cells. Together, these are attributes that are very likely to make them important tools in functional genomics and proteomics.


Fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder.
Fragmentary myoclonus is a result of muscle activity consisting of brief potentials in surface electromyography during polysomnography. Excessive fragmentary myoclonus is defined by increased intensity of the potentials. A few studies report excessive fragmentary myoclonus occurrence in neurodegenerative diseases. Because idiopathic rapid eye movement sleep behaviour disorder is considered as an early stage of neurodegeneration with involvement of the brainstem, we charted the prevalence and quantified the intensity of excessive fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder. Twenty-nine patients (one woman, 28 men, mean age 68 years, SD 6.2) and 29 controls (two women, 27 men, mean age 65.6 years, SD 8.6) underwent polysomnography. Fragmentary myoclonus potentials were identified and counted according to internationally used criteria. Fragmentary myoclonus intensity was quantified by the fragmentary myoclonus index. Excessive fragmentary myoclonus was diagnosed in 75.9% (22 subjects) in idiopathic rapid eye movement sleep behaviour disorder, while in 34.5% (10 subjects) among the controls (p = 0.003). Quantitative analysis showed a wide-range fragmentary myoclonus index in idiopathic rapid eye movement sleep behaviour disorder (4.0-632.4; median 60.7) and in the controls (0.8-938.1; median 34.3). The overall difference in fragmentary myoclonus index was not significant between the groups; however, patients with idiopathic rapid eye movement sleep behaviour disorder showed trends for higher fragmentary myoclonus index scores in wakefulness (p = 0.027), N1 (p = 0.032), N3 (p = 0.046) and R (p = 0.007). Fragmentary myoclonus index does not correlate with age, idiopathic rapid eye movement sleep behaviour disorder duration or R stage atonia deficiency. The prevalence of excessive fragmentary myoclonus is higher in idiopathic rapid eye movement sleep behaviour disorder compared with the controls, so fragmentary myoclonus should be taken into account in future research of rapid eye movement sleep behaviour disorder and motor control in sleep.


The global phylogeny of glycolytic enzymes.
Genes encoding the glycolytic enzymes of the facultative endocellular parasite Bartonella henselae have been analyzed phylogenetically within a very large cohort of homologues from bacteria and eukaryotes. We focus on this relative of Rickettsia prowazekii along with homologues from other alpha-proteobacteria to determine whether there have been systematic transfers of glycolytic genes from the presumed alpha-proteobacterial ancestor of the mitochondrion to the nucleus of the early eukaryote. The alpha-proteobacterial homologues representing the eight glycolytic enzymes studied here tend to cluster in well-supported nodes. Nevertheless, not one of these alpha-proteobacterial enzymes is related as a sister clade to the corresponding eukaryotic homologues. Nor is there a close phylogenetic relationship between glycolytic genes from Eucarya and any other bacterial phylum. In contrast, several of the reconstructions suggest that there may have been systematic transfer of sequences encoding glycolytic enzymes from cyanobacteria to some green plants. Otherwise, surprisingly little exchange between the bacterial and eukaryotic domains is observed. The descent of eukaryotic genes encoding enzymes of intermediary metabolism is reevaluated.


Effects of oxodipine and nitrendipine on the size of experimental myocardial infarct in the rat.
The protective effect of either oxodipine or nitrendipine (4 mg/kg/twice daily, orally), two dihydropyridines exhibiting calcium channel-blocking properties, against induced infarct-like lesions was examined. Experimental myocardial infarct-like lesions were induced in rats by subcutaneous injection of isoproterenol (0.5 mg/kg). The lesions were mainly located in subendocardial areas of the free wall of the left ventricle, and were intramural at the apex and ventricular septum. Pretreatment with oxodipine significantly reduced the infarct size in the apical and basal myocardium (P < 0.05). Possible explanations for the lack of effect of nitrendipine pretreatment are discussed.


Trunk Muscle Strength After Lumbar Spine Fusion: A 12-Month Follow-up.
The aim of this study was to investigate changes in trunk muscle strength 12 months after lumbar spine fusion (LSF) compared to preoperative strength. A total of 194 patients (mean±standard deviation [SD] age, 61±21 years) who underwent LSF participated in this prospective longitudinal study. Physical measurements of the participants were made before surgery and 12 months postoperatively. Isometric trunk extension and flexion strength was measured using a strain-gauge dynamometer in the standing position. Strength changes were calculated. Regression analysis was performed to explore which factors predicted strength levels at 12 months postoperatively. The preoperative mean±SD extension strength was 205±144 N, which increased to 258±142 N (p<0.001) at the 12-month follow-up. Flexion strength increased from 295±172 N to 364±164 N (p<0.001). The preoperative extension/flexion strength ratio was 0.75±0.38 and remained similar (0.73±0.26) at 12 months postoperatively (p=0.39). Although trunk muscle strength increased by 26% for extension and 23% for flexion at the 12-month postoperative follow-up, both values remained objectively low. In addition, flexion strength remained higher than extension strength, which indicates an imbalance between those muscle groups. Age, severe back pain, and low trunk muscle strength before surgery predicted low trunk muscle strength at 1 year after spinal fusion.


Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy.
While daily intravaginal administration of 0.50% (6.5 mg) dehydroepiandrosterone (DHEA, prasterone) for 12 weeks has shown clinically and statistically significant effects on moderate to severe (MS) dyspareunia as the most bothersome symptom (MBS), the present study analyzes the effect of a reduced dosing regimen on MBS vaginal dryness. Daily intravaginal 0.50% prasterone for 2 weeks followed by twice weekly for 10 weeks versus placebo. Maximal beneficial changes in vaginal parabasal and superficial cells and pH were observed at 2 weeks as observed for intravaginal 10 μg estradiol (E2). This was followed by a decrease or lack of efficacy improvement after switching to twice-weekly dosing. The decrease in percentage of parabasal cells, increase in percentage of superficial cells and decrease in vaginal pH were all highly significant (p < 0.0001 to 0.0002 over placebo) at 12 weeks. In parallel, the statistical significance over placebo (p value) on MBS vaginal dryness at 6 weeks was 0.09 followed by an increase to 0.198 at 12 weeks. For MBS dyspareunia, the p value of 0.008 at 6 weeks was followed by a p value of 0.077 at 12 weeks, thus illustrating a decrease of efficacy at the lower dosing regimen. The improvements of vaginal secretions, color, epithelial integrity and epithelial surface thickness were observed at a p value < 0.01 or 0.05 over placebo at 2 weeks, with a similar or loss of statistical difference compared to placebo at later time intervals. No significant adverse event was observed. Vaginal discharge related to the melting of Witepsol was reported in 1.8% of subjects. The present data show that daily dosing with 0.50% DHEA for 2 weeks followed by twice-weekly dosing is a suboptimal treatment of the symptoms/signs of vulvovaginal atrophy resulting from a substantial loss of the efficacy achieved at daily dosing.


Correlation of the corneal toricity between anterior and posterior corneal surfaces in the normal human eye.
To evaluate the correlation of the magnitude of corneal toricity and power vector components of both corneal surfaces measured with a Scheimpflug photography-based system. A total of 117 healthy normal eyes of 117 subjects selected randomly with ages ranging from 7 to 80 years were included. All eyes received an anterior segment and corneal analysis with the Sirius system (CSO) evaluating the anterior and posterior mean toricity for 3 and 7 mm (aAST and pAST). The vector components J0 and J45 as well as the overall strength blur (B) were calculated for each keratometric measurement using the procedure defined by Thibos and Horner. The coefficient of correlation between aAST and pAST was 0.52 and 0.62 and the mean anteroposterior ratio for toricity was 0.46 ± 0.39 and 0.57 ± 0.75 for 3 and 7 mm, respectively. These ratios correlated significantly with aAST, anterior corneal J0, and manifest refraction J0 (r ≥ 0.39, P < 0.01). The coefficient of correlation was 0.69 and 0.81 between anterior and posterior J0 for 3 and 7 mm, respectively. For J45, the coefficients were 0.62 and 0.71, respectively. The linear regression analysis revealed that the pAST and power vectors could be predicted from the anterior corneal data (R2 ≥ 0.40, P < 0.01). The toricity and astigmatic power vector components of the posterior corneal surface in the human healthy eye are related to those of the anterior and therefore can be predicted consistently from the anterior toricity and astigmatic power vectors.


Risk of hypertension with ramucirumab-based therapy in solid tumors: data from a literature based meta-analysis.
Ramucirumab is a monoclonal antibody against Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) approved for the treatment of several solid tumours. As shown in recent trials results, new-onset hypertension is one of the most frequent adverse events associated with ramucirumab therapy. Recent studies looked at the quantification of the risk of hypertension in patients receiving other anti-angiogenesis medications. We conducted a meta-analysis of randomized clinical trials with the aim to investigate the incidence and quantify the risk of new-onset hypertension of any grade in patients treated with ramucirumab. Our research suggests that hypertension is frequently associated with ramucirumab therapy, with an OR of 3.60 for any grade of hypertension and an even stronger correlation with grade 3-4 hypertension (OR 4.16). These data suggest that a strict monitoring, as well as early intervention protocols, are recommended in patients receiving the drug.


Electrophoretic profiling of both RNA and protein from a single 250-pL sample.
A novel approach is described that uses capillary electrophoresis (CE) to electrophoretically sample and separate both protein and RNA from a single injected plug of cell lysate. A 250-pL sample of lysate from Chinese hamster ovary cells (9.6 x 10(7) cells/mL) was hydrodynamically injected into a capillary containing a Tris-based aqueous buffer. This was followed by selective electrokinetic ejection of RNA from the lysate into water, yielding an effective cell concentration of RNA of 3000 cells/mL. The cellular components (e.g., proteins) retained in the capillary were separated and then detected with laser-induced fluorescence (LIF) using 275-nm excitation. The ejected/diluted sample was subsequently injected into a separate CE-LIF system, which utilized an entangled polymer sieving matrix and 543-nm excitation for the detection of ethidium bromide-labeled nucleic acids (i.e., RNA). Virtually no sample preparation is required other than simple washing and lysing of the cells isolated from culture. This combined approach can be easily modified for the detection of any analyte through adjustment of CE-HF conditions. In addition, it provides an effective method for desalting cellular RNA samples having complex matrixes, which results in improved RNA injection efficiency and a 7600-fold effective signal enhancement over total lysate injection.


Molecular Subtypes of High-Grade Neuroendocrine Carcinoma (HGNEC): What is YAP1-Positive HGNEC?
Small cell lung cancer (SCLC) subtype classification, based on high-level expression of key transcriptional regulators; ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y), has recently been proposed. YAP1 (and POU2F3) has attracted attention as an important factor for non-neuroendocrine (non-NE) phenotypic subtyping of SCLC. However, subsequent studies reported that YAP1 expression alone cannot define a single group in primary SCLC, which makes it difficult to understand what SCLC-Y is by focusing only on SCLC. In this review, we concluded that YAP1 is an essential anti-neuroendocrine factor in both SCLC and non-small cell lung cancer (NSCLC) based on previous studies, including our own analysis of the cell lines and primary tumors of SCLC and NSCLC. The classification of SCLC-Y is a concept mainly established from the analysis of cell lines, and SCLC-Y cell lines correspond to "variant type" SCLC cell lines. Primary SCLC and large cell neuroendocrine carcinoma (LCNEC) are typically heterogeneous tumors composed mostly of NE-type cells, but they contain a small number of non-NE-type cells. Importantly, individual cells with NE features exhibit YAP1 loss, whereas the non-NE-type cells exhibit YAP1 expression. Although rare in primary SCLC, some cases of primary LCNEC have many YAP1-positive cells, which is correlated with chemotherapy resistance. YAP1 staining may be useful in the exclusion diagnosis of SCLC or in the selection of treatment for LCNEC.


A marketing model: applications for dietetic professionals.
Traditionally, dietitians have communicated the availability of their services to the "public at large." The expectation was that the public would respond favorably to nutrition programs simply because there was a consumer need for them. Recently, however, both societal and consumer needs have changed dramatically, making old communication strategies ineffective and obsolete. The marketing discipline has provided a new model and new decision-making tools for many health professionals to use to more effectively make their services known to multiple consumer groups. This article provides one such model as applied to the dietetic profession. The model explores a definition of the business of dietetics, how to conduct an analysis of the environment, and, finally, the use of both in the choice of new target markets. Further, the model discusses the major components of developing a marketing strategy that will help the practitioner to be competitive in the marketplace. Presented are strategies for defining and re-evaluating the mission of the profession, for using future trends to identify new markets and roles for the profession, and for developing services that make the profession more competitive by better meeting the needs of the consumer.


Biosynthesis of lycosantalonol, a cis-prenyl derived diterpenoid.
Terpenoid natural products are generally derived from isoprenyl diphosphate precursors with trans double-bond configuration, and no diterpenoid derived from the cisoid precursor (Z,Z,Z)-nerylneryl diphosphate (1) has yet been identified. Here further investigation of a terpenoid biosynthetic gene cluster from tomato is reported, which resulted in identification of a biosynthetic pathway from 1, in a pathway featuring a number of interesting transformations. Compound 1 is first cyclized to a tricyclene core ring structure analogous to that found in α-santalene, with the resulting diterpene termed here lycosantalene (2). Quantum chemical calculations indicate a role for the diphosphate anion coproduct in this cyclization reaction. Subsequently, the internal cis double bond of the neryl side chain in 2 is then further transformed to an α-hydroxy ketone moiety via an epoxide intermediate (3). Oxygen labeling studies indicate 3 undergoes oxidative conversion to lycosantalonol (4). Thus, in addition to elucidating the cisoid origins of 4, this work has further provided mechanistic insight into the interesting transformations required for its production.


Percutaneous aspiration and drainage of hydatid cysts in the liver.
Percutaneous aspiration of hydatid cysts of the liver was performed in 13 patients, and subsequent percutaneous drainage was performed in three of the 13. Aspiration was performed with ultrasound or computed tomographic guidance with 22-gauge to 19-gauge needles. Analysis of the aspirated specimen established the diagnosis of hydatid cysts in nine of the 13 patients. Fragments of the laminated membrane were seen in seven cases, scolices in two cases, and hooklets in two cases. In the four cases with negative results on aspiration, the diagnosis was established with surgical findings in one case and unequivocal immunologic results in three cases. In two patients, a mild allergic reaction with temporary pruritus was observed. In three patients, percutaneous drainage was performed with a 5-F to 8.3-F catheter, and sterilization of the cyst was achieved by injection of a scolicidal agent. No complications occurred at the time of drainage, and no recurrences developed during 6 months to 1 year after drainage.


Using angiographic parametric imaging-derived radiomics features to predict complications and embolization outcomes of intracranial aneurysms treated by pipeline embolization devices.
Pipeline embolization devices (PEDs) have gained widespread popularity in the treatment of intracranial aneurysms (IAs). However, precise predictors of treatment outcomes are still lacking. This study aimed to use angiographic parametric imaging (API)-derived radiomics features to explore whether biomarkers extracted from immediate postprocedural digital subtraction angiography (DSA) were associated with complications and embolization outcomes of IAs treated with PED without adjunctive coils. Radiomic features were extracted from postprocedural DSA by API, and radiomics feature selection and radiomics score calculation were performed by the least absolute shrinkage and selection operator (LASSO) logistic regression. Angiographic findings and clinical characteristics were screened using stepwise multivariable logistic regression analysis to identify significant variables for predicting the complication endpoint. Radiomics feature selection and radiomics risk score (RadRS) calculations were performed by LASSO Cox regression. Univariate and multivariate Cox regression analyses were used to identify significant predictors for the occlusion endpoint. We screened 281 observations for complications and 235 observations for embolization outcomes from IAs treated in our center using PED between June 2015 and July 2020. Multivariate regression analysis showed association of the radiomics score (p<0.01) and hypertension (p=0.04) with complications. RadRS (p<0.01), symptoms (p<0.01), and age (p=0.03) were predictors of embolization outcomes. Kaplan-Meier analysis revealed that symptomatic patients (p<0.01) and those with off-label IAs (p=0.03) had shorter intervals to complete occlusion. Biomarkers extracted from immediate postprocedural DSA by API could be potential indicators for assessing treatment outcomes of IAs treated by PED without adjunctive coils.


Regulation of the metabolism of pituitary nucleic acids in female rats.
Ovariectomy caused an increase in the metabolism of pituitary nucleic acids. This effect was reversed in vivo by a biphasic action of oestradiol-17 beta which first facilitated RNA metabolism after 8 h and then inhibited it 16 h after intraperitoneal injection. To analyse the origin of this biphasic effect the roles of LH releasing hormone (LH-RH) and hysterectomy were examined. Incorporation of uridine into the RNA of the anterior pituitary gland of female rats was inhibited both in vivo and in vitro by LH-RH. Hysterectomy augmented the increase in the RNA metabolism caused by ovariectomy whereas steroid-free uterine extracts inhibited the increase significantly. We have concluded that extrapituitary factors may be involved in the effects of oestrogen on the metabolism of pituitary nucleic acids.


Validity and Reliability of a Self-administered Food Frequency Questionnaire to Assess Vitamin K Intake in Korean Adults.
This study was conducted to validate a food frequency questionnaire (FFQ) to assess vitamin K intake in clinical and research settings based on data from the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V). We collected a subset of data on informative food items using the 24-hour recall method from adults aged 19 to 64 years from KNHANES V. The cumulative percent contribution and cumulative multiple regression coefficients for vitamin K intake from each food were computed. Twenty-five foods items were selected for the FFQ to assess vitamin K intake. The FFQ was validated against intakes derived from a 5-day food record (5DR) (n = 48). To assess the reliability of the FFQ, participants completed the self-administered FFQ (FFQ1) and a second FFQ (FFQ2) after a 6-month period (n = 54). Data were analyzed using Pearson's correlation coefficients, the cross-classification method, and Bland-Altman plots. Mean intakes were similar for vitamin K between the FFQ and dietary records, with significant correlations observed (r = 0.652), and cross-classification analyses demonstrated no major misclassification of participants into intake quartiles. Bland-Altman plots showed no serious systematic bias between the administrations of the two dietary assessment methods over the range of mean intakes. FFQ reliability was high, with a Pearson's correlation coefficient of 0.560. This pilot study shows promising validation and reliability evidence for the use of this FFQ, which is focused on vitamin K intake in adults, as an efficient screening tool in clinical and research settings.


Blocking cholesterol efflux mechanism is a potential target for antilymphoma therapy.
Cholesterol is an essential plasma membrane lipid for the maintenance of cellular homeostasis and cancer cell proliferation. Free cholesterol is harmful to cells; therefore, excessive free cholesterol must be quickly esterified by acetyl-coenzyme A:cholesterol acetyltransferase (ACAT) and exported by scavenger receptor class B member I (SR-BI) or ATP-binding cassette protein A1 from specific cells such as macrophage foam cells, which contain cholesteryl ester-derived vacuoles. Many vacuoles are present in the cytoplasm of Burkitt lymphoma cells. In this study, we observed that these vacuoles are often seen in high-grade lymphomas. Cell culture study using lymphoma cell lines found that esterified cholesterol is the main component of these vacuoles and the expression of cholesterol metabolism-related molecules was significantly upregulated in lymphoma cell lines, with SR-BI and ACAT inhibitors (BLT-1 and CI-976, respectively) impeding lymphoma cell proliferation. Cytoplasmic free cholesterol was increased by ACAT and SR-BI inhibitors, and the accumulation of free cholesterol induced lymphoma cell apoptosis by inducing endoplasmic reticulum stress. Furthermore, synergistic effects of SR-BI and ACAT inhibitors were observed in a preclinical study. Treatment with SR-BI inhibitor suppressed lymphoma progression in a tumor-bearing mouse model, whereas ACAT inhibitor did not. Therefore, SR-BI inhibitors are potential new antilymphoma therapeutics that target cholesterol metabolism.


Lymph transport in rat mesenteric lymphatics experiencing edemagenic stress.
To assess lymphatic flow adaptations to edema, we evaluated lymph transport function in rat mesenteric lymphatics under normal and increased fluid volume (edemagenic) conditions in situ. Twelve rats were infused with saline (intravenous infusion, 0.2 mL/min/100 g body weight) to induce edema. We intravitally measured mesenteric lymphatic diameter and contraction frequency, as well as lymphocyte velocity and density before, during, and after infusion. A 10-fold increase in lymphocyte velocity (0.1-1 mm/s) and a sixfold increase in flow rate (0.1-0.6 μL/min), were observed post infusion, respectively. There were also increases in contraction frequency and fractional pump flow one minute post infusion. Time-averaged wall shear stress increased 10 fold post infusion to nearly 1.5 dynes/cm(2) . Similarly, maximum shear stress rose from 5 to 40 dynes/cm(2) . Lymphatic vessels adapted to edemagenic stress by increasing lymph transport. Specifically, the increases in lymphatic contraction frequency, lymphocyte velocity, and shear stress were significant. Lymph pumping increased post infusion, though changes in lymphatic diameter were not statistically significant. These results indicate that edemagenic conditions stimulate lymph transport via increases in lymphatic contraction frequency, lymphocyte velocity, and flow. These changes, consequently, resulted in large increases in wall shear stress, which could then activate NO pathways and modulate lymphatic transport function.


Inhibition of intravascular mouse melanoma dissemination by recombinant human interferon alpha A/D.
The effects of pure recombinant human interferon alpha A/D (IFN alpha A/D) on natural killer (NK) activity and the experimental lung metastasis of B16-F10 melanoma were studied. Treatment of C57BL/6 mice with IFN alpha A/D augmented splenic NK activity and also inhibited the experimental lung metastasis of B16-F10 melanoma in a dose-dependent manner. The augmentation of NK activity and the inhibition of experimental lung metastasis by IFN alpha A/D were completely abolished in anti-asialo GM1-pretreated mice. These results suggested that the effector cells which inhibited melanoma metastasis in the present system were mainly NK cells, and that it was by activating NK cells that IFN alpha A/D had its effect. We next studied the timing of IFN alpha A/D administration for the most effective prevention of melanoma metastasis. The inhibitory effect of IFN alpha A/D was most pronounced when it was given 12 hr before or at the same time as melanoma inoculation. This suggested that melanoma cells were susceptible to NK cells only for a short period of time after intravascular invasion.


Acetylated Signal Transducer and Activator of Transcription 3 Functions as Molecular Adaptor Independent of Transcriptional Activity During Human Cardiogenesis.
Activation of signal transducer and activator of transcription 3 (STAT3) is imperative for mammalian development, specifically cardiogenesis. STAT3 phosphorylation and acetylation are key post-translational modifications that regulate its transcriptional activity. Significance of such modifications during human cardiogenesis remains elusive. Using human pluripotent stem cells to recapitulate cardiogenesis, two independently modified STAT3α (92 kDa) isoforms (phosphorylated and acetylated), which perform divergent functions were identified during cardiomyocyte (CM) formation. Phosphorylated STAT3α functioned as the canonical transcriptional activator, while acetylated STAT3α underwent caspase-3-mediated cleavage to generate a novel STAT3ζ fragment (∼45 kDa), which acted as a molecular adaptor integral to the ErbB4-p38γ signaling cascade in driving CM formation. While STAT3α knockdown perturbed cardiogenesis by eliminating both post-translationally modified STAT3α isoforms, caspase-3 knockdown specifically abrogates the function of acetylated STAT3α, resulting in limited STAT3ζ formation thereby preventing nuclear translocation of key cardiac transcription factor Nkx2-5 that disrupted CM formation. Our findings show the coexistence of two post-translationally modified STAT3α isoforms with distinct functions and define a new role for STAT3 as a molecular adaptor that functions independently of its canonical transcriptional activity during human cardiogenesis. Stem Cells 2017;35:2129-2137.