Expression and implication of toll-like receptors TLR2, TLR4 and TLR9 in colonic mucosa of patients with ulcerative colitis.
Toll-like receptors (TLRs) family may play important roles in inflammatory bowel disease. This study examined the expression of TLR2, TLR4 and TLR9 in the colonic tissues of patients with ulcerative colitis (UC) and explored their roles in the pathogenesis of UC. Colonic biopsies were taken from the colon of 30 patients with mild or moderate UC (at active phase) and 10 healthy controls during colonoscopy. TLR2, TLR4 and TLR9 protein expression levels were immunohistochemically detected. The mRNA expression levels of TLR2, TLR4 and TLR9 were assessed by reverse transcription polymerase chain reaction (RT-PCR). The disease activity index (DAI), colonoscopic and histologic grades and fecal microbial flora were determined. Histological examination showed that the intestinal mucous membrane of UC patients underwent acute inflammation changes. Immunohistochemistry exhibited that the expression levels of TLR2, TLR4 and TLR9 in colon epithelia and inflammatory cells were higher in UC patients than in control group (P<0.01). The mRNA expression levels of TLR2, TLR4 and TLR9 were increased in UC patients but were not detected in the normal controls. Expression levels of TLR2, TLR4 and TLR9 were positively correlated, and bore close correlation with DAI, colonoscopic and histologic grades and fecal microbial flora. An important mechanism of UC might be that abnormal activation of mucosal immunity by intestinal dysbacteriosis caused dysregulation of TLRS that mediates innate immunity.


Current issues in varicocele management: a review.
The most common cause of male infertility is varicocele, and varicocele is the most common correctable cause of male factor infertility. In this article we reviewed the concept of varicocele in terms of its diagnosis, method of treatment, indications for treatment, treatment outcomes, and prognostic factors. Physical examination is an essential diagnostic tool in the evaluation of a patient with a varicocele. However, as it depends on subjective findings, standardization of the physical examination method is needed. Various methods for treatment of varicocele exist, including open surgical, laparoscopic, microscopic surgical, and radiologic treatment such as embolization. Among these treatment approaches, microscopic inguinal or subinguinal varicocelectomy has superior outcomes, with a low complication rate. The influence of the treatment of varicocele on fertility is still a controversial issue and a difficult question to address, because there are limitations to performing a randomized control study, and previous studies had a heterogeneity of subjects and high dropout rate. However, there is robust evidence that varicocelectomy improves semen parameters as a surrogate marker of the potential for fertility. To date, general indications for treatment of varicocele are limited in patients with proven infertility, clinical palpable varicocele, and abnormal semen characteristics. Recently, it was shown that some symptoms other than infertility could be an indication for varicocelectomy because these symptoms are frequently related to deterioration of semen parameters. Varicocele in the adolescent presents a more difficult decision regarding whether to treat. A testicular size discrepancy of more than 20% is helpful for treatment decisions. Various prognostic factors were noted in several studies without, however, a consistent consensus.


[Changing distribution of university graduates in Japan--from a cohort-by-cohort perspective].
"This paper aims at describing and explaining the changing distribution of university graduates [UGs] in Japan in order to clarify the effects of interregional migration on changes in the social class composition of the Tokyo metropolitan area (TMA) and the rest of Japan (Non-TMA).... The analysis thereby begins with the distribution of the UGs by 5-year cohort in 1970, 1980 and 1990 measured by location quotients (LQs) of UGs in the TMA.... The paper then proceeds to an analysis of the determining process of the distribution pattern of the UGs by 5-year cohort." (SUMMARY IN ENG)


Some innovative methods in demographic analysis.
"This paper suggests the use of the Matusita affinity and distance measures for the relative ranking of human populations and for developing an age distribution free index of demographic phenomena. A plea for modifying the conventional parity progression rates through semi-Markov analysis is made. The input-output model, the notion of entropy, etc., are suggested as new tools for looking at demographic events." Some illustrations based on Canadian and U.S. data concerning family planning attitudes, mortality, migration, and stable populations are included.


Pseudomonas fluorescens and Pseudomonas putida from refrigerated raw milk: genetic diversity and lipoproteolytic activity.
In this research communication the genetic diversity of Pseudomonas fluorescens (n = 67) and Pseudomonas putida (n = 44) isolated from refrigerated raw milk from bulk tank trucks were verified. The relationship between the genetic profile of the isolates and their lipoproteolytic potential was evaluated using skim milk agar and tributyrin agar (21°C/72 h). The lipoproteolytic potential (low or high), evaluated by the diameter of the halos (cm), was correlated with the number of milk producing properties that contributed to each sample (one sample = one bulk tank truck; 8-80 producers/sample) and the distance between the dairy properties and the processing plant (21-370 km). P. fluorescens was confirmed in all samples, while P. putida in 60% samples. For both species, two clusters (I and II) were observed, and the first one showed lower genotypic diversity and the presence of isolates with 100% similarity. P. fluorescens isolates presenting at least 70% similarity were 83.9% in Cluster I (n = 31) and 44.4% in Cluster II. In both clusters (I and II) observed in the P. fluorescens dendrogram, the occurrence of high proteolytic and lipolytic potential were equivalent. The higher the number of farms per milk sample, the greater the lipoproteolytic intensity of P. fluorescens isolates. In relation to P. putida isolates, 74% presented at least 50% similarity in Cluster I (n = 27) and only 35% in Cluster II (n = 17). The occurrence of high proteolysis linked to P. putida was proportional between both Clusters, but the occurrence of high lipolysis was greater in Cluster II. No significant association was detected between P. putida isolates and the variables studied. The results indicate the circulation of P. putida and P. fluorescens with 100% similarity in different milk producing regions. The level of genetic diversity was related only to the lipolytic capacity of P. putida.


Site-specific acetylation of polynucleotide kinase 3'-phosphatase (PNKP) regulates its distinct role in DNA repair pathways.
Mammalian polynucleotide kinase 3'-phosphatase (PNKP) is a dual-function DNA end-processing enzyme with 3'-phosphatase and 5'-kinase activities, which generate 3'-OH and 5'-phosphate termini respectively, as substrates for DNA polymerase and DNA ligase to complete DNA repair. PNKP is thus involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes, which involve distinct sets of proteins. In this study, we report that PNKP is acetylated at two lysine (K142 and K226) residues. While K142 (AcK142) is constitutively acetylated by p300, CBP acetylates K226 (AcK226) only after DSB induction. Co-immunoprecipitation analysis using antibodies specific for PNKP peptides containing AcK142 or AcK226 of PNKP showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP only with DSBR proteins. Although acetylation at these residues did not significantly affect the enzymatic activity of PNKP in vitro, cells expressing nonacetylable PNKP (K142R or K226R) accumulated DNA damage, specifically in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This observation is consistent with the reported degradation of CBP but not p300 in HD cells. Moreover, genomes of HD cells progressively accumulated DSBs specifically in the transcribed genes. Chromatin-immunoprecipitation analysis using anti-AcK142 or anti-AcK226 antibodies demonstrated an association of Ac-PNKP with the transcribed genes, consistent with PNKP's role in transcription-coupled repair. Thus, our findings collectively demonstrate that acetylation at two lysine residues located in different domains of PNKP regulates its functionally distinct role in BER/SSBR vs. DSBR.


Basic hue-meaning associations.
Color may not only be pleasing to the eye, but may also carry important associations relevant for psychological functioning. Two experiments were conducted to test for basic hue-meaning associations, controlling for lightness and chroma. Specifically, we used a reaction time paradigm to test for links between red and green, and words that varied in achievement content (failure and success) or valence more generally. Results revealed that red was positively associated with failure and general negative words, and was negatively associated with success and general positive words, whereas green was positively associated with success words only. These findings directly document that hue carries psychologically relevant meaning. Implications both within and beyond the achievement domain are discussed.


Natural, unexpected deaths: reliability of a presumptive diagnosis.
We retrospectively analyzed 100 deaths because of suspicions and concerns expressed by the family. We compared the preautopsy cause of death, as determined by a thorough review of the clinical data and circumstances, to the autopsy-derived cause of death. In the majority (91/100), the preautopsy and postautopsy proximate causes of death were in agreement. In 9%, the autopsy provided information that resulted in a proximate cause of death different than anticipated. In four instances, the manner of death also was incorrect and was determined to be an accident rather than the originally presumed natural. No homicide or suicide would have been misclassified. In another nine instances, where the premortem and postmortem proximate causes of death were in agreement, the autopsy provided a specific mechanism of death. With a quality initial medicolegal death investigation, a subset of sudden deaths in adults may be reliably certified without an autopsy.


Thyrotropin (TSH) action on thyroid hormone deiodination and secretion: one aspect of thyrotropin regulation of thyroid cell biology.
TSH, the major signalling factor for the thyroid follicles, controls thyrocyte function in concert with other modulators of cell growth, differentiation and structural organization of the follicular-endothelial network. Most of the TSH effects are mediated by TSH binding to the TSH receptor which stimulates adenylate cyclase catalyzed cAMP production. TSH is involved in the regulation of thyroidal uptake of small molecules and nutrients, intracellular transport of thyrocyte specific proteins, and in most of the steps of thyroid hormone synthesis, storage and release. These cellular events require the fine tuned regulation of metabolic reactions, morphological differentiation and cell proliferation. Thyrocytes also express a highly active Type I iodothyronine 5' deiodinase which is controlled by TSH stimulated cAMP production. The thyrocyte specific 5' deiodinase isozyme has marked influence on the amount of T3 secreted by the thyroid. This 5' deiodinase isozyme shows most of the characteristics of the type I 5' deiodinase found in liver and kidney and is also blocked by PTU, other 5' deiodinase inhibitors, and iodinated X-ray contrast agents such as iopanoic acid, which are occasionally used in thyrotoxicosis to inhibit thyroidal T3-production by this enzyme. In contrast to the liver and kidney type I 5' deiodinase T4 and T3 are not able to induce this enzyme in thyrocytes. However, TSH stimulated cAMP production increases the thyroidal isozyme activity in contrast to the liver and kidney enzyme. This review summarizes the data on the various experimental models used up to date to characterize the thyroidal type I 5' deiodinase in various species including man.


Examining the Relationship Between Preference for Solitude and Subjective Well-Being Among Japanese Older Adults.
Focusing on the fact that older adults with positive emotions tend to spend time alone, this study aimed to examine the relationship between preference for solitude and subjective well-being among older adults. In Study 1, we developed a revised version of the Preference for Solitude Scale with a 3-factor structure, unlike the single-factor structure of the original scale. In Study 2, we examined the relationship between preference for solitude and subjective well-being using the revised scale. We conducted an Internet survey with 210 older adults in Study 1 to develop a revised Japanese scale. In Study 2, to address the possible research method bias in Study 1, we conducted a mail survey with 276 older adults. We examined the replicability of Study 1, confirming metric invariance through multigroup analysis and hypothesis model through path analysis. The results of the path analysis indicated that "Productivity during solitude" (Factor 3) was positively related with positive affect and life satisfaction, and "Enjoyment of solitude" (Factor 2) was negatively related with negative affect. However, the results of the mediation analysis suggested that preference for solitude was also related to loneliness, and the indirect effect of preference for solitude on well-being was negative. "Enjoyment of solitude" and "Productivity during solitude" were related to maintaining subjective well-being among older adults, although the effects were marginal. The impact of preference for solitude was mixed in enhancing and decreasing subjective well-being.


Inhibitory effects of alcohols on thermolysin activity as examined using a fluorescent substrate.
Alcohols inhibit the thermolysin-catalyzed hydrolysis of N-[3-(2-furyl)acryloyl]-Gly-L-Leu-NH(2) and decrease the NaCl-induced activation of thermolysin in a concentration-dependent manner [K. Inouye et al. (1997) J. Biochem. 122, 358-364]. In this study, the inhibitory effects of alcohols on thermolysin activity were examined in detail using 10 different alcohols and a fluorescent substrate, (7-methoxycoumarin-4-yl) acetyl-L-Pro-L-Leu-Gly-L-Leu-[N(3)-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl]-L-Ala-L-Arg-NH(2). The inhibition by all alcohols examined is completely reversible, and thermolysin activity is recovered by dilution. The inhibitor constants (K(i)) are in the range of 35-430 mM, and the order of the inhibitory effect is 1-pentanol, 1-propanol, 2-butanol, 2-methyl-1-propanol > 1-butanol > 2-propanol > ethanol, tert-amyl alcohol >> tert-butyl alcohol >> methanol. Linear and secondary alcohols whose mains chains consist of more than 3 carbons inhibit thermolysin effectively. Thermolysin activity is decreased by decreasing the dielectric constant, D, of the reaction medium containing the alcohol, and the decrease depending on the D value was almost the same manner for all alcohols except methanol, tert-butyl alcohol, and tert-amyl alcohol. Alcohols may inhibit thermolysin activity both by binding to the active site, most possibly to the S1' subsite, of thermolysin and by altering the electrostatic and hydrophobic environment around the thermolysin molecule.


SMARCC1 expression is positively correlated with pathological grade and good prognosis in renal cell carcinoma.
Renal cell carcinoma (RCC), which is derived from the renal tubular epithelium, is now the most common urological cancer. Of the four RCC subtypes, clear cell RCC (ccRCC) is the most common subtype and accounts for 75-80% of all RCC cases. SMARCC1, also known as BAF155, together with SMARCA4, SMARCA2, and SMARCB1, comprises the SWI/SNF protein family. It has been reported that the expression of SMARCC1 was correlated with some human cancers including prostate cancer, colon cancer, and pancreatic cancer. However, the mechanisms and regulatory roles of SMARCC1 in ccRCC are not well defined. Our current study primarily investigated the expression of SMARCC1 and its clinical importance in two common histological types of ccRCC using microarrays (HKidE180Su02, MecDNA-HKidE030CS01). The results showed that the expression of SMARCC1 in ccRCC tissues was significantly decreased compared with that in corresponding para-tumor tissue (4.370±2.036 vs. 6.167±1.162, P=0.001). SMARCC1 expression was positively correlated with pathological grade (r=0.224, P=0.011). Moreover, ccRCC patients with high SMARCC1 expression had a better prognosis than those with low SMARCC1 expression (40.0% vs. 95.2%, P=0.000) in the following sub-groups: pathological grade (III and IV), male sex (73.5% vs. 95.3%, P=0.004), and tumor size >5 cm (62.5% vs. 89.5%, P=0.044). A further study is necessary to explain the mechanism of the occurrence and progression of ccRCC.


Successful Treatment of Hemophagocytic Lymphohistiocytosis Associated with Lupus Nephritis by Using Mycophenolate Mofetil.
An estimated 0.9% to 2.4% of patients with systemic lupus erythematosus (SLE) also have hemophagocytic lymphohistiocytosis (HLH). HLH associated with autoimmune diseases is often refractory to corticosteroid treatment; thus, additional immunosuppressive drugs, such as cyclosporine, cyclophosphamide, or tacrolimus, are required. Here, we describe the case of a 44-year-old Japanese woman who developed HLH associated with lupus nephritis. Initially, her HLH was refractory to treatment with a corticosteroid, tacrolimus, and mizoribine. However, alternative treatment with a corticosteroid, mycophenolate mofetil, and tacrolimus improved both her HLH and lupus nephritis. This case suggests the possibility of mycophenolate mofetil as a key drug for treating HLH associated with SLE.


Carbamazepine-responsive paroxysmal nausea and vomiting in a patient with meningeal carcinomatosis.
In neurology, paroxysmal syndromes are well-known, eg, as manifestations of multiple sclerosis. We report a patient with meningeal carcinomatosis, who presented with therapy-refractory nausea and vomiting. The clinical suspicion of a paroxysmal syndrome prompted a trial of carbamazepine, which resulted in complete cessation of the symptoms. In cancer patients with central nervous system (CNS) involvement and therapy-refractory symptoms with sudden onset, carbamazepine treatment should be considered.


Simulations of blood pressure and identification of atrial fibrillation and arterial stiffness using an extended Kalman filter with oscillometric pulsation measurements.
The accuracy of systolic and diastolic blood pressure levels from oscillometric devices is difficult to assess for patients with atrial fibrillation and arterial stiffness; in such cases, changes in these levels from heartbeat to heartbeat can only be known if the actual total waveform during a test can be observed. Variation in these levels affects the accuracy of the algorithms in oscillometric devices where precision is of paramount importance according to the American College of Cardiology and the American Heart Association. Recently issued guidelines lowered the definition of high blood pressure; approximately three-quarters of men over 65 years of age meet the criterion and are diagnosed as hypertensive. A review in 2019 reported that atrial fibrillation affects approximately 3% of the general population in the U.S. and is twice as common in hypertensive patients. The actual shape and details of the arterial blood pressure waveform not only reveal variations in rhythm and in systolic and diastolic levels but has also proven to be valuable in the diagnosis of arterial stiffness and atrial fibrillation which are vital to determining the physiological status of a patient's cardiovascular system. This research pertains to the identification of a patient's total arterial blood pressure waveform using only the measured pulsations in the cuff of an oscillometric device. Empirically formulated hypothetical arterial blood pressure waveforms were simulated and assumed to be unknown. Oscillometric pulsations corresponding to these simulated unknown waveforms were used as input to a new model-based extended Kalman filter algorithm for identifying the levels, shape and features of the unknown waveforms. Simulations with hypothetical waveforms with varying systolic and diastolic levels and with variations in heartbeat rhythm associated arterial fibrillation and stiff arteries, demonstrate potential arterial pressure estimate accuracies of 1.5 mmHg with standard deviations on the order of 0.1 mmHg; in addition, variations in heartbeat rhythm were observed and degrees of arterial stiffness identified and quantified. Computational analysis of the oscillometric cuff pulsations with the extended Kalman filter can be used to detect variations in heartbeat rhythm and blood pressure levels associated atrial fibrillation, quantify arterial stiffness, and provide noninvasive continuous blood pressure monitoring without the need for electrocardiogram or photoplethysmography sensors.


Traumatically Intruded Permanent Teeth: Three Case Reports and a Review of Current Recommendations.
Intrusion of permanent teeth is not extensively covered in the literature compared to other injuries. Treatment guidelines have been published and clinical data is accumulating to support the current recommendations, which are illustrated in the three cases here. This review evaluates the current information about management of traumatically intruded permanent teeth. As more data accumulates, uncertainties with respect to both treatment recommendations and long-term outcomes can be expected to be elucidated.


Attention switching and patterns of sound locations in counting clicks.
The present study investigates the process of auditory attention switching by means of experiments in which observers counted the number of monaurally and interaurally presented clicks. Several studies have reported that the number of interaurally presented events was underestimated relative to monaurally presented ones. Ten Hoopen and Vos, however, could not replicate this phenomenon. The data from Experiment 1 demonstrate that such a discrepancy is caused by the different orders in which the monaural and interaural sequences were presented. With blocked presentation, interaural sequences were counted less well than monaural sequences, whereas there was no difference when all sequence types were randomized. An attention-switching mechanism was proposed to account for performance on interaural sequences during blocked presentation. In the random case observers presumably did not switch their attention to and fro, but "multiplexed" the channels. Experiment 2 investigated whether observers can deliberately suppress the process of attention switching when confronted with blocked interaural sequences. The results show that they cannot, which suggests that attention switching is an automatic process.


The Management of Acute Onset Complete Heart Block and Atrial Flutter in a Patient with COVID-19.
Coronavirus disease (COVID-19) has infected millions of people worldwide. Its cardiac presentations include myocarditis, arrhythmias and structural heart changes even in young and healthy individuals. The long-term sequelae of these manifestations are unknown. We describe a unique combination of complete heart block and atrial flutter in the setting of COVID-19. SARS-CoV-2 virulence mechanisms can cause fibrosis in the myocardium resulting in loss of sinus node dominance. The paradoxical finding of atrial flutter and complete heart block is very rare. Prompt cardiac evaluation and electrophysiological testing are important. Cardiac magnetic resonance imaging (cMRI) and endomyocardial biopsies are the gold standard investigations. Anticoagulation should be administered until atrioventricular synchrony is achieved. Simultaneous atrial flutter and third-degree atrioventricular block (AVB) caused by COVID-19 infection should be treated with a pacemaker according to heart block guidelines.During the COVID-19 pandemic, we recommend leadless pacemaker implantation for third-degree AVB as it has a lower risk of infection compared with traditional percutaneous procedures.Due to a lack of long-term data, patients with cardiac manifestations from COVID-19 require close follow-up with individualized surveillance schedules.


[Idiopathic orbital myositis].
Orbital myositis is a rare disorder considered as a subgroup of inflammatory orbital pseudotumors. The pathophysiology is still unknown. Patients typically present with orbital pain exacerbated by eye movement and diplopia. Response to steroids is dramatic. We report a case of idiopathic myositis of the right inferior muscle, which recovered after steroid therapy.


Superinfection with woodchuck hepatitis virus strain WHVNY of livers chronically infected with strain WHV7.
The determinants of the maintenance of chronic hepadnaviral infection are yet to be fully understood. A long-standing unresolved argument in the hepatitis B virus (HBV) research field suggests that during chronic hepadnaviral infection, cell-to-cell spread of hepadnavirus is at least very inefficient (if it occurs at all), virus superinfection is an unlikely event, and chronic hepadnavirus infection can be maintained exclusively via division of infected hepatocytes in the absence of virus spread. Superinfection exclusion was previously shown for duck HBV, but it was not demonstrated for HBV or HBV-related woodchuck hepatitis virus (WHV). Three woodchucks, which were chronically infected with the strain WHV7 and already developed WHV-induced hepatocellular carcinomas (HCCs), were superinfected with another WHV strain, WHVNY. Six weeks after the superinfection, the woodchucks were sacrificed and tissues of the livers and HCCs were examined. The WHVNY superinfection was demonstrated by using WHV strain-specific PCR assays and (i) finding WHVNY relaxed circular DNA in the serum samples collected from all superinfected animals during weeks one through six after the superinfection, (ii) detecting replication-derived WHVNY RNA in the tissue samples of the livers and HCCs collected from three superinfected woodchucks, and (iii) finding WHVNY DNA replication intermediates in tissues harvested after the superinfection. The results are consistent with the occurrence of continuous but inefficient hepadnavirus cell-to-cell spread and superinfection during chronic infection and suggest that the replication space occupied by the superinfecting hepadnavirus in chronically infected livers is limited. The findings are discussed in the context of the mechanism of chronic hepadnavirus infection. This study aimed to better understand the determinants of the maintenance of chronic hepadnavirus infection. The generated data suggest that in the livers chronically infected with woodchuck hepatitis virus, (i) hepadnavirus superinfection and cell-to-cell spread likely continue to occur and (ii) the virus spread is apparently inefficient, which is consistent with the interpretation that a limited number of cells in the livers facilitates the spread of hepadnavirus. The limitations of the cell-to-cell virus spread most likely are mediated at the level of the cells and do not reflect the properties of the virus. Our results further advance the understanding of the mechanism of chronic hepadnavirus infection. The significance of the continuous but limited hepadnavirus spread and superinfection for the maintenance of the chronic state of infection should be further evaluated in follow-up studies in order to determine whether blocking the virus spread would facilitate the suppression of chronic hepadnavirus infection.


Temporomandibular disorders. 1. Clinical evaluation.
The treatment of temporomandibular disorders continues to provide dental practitioners with a difficult challenge that has yet to overcome numerous major obstacles. In this, the first of a series of three articles, an overview of the current understanding of the diagnosis of temporomandibular disorders will be presented. The subsequent two articles will present an overview of the management strategies that have appeared in the literature in recent years.


Intraocular pressure in captive black-footed penguins (Spheniscus demevsus) measured by rebound tonometry.
Intraocular pressure (IOP) measurement is a common procedure during eye examinations in birds. Differences in the IOP between avian species have been reported, which suggests the need to establish species-specific reference ranges. To determine IOP values of captive black-footed penguins (Spheniscus demersus), we obtained IOP readings with the use of a rebound tonometer by using two established calibration settings (dog and horse). No difference was seen in the IOP between the left and right eye when the horse setting was used; however, a difference was present when using the dog setting. No significant difference between the IOP of male and female penguins was seen in both eyes when the dog or horse setting was used. Rebound tonometry appears to be a safe and repeatable method to obtain IOP values in black-footed penguins.


Essential fatty acids: biochemistry, physiology and pathology.
Essential fatty acids (EFAs), linoleic acid (LA), and alpha-linolenic acid (ALA) are essential for humans, and are freely available in the diet. Hence, EFA deficiency is extremely rare in humans. To derive the full benefits of EFAs, they need to be metabolized to their respective long-chain metabolites, i.e., dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites not only form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), but also give rise to lipoxins (LXs) and resolvins that have potent anti-inflammatory actions. Furthermore, EFAs and their metabolites may function as endogenous angiotensin-converting enzyme and 3-hdroxy-3-methylglutaryl coenzyme A reductase inhibitors, nitric oxide (NO) enhancers, anti-hypertensives, and anti-atherosclerotic molecules. Recent studies revealed that EFAs react with NO to yield respective nitroalkene derivatives that exert cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors. The metabolism of EFAs is altered in several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer. Thus, EFAs and their derivatives have varied biological actions and seem to be involved in several physiological and pathological processes.


Specificity of protein lysine methyltransferases and methods for detection of lysine methylation of non-histone proteins.
Post translational modification of histone proteins including lysine methylation is an important epigenetic mark, essential for gene regulation and development. Recently, several examples of lysine methylation of non-histone proteins have been discovered suggesting that this is a common post-translational modification for regulation of protein activity. Here, we review assays for the detection of protein methylation based on mass spectrometry, radiolabel and immunological approaches using protein and peptide substrates including application of SPOT peptide arrays. Candidates for new methylation targets of protein methyltransferases can be predicted using the specificity of the enzyme and protein interaction data.


Determination of active ingredient in synthetic pyrethroid formulations by high-performance thin-layer chromatography/densitometry.
A new, simple, precise, and rapid high-performance thin-layer chromatography (HPTLC) method was developed for the analysis of commercial emulsifiable concentrate (EC) formulations of cypermethrin, alpha-cypermethrin, and lambda-cyhalothrin. A known amount of reference grade synthetic pyrethroid and its EC formulation was subjected to TLC, and the amount of pesticide present in the active ingredient spot was estimated by densitometry in a single beam, single wavelength reflectance mode. Calibration curves of the synthetic pyrethroid was linear in the range of 8-24 microg, and the correlation coefficient for the calibration equation ranged between 0.97 and 0.99. Recoveries from laboratory-prepared test samples of the EC formulation were in the range of 95-99%. Pesticide formulations were further analyzed by gas liquid chromatography using flame ionization detector, and results were comparable. The proposed HPTLC method has application for quality control and determination of the shelf life of EC formulations.


TTRAP is a novel PML nuclear bodies-associated protein.
PML nuclear body (PML NB) is an important macromolecular nuclear structure that is involved in many essential aspects of cellular function. Tens of proteins have been found in PML NBs, and promyelocytic leukemia protein (PML) has been proven to be essential for the formation of this structure. Here, we showed that TRAF and TNF receptor-associated protein (TTRAP) was a novel PML NBs-associated protein. TTRAP colocalized with three important PML NBs-associated proteins, PML, DAXX and Sp100 in the typical fashion of PML NBs. By yeast mating assay, TTRAP was identified to interact with these PML NBs-associated proteins. The transcription and expression of TTRAP could be induced by IFN-gamma, representing another common feature of PML NBs-associated proteins. These results would not only be important for understanding PML NBs but also be helpful in studying the TTRAP function in the future.


Scientific evaluation of traditional Chinese medicine under DSHEA: a conundrum. Dietary Supplement Health and Education Act.
In the United States, traditional Chinese medicines (TCM) are currently sold as dietary supplements, as defined by The Dietary Supplement Health and Education Act (DSHEA). This legislation is unique to the United States and while "structure and function" claims are allowable under DSHEA, disease claims are not. The narrow definition, however, poses a challenge to designing appropriate clinical studies that can provide data for "structure and function" claim substantiation. The process of melding Chinese herbal medicines into the dietary supplement category is complex and there is a need to define a clinical trial paradigm carefully that addresses "structure and function claims" without sacrificing scientific rigor. It is frequently not recognized that TCM favors an amalgamation of several herbs to generate the putative clinical effect. Because of this historical multiherb approach, the reliance on retrospective data to support the potential health benefits of an herb extract has severe limitations. Notwithstanding the immense value of identifying the pharmacological activity of a TCM herb to a chemical suitable for pharmaceutical development, another approach to safe and efficacious herbal products is to develop a standardized herbal extract. This article highlights issues related to the latter approach and will discuss a research-based strategy that may be suitable for validating, in part, the putative health benefits of TCM.


Perioperative participation of orthopedic patients and surgical staff in a nasal decolonization intervention to reduce Staphylococcus spp surgical site infections.
With the goal of reducing rates of surgical site infections in our spine patients, we initiated a trial to investigate the impact of adding perisurgical nasal decolonization involving patients and surgical and nursing staff. We combined immediate presurgical application of a nonantibiotic alcohol-based nasal antiseptic with existing chlorhexidine bath or wipes in a comprehensive pre- and postoperative decolonization protocol. Mean infection rates were significantly decreased by 81% from 1.76 to 0.33 per 100 surgeries during the 15-month trial, when compared with the prior 9-month baseline.


Improving Kinetics of "Click-Crosslinking" for Self-Healing Nanocomposites by Graphene-Supported Cu-Nanoparticles.
Investigation of the curing kinetics of crosslinking reactions and the development of optimized catalyst systems is of importance for the preparation of self-healing nanocomposites, able to significantly extend their service lifetimes. Here we study different modified low molecular weight multivalent azides for a capsule-based self-healing approach, where self-healing is mediated by graphene-supported copper-nanoparticles, able to trigger "click"-based crosslinking of trivalent azides and alkynes. When monitoring the reaction kinetics of the curing reaction via reactive dynamic scanning calorimetry (DSC), it was found that the "click-crosslinking" reactivity decreased with increasing chain length of the according azide. Additionally, we could show a remarkable "click" reactivity already at 0 °C, highlighting the potential of click-based self-healing approaches. Furthermore, we varied the reaction temperature during the preparation of our tailor-made graphene-based copper(I) catalyst to further optimize its catalytic activity. With the most active catalyst prepared at 700 °C and the optimized set-up of reactants on hand, we prepared capsule-based self-healing epoxy nanocomposites.


Characterization of Four Novel dsRNA Viruses Isolated from Mucor hiemalis Strains.
We previously screened the total nucleic acid extracts of 123 Mucor strains for the presence of dsRNA molecules without further molecular analyses. Here, we characterized five novel dsRNA genomes isolated from four different Mucor hiemalis strains with next-generation sequencing (NGS), namely Mucor hiemalis virus 1a (MhV1a) from WRL CN(M) 122; Mucor hiemalis virus 1b (MhV1b) from NRRL 3624; Mucor hiemalis virus 2 (MhV2) from NRRL 3616; and Mucor hiemalis virus 3 (MhV3) and Mucor hiemalis virus (MhV4) from NRRL 3617 strains. Genomes contain two open reading frames (ORF), which encode the coat protein (CP) and the RNA dependent RNA polymerase (RdRp), respectively. In MhV1a and MhV1b, it is predicted to be translated as a fusion protein via -1 ribosomal frameshift, while in MhV4 via a rare +1 (or-2) ribosomal frameshift. In MhV2 and MhV3, the presence of specific UAAUG pentanucleotide motif points to the fact for coupled translation termination and reinitialization. MhV1a, MhV2, and MhV3 are part of the clade representing the genus Victorivirus, while MhV4 is seated in Totivirus genus clade. The detected VLPs in Mucor strains were from 33 to 36 nm in diameter. Hybridization analysis revealed that the dsRNA molecules of MhV1a-MhV4 hybridized to the corresponding molecules.


[Planning and assessing the activity of a school health service based on health and social indicators: the experience of Villeurbanne].
In 1998, the municipality of Villeurbanne decided to review its school health service in order to restructure and adjust its activity to better meet the needs of schools which had evolved and developed differently according to their areas of location. In view of the rarity of available information to measure the needs, an information system was built using a participatory and consensual approach. The system has been operational since the year 2000. It was evaluated in 2003 and then adapted according to the results. It has a variety of uses for planning purposes: to classify the schools according to their requirements, to plan the working time and schedules of the nurses, and to programme and evaluate specific actions. It also allows for mapping the health status of the pupils in Villeurbanne and to describe the service's activity. This article presents the design and construction of the information system and serves as a platform to debate the benefits and limitations of this approach in Villeurbanne.


[Definition of a new temporal voice onset measurement].
The aim of this study was to define a new temporal measurement of voice onset. If in fact it has been established that voice onset contains perceptive information which the listening panel uses to evaluate dysphonia, up till now there has been no objective measurement of this. In order to be able to use instrumental measurement of voice onset, it was first necessary to arrivee at a definition of the limits of onset and end. In electronics, the method of "10%-90%" is used to calculate the rise time (onset) of any signal. It is possible to apply this method to the voice signal using the intensity curve. We have made such measurements on 240 examples of the sustained lal sound produced by 60 dysphonic subjects and 20 normals. The results have shown that measurement of the duration of onset was in the main relevant for the mild (G1) and moderate (G2) dysphonias. We have concluded that the "10%-90%" method allows definition of the contours of onset, and measurement of its duration in a reproducible and standardised way.


In vitro Candida albicans biofilm formation on different titanium surface topographies.
To investigate if differences in titanium implant surface topography influence Candida albicans biofilm formation. Titanium discs were prepared and characterized using a profilometer: Group A (R a 0.15 µm, smooth), Group B (R a 0.64 µm, minimally rough) and Group C (R a 1.3 µm, moderately rough). Contact angle and surface free energy (SFE) were determined for each group. Non-preconditioned titanium discs were incubated with C. albicans for 24 h. In additional experiments, the titanium discs were initially coated with human saliva, bovine serum albumin or phosphate-buffered saline for 2 h before incubation with C. albicans for 24 h. The amount of fungal biofilm formation was quantified using a colorimetric assay. C. albicans biofilm formation was significantly lower (p < 0.05) on the minimally rough titanium surface compared to smooth and moderately rough surfaces. The titanium surface displaying the lowest SFE (Group B) was associated with significantly lower (p < 0.05) C. albicans biofilm formation than the other two groups. Salivary coating resulted in greater adherence of C. albicans with increased surface roughness. The minimally rough titanium discs displayed lowest SFE compared to smooth and moderately rough surfaces and showed the least C. albicans biofilm formation. This study demonstrated that C. albicans biofilm formation increased in a SFE-dependent manner. These findings suggest that SFE might be a more explanatory factor for C. albicans biofilm formation on titanium surfaces than roughness. The presence of a pellicle coating may negate the impact of SFE on C. albicans biofilm formation on titanium surfaces.


[Extensive grazing and designed feeding with supplemented legume forages on natural grassland].
Livestock needs to be fully stuffed and fed well. Eating-well can compensate eating-full, and can rapidly increase the body weight of livestock, shorten its feeding period, enhance its production, and protect natural grassland from overgrazing. A designed feeding based on extensive grazing on natural grassland by supplementing rich crude protein-contained forage might be a new trend for optimizing the animal husbandry on grassland. Adding 20% legume forages to the diets for wethers could make the live body weight get a 40%-65% increase, achieving 52-61 kg in October extending to December. Forage production, animal nutrition and animal production were the three relatively primary factors for grassland management while focusing on grazing. Some terms such as eating-well, eating-well degree, eating-full, eating-full degree, extensive grazing and designed feeding were also defined respectively in this paper.


[Tumor markers in gastrointestinal cancer and its clinical significance].
The clinical usefulness of tumor markers was discussed in gastrointestinal cancer. SCC antigen (subfraction of TA-4) was useful marker in esophageal squamous cell cancer, but was not so helpful in cancer treatment. CEA and CA19-9 were also available as tumor markers of gastric and colorectal cancers, but extremely increased levels were found in only advanced but in early cancer. There was no significant correlation between CEA and CA19-9 so the combination assay of a few kinds of tumor markers, especially CEA and CA19-9 were helpful in cancer treatment.


Ventricular Arrhythmias in Cardiac Amyloidosis: A Review of Current Literature.
Cardiac Amyloidosis is an infiltrative cardiomyopathy which occurs secondary to deposition of mis-folded protein in the myocardium, with the two most common subtypes being AL amyloidosis and TTR amyloidosis. The pathogenesis of the disease is multifaceted and involves a variety of mechanisms including an inflammatory response cascade, oxidative stress and subsequent separation of myocyte fibrils. Cardiac Amyloidosis frequently results in congestive cardiac failure and arrhythmias, from a disruption in cardiac substrate with subsequent electro-mechanical remodelling. Disease progression is usually demonstrated by development of progressive pump failure, which may be seen with a high arrhythmic burden, usually portending a poor prognosis. There is a paucity of literature on the clinical implications of ventricular arrhythmias in the context of cardiac amyloidosis. The important diagnostic investigations for these patients include transthoracic echocardiography, cardiac magnetic resonance imaging and an electrophysiology study. Whilst there are no robust management guidelines, studies have indicated benefits from contemporary pharmacological therapy and case-by-case catheter ablation. There are novel directed therapies available for TTR amyloidosis that have shown to improve overall survival. The role of ICD therapy in cardiac amyloidosis is controversial, with benefits seen predominantly in early phases of the disease process. The only definitive surgical therapy includes heart transplantation, but is largely indicated for progressive decompensated heart failure (Figure 1). Further large-scale studies are required to better outline management paradigms for treating ventricular arrhythmias in cardiac amyloidosis.


[Function of CDK12 in Tumor initiation and progression and its clinical consequences].
Cyclin-dependent kinases (CDKs) participate in many cellular processes and play a crucial role in the regulation of cell cycle and transcription processes. Recently, CDK12 was identified as a key factor orchestrating transcription of genes, such as BRCA1, ATM, ATR, FANCI and FANCD2, which are involved in the DNA-damage response pathway. Importantly, inhibition of function of these genes commonly leads to induction of genomic instability followed by cancer development, but the precise contribution of CDK12 to these processes is to be unveiled. Nevertheless, several mutations affecting function of CDK12 were already identified in a variety of tumors of different origin (ovary, breast, prostate, intestine) making tumors sensitive to cytostatics promot-ing DNA damage (platin derivatives, alkylating regimens) and inhibitors of DNA repair (PARP inhibitors). Such an effect has been already observed in the model of high grade serous ovarian carcinomas. Thus, CDK12 is becoming a potential therapeutic target of drugs causing synthetic lethality in these cells. Our review summarizes most recent information about CDK12 function in cancer and discusses potential use of CDK12 in clinics.


Polyacrylamide gel electrophoresis of reducing saccharides labeled with the fluorophore 8-aminonaphthalene-1,3,6-trisulphonic acid: application to the enzymological structural analysis of oligosaccharides.
Mono- and oligosaccharides, each containing a reducing end group, were labeled with the charged fluorophore 8-aminonaphthalene-1,3,6-trisulphonic acid and the resulting derivatives were separated with high resolution by polyacrylamide gel electrophoresis using a method developed recently (P. Jackson, Biochem. J. 1990, 270, 705-713) but with an alternative electrophoretic buffer system. The fluorescent derivatives of glucose and all its straight chain, alpha 1-4 linked, oligomers from maltose to maltoheptaose were well resolved. Various isomers such as maltose and lactose could be separated, as were maltose and cellobiose and some epimers, for instance glucose and galactose. The method was applied to the analysis of the partial sequential degradation of a complex oligosaccharide with neuraminidase and beta-galactosidase. Gels showing fluorescent saccharide band patterns were recorded in picomolar quantities either photographically or using an imaging system based on a cooled charge-coupled device.


[Leaching Remediation of Copper and Lead Contaminated Lou Soil by Saponin Under Different Conditions].
In order to investigate the leaching remediation effect of the eco-friendly biosurfactant saponin for Cu and Pb in contaminated Lou soil, batch tests method was used to study the leaching effect of saponin solution on single Cu, Pb contaminated Lou soil and mixed Cu and Pb contaminated Lou soil under different conditions such as reaction time, mass concentration of saponin, pH, concentration of background electrolyte and leaching times. The results showed that the maximum leaching removal effect of Cu and Pb in contaminated Lou soil was achieved by complexation of the heavy metals with saponin micelle, when the mass concentration of saponin solution was 50 g x L(-1), pH was 5.0, the reaction time was 240 min, and there was no background electrolyte. In single and mixed contaminated Lou soil, the leaching percentages of Cu were 29.02% and 25.09% after a single leaching with 50 g x L(-1) saponin under optimal condition, while the single leaching percentages of Pb were 31.56% and 28.03%, respectively. The result indicated the removal efficiency of Pb was more significant than that of Cu. After 4 times of leaching, the cumulative leaching percentages of Cu reached 58.92% and 53.11%, while the cumulative leaching percentages of Pb reached 77.69% and 65.32% for single and mixed contaminated Lou soil, respectively. The fractionation results of heavy metals in soil before and after a single leaching showed that the contents of adsorbed and exchangeable Cu and Pb increased in the contaminated soil, while the carbonate-bound, organic bound and sulfide residual Cu and Pb in the contaminated Lou soil could be effectively removed by saponin.


Modified contralateral C7 nerve transfer: the possibility of permitting ulnar nerve recovery is confirmed by 10 cases of autopsy.
Contralateral C7 nerve transfer surgery is one of the most important surgical techniques for treating total brachial plexus nerve injury. In the traditional contralateral C7 nerve transfer surgery, the whole ulnar nerve on the paralyzed side is harvested for transfer, which completely sacrifices its potential of recovery. In the present, novel study, we report on the anatomical feasibility of a modified contralateral C7 nerve transfer surgery. Ten fresh cadavers (4 males and 6 females) provided by the Department of Anatomy, Histology, and Embryology at the Medical College of Fudan University, China were used in modified contralateral C7 nerve transfer surgery. In this surgical model, only the dorsal and superficial branches of the ulnar nerve and the medial antebrachial cutaneous nerve on the paralyzed side (left) were harvested for grafting the contralateral (right) C7 nerve and the recipient nerves. Both the median nerve and deep branch of the ulnar nerve on the paralyzed (left) side were recipient nerves. To verify the feasibility of this surgery, the distances between each pair of coaptating nerve ends were measured by a vernier caliper. The results validated that starting point of the deep branch of ulnar nerve and the starting point of the medial antebrachial cutaneous nerve at the elbow were close to each other and could be readily anastomosed. We investigated whether the fiber number of donor and recipient nerves matched one another. The axons were counted in sections of nerve segments distal and proximal to the coaptation sites after silver impregnation. Averaged axon number of the ulnar nerve at the upper arm level was approximately equal to the sum of the median nerve and proximal end of medial antebrachial cutaneous nerve (left: 0.94:1; right: 0.93:1). In conclusion, the contralateral C7 nerve could be transferred to the median nerve but also to the deep branch of the ulnar nerve via grafts of the ulnar nerve without deep branch and the medial antebrachial cutaneous nerve. The advantage over traditional surgery was that the recovery potential of the deep branch of ulnar nerve was preserved. The study was approved by the Ethics Committee of Fudan University (approval number: 2015-064) in July, 2015.


Monitoring hepatic venous hemoglobin oxygen saturation during Appleby operation for pancreatic cancer.
When an Appleby operation is performed for pancreatic body and tail carcinoma, it is necessary for prevention of hepatic ischemia to estimate accurately the hepatic circulation after resection of the celiac artery, the common hepatic artery and the portal vein. We studied the hepatic circulation by monitoring the ShvO2 (hepatic venous hemoglobin oxygen saturation) during an Appleby operation. We performed an Appleby operation on 8 patients with pancreatic cancer. In 6 of 8 patients, a 7-Fr fiberoptic flow direct catheter was inserted in the right hepatic vein. The ShvO2 values were monitored continuously during surgery. The ShvO2 value was 76 +/- 3.5% just after laparotomy, and reduced to 61 +/- 13.2% after clamping the common hepatic artery. The values of the ShvO2 returned to 70.8 +/- 10.9% one hour after clamping. But, one patient underwent reconstruction of the common hepatic artery, because the ShvO2 value still stood at 50%. Combined resection of the portal vein was performed in 5 out of 8 patients. Two patients underwent resection of the portal vein without reconstruction due to the development of the collateral vein, one patients; resection of the portal vein with reconstruction, and two patients; wedge resection. In all 5 patients, the ShvO2 was stable during resection of the portal vein. Monitoring the ShvO2 is a useful method to evaluate at real time the hepatic circulation during the Appleby operation, and to decide if reconstruction of the common hepatic artery or the portal vein is needed or not.


Identification of Iowa live births in the Agricultural Health Study.
In the Agricultural Health Study, information on participant live births was largely provided by female partners of male private applicators. At the Iowa site, such information was available for 13,599 (42.9%) of 31,707 applicators. To improve identification of live births among Iowa participants, we used a probabilistic and deterministic approach to link available demographic data from 31,707 households and information on live births from 13,599 households with 1,014,916 Iowa birth certificates. Record linkage identified 16,611 (93.7%) of 17,719 reported live births and 17,883 additional live births, most (14,411 or 80.6%) not reported due to nonresponse by female partners. This record linkage produced an expanded cohort of live-born children among Iowa participants, which will facilitate improved study of the effects of agricultural exposures, including pesticides, on selected birth outcomes and childhood disease.


When dead cells tell tales-cutaneous involvement by precursor T-cell acute lymphoblastic lymphoma with an uncommon phenotype.
The thymic type of precursor T-cell acute lymphoblastic lymphoma (pre-T ALL), an uncommon T-cell malignancy, typically presents as a thymic mass and expresses terminal deoxonucleotidyl transferase, CD7, and cytoplasmic CD3, with variable expression of other markers. Cutaneous presentation in pre-T ALL is highly unusual. We describe a case of pre-T ALL presenting as 2 papulonodular lesions on the face of an otherwise asymptomatic 27-year-old man. Microscopic examination of both lesions revealed a moderate to dense pandermal infiltrate of medium-sized lymphocytes with extensive "crush" artifact, whereas immunohistochemistry revealed positive staining of lesional cells for CD45, CD3, Bcl-2, Ki-67, CD5, CD7, and CD34 but negative staining for CD4, CD8, CD30, CD56, CD10, CD117, anaplastic lymphoma kinase protein, TdT, myeloperoxidase, CD79a, and CD20. Gene rearrangement studies performed on both biopsies identified a clonal population of T lymphocytes. A subsequent computed tomography scan revealed a 9-cm mediastinal mass encasing all major mediastinal vessels, whereas a bone marrow biopsy revealed blasts with an immunophenotype similar to that of the cutaneous lesions. Features unique to this case include the cutaneous presentation and the immunophenotype-absence of CD4, CD8, and TdT with expression of CD34-both highly unusual features for pre-T ALL.


Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites.
Pentraxins, which include C reactive protein (CRP) and serum amyloid P component (SAP), are prototypic acute phase reactants that serve as indicators of inflammatory reactions. Here we report genomic and cDNA cloning of mouse ptx3 (mptx3), a member of the pentraxin gene family and characterize its extrahepatic expression in vitro and in vivo. mptx3 is organized into three exons on chromosome 3: the first (43 aa) and second exon (175 aa) code for the signal peptide and for a protein portion with no high similarity to known sequences the third (203 aa) for a domain related to classical pentraxins, which contains the "pentraxin family signature." Analysis of the N terminal portion predicts a predominantly alpha helical structure, while the pentraxin domain of ptx3 is accommodated comfortably in the tertiary structure fold of SAP. Normal and transformed fibroblasts, undifferentiated and differentiated myoblasts, normal endothelial cells, and mononuclear phagocytes express mptx3 mRNA and release the protein in vitro on exposure to interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF)alpha. mptx3 was induced by bacterial lipopolysaccharide in vivo in a variety of organs and, most strongly, in the vascular endothelium of skeletal muscle and heart. Thus, mptx3 shows a distinct pattern of in vivo expression indicative of a significant role in cardiovascular and inflammatory pathology.


Amino acid sequence of a sea anemone toxin from Parasicyonis actinostoloides.
Amino-acid sequence of a toxin from sea anemone, Parasicyonis actinostoloides, is determined. The toxin consists of 31 amino acid residues and is cross-linked with four disulphide bridges. The sequence has some similarity to that of toxin III and no similarity to those of toxin I and toxin II both from sea anemone, Anemonia sulcata, or to that of Anthopleurin A from Anthopleura xanthogrammica.


Interactions of saturated diacylglycerols with phosphatidylcholine bilayers: A 2H NMR study.
The interactions of a series of saturated diacylglycerols (DAGs) with fatty acid side chain lengths of 6-14 carbons with multilamellar phospholipid bilayers consisting either of dipalmitoylphosphatidylcholine (DPPC) or of a mixture of DPPC and bovine liver phosphatidylcholine (BL-PC) extracts were studied by 2H NMR spectrometry. We found that the perturbation induced by the DAGs into the bilayer structure strongly depends on the length of the DAG fatty acid side chain. Shorter chain 1,2-sn-dihexanoylglycerol and, to a larger degree, 1,2-sn-dioctanoylglycerol (diC8) induce transverse perturbation of the bilayer structure: the order parameters of the phospholipid side chains are increased by the intercalating DAG molecules in the region adjacent to the phospholipid headgroups and decreased toward the terminal methyls, corresponding to the bilayer interior. The longer chain DAGs (C greater than or equal to 12) studied in this and previous [De Boeck & Zidovetzki (1989) Biochemistry 28, 7439] work induce lateral phase separation of the lipids into DAG-enriched gellike domains and relatively DAG-free regions in the liquid-crystalline phase. Each of the DAGs studied induces a decrease in the area per phospholipid molecule, and a corresponding increase in the lateral surface pressure of the bilayers.(ABSTRACT TRUNCATED AT 250 WORDS)


Methylammonium Transport in Phaseolus vulgaris Leaf Slices.
Methylammonium (as a nonmetabolized analog of ammonium) transport was studied in leaf slices of Phaseolus vulgaris L. var. ;Hawkesbury Wonder.' The relationship of influx to external pH (6.0-10.5) shows that the influx at low external pH is a larger fraction of that at high external pH than would be expected from the pK(alpha) of methylammonium and the assumption that only CH(3)NH(2) is entering the cells. The relationship between methylammonium influx and external methylammonium concentration shows some evidence of saturation; this is a function of the transport system rather than of the (limited) methylammonium metabolism in the cells. The "equilibrium" concentration ratio for methylammonium between leaf slices and bathing medium is far higher than can be explained by the transport of CH(3)NH(2) alone and the pH of the compartments involved. These three lines of evidence strongly suggest that there is an influx of CH(3)NH(3) (+), possibly by a uniporter driven by the electrical potential of the cytoplasm with respect to the medium, as has been shown for other plant cells. Competitive inhibition of methylammonium influx by ammonium suggests that there is also an ammonium transport system. The significance of this for the recycling of N within the plant and for exchange of gaseous NH(3) between leaves and the atmosphere is discussed.


Mechanism of hypertension in diabetic nephropathy.
High prevalence of hypertension is observed in diabetic patients of both the types. Diabetic nephropathy is one of the major reason for high morbidity, mortality and financial burden in such hypertensive diabetic patients. For this review, electronic databases including PubMed/Medline, Embase, Cochrane and Google scholar were searched from 1990-2013. Multiple inter-related factors are responsible for the development of hypertension and therefore nephropathy in the chronic diabetic patients. Majority of such factors are identified to lead to extensive sodium reabsorption and peripheral vasoconstriction and thus leading to microvascular complications like nephropathy. Management of hypertension by targeting such mediators is the highly recommended therapy for controlling and treating diabetic nephropathy. Clinical trials suggests that drugs inhibiting the renin-angiotensin-aldosterone pathway should be used as the first-line agents for the management of hypertensive diabetic nephropathy patients. These agents are effective in slowing the progression of the end-stage kidney disease as well as lowering albuminuria. Researchers are also investigating the effectiveness of drug combination for better management of hypertension and diabetic nephropathy. The present article is a review of the evidences which explains the underlying pathological changes which leads to the development of nephropathy in a hypertensive diabetic patients. The review also observes the clinical trials for different anti-hypertensive drugs which are recommended for the treatment of such patients.


Reliability of Central Adiposity Assessments Using B-Mode Ultrasound: A Comparison of Linear and Curved Array Transducers.
Recently, it was reported that intra-abdominal thickness (IAT) assessments using ultrasound are most reliable if measured from the linea alba to the anterior vertebral column. These 2 anatomical sites can be simultaneously visualized using a linear array transducer. Linear array transducers have different operational characteristics when compared with conventional curved array transducers and are more reliable for some ultrasound-derived measures such as abdominal subcutaneous fat thickness. However, it is unknown whether linear array transducers facilitate more reliable IAT measurements than curved array transducers. The purpose of the current study was to (1) compare the reliability of linear and curved array transducer assessments of IAT and maximal abdominal ratio (MAR) and (2) use the findings to update central adiposity measurement guidelines. Fifteen healthy adults (mean [SD], 27 [10] years; 60% female) with a range of somatotypes (body mass index: mean [SD], 24 [4]; range, 19-33 kg/m; waist circumference: mean [SD], 75 [11]; range, 61-96 cm) were tested on 3 mornings under standardized conditions. Intra-abdominal thickness was assessed 2 cm above the umbilicus (transverse plane), measuring from linea alba to the anterior vertebral column. Maximal abdominal ratio was defined as the ratio of IAT to abdominal subcutaneous fat thickness. The IAT range was 25 to 87 mm, and the MAR range was 0.15 to 0.77. Between-day intraclass correlation coefficient values for IAT measurements made were comparable (0.96-0.97) for both transducers, as were MAR values (0.95). In conclusion, while both transducers provided equally reliable measurement of IAT, the use of a single linear array transducer simplifies the assessment of central adiposity.


[Antibodies to skeletal muscle myofibrillar proteins in the diagnosis of rheumatoid arthritis].
One of the mechanisms of muscular involvement in RA patients was elucidated by identification of antibodies to skeletal muscle components (actin and tropomyosin). Clinical symptoms of skeletal muscles involvement in RA proved to be associated with elevated count of tropomyosin antibodies against an insignificant informative value of actin. Enzyme immunoassay with tropomyosin has established a direct correlation between the number of the antibodies and RA activity.


Berberine induces pacemaker potential inhibition via cGMP-dependent ATP-sensitive K+ channels by stimulating mu/delta opioid receptors in cultured interstitial cells of Cajal from mouse small intestine.
Berberine is traditionally used to treat gastrointestinal (GI) motility disorders. The interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal tract, which are responsible for the production of gut movements. The present study aimed to investigate the effects of berberine on pacemaker potentials (PPs) in cultured ICC clusters from the mouse small intestine, and sought to identify the receptors involved and the underlying mechanisms of action. All experiments were performed on cultured ICCs, and a whole‑cell patch‑clamp configuration was used to record PPs from ICC clusters (current clamp mode). Under current clamp mode, berberine was shown to decrease the amplitude and frequency of PPs. However, these effects were suppressed by treatment with glibenclamide, a specific ATP‑sensitive K+ channel blocker. Nor‑binaltorphimine dihydrochloride (a kappa opioid receptor antagonist) did not suppress berberine‑induced PP inhibition, whereas ICI 174,864 (a delta opioid receptor antagonist) and CTOP (a mu opioid receptor antagonist) did suppress the inhibitory effects of berberine. Pretreatment with SQ‑22536 (an adenylate cyclase inhibitor) or with KT‑5720 (a protein kinase A inhibitor) did not suppress the effects of berberine; however, pretreatment with 1H‑[1,2,4] oxadiazolo [4,3‑a] quinoxalin‑1‑one (a guanylate cyclase inhibitor) or KT‑5823 [a protein kinase G (PKG) inhibitor] did. In addition, berberine stimulated cyclic guanosine monophosphate (cGMP) production in ICCs. These observations indicate that berberine may inhibit the pacemaker activity of ICC clusters via ATP‑sensitive K+ channels and the cGMP‑PKG‑dependent pathway by stimulating mu and delta opioid receptors. Therefore, berberine may provide a basis for the development of novel agents for the treatment of GI motility dysfunction.


Pneumomediastinum after rigid bronchoscopy.
The accumulation of extrapulmonary air is a well-known complication of airway endoscopic procedures. However, pulmonic disease alone can predispose toward pneumomediastinum and pneumothorax, without iatrogenic manipulation. In this case, a portable chest radiograph diagnosed the cause of the sudden accumulation of extrapulmonary air after rigid bronchoscopy as alveolar rupture, rather than iatrogenic airway perforation. The pathophysiology of pneumothorax and pneumomediastinum and the interpretation of chest radiographs in these situations is reviewed.


Neutralization of human cytomegalovirus by human CD13-specific antibodies.
The mechanisms of inhibition of cytomegalovirus (CMV) infection by human CD13 (aminopeptidase N)-specific antibodies were studied. These antibodies protect CD13-negative and -positive cells from CMV infection only if incubated with the virus inoculum, suggesting they bind to CMV virions. The association of a CD13-like molecule with virions was further supported by the transfer of CD13 immunoreactivity to the surface of CD13-negative cells upon binding of CMV; the binding of CD13-specific antibodies directly to the surface of CMV virions; and the presence of anti-CD13 immunoreactive bands, including one with mobility similar to that of native cellular CD13 on immunoblots of proteins of purified CMV particles. Importantly, CD13-specific antibodies neutralize CMV in urine of neonates with congenital CMV, indicating that the CD13-like molecule is associated with natural CMV and not acquired in vitro. These studies demonstrate that a CD13-like molecule is associated with CMV particles and may be important in CMV pathogenesis.


Lower vitamin D levels at first trimester are associated with higher risk of developing gestational diabetes mellitus.
The progressive increase of insulin resistance observed in pregnancy contributes to the pathophysiology of gestational diabetes mellitus (GDM). There is controversy whether vitamin D deficiency contributes to abnormal glycemic regulation in pregnancy. We tested the associations between first trimester 25-hydroxyvitamin D (25OHD) levels and: 1) the risk of developing GDM; 2) insulin resistance/sensitivity, beta cell function and compensation indices in a large population-based prospective cohort of pregnant women. Participants (n = 655) were seen at first (6-13 weeks) and second (24-28 weeks) trimesters for blood samples. At first trimester, 25OHD levels were measured. At second trimester, glucose and insulin were measured 3 times during the oral glucose tolerance test to estimate insulin resistance (HOMA-IR), beta cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUCins/gluc) and beta cell compensation (ISSI-2). Based on IADPSG criteria, 54 participants (8.2 %) developed GDM. Lower first trimester 25OHD levels were associated with higher risk of developing GDM even after adjustment for vitamin D confounding factors and GDM risk factors (OR = 1.48 per decrease of one SD in 25OHD levels; P = 0.04). Lower first trimester 25OHD levels were associated with higher HOMA-IR (r = - 0.08; P = 0.03), lower Matsuda index (r = 0.13; P = 0.001) and lower ISSI-2 (r = 0.08; P = 0.04). After adjustment for confounders, we found no significant association with HOMA-B and AUCins/gluc. Our results suggest that low levels of 25OHD at first trimester are (1) an independent risk factor for developing GDM and (2) associated with insulin resistance at second trimester.


Yellow fever virus infectivity for Bolivian Aedes aegypti mosquitoes.
The absence of urban yellow fever virus (YFV) in Bolivian cities has been attributed to the lack of competent urban mosquito vectors. Experiments with Aedes aegypti from Santa Cruz, Bolivia, demonstrated infection (100%), dissemination (20%), and transmission of a Bolivian YFV strain (CENETROP-322).


Generalized melanosis associated with malignant melanoma: unusual histologic appearance.
A case of generalized melanosis associated with malignant melanoma, characterized by up-to-date, previously undescribed histologic findings, is reported. Markedly dilated dermal lymphatics with features resembling secondary lymphangioma were found. We speculate that a further mechanism, as well as those previously reported in the literature, could be operative in the pathogenesis of this disorder of altered pigmentation.


Mouse CLK-1 is imported into mitochondria by an unusual process that requires a leader sequence but no membrane potential.
clk-1 has been identified and characterized in the nematode Caenorhabditis elegans as a gene that affects the rates, regularity, and synchrony of physiological processes. The CLK-1 protein is mitochondrial and is required for ubiquinone biosynthesis in yeast and in worms, but its biochemical function remains unclear. We have studied the expression of murine mclk1 in a variety of tissues, and we find that the pattern of mclk1 mRNA accumulation closely resembles that of mitochondrial genes involved in oxidative phosphorylation. The pattern of protein accumulation, however, is sharply distinct in some tissues; mCLK1 appears relatively enriched in the gut and depleted in the nervous tissue. We also show that mCLK1 is synthesized as a preprotein that is imported into the mitochondrial matrix, where a leader sequence is cleaved off and the protein becomes loosely associated with the inner membrane. However, in contrast to all known mitochondrial proteins that contain a cleavable pre-sequence, the import of mCLK1 does not require a mitochondrial membrane potential.


Trends in the evaluation of abnormal uterine bleedings with the introduction of manual vacuum aspiration.
In a 12-month period, a total of 507 diagnostic curettages were performed with manual vacuum aspiration (MVA) and sharp metallic curettage (SMC), at the Gandhi Memorial Hospital (GMH). Of these, 406(80.1%) and 101(19.9%) were managed with MVA and SMC, respectively. The bulk of the study population were married, of urban residence, paying and treated on ambulatory basis in the minor operation theater without anaesthesia and analgesia. There were significant differences in the gravidity, parity and abortion frequency of the groups (P < 0.05). The mean ages for MVA and SMC were 35.9 years +/- SD 7.6 years and 36.5 years +/- SD 8.5, years respectively (P < 0.05). The majority of the study population that were subjected for histopathological evaluation of the corpus uteri were in the age group of 35-39 years and accounted for 137 (27.0%) with a cumulative frequency of 66.1%. The service providers handled most of the cases with MVA (P > 0.05) and the indications were mainly for abnormal uterine bleeding and endometrial dating. The histological yields were 97.0% for MVA and 80.2% for SMC. The adequacy of the specimen for MVA and SMC were 0.95 and 0.78, respectively. Even if inadequate and non-conclusive are merged together, the adequacy of the specimen would still be 0.91 and 0.74 for MVA and SMC respectively, maintaining the same proportion. Coincidentally, the diagnostic accuracy for endometrial polyp and also for endometrial carcinoma were 0.7 for MVA and 0.3 for SMC. Our results are similar to that of other researchers.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of the clinical phenotype and haematological course of siblings with Fanconi anaemia.
Fanconi anaemia (FA) is a genetic disorder due to mutations in any of the 22 FANC genes (FANCA-FANCW) and has high phenotypic variation. Siblings may have similar clinical outcome because they share the same variants; however, such association has not been reported. We present the detailed phenotype and clinical course of 25 sibling sets with FA from two institutions. Haematological progression significantly correlated between siblings, which was confirmed in an additional 55 sibling pairs from the International Fanconi Anemia Registry. Constitutional abnormalities were not concordant, except for a moderate degree of concordance in kidney abnormalities and microcephaly.


Homograft microlathed femur prosthesis in stapedectomy.
The use of homografts in ossiculoplasty has been well documented in the literature. In the early 1980s, nonossicular homograft otic capsule bone was used as a prosthetic material in stapedectomy. We began using homograft femur as a prosthetic material in the early 1990s. In this article, we report the results of a retrospective study of the use of homograft femur prostheses. A series of 300 stapedectomies was performed between Aug. 24, 1992, and Jan. 20, 2000. Total footplate removal with preservation of the posterior crus was our procedure of choice. However, in 116 of these cases, the posterior crus could not be used, and a homograft femur prosthesis was substituted. For these prostheses, all homograft femurs were obtained from the American Red Cross. All prostheses were prepared in the bone laboratory and stored in the bone bank until needed. After an adequate period of follow-up, we tabulated our results. We found that in 89 of 113 cases (78.8%) available for follow-up, the air-bone gap was completely closed. In addition, the air-bone gap was closed to within 5 dB in 11 patients (9.7%) and closed to within 10 dB in five patients (4.4%). In all, 105 of the 113 homograft femur prosthetic procedures (92.9%) resulted in a successful outcome.


Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells.
The chemokine monocyte chemoattractant protein-1 [MCP-1; also known as chemokine (C-C motif) ligand 2] is an important mediator of monocyte recruitment during inflammatory processes. Pathologically high expression levels of MCP-1 by tumor cells have been observed in a variety of cancer types. In the majority of cases, high MCP-1 expression is associated with a poor prognosis, as infiltration of the tumor with inflammatory monocytes promotes tumor progression and metastasis. MCP-1 is also expressed in renal cell carcinoma (RCC). In the present study, the function and the regulation of MCP-1 was investigated in two RCC cell lines, CaKi-1 and 786-O. In both cell lines, expression of MCP-1 was significantly enhanced compared with non-cancerous control cells. As expected, secretion of MCP-1 into the medium facilitated the recruitment of peripheral blood monocytes via the chemokine (C-C motif) receptor type 2 (CCR2). As expression of CCR2 was also detected in 786-O and CaKi-1 cells, the effect of autocrine MCP-1/CCR2 signaling was evaluated in these cells. In proliferation assays, administration of an MCP-1 neutralizing antibody or of a CCR2 antagonist to CaKi-1 and 786-O cells significantly decreased cell growth; supplementation of the growth medium with recombinant human MCP-1 had no additional effect on proliferation. The migration ability of RCC cells was impaired by MCP-1 neutralization or pharmacological CCR2 inhibition, while it was stimulated by the addition of recombinant human MCP-1, compared with untreated control cells. Finally, substantial differences in the regulation of MCP-1 expression were observed between RCC cell lines. In CaKi-1 cells, expression of MCP-1 appears to be largely mediated by the transcription factor nuclear factor of activated T cells 5, while in 786-O cells, deletion of the tumor suppressor gene Von-Hippel-Lindau appeared to be responsible for MCP-1 upregulation, as suggested by previous studies. Taken together, the results of the current study indicate that expression of MCP-1 in RCC cells promotes tumor progression and metastasis not only by paracrine, but also by autocrine, MCP-1/CCR2 signaling events, enhancing cell proliferation and migration ability. Therefore, the present findings suggest the MCP-1/CCR2 axis is a potential target for future therapeutic strategies in the treatment of metastatic RCC.


Acute progression of electrophysiologically affected fellow eye in unilaterally symptomatic acute zonal occult outer retinopathy.
Some patients with acute zonal occult outer retinopathy (AZOOR) show symptomatic acute visual impairment in one eye only, but electrophysiological abnormalities in both eyes. A 46-year-old female who had noticed paracentral scotoma of her right eye six months previously was referred to our hospital. At initial examination, her best-corrected visual acuity was 0.7 in the right eye and 1.2 in the left. Whereas the full-field rod electroretinogram (ERG) was normal in both eyes, the cone response was nonrecordable in the right eye and showed a significant decrease in amplitude in the left eye. The 30 Hz flicker ERG showed similar results. Multifocal ERG was nonrecordable in the right eye and showed a residual response in only the central part of the left. Fourteen months after the first visit, the patient presented complaining of acute visual acuity loss in the left eye. Visual acuity in her left eye had decreased to 0.01. The multifocal ERG was nonrecordable. Although the patient chose oral prednisolone therapy, only limited recovery was observed in the patient. Even if only the ERG shows changes and there are no other symptoms, ophthalmologists should continue observation in view of the possibility of an acute exacerbation.


The Role of Mosquitoes in the Diet of Adult Dragon and Damselflies (Odonata).
The flood plains of the Upper Rhine Valley provide excellent conditions for the proliferation of mosquitoes as well as for the development of dragon and damselflies. It could be assumed that mosquitoes belong to the diet of the Odonata and that the latter could be harmed by the reduction of the mosquito population with the purpose of diminishing the massive nuisance for the people living there. A total of 41 adult dragonflies and damselflies were examined by immunoblot for remnants of mosquitoes in their guts. A rabbit antiserum against Aedes vexans proteins was used for the immunoblot. Only 3 Aeshna cyanea and 1 Platycnemis pennipes could be shown to have fed on mosquitoes. In specimens of the genus Sympetrum no mosquitoes were detected. It seems very doubtful that mosquitoes are an essential part of the Odonata diet.


Study on the Effect of Molecular Weight on the Gut Microbiota Fermentation Properties of Blackberry Polysaccharides In Vitro.
This study aimed to investigate the effect of different molecular weights on the metabolic characteristics of blackberry polysaccharides (BBP). After degradation, three fractions, namely, BBP-8, BBP-16, and BBP-24, were obtained. During fermentation, all polysaccharide fractions were significantly degraded and utilized by the intestinal microbiota, and the lower-molecular-weight polysaccharides were easier to be fermented with higher gas production and carbohydrate consumption rates. Furthermore, the monosaccharide utilization sequence of all polysaccharides was glucose > galactose > arabinose > galacturonic acid. In addition, the lower-molecular-weight polysaccharides had a faster short-chain fatty acid (SCFA) production rate but did not affect the final SCFA yields. The fermentation of BBP promoted the increase of Bacteroidetes and the decrease of Firmicutes. The proportions of Bacteroidetes in BBP, BBP-8, BBP-16, and BBP-24 were 45.41, 47.50, 48.08, and 50.09%, respectively.


Cognitive control in the self-regulation of physical activity and sedentary behavior.
Cognitive control of physical activity and sedentary behavior is receiving increased attention in the neuroscientific and behavioral medicine literature as a means of better understanding and improving the self-regulation of physical activity. Enhancing individuals' cognitive control capacities may provide a means to increase physical activity and reduce sedentary behavior. First, this paper reviews emerging evidence of the antecedence of cognitive control abilities in successful self-regulation of physical activity, and in precipitating self-regulation failure that predisposes to sedentary behavior. We then highlight the brain networks that may underpin the cognitive control and self-regulation of physical activity, including the default mode network, prefrontal cortical networks and brain regions and pathways associated with reward. We then discuss research on cognitive training interventions that document improved cognitive control and that suggest promise of influencing physical activity regulation. Key cognitive training components likely to be the most effective at improving self-regulation are also highlighted. The review concludes with suggestions for future research.


[Personal dose monitoring of radiation workers in medical institutions at the municipal level and below in a city from 2011 to 2014].
Objective: To determine the personal dose level of radiation workers in medical institutions at the municipal level and below in a city, and to provide a scientific support for strengthening the radiation protection in the city's medical institutions. Methods: Information of the successful applicants for the "Radiation Worker Permit" from 174 medical institutions at the municipal level and below was collected from October 1, 2011 to December 31, 2014. The annual effective dose was calculated based on the personal dose monitoring report, and indicators including sex, permit application time, hospital level, type of occupational radiation, length of radiation work, blood test, and micronucleated lymphocyte rate were analyzed. Results: Of the 1 143 radiation worker permit applications submitted by medical institutions the municipal level and below in this city from 2011 to 2014, 1 123 provided at least one personal dose monitoring report. The annual effective dose of the radiation workers was 0-4.76 mSv (mean 0.31±0.40 mSv) , and the collective annual effective dose was 351.96 mSv. The annual effective dose was significantly different between radiation workers with different times of permit application, hospital levels, and types of occupational radiation (P<0.05) . Interventional radiology workers had the highest annual effective dose (0.63 mSv) , and annual effective dose was significantly different between interventional radiology workers with different lengths of radiation work (H=10.812, P<0.05) . Conclusion: The personal radiation dose of radiation workers in medical institutions at the municipal level and below in this city is maintained at a relatively low level, suggesting that the occupational environment is relatively safe for these workers. However, more focus should be placed on clinical interventional radiology workers.


Isopentenyl Pyrophosphate cis-1,4-Polyisoprenyl Transferase from Guayule (Parthenium argentatum Gray).
Electron micrographs of the mesophyll cells of guayule Parthenium argentatum Gray leaves show deposits of cis-polyisoprene (rubber) in the cytoplasm in the vicinity of mitochondria and chloroplasts and demonstrate that the rubber-synthesizing enzymes are present in guayule leaves. The terminal step in the synthesis of cis-polyisoprene from isopentenyl pyrophosphate (IPP) catalyzed by isopentenyl pyrophosphate cis-1,4-polyisoprenyl transferase has been demonstrated in crude leaf extracts by the enzymic incorporation of [(14)C]isopentenyl pyrophosphate into the polymer and the recovery of [(14)C]levulinic acid following ozonolysis. The rubber transferase activity in the crude extracts of guayule leaves was 5.8 nanomoles isopentenyl pyrophosphate incorporated per milligram protein per hour. This is the first description of the rubber transferase from a nonlaticiferous plant.The specific activity (in units of nanomoles IPP converted per milligram protein per hour) of the partially purified enzyme following chromatography on diethylaminoethyl-cellulose columns was 41.7 units and contained 0.29 units of IPP isomerase activity and 0.08 units of farnesyl pyrophosphate synthetase activity. The rubber transferase requires reduced glutathione and Mg(2+) for maximal activity. There was no incorporation of IPP into cis-1,4-polyisoprene in the absence of rubber particles as primer, and Langmuir isotherm plots showed that the specific activity of the enzyme was proportional to the concentration of the enzyme on the surface of the rubber particles. For a given rubber particle distribution, enzyme activity was proportional to time, IPP concentration, and rubber concentration. The addition of 0.4 millimolar dimethylallyl pyrophosphate to the rubber transferase reaction resulted in a 2-fold increase in the incorporation of IPP into rubber. A comparison was made of the relative activities of rubber transferase in different species of Parthenium, Ficus, and Euphorbia.


Defining overweight in children using growth charts.
Although the increase in pediatric overweight has paralleled the increase in obesity among adults, the definitions of obesity in adults and overweight in children are not the same. Empirically determined fixed cutoffs that identify increased risk are used for adults while statistical definitions based on reference populations are used for children. A variety of reference-data sets for BMI in childhood exist. In the United States, the 2000 Centers for Disease Control and Prevention (CDC) BMI-for-age growth charts are recommended for screening of overweight and at-risk for overweight in childhood. For children and teens ages two to 19 years, overweight is defined as a BMI-for-age > or = 95th percentile and atrisk for overweight is defined as a BMI-for-age between the 85th and 95th percentiles. The 2000 CDC growth charts provide a growth reference, not a prescriptive standard, for U.S. children.


Perceived Impacts of the COVID-19 Pandemic on Pediatric Care in Canada: A Roundtable Discussion.
Like other recipients of health care services, pediatric patients and their families/caregivers have been profoundly impacted by health care shifts and broader societal restrictions associated with the COVID-19 pandemic. An online roundtable discussion was facilitated with 7 pediatric clinicians and investigators of a current study examining the impacts of COVID-19 on pediatric care at multiple Canadian sites. Discussants represented a range of pediatric specialities: developmental disability, mental health, cardiac transplantation, respiratory medicine, hematology, and palliative care. We offer the transcript of the roundtable in which discussants reflected on clinical and programmatic experiences of the pandemic, including perceived impacts on children receiving care and their families, potential opportunities for improved health care delivery, impacts on health care providers, and recommendations as we move toward easing restrictions and pandemic recovery. Discussants convey a range of considerations that may have varying relevance for pediatric specialities in terms of practice and program planning.


Glutathione in the treatment of liver diseases: insights from clinical practice.
Liver diseases markedly contribute to the global burden of mortality and morbidity. The pathogenesis of alcohol- and non-alcohol-induced liver diseases is complex, and many factors have been described to contribute to the progressive loss of liver functions, including the over-generation of reactive oxygen species. Glutathione (GSH) is the most important low-molecular-weight antioxidant synthesized in cells, as it is a reducing molecule which can react to oxygen species by neutralizing the unpaired electrons that make them highly reactive and dangerous. ROS over-production impairs the intracellular GSH homeostasis, leading to GSH deficiency, a pathophysiological hallmark in alcoholic and non-alcoholic liver diseases.Judging on the basis of the evidence obtained from experimental research and previous clinical studies, GSH administration seems to be a promising strategy to recover oxidative stress-induced liver damages in alcoholic and non-alcoholic liver diseases.


Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania.
Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.


The impact of transposable elements in genome evolution and genetic instability and their implications in various diseases.
Approximately 45% of the human genome is comprised of transposable elements (TEs). Results from the Human Genome Project have emphasized the biological importance of TEs. Many studies have revealed that TEs are not simply "junk" DNA, but rather, they play various roles in processes, including genome evolution, gene expression regulation, genetic instability, and cancer disposition. The effects of TE insertion in the genome varies from negligible to disease conditions. For the past two decades, many studies have shown that TEs are the causative factors of various genetic disorders and cancer. TEs are a subject of interest worldwide, not only in terms of their clinical aspects but also in basic research, such as evolutionary tracking. Although active TEs contribute to genetic instability and disease states, non-long terminal repeat transposons are well studied, and their roles in these processes have been confirmed. In this review, we will give an overview of the importance of TEs in studying genome evolution and genetic instability, and we suggest that further in-depth studies on the mechanisms related to these phenomena will be useful for both evolutionary tracking and clinical diagnostics.


The HOG pathway and the regulation of osmoadaptive responses in yeast.
Cells coordinate intracellular activities in response to changes in the extracellular environment to maximize their probability of survival and proliferation. Eukaryotic cells need to adapt to constant changes in the osmolarity of their environment. In yeast, the high-osmolarity glycerol (HOG) pathway is responsible for the response to high osmolarity. Activation of the Hog1 stress-activated protein kinase (SAPK) induces a complex program required for cellular adaptation that includes temporary arrest of cell cycle progression, adjustment of transcription and translation patterns, and the regulation of metabolism, including the synthesis and retention of the compatible osmolyte glycerol. Hog1 is a member of the family of p38 SAPKs, which are present across eukaryotes. Many of the properties of the HOG pathway and downstream-regulated proteins are conserved from yeast to mammals. This review addresses the global view of this signaling pathway in yeast, as well as the contribution of Dr Hohmann's group to its understanding.


TSG-14 transgenic mice have improved survival to endotoxemia and to CLP-induced sepsis.
Tumor necrosis factor-stimulated gene 14 (TSG-14)/PTX3 was identified originally as a TNF-alpha and IL-1beta-stimulated gene from normal, human foreskin fibroblasts and vascular endothelial cells, respectively. TSG-14 gene encodes a 42-kDa-secreted glycoprotein with a carboxy-terminal half that shares homology with the entire sequence of C-reactive protein (CRP) and serum amyloid P component (SAP), acute-phase proteins of the pentraxin family. Some experimental evidence suggests that TSG-14 plays a role in inflammation, yet its function and mechanism of action remain unclear. We have generated transgenic mice that overexpress the murine TSG-14 gene under the control of its own promoter. From eight transgenic founders, two lineages were derived and better characterized: Tg2 and Tg4, carrying two and four copies of the transgene, respectively. TSG-14 transgenic mice were found to be more resistant to the endotoxic shock induced by LPS and to the polymicrobial sepsis caused by cecal ligation and puncture (CLP). Moreover, macrophages derived from the transgenic mice produced higher amounts of nitric oxide in response to IFN-gamma, TNF-alpha, and LPS as compared with macrophages from wild-type animals, and the augmented response appears to be the consequence of a higher responsiveness of transgenic macrophages to IFN-gamma. The data shown here are the first in vivo evidence of the involvement of TSG-14 in the inflammatory process and suggest a role for TSG-14 in the defense against bacterial infections.


The Prevalence of Uncontrolled Hypertension among Patients Taking Antihypertensive Medications and the Associated Risk Factors in North Palestine: A Cross-Sectional Study.
Uncontrolled hypertension (HTN) is a challenge for public health professionals all over the world. It is the leading and most important modifiable risk factor for coronary artery disease, congestive heart failure, stroke, renal diseases, and retinopathy. The aim of the present study was to estimate the prevalence of uncontrolled HTN among Palestinian hypertensive patients on treatment. In addition, the study aimed to explore the relationship between socio-demographic and clinical factors with HTN control as well as establish a comprehensive literature review for similar studies. A cross-sectional study was conducted. 218 hypertensive patients who met the inclusion criteria were included in the study. HTN is not adequately controlled in over 60% of treated patients. Factors that were linked to uncontrolled HTN and were statistically significant as per this study were diabetes (p=0.010), high BMI (p=0.009), smoking (p < 0.0001), lower educational level (p=0.002), and monotherapy (p=0.004). The results suggest that effective efforts on improving HTN control are strongly needed. The efforts need to target hypertensive patients who are also smokers, diabetics, having a low education level, and have a higher-than-normal BMI.