The effect of disorder of small spheres on the photonic properties of the inverse binary NaCl-like structure.
Inverse opal structures are experimentally realisable photonic band gap materials. They suffer from the drawback of possessing band gaps that are extremely susceptible to structural disorders. A binary colloidal NaCl lattice, which is also experimentally realisable, is a promising alternative to these opals. In this work, we systematically analyse the effect of structural disorder of the small spheres on the photonic properties of an inverse binary NaCl lattice with a size ratio of 0.30 between the small and large spheres. The types of structural disorders studied include the position of the small spheres in the octahedral void of the large spheres, polydispersity in size of the small spheres, and the fraction of small spheres in the crystal. We find a low susceptibility of the band gap of the inverse NaCl lattice to the disorder of the small spheres.


Identification of novel protein domain for sialyloligosaccharide binding essential to Mycoplasma mobile gliding.
Sialic acids, terminal structures of sialylated glycoconjugates, are widely distributed in animal tissues and are often involved in intercellular recognitions, including some bacteria and viruses. Mycoplasma mobile, a fish pathogenic bacterium, binds to sialyloligosaccharide (SO) through adhesin Gli349 and glides on host cell surfaces. The amino acid sequence of Gli349 shows no similarity to known SO-binding proteins. In the present study, we predicted the binding part of Gli349, produced it in Escherichia coli and proved its binding activity to SOs of fetuin using atomic force microscopy. Binding was detected with a frequency of 10.3% under retraction speed of 400 nm/s and was shown to be specific for SO, as binding events were competitively inhibited by the addition of free 3'-sialyllactose. The histogram of the unbinding forces showed 24 pN and additional peaks. These results suggested that the distal end of Gli349 constitutes a novel sialoadhesin domain and is directly involved in the gliding mechanism of M. mobile.


[A case of esophageal squamous cell carcinoma with submucosal tumor-like tumor due to direct invasion of the gastric wall].
We encountered a case of esophageal squamous cell carcinoma (ESCC) with submucosal tumor (SMT)-like tumor in the cardia of the stomach, formed by direct invasion of the gastric wall. The patient was a 72-year-old woman with dysphagia. Upper endoscopy showed a giant SMT-like tumor in the cardia of the stomach, and imaging studies revealed metastasis to the nearby and distant lymph nodes. Although squamous cell carcinoma was diagnosed by biopsy of the SMT-like tumor in the gastric cardia, gastric involvement was suspected via metastasis to the perigastric lymph nodes or direct invasion of the gastric wall by the ESCC, because the primary lesion of ESCC could not be identified during the examinations. FP chemotherapy (days 1-5, 800 mg/m2 5-fluorouracil[5-FU]; day 1, 80 mg/m2 cisplatin[CDDP]) was initiated for the treatment of ESCC. Considering the risk of invasion, we discontinued the chemotherapy and performed lower esophagectomy and cardiectomy. Pathologically, the primary lesion of the ESCC was detected in the abdominal esophagus, and the SMT-like tumor in the gastric cardia was determined to result from direct invasion of the gastric wall by the ESCC. We herein report a rare case of ESCC with an SMT-like tumor in the gastric cardia formed by direct invasion of the gastric wall.


Application of systemic treatment in conversion therapy options for liver cancer.
Radical hepatectomy is the main treatment method to improve the prognosis of patients with intermediate and early-stage liver cancer. Most liver cancer patients in China are in the advanced stage at the initial diagnosis, losing the opportunity for surgical treatment. Therefore, it is essential to down-stage unresectable liver cancer to resectable liver cancer clinically, which is an important way to improve patients' survival and a hotspot of current clinical research. In recent years, with the increase in effective treatment methods for liver cancer, the resection rate of conversion surgery for unresectable advanced liver cancer has been significantly improved, and a growing number of patients benefit from conversion therapy. This article mainly reviews the connotation of conversion therapy for liver cancer, the patient selection, the selection of conversion strategy, the timing of sequential operations, the scheme and safety, etc.


[Expression of a shrimp Kunitz-type protease inhibitor in Pichia pastoris and activity analysis].
SKPI (shrimp Kunitz-type protease inhibitor) from Marsupenaeus japonicus is a member of serine protease inhibitors which play an important role in the arthropod immunity. To fully understand its function in the innate immunity of shrimp, the skpi gene was cloned into a modified pPIC9K vector with a 6-His tag and expressed by Pichia pastoris GS115. The secretory SKPI was purified from the medium with high purity by using Ni Sepharose High Performance. This results also indicated that the purified SKPI could inhibit the activity of trypsin specifically.


Does Disseminated Nontuberculous Mycobacterial Disease Cause False-Positive Determine TB-LAM Lateral Flow Assay Results? A Retrospective Review.
We retrospectively reviewed the Determine TB-LAM lateral flow assay (LF-LAM) results among human immunodeficiency virus-infected patients with disseminated nontuberculous mycobacterial (NTM) disease. LF-LAM was positive in 19 of 21 patients without evidence of tuberculosis (TB) coinfection. Although TB-NTM coinfection may have been underdiagnosed, our results suggest that disseminated NTM disease may cause false-positive LF-LAM results.


Oxidative stress in the pathogenesis of hepatic encephalopathy.
The pathogenesis of hepatic encephalopathy (HE) remains elusive. While it is clear that ammonia is the likely toxin and that astrocytes are the main target of its neurotoxicity, precisely how ammonia brings about cellular injury is poorly understood. Studies over the past decade have invoked the concept of oxidative stress as a pathogenetic mechanism for ammonia neurotoxicity. This review sets out the arguments in support of this concept based on evidence derived from human observations, animal studies, and cell culture investigations. The consequences and potential therapeutic implications of oxidative stress in HE are also discussed.


A Newly Identified lncBCAS1-4_1 Associated With Vitamin D Signaling and EMT in Ovarian Cancer Cells.
Long noncoding RNAs (lncRNAs) were identified rapidly due to their important role in many biological processes and human diseases including cancer. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and its analogues are widely applied as preventative and therapeutic anticancer agents. However, the expression profile of lncRNAs regulated by 1α,25(OH)2D3 in ovarian cancer remains to be clarified. In the present study, we found 606 lncRNAs and 102 mRNAs that showed differential expression (DE) based on microarray data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the DE genes were mainly enriched in TGF-β, MAPK, Ras, PI3K-Akt, and Hippo signaling pathways, as well as the vitamin D-related pathway. We further assessed the potential lncRNAs that linked vitamin D signaling with EMT, and lncBCAS1-4_1 was identified in the first time. Moreover, we found that the most upregulated lncBCAS1-4_1 showed 75% same transcripts with CYP24A1 (metabolic enzyme of 1α,25(OH)2D3). Finally, the lncBCAS1-4_1 gain-of-function cell model was established, which demonstrated that the knockdown of lncBCAS1-4_1 inhibited the proliferation and migration of ovarian cancer cells. Furthermore, lncBCAS1-4_1 could resist the antitumor effect of 1α,25(OH)2D3, which was associated with upregulated ZEB1. These data provide new evidences that lncRNAs served as a target for the antitumor effect of 1α,25(OH)2D3.


Comparing a generic and individualized information decision support intervention for men newly diagnosed with localized prostate cancer.
A randomized study was conducted to compare a generic and individualized approach to providing decisional support to men newly diagnosed with localized prostate cancer. Patients (N = 324) were referred by community urologists to a patient education center where they were randomly assigned to receive either an individualized or generic information intervention. Men assigned to the generic group viewed a video on the various treatments available for localized prostate cancer. Men in the individualized information group used a computer program to identify their information preferences. Computer printouts on top information preferences were individualized according to patient's specific disease characteristics, followed by a discussion of the pros and cons of each recommended treatment option. Both groups received a standardized package of written information. Men completed measures of decision control, satisfaction, and decision conflict at baseline and after a definitive treatment decision was made. Results demonstrated that overall both groups reported increased levels of decision control and lower levels of decision conflict after their treatment decision. All men reported being satisfied with their preparation to make a treatment decision. Compared to the generic information group, men who received the individualized information were more satisfied with the type, amount and method of providing information, and role played in treatment decision making with their physician (P < .002). Both information interventions seem to be similar in providing decisional support to this group of men at the time of diagnosis. Further research is required to determine how to identify men who may benefit from a more individualized approach.


Dissimilar Crystal Proteins Cry5Ca1 and Cry5Da1 Synergistically Act against Meloidogyne incognita and Delay Cry5Ba-Based Nematode Resistance.
Cry proteins of Bacillus thuringiensis (Bt) have been successfully used as biopesticides and in transgenic crops throughout the world. However, resources against the most serious agricultural pathogens, plant root-knot nematodes, are limited. The genomes of several highly nematicidal virulent Bt strains from our laboratory have been sequenced, facilitating the identification of novel Cry proteins and other virulence factors. We identified two novel Cry proteins, Cry5Ca1 and Cry5Da1, that exhibit high toxicity against Meloidogyne incognita Using the Caenorhabditis elegans model, the two Cry5 toxins were shown to negatively affect nematode life span, fertility, and survival. The 50% lethal concentrations (LC50s) of Cry5Ca1 and Cry5Da1 were 57.22 μg/ml and 36.69 μg/ml, respectively. Moreover, a synergistic effect (synergism factor, 1.61 to 2.04) was observed for nematicidal toxicity of Cry5Ca1 and Cry5Da1, which is accordant with the phylogenetic results suggesting that domain II of the two novel Cry5 toxins evolved into two independent clades. Through comparison of the depressed degree of toxicity in the β-methylgalactoside detoxification test, we found that the novel toxin Cry5D possesses a different galactose-binding epitope; meanwhile, the finding that Cry5D does not share a motif (GXXXE) in the corresponding loop of domain II with Cry5B could explain the different galactose binding performance. Additionally, low-level cross-resistance of C. elegans bre mutant strains was evident between Cry5B and Cry5D. These results suggest that Cry5D can be used as an alternative to delay the potential resistance of nematodes to Cry5B.IMPORTANCE Although proper gene resources for Bt crops against the most serious agricultural pathogens, plant root-knot nematodes, are limited, we have identified two novel nematicidal toxins, Cry5Ca1 and Cry5Da1, against M. incognita, which have supplied more gene candidates for Bt crops designed against nematodes. Moreover, the association of the dissimilarity between Cry5Da1 and Cry5Ba1 and their low cross-resistance can be attributed not only to a low sequence similarity of domain II but also to the structural difference of the key motif and receptor-binding epitope in the loops. This association facilitates the selection of a proper candidate for the prospective design of pyramided Bt crops that can delay potential resistance.


Demonstration of intratumoral infiltration of tumor-specific Lyt-1+2- T cells mediating delayed-type hypersensitivity response and in vivo protective immunity.
The present study demonstrates the intratumoral infiltration of lymphocytes mediating anti-tumor delayed-type-hypersensitivity (DTH) responses as well as in vivo protective immunity. The surface phenotype and tumor specificity of these effector lymphocytes were determined. X5563 tumor-infiltrating lymphoid cells were obtained from the tumor mass of syngeneic C3H/HeN mice 2 weeks after the intradermal inoculation of 10(6) viable X5563 tumor cells. These lymphoid cells consisted of Thy-1-positive (29-35%), surface immunoglobulin-positive (16-29%), large granule-positive (15-25%) and esterase-staining-positive (10-20%) cells. They were tested for anti-X5563 DTH responses by utilizing a local adoptive transfer system and for tumor-neutralizing activity in a Winn assay. The results indicate that X5563 tumor-infiltrating lymphoid cells exhibited appreciable anti-X5563 DTH responses and conveyed complete protection against the tumor. Treatment of these lymphoid cells with anti-Thy-1.2 or anti-Lyt antibodies plus complement revealed that the in vivo anti-tumor immune responses were mediated predominantly by a Lyt-1+2- T cell subset. Such Lyt-1+2- T cell-mediated immunity was tumor-specific, since X5563-infiltrating and syngeneic MH134 hepatoma-infiltrating cells exhibited DTH response and tumor-neutralizing activity selectively against the respective tumor cell types. Thus, these results indicate that tumor-specific in vivo-protective Lyt-1+2- T cells infiltrate into the tumor mass. The results are discussed in the context of 1) the interrelation of DTH responses and the tumor protection mediated by the Lyt-1+2- T cell subset and 2) possible cellular interactions between Lyt-1+2- T cells and co-existing nonspecific tumoricidal effector cells such as macrophages.


The R2R3MYB VvMYBPA1 from grape reprograms the phenylpropanoid pathway in tobacco flowers.
This work shows that, in tobacco, the ectopic expression of VvMYBPA1 , a grape regulator of proanthocyanidin biosynthesis, up- or down-regulates different branches of the phenylproanoid pathway, in a structure-specific fashion. Proanthocyanidins are flavonoids of paramount importance for animal and human diet. Research interest increasingly tilts towards generating crops enriched with these health-promoting compounds. Flavonoids synthesis is regulated by the MBW transcriptional complex, made of R2R3MYB, bHLH and WD40 proteins, with the MYB components liable for channeling the complex towards specific branches of the pathway. Hence, using tobacco as a model, here, we tested if the ectopic expression of the proanthocyanidin regulator VvMYBPA1 from grape induces the biosynthesis of these compounds in not-naturally committed cells. Here, we show, via targeted transcriptomic and metabolic analyses of primary transgenic lines and their progeny, that VvMYBPA1 alters the phenylpropanoid pathway in tobacco floral organs, in a structure-specific fashion. We also report that a modest VvMYBPA1 expression is sufficient to induce the expression of both proanthocyanidin-specific and early genes of the phenylpropanoid pathway. Consequently, proanthocyanidins and chlorogenic acids are induced or de novo synthetised in floral limbs, tubes and stamens. Other phenylpropanoid branches are conversely induced or depleted according to the floral structure. Our study documents a novel and distinct function of VvMYBPA1 with respect to other MYBs regulating proanthocyanidins. Present findings may have major implications in designing strategies for enriching crops with health-promoting compounds.


Renal function and blood pressure in 11 year old children born extremely preterm or small for gestational age.
Preterm birth and low birth weight are associated with reduced nephron numbers and increased risk of hypertension and kidney disease in later life. We tested the hypothesis that extremely preterm birth and intrauterine growth restriction is associated with decreased renal function in mid childhood. At 11 years of age the following measures were obtained in a regional cohort of children born extremely premature (EP, i.e. < 28 weeks gestational age-GA) or with extremely low birth weight (ELBW, i.e. BW < 1000 grams) and in matched controls born at term with appropriate BW (AGA): Height, weight, abdominal circumference, triceps and subscapular skin fold thicknesses, blood pressure, plasma levels of creatinine, cystatin C and symmetric dimethyl arginine (SDMA). Small for gestational age (SGA) was defined as a BW < 10th percentile for GA. Glomerular filtration rate (GFR) was estimated according to the equations by Schwartz, Zappitelli and Gao. Fifty-seven of 61 eligible EP/ELBW children, 20 (35%) born SGA, and 54 controls, were assessed. Estimated GFR decreased while plasma SDMA increased from the children born AGA at term through those born preterm AGA to preterm SGA. Systolic BP was correlated to fat mass indices (p<0.03), but not to renal function (p>0.2) and did not differ between the groups. Children born EP/ELBW, particularly those born SGA, had impaired renal function at age 11 years as judged from estimated GFRs and plasma levels of SDMA. Since reduced renal function is associated with an increased risk of later disease, these children should be followed in order to minimize additional risk factors.


The rise and fall of tobacco smoking and associated rise and fall of coronary atherosclerosis the lethal role of tobacco.
In this review two new hypotheses are explored, one, that the decline in coronary heart disease is mainly due to a dramatic decline in the prevalence of underlying atherosclerosis and two, that tobacco smoking has been a much greater influence on atherosclerosis than previously estimated. The major outcome of coronary atherosclerosis is myocardial infarction. Between 1900 and 1960 the prevalence of coronary atherosclerosis dramatically rose in young male soldiers. Between 1960 and 2010 the prevalence of coronary atherosclerosis in young US soldiers equally dramatically fell. Understanding the reasons for this rise and fall offers important insights into the causes of atherosclerosis. In 1960 over 50% of US military personnel were tobacco smokers but by 1988 the rate had reduced to 30%. The increased prevalence of coronary atherosclerosis in young soldiers between 1900 and 1960 was mainly due to increased tobacco smoking. An additional influence was an increase in food and sugar consumption. The fall in atherosclerosis between 1960 and 2010 was probably due to a reduction in tobacco smoking and to a lesser extent, control of hypertension and lowering of high serum total cholesterol. In Western populations up to two thirds of the fall in deaths due to myocardial infarction has been shown to be due to declines in the incidence of heart attacks. Based on the data included in this review it is arguable that the main reason for the fall in the incidence of heart attacks is the fall in the prevalence of underlying coronary atherosclerosis. The adverse influences of tobacco have been well documented. However the enormity of these adverse influences has not been recognised. Over 50% of men continue to smoke tobacco in China, Indonesia, Russia and middle eastern countries. Based on the experience of Western countries over half of these men will die of smoking related conditions.


[Enzymatic and morphological study of the liver in acute radiation sickness].
The morphologic changes in the liver were investigated along with those in the activity of the specific liver enzymes in the blood plasma of rats in the case of the severe form of acute radiation disease. The rats were treated with 670 Rad at the rate of 90 Rad/min. The studies were carried out on the 1st, 8th , 15th, 22nd, and 30th day following irradiation. It was found that under the conditions of the experiment the activity of the cytoplasmic enzymes sorbitoldehydrogenase , cholinesterase, and leucinaminopeptidase strongly rose on the 1st day after treatment (the activity of sorbitoldehydrogenase increased 11 times). The activity of acid phosphatase and glutamate dehydrogenase also increased strongly, whereupon there was deterioration of the mitochondrial and lysosomal structures. Seen were well expressed processes of fatty and parenchymal dystrophy. The studies on the changes in the activity of these enzymes can be used as an adjunct, resp., an auxiliary test to the haematologic indices in the evaluation of the severity of radiation disease.


Structural basis for the ligand recognition and signaling of free fatty acid receptors.
Free fatty acid receptors 1-4 (FFA1-4) are class A G protein-coupled receptors (GPCRs). FFA1-3 share substantial sequence similarity whereas FFA4 is unrelated. Despite this FFA1 and FFA4 are activated by the same range of long chain fatty acids (LCFAs) whilst FFA2 and FFA3 are instead activated by short chain fatty acids (SCFAs) generated by the intestinal microbiota. Each of FFA1, 2 and 4 are promising targets for novel drug development in metabolic and inflammatory conditions. To gain insights into the basis of ligand interactions with, and molecular mechanisms underlying activation of, FFAs by LCFAs and SCFAs, we determined the active structures of FFA1 and FFA4 bound to the polyunsaturated LCFA docosahexaenoic acid (DHA), FFA4 bound to the synthetic agonist TUG-891, as well as SCFA butyrate-bound FFA2, each complexed with an engineered heterotrimeric Gq protein (miniGq), by cryo-electron microscopy. Together with computational simulations and mutagenesis studies, we elucidated the similarities and differences in the binding modes of fatty acid ligands with varying chain lengths to their respective GPCRs. Our findings unveil distinct mechanisms of receptor activation and G protein coupling. We anticipate that these outcomes will facilitate structure-based drug development and underpin future research to understand allosteric modulation and biased signaling of this group of GPCRs.


In vitro culture studies of childhood myelodysplastic syndrome: establishment of the cell line MUTZ-1.
Myelodysplastic syndrome (MDS) in childhood is considered to be very rare and detailed pathobiological data are scarce. More biological information regarding MDS in children is clearly needed and in vitro culture studies provide one possibility for gaining further pathophysiological insights into this malignancy. Here, we incubated bone marrow samples from 30 children with MDS in liquid suspension culture in order to grow the transformed cells in vitro. In most cultures, the hematopoietic cells died quickly and only fibroblastic (stromal) background layers proliferated temporarily; several normal Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines (B-LCL) were established. Only in one instance, albeit from the peripheral blood and not from the bone marrow, could we establish a cell line, termed MUTZ-1, from the malignant cells of a 5-year-old girl with MDS (FAB subtype refractory anemia with excess of blasts). The MDS arose from a pre-existing Fanconi anemia and progressed quickly to an acute myeloid leukemia (FAB M2). Despite positivity for EBV, MUTZ-1 is not an EBV + B-LCL and further characterization of MUTZ-1 confirmed the derivation from the transformed clonal cells. Immunophenotyping showed a pre B-cell surface marker profile (CD10+ CD19+ cytoplasmic IgM+); receptor gene rearrangement analyses underlined the clonal B-cell nature of MUTZ-1 cells. MUTZ-1 cells exhibit a highly rearranged, unstable karyotype with a high frequency of spontaneous chromatid breaks and exchanges; del(5q) and additional rearrangements involving chromosome 5 [der(15)t(5;15)] were detected. The present data and results from a few other MDS-derived cell lines suggest that the transforming event in MDS seems to occur in an immature pluripotent progenitor cell. The new MDS-derived continuous cell line MUTZ-1 provides a useful in vitro model system for studies on the pathogenetic events leading to MDS.


Prenatal education for congenital toxoplasmosis.
Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. To assess the effects of prenatal education for preventing congenital toxoplasmosis. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015), and reference lists of relevant papers, reviews and websites. Randomized and quasi-randomized controlled trials of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were eligible for inclusion. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two cluster-randomized controlled trials (RCTs) (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways, which meant that meta-analysis of the results was not possible. The overall quality of the two studies, as assessed using the GRADE approach, was low, with high risk of detection and attrition bias in both included trials.One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. This trial did not report on any of the review's pre-specified primary outcomes and the secondary outcomes reported results only as P values. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were also high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a significant effect on improving women's knowledge, whereas it has no effect on changing women's behavior. In this trial 17/3949 pregnant women seroconverted for toxoplasmosis: 13/2591 (0.5%) in the intervention group and 4/1358 (0.3%) in the control group. The rate of seroconversion detected during the study did not differ between groups (risk ratio (RR) 1.70, 95% confidence interval (CI) 0.56 to 5.21; participants = 3949; studies = one, low quality evidence). The number of events was too small to reach conclusions about the effect of prenatal education on seroconversion rate during pregnancy.No other randomized trials on the effect of prenatal education on congenital toxoplasmosis rate, or toxoplasmosis seroconversion rate during pregnancy were detected. Even though primary prevention of congenital toxoplasmosis is considered a desirable intervention, given the lack of related risks compared to secondary and tertiary prevention, its effectiveness has not been adequately evaluated. There is very little evidence from RCTs that prenatal education is effective in reducing congenital toxoplasmosis even though evidence from observational studies suggests it is. Given the lack of good evidence supporting prenatal education for congenital toxoplasmosis prevention, further RCTs are needed to confirm any potential benefits and to further quantify the impact of different sets of educational intervention.


Assessing attitudes towards statistics among medical students: psychometric properties of the Serbian version of the Survey of Attitudes Towards Statistics (SATS).
Medical statistics has become important and relevant for future doctors, enabling them to practice evidence based medicine. Recent studies report that students' attitudes towards statistics play an important role in their statistics achievements. The aim of the study was to test the psychometric properties of the Serbian version of the Survey of Attitudes Towards Statistics (SATS) in order to acquire a valid instrument to measure attitudes inside the Serbian educational context. The validation study was performed on a cohort of 417 medical students who were enrolled in an obligatory introductory statistics course. The SATS adaptation was based on an internationally accepted methodology for translation and cultural adaptation. Psychometric properties of the Serbian version of the SATS were analyzed through the examination of factorial structure and internal consistency. Most medical students held positive attitudes towards statistics. The average total SATS score was above neutral (4.3±0.8), and varied from 1.9 to 6.2. Confirmatory factor analysis validated the six-factor structure of the questionnaire (Affect, Cognitive Competence, Value, Difficulty, Interest and Effort). Values for fit indices TLI (0.940) and CFI (0.961) were above the cut-off of ≥0.90. The RMSEA value of 0.064 (0.051-0.078) was below the suggested value of ≤0.08. Cronbach's alpha of the entire scale was 0.90, indicating scale reliability. In a multivariate regression model, self-rating of ability in mathematics and current grade point average were significantly associated with the total SATS score after adjusting for age and gender. Present study provided the evidence for the appropriate metric properties of the Serbian version of SATS. Confirmatory factor analysis validated the six-factor structure of the scale. The SATS might be reliable and a valid instrument for identifying medical students' attitudes towards statistics in the Serbian educational context.


Comparing the efficacy and safety of atomization of traditional Chinese medicine Kai Hou Jian and budesonide suspension in adult acute laryngitis: a randomized control trial.
Kai Hou Jian has an outstanding therapeutic effect and clinical use against pharyngeal infection for many years, while a few studies reported it also had an effect in laryngitis. This study aimed to evaluate the efficacy and safety of short-course oral inhalation of traditional Chinese medicine Kai Hou Jian in adults with acute laryngitis. A total of 86 patients with acute laryngitis who met the inclusion criteria were randomly assigned according to the random number table method into a Kai Hou Jian treatment group or a budesonide control group. Patients received 2.5 mL of Kai Hou Jian via transoral atomization twice daily for 1 week, while the control group received budesonide nebulization (1 mg, bid) for 1 week. The change of symptoms scores of acute laryngitis and laryngoscopy scores before and after treatment were performed to value the effect of Kai Hou Jian and the safety was assessed by the patient's discomfort and the incidence and self-reported adverse events during treatment. The symptoms of acute laryngitis were significantly reduced in patients treated with Kai Hou Jian on day-3. Forty-two patients from the Kai Hou Jian and 40 patients from budesonide treated groups both experienced notable clinical improvement after 1 week. There was no difference in the two groups at the baseline. For individual symptoms, Kai Hou Jian could significantly improve sore throat [95% confidence interval (CI): -1.81 to -0.14, P=0.03], while budesonide yielded better improvement in hoarseness (95% CI: 0.67 to 0.20, P=0.001). For laryngoscopic parameters, the scores of laryngeal mucosa were significantly decreased in both groups from baseline, and there were no statistical differences in vocal cord hyperemia, edema, sputum congestion, edema, mucus adhesion, or epiglottic congestion between the groups after 1 week. We also found that the treatment of Kai Hou Jian nebulization could reduce the extent or range of vocal cord leukoplakia after 1 week. The short-course treatment of Kai Hou Jian atomization had significant effect in improving adult acute laryngitis and it was also possibly exhibiting a positive effect on vocal cord leukoplakia. Chinese Clinical Trial Registry identifier: ChiCTR1900026660.


CMOS-based opto-electronic neural interface devices for optogenetics.
CMOS-based opto-electronic neural interface devices are presented. The devices are designed with target application of in vitro and in vivo optogenetics. Two types of the opto-electronic neural interface devices are presented. One is single-chip type device for on-chip optogenetics, and the other is multi-chip type device with flexibility and wide-area coverage for in vivo optogenetics on brain. Design, packaging and functional evaluations are presented.


Blended smartphone intervention for patients in opioid maintenance treatment in Iran: protocol for a randomized controlled trial.
The pattern of substance use in Iran is characterized by a high prevalence of opioid use and opioid use disorder (OUD). Although opioid maintenance therapy (OMT) has been introduced in Iran, approximately 50% of people with opioid use disorder remain unreached. Moreover, psychosocial treatment of OUD and common mental health symptoms during OMT is limited. Digital interventions have been shown to improve psychological distress, depression, anxiety, and post-traumatic stress disorder symptoms. In addition, providing psychoeducation and risk reduction counseling to prevent communicable diseases like HIV and infectious hepatitis is common via the Internet. However, despite these promising advances, no smartphone intervention in OMT has been investigated for the treatment of OUD and common comorbid mental health symptoms. We examine the effectiveness of adding a blended smartphone intervention based on community reinforcement approach, motivational interviewing- and cognitive behavioral therapy compared to OMT as usual that aims to improve OMT outcomes and addresses common mental health symptoms in OMT patients in Iran. Adults with opioid dependence entering 8 treatment centers in Tehran, Iran will be randomly assigned to receive either OMT plus a smartphone intervention or OMT as usual. The primary outcomes will be the percentage of negative urine tests for illicit, non-prescribed use of opioids (opium, heroin, tramadol) and treatment retention. Secondary outcomes will include the longest period of abstinence from the illicit, non-prescribed use of opioids (opium, heroin, and tramadol) confirmed by urine samples, changes in communicable disease risk-taking behaviors, changes in stress and common mental health symptoms, and client satisfaction. Data analysis will follow the intention-to-treat principle and employ (generalized) linear mixed models. This study will provide substantial knowledge for designing effective blended interventions for OUD. Moreover, it will investigate if treatment retention and OMT-related outcomes and common mental health symptoms can be improved by adding a smartphone intervention to OMT. https://en.irct.ir/trial/53578 .


MOZ and MOZ-CBP cooperate with NF-kappaB to activate transcription from NF-kappaB-dependent promoters.
Monocytic zinc finger (MOZ) maintains hematopoietic stem cells and, upon fusion to the coactivator CREB-binding protein (CBP), induces acute myeloid leukemia (AML). Leukemic stem cells in AML often exhibit excessive signal-dependent activity of the transcription factor nuclear factor (NF)-kappaB. Because aberrant interaction between NF-kappaB and coactivators represents an alternative mechanism for enhancing NF-kappaB activity, we evaluated whether MOZ and MOZ-CBP cooperate with NF-kappaB to activate transcription from NF-kappaB-dependent promoters. The ability of MOZ, MOZ mutants, and MOZ-CBP to enhance expression of NF-kappaB-dependent promoters was tested in reporter studies. The interaction between MOZ and NF-kappaB was evaluated by both coimmunoprecipitation and glutathione S-transferase pulldown assays. MOZ activates transcription from the NF-kappaB-dependent interleukin-8 promoter; interestingly, this effect is markedly enhanced by CBP. Although MOZ has less potent transcriptional activity than MOZ-CBP, both proteins cooperate with steroid receptor coactivator-1 to activate transcription. MOZ also induces multiple NF-kappaB-dependent viral promoters. Importantly, MOZ associates in a protein complex with the p65 subunit of NF-kappaB and interacts directly with p65 in vitro. Transcriptional activity of MOZ requires its C-terminal domain, which is absent from MOZ-CBP, indicating that the transcriptional activity of MOZ-CBP derives from its CBP sequence. MOZ interacts with the p65 subunit of NF-kappaB and enhances expression of NF-kappaB-dependent promoters. The more potent transcriptional activity of MOZ-CBP derives from its CBP sequence. Thus, interaction between NF-kappaB and MOZ-CBP may play an important role in the pathogenesis of certain acute myeloid leukemias.


Abnormal expression of long non-coding RNAs in myocardial infarction.
Myocardial infarction (MI) is the leading cause of fatality worldwide. Our study aimed to investigate the dysregulated long non-coding RNA (lncRNA) in MI and elucidate the mechanism of it in MI. The lncRNA and mRNA expression profiling of the whole left ventricular tissue of MI mice model (8 mice) and Sham group (8 mice) was obtained based on microarray analysis. Differentially expressed lnRNAs/mRNA (DELs/DEMs) were identified in MI. DELs/DEMs co-expression network construction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to predict the biological functions of DEMs. Quantitative real-time polymerase chain reaction (qRT-PCR) was subjected to validate the abnormally expressed DELs in left ventricular tissues of MI mice model. Total of 168 DELs (37 up- and 131 down-regulated) and 126 DEMs (87 up- and 39 down-regulated) were identified in MI compared with Sham group. The co-expression network of candidate DELs and DEMs was constructed, which covered 219 nodes and 1775 edges. The qRT-PCR validation results indicated that ENSMUST00000124047 was significantly down-regulated in MI group and AK166279 was significantly up-regulated in MI group. ENSMUST00000121611 and NR_015515 had the up-regulated tendency in MI group compared with Sham group. The DEMs in MI were significantly enriched in 41 signaling pathways including complement and coagulation cascades, cytokine-cytokine receptor interaction and chemokine signaling pathway. The expression profiling of dysregulated DELs in MI was identified. Our results might provide useful information for exploring the pathogenesis mechanism of MI.


[Arteriovenous fistulae following percutaneous renal biopsy in renal transplantation. Selective arterial embolization].
Five cases of clinically severe arteriovenous fistulae (AVF) secondary to percutaneous renal biopsy in patients carrying a functional renal graft were diagnosed and treated in our centre. Occlusion via superselective intraarterial embolization accomplished successful control in every case. We insist on the therapeutical value of this minimally invasive technique, which furnish it with a particularly relevant role in renal transplantation.


Sex differences in telomeres and lifespan in Soay sheep: From the beginning to the end.
There is tremendous diversity in ageing rates and lifespan not only among taxa but within species, and particularly between the sexes. Women often live longer than men, and considerable research on this topic has revealed some of the potential biological, psychological and cultural causes of sex differences in human ageing and lifespan. However, sex differences in lifespan are widespread in nonhuman animals suggesting biology plays a prominent role in variation in ageing and lifespan. Recently, evolutionary biologists have borrowed techniques from biomedicine to identify whether similar mechanisms causing or contributing to variation in ageing and lifespan in humans and laboratory animals also operate in wild animals. Telomeres are repetitive noncoding DNA sequences capping the ends of chromosomes that are important for chromosomal stability but that can shorten during normal cell division and exposure to stress. Telomere shortening is hypothesized to directly contribute to the ageing process as once telomeres shorten to some length, the cells stop dividing and die. Men tend to have shorter telomeres and faster rates of telomere attrition with age than women, suggesting one possible biological cause of sex differences in lifespan. In this issue of Molecular Ecology, Watson et al. () show that telomere lengths in wild Soay sheep are similar between females and males near the beginning of life but quickly diverge with age because males but not females showed reduced telomere lengths at older ages. The authors further show that some of the observed sex difference in telomere lengths in old age may be due to male investment in horn growth earlier in life, suggesting that sexually dimorphic allocation to traits involved in sexual selection might underlie sex differences in telomere attrition. This study provides a rare example of how biological mechanisms potentially contributing to sex differences in lifespan in humans may also operate in free-living animals. However, future studies using a longitudinal approach are necessary to confirm these observations and identify the ultimate and proximate causes of any sex differences in telomere lengths. Collaborations between evolutionary biologists and gerontologists are especially needed to identify whether telomere lengths have a causal role in ageing, particularly in natural conditions, and whether this directly contributes to sex differences in lifespan.


[EFFECT OF POLYCOMPONENT PROBIOTICS ON THE COMPOSITION OF COLON MICROBIOCENOSIS DURING EXPERIMENTAL DYSBIOSIS].
Study the effect of RioFlora Immuno Neo and Bifiform probiotics on the colon microflora composition under the conditions of experimental dysbiosis in mice. Medicinal dysbiosis was modelled in animals by gentamicin administration, probiotics were administered intragastrally by the end of dysbiosis formation. Quantitative and qualitative study of mucous microflora of mice colon was carried out by a bacteriological method. Correction of dysbiosis by probiotics has resulted in correction of the intestine microflora composition, and more pronounced when RioFlora Immuno Neo was used. CONCLUSION. The results of the study allow to recommend the use of these preparations for selective correction of colon dysbiosis.


Metabolically Healthy Obesity Is Not Associated with Food Intake in White or Black Men.
Healthy obese individuals may be protected against adverse health outcomes. Diet and race might influence healthy obesity, but data on their roles and interactions on the phenotype are limited. We compared the food intake of metabolically healthy obese men to those of other weight status-metabolic health phenotypes. Men (n = 4855) aged ≥ 45 y with BMI ≥ 18.5 kg/m(2) and free of cardiovascular diseases, diabetes, and cancer were evaluated in a cross-sectional study of the REGARDS (REasons for Geographic And Racial Differences in Stroke) study cohort. Food intake was assessed with the use of a food frequency questionnaire. Weight status-metabolic health phenotypes were defined by using metabolic syndrome (MetS) and homeostasis model assessment of insulin resistance (HOMA-IR) criteria. Mean differences in food intake among weight status-metabolic health phenotypes were compared with the use of linear regression. MetS-defined healthy obesity was present in 44% of white obese men and 58% of black obese men; the healthy obese phenotype, based on HOMA-IR, was equally prevalent in both white (20%) and black (21%) obese men. Among white men, MetS-defined healthy and unhealthy obesity were associated with lower wholegrain bread intake and higher consumption of red meat (P < 0.001), whereas HOMA-IR-defined healthy and unhealthy obesity were associated with lower red meat intake (P < 0.0001) compared with healthy normal weight in multivariable-adjusted analyses that adjusted for sociodemographic, lifestyle, and clinical confounders. However, results were attenuated and became nonsignificant after further adjustment for BMI. Healthy and unhealthy overweight, defined by both criteria, were associated with lower whole grain bread intake (P < 0.001) in all models. Among black men, weight status-metabolic health phenotypes were not associated with food intake in all models. Healthy obesity in men is not associated with a healthier diet. Future studies need to consider dietary patterns, which may better inform the holistic effect of diet on healthy obesity, in prospective analyses.


The second window ICG technique demonstrates a broad plateau period for near infrared fluorescence tumor contrast in glioblastoma.
Fluorescence-guided surgery has emerged as a powerful tool to detect, localize and resect tumors in the operative setting. Our laboratory has pioneered a novel way to administer an FDA-approved near-infrared (NIR) contrast agent to help surgeons with this task. This technique, coined Second Window ICG, exploits the natural permeability of tumor vasculature and its poor clearance to deliver high doses of indocyanine green (ICG) to tumors. This technique differs substantially from established ICG video angiography techniques that visualize ICG within minutes of injection. We hypothesized that Second Window ICG can provide NIR optical contrast with good signal characteristics in intracranial brain tumors over a longer period of time than previously appreciated with ICG video angiography alone. We tested this hypothesis in an intracranial mouse glioblastoma model, and corroborated this in a human clinical trial. Intracranial tumors were established in 20 mice using the U251-Luc-GFP cell line. Successful grafts were confirmed with bioluminescence. Intravenous tail vein injections of 5.0 mg/kg (high dose) or 2.5 mg/kg (low dose) ICG were performed. The Perkin Elmer IVIS Spectrum (closed field) was used to visualize NIR fluorescence signal at seven delayed time points following ICG injection. NIR signals were quantified using LivingImage software. Based on the success of our results, human subjects were recruited to a clinical trial and intravenously injected with high dose 5.0 mg/kg. Imaging was performed with the VisionSense Iridium (open field) during surgery one day after ICG injection. In the murine model, the NIR signal-to-background ratio (SBR) in gliomas peaks at one hour after infusion, then plateaus and remains strong and stable for at least 48 hours. Higher dose 5.0 mg/kg improves NIR signal as compared to lower dose at 2.5 mg/kg (SBR = 3.5 vs. 2.8; P = 0.0624). Although early (≤ 6 hrs) visualization of the Second Window ICG accumulation in gliomas is stronger than late (≥24 hrs) visualization (SBR = 3.94 vs. 2.32; p<0.05) there appears to be a long plateau period of stable ICG NIR signal accumulation within tumors in the murine model. We call this long plateau period the "Second Window" of ICG. In glioblastoma patients, the delayed visualization of intratumoral NIR signal was strong (SBR 7.50 ± 0.74), without any significant difference within the 19 to 30 hour visualization window (R2 = 0.019). The Second Window ICG technique allows neurosurgeons to deliver NIR optical contrast agent to human glioblastoma patients, thus providing real-time tumor identification in the operating room. This nonspecific tumor accumulation of ICG within the tumor provides strong signal to background contrast, and is not significantly time dependent between 6 hours to 48 hours, providing a broad plateau for stable visualization. This finding suggests that optimal imaging of the "Second Window of ICG" may be within this plateau period, thus providing signal uniformity across subjects.


An unusual intragenic promoter of PIWIL2 contributes to aberrant activation of oncogenic PL2L60.
PIWIL2-like (PL2L) protein 60 (PL2L60), a product of aberrantly activated PIWIL2 gene, is widely expressed in various types of tumors and may promote tumorigenesis. However, the mechanisms underlying the activation of expression of PL2L60 remain unknown. In this study, an intragenic promoter responsible for the activation of PL2L60 within the human PIWIL2 gene has been identified, cloned and characterized. The promoter of PL2L60 is located in the intron 10 of the host gene PIWIL2. Bioinformatic and mutagenic analysis reveals that this intragenic promoter within the sequence of 50 nucleotides contains two closely arranged cis-acting elements specific for the hepatic leukemia factor (HLF) in the positive strand and signal transducer and activator of transcription 3 (STAT3) in the negative strand. Chromatin immunoprecipitation analysis demonstrates that both the HLF and polymerase II (Pol II), a hallmark of active promoters, directly bind to the sequence, although STAT3 does not. Knockdown of HLF and STAT3 alone or both by RNA interference significantly reduced both promoter activity and the PL2L60 protein expression, although there is no additive effect. The expression of PL2L60 proteins was enhanced when host gene Piwil2 was genetically disrupted in a murine cell model. Taken together, we have identified a PL2L60-specific intragenic promoter in the host gene of PIWIL2, which is interdependently activated by HLF and STAT3 through steric interaction. This activation is dependent on cellular milieu rather than the integrity of host gene PIWIL2, highlighting a novel, important mechanism for a cancer-causing gene to be activated during tumorigenesis.


Magnetochromatic thin-film microplates.
A new type of magnetochromatic material is developed based on thin-film interference of microplates self-assembled from super-paramagnetic nanocrystals. Dynamic optical tuning can be achieved through orientational manipulation of free-standing super-paramagnetic thin-film microplates using external magnetic fields.


Adverse drug events in Chinese elder inpatients: a retrospective review for evaluating the efficiency of the Global Trigger Tool.
Elderly patients frequently experience a high incidence of adverse drug events (ADEs) due to the coexistence of multiple diseases, the combination of various medications, poor medication compliance, and other factors. Global Trigger Tool (GTT) is a new method for identifying ADEs, introducing the concept of a trigger, that is, clues including abnormal laboratory values, reversal drugs, and clinical symptoms that may suggest ADEs, and specifically locating information related to ADEs in the medical record to identify ADEs. The aim of this study was to establish a GTT-based trigger tool for adverse medication events in elderly patients and to investigate the risk variables associated with such events. The triggers were identified by reviewing the frequency of ADEs in elderly patients in Sichuan, China, retrieving relevant literature, and consulting experts. A retrospective analysis was carried out to identify adverse medication occurrences among 480 elderly inpatients in Sichuan People's Hospital. A total of 56 ADEs were detected in 51 patients (10.62%), 13.04 per 1,000 patient days, and 11.67 per 100 admissions. The overall positive predictive value (PPV) of the triggers was 23.84, and 94.64% of ADEs caused temporary injury. Gastrointestinal system injury (27.87%) and metabolic and nutritional disorders (24.53%) were the primary organ-systems affected by ADEs. The majority of ADEs were caused by drugs used to treat cardiovascular diseases. 71.43% of ADE occurred within 2 days of administration and the risk factor analysis of ADE revealed that the number of medicines had a significant correlation. This study demonstrated GTT's value as a tool for ADEs detection in elderly inpatients in China. It enhances the level of medication management and comprehensively reflects the situation of ADE of the elderly.


Hypermutation and unique mutational signatures of occupational cholangiocarcinoma in printing workers exposed to haloalkanes.
Cholangiocarcinoma is a relatively rare cancer, but its incidence is increasing worldwide. Although several risk factors have been suggested, the etiology and pathogenesis of the majority of cholangiocarcinomas remain unclear. Recently, a high incidence of early-onset cholangiocarcinoma was reported among the workers of a printing company in Osaka, Japan. These workers underwent high exposure to organic solvents, mainly haloalkanes such as 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. We performed whole-exome analysis on four cases of cholangiocarcinoma among the printing workers. An average of 44.8 somatic mutations was detected per Mb in the genome of the printing workers' cholangiocarcinoma tissues, approximately 30-fold higher than that found in control common cholangiocarcinoma tissues. Furthermore, C:G-to-T:A transitions with substantial strand bias as well as unique trinucleotide mutational changes of GpCpY to GpTpY and NpCpY to NpTpY or NpApY were predominant in all of the printing workers' cholangiocarcinoma genomes. These results were consistent with the epidemiological observation that they had been exposed to high concentrations of chemical compounds. Whole-genome analysis of Salmonella typhimurium strain TA100 exposed to 1,2-DCP revealed a partial recapitulation of the mutational signature in the printing workers' cholangiocarcinoma. Although our results provide mutational signatures unique to occupational cholangiocarcinoma, the underlying mechanisms of the disease should be further investigated by using appropriate model systems and by comparison with genomic data from other cancers.


Sequence Analysis of Native Oligosaccharides Using Negative ESI Tandem MS.
Carbohydrates exhibit many physiologically and pharmacologically important activities, yet their complicated structure and sequence pose major analytical challenges. Although their structural complexity makes analysis of carbohydrate difficult, mass spectrometry (MS) with high sensitivity, resolution and accuracy has become a vital tool in many applications related to analysis of carbohydrates or oligosaccharides. This application is essentially based on soft ionization technique which facilitates the ionization and vaporization of large, polar and thermally labile biomolecules. Electrospray-ionization (ESI), one of the soft ionization technique, tandem MS has been used in the sequencing of peptides, proteins, lipids, nucleic acids and more recently carbohydrates. The development of the ESI and tandem MS has begun to make carbohydrate analysis more routine. This review will focus on the application of the ESI tandem MS for the sequence analysis of native oligosaccharides, including neutral saccharides with multiple linkages, and the uronic acid polymers, alginate and glycosaminoglycans structures containing epimers.


[A clinical research of Naoxinqing tablet's effects on blood fat and viscosity].
To investigate the effects on blood fat and viscosity of Naoxinqing tablet. 66 patients of primary hyperlipoidemia were randomly divided into three groups. The first group was treated by Naoxinqing tablet, the second group was treated by Naoxinqing and combined with half dose Simvastatin, the third group was treated by full dose Simvastatin. Then the clinical effect, fasting plasma lipid, the index of blood viscosity and side effect of the three group' patients were compared after 8 weeks. The index of blood fat improved obviously after treatment of the three groups ( P < 0.05, P < 0. 01), group 2 and 3 were significantly superior to group 1 (P < 0.05), and no significance between group 2 and 3 (P > 0.05). The Naoxinqing tablet can improve the metabolism of blood fat, decrease blood viscosity obviously and treat hyperlipoidemia effectively with little side effect.


Total energy expenditure measured by doubly labeled water method in children and adolescents: a systematic review.
Total energy expenditure (TEE) is essential for understanding the growth, development, and physical activity of children and adolescents. This study aimed to summarize the existing evidence on TEE measured using the doubly labeled water (DLW) technique in children and adolescents aged 1-18 years. Furthermore, this review compared TEE between obese and normal-weight participants. This systematic review used the PubMed, ScienceDirect, Web of Science, and EBSCO databases. These studies were limited to those published in English between January 2000 and December 2021. Articles presenting objectively measured data on the TEE of children and adolescents aged 1-18 years measured using the DLW method were included. Physical activity level (PAL; TEE/basal metabolic rate [BMR]) and BMR data were also obtained. The search strategy identified 2,351 articles, of which 63 (n=4,283 children and adolescents; 45.4% male) met the selection criteria. The participants in the 10 studies were overweight or obese (n=413). In our study, TEE increased in male and female participants aged 1-18 years. PAL increased with age in males (y=0.0272x+1.3887, r2=0.511) and females (y=0.0199x+1.401, r2=0.335), and the slope of PAL with age did not differ between males and females. The TEE of obese and overweight participants was higher than that of normal-weight participants, but the slope of TEE did not differ between normal-weight (y=132.99x+702.24, r2=0.877) and obese individuals (y=136.18x+1,037.9, r2=0.842). In conclusion, this review provides convincing evidence that daily TEE progressively increases with growth in males and females aged 1-18 years.


Introduction of a Capillary Gel Electrophoresis-Based Workflow for Biotherapeutics Characterization: Size, Charge, and N-Glycosylation Variant Analysis of Bamlanivimab, an Anti-SARS-CoV-2 Product.
Coronavirus Disease 2019 (COVID-19) is a major public health problem worldwide with 5-10% hospitalization and 2-3% global mortality rates at the time of this publication. The disease is caused by a betacoronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The receptor-binding domain (RBD) of the Spike protein expressed on the surface of the virus plays a key role in the viral entry into the host cell via the angiotensin-converting enzyme 2 receptor. Neutralizing monoclonal antibodies having the RBD as a target have the ability to inhibit angiotensin-converting enzyme 2 (ACE2) receptor binding, therefore, prevent SARS-CoV-2 infection, represent a promising pharmacological strategy. Bamlanivimab is the first anti-spike neutralizing monoclonal antibody, which got an emergency use authorization from the FDA for COVID-19 treatment. Albeit, bamlanivimab is primarily a neutralizing mAb, some of its effector function related activity was also emphasized. The effector function of antibody therapeutics is greatly affected by their N-linked carbohydrates at the conserved Fc region, possibly influenced by the manufacturing process. Various capillary gel electrophoresis methods are widely accepted in the biopharmaceutical industry for the characterization of therapeutic antibodies. In this paper we introduce a capillary gel electrophoresis based workflow for 1) size heterogeneity analysis to determine the presence/absence of the non-glycosylated heavy chain (NGHC) fragment (SDS-CGE); 2) capillary gel isoelectric focusing for possible N-glycosylation mediated charge heterogeneity determination, e.g., for excess sialylation and finally, 3) capillary gel electrophoresis for N-glycosylation profiling and sequencing. Our results have shown the presence of negligible amount of non-glycosylated heavy chain (NGHC) while 25% acidic charge variants were detected. Comprehensive N-glycosylation characterization revealed the occurrence of approximately 8.2% core-afucosylated complex and 17% galactosylated N-linked oligosaccharides, suggesting the possible existence of antibody dependent cell mediated cytotoxicity (ADCC) effector function in addition to the generally considered neutralizing effect of this particular therapeutic antibody molecule.


Factor V A4070G (His1299Arg) mutation in Turkish pediatric patients with thrombosis.
The role of the prothrombotic mutations in pediatric thrombosis are being investigated. Mutations in the factor V gene (FV G1691A and FV A4070G) leading to activated protein C resistance, the main pathological condition in thrombosis and prothrombotic mutations contributing to thrombosis have been identified. The aim of this study is to reveal the role of FV A4070G mutation in pediatric thrombosis. 314 patients with thrombosis at pediatric age including also 111 stroke patients and 127 healthy controls were included to the study. The FV A4070G mutation was evaluated independently and also the combined effects with other prothrombotic mutations were also investigated. In pediatric stroke group FV A4070G was found not to be a risk factor with an OR of 1.04 (CI 95%: 0.56-1.93, p= 0.884). Further studies are needed to study the role of FV A4070G with other risk factors belong to HR2 haplotype.


Renin-producing ovarian tumor. A case report with immunohistochemical and electron-microscopic study.
A 39-year-old woman presented with arterial hypertension. Examination of the patient revealed elevated plasma renin activity, hyperaldosteronemia, hypokalemia, and a pelvic mass. Subsequently, an 11-cm right ovarian tumor mass with histologic features of an unusual stromal cell tumor was resected. Immunohistochemical studies demonstrated renin production by tumor cells. Organelles resembling mature renin granules were identified by electron microscopy. Although blood pressure normalized after the initial surgery, the hypertension resumed with later recurrence of the tumor. We believe the tumor originated from renin-secreting ovarian stromal cells, possibly granulosa cells.


Low-dose Radiation Therapy in the Management of COVID-19 Pneumonia (LOWRAD-Cov19). Final results of a prospective phase I-II trial.
To evaluate the results of low-dose radiation therapy (LD-RT) to lungs in the management of patients with COVID-19 pneumonia. We conducted a prospective phase I-II trial enrolling COVID-19 patients ≥50 years-old, with bilateral lung involvement at imaging study and oxygen requirement (oxygen saturation ≤93% on room air). Patients received 1 Gy to whole lungs in a single fraction. Primary outcome was a radiological response assessed as severity and extension scores at days +3 and +7. Secondary outcomes were toxicity (CTCAE v5.0), days of hospitalization, changes in inflammatory blood parameters (ferritin, lymphocytes, C-reactive protein, d-dimer and LDH) and SatO2/FiO2 index (SAFI), at day +3 and +7. Descriptive analyses were summarized as means with standard deviation (SD) and/or medians with interquartile ranges (IQR). A Wilcoxon sign rank test for paired data was used to assess the CT scores and Chi Square was used to assess for comparison of categorical variables. Forty-one patients were included. Median age was 71 (IQR 60-84). Eighteen patients (44%) previously received an anti-COVID treatment (tocilizumab, lopinavir/ritonavir, remdesivir) and thirty-two patients (84%) received steroids during LD-RT. The extension score improved significantly (p = 0.02) on day +7. Mean baseline extension score was 13.7 (SD ± 4.9) with a score of 12.2 (±5.2) at day 3, and 12.4 ± 4.7 at day 7. No differences were found in the severity score. SAFI improved significantly on day +3 and +7 (p < 0.01). Median SAFI on day 0 was 147 (IQR 118-264), 230 (IQR 120-343) on day +3 and 293 (IQR 121-353) on day +7. Significant decrease was found in C-reactive protein on day +7 (p = 0.02) and in lymphocytes counts on day +3 and +7 (p = 0.02). The median number of days in hospital after RT was 11 (range 4-78). With a median follow-up of 60 days after LD-RT, 26 (63%) patients were discharged, 11 (27%) died because of COVID respiratory failure and 4 (10%) died of other causes. LD-RT is a feasible and well-tolerated treatment that could lead to rapid clinical improvement. Large randomized trials would be required to establish the efficacy of LD-RT to treat COVID-19 pneumonia.


Effect of light wavelength on polymerization of light-cured resins.
Experimental light-cured composite resins were exposed to a narrow-band light at a constant quantum number using a narrow-band interference filter. The IR spectra of the cured resin specimens were measured before and after extraction of residual monomers. Degree of conversion (DC) and polymerization conversion (PC) were calculated from these IR spectra. The light in 410-550 nm could be polymerized. With a brief exposure (5 s), DC and PC were affected by the wavelength. The effect of wavelength between 410 and 490 nm decreased with increasing duration of exposure. The most efficient wavelength was 470 nm and the most adequate wavelength was in the 450-490 nm wavelength range. The absorbance of camphorquinone strongly affected polymerization, especially during the initial stage. However, from the relationship between DC or PC and exposure energy, polymerization depended not only on the wavelength of the light, but also on the exposure energy.


Blind RSSD-Based Indoor Localization with Confidence Calibration and Energy Control.
Indoor localization based on wireless sensor networks (WSNs) is an important field of research with numerous applications, such as elderly care, miner security, and smart buildings. In this paper, we present a localization method based on the received signal strength difference (RSSD) to determine a target on a map with unknown transmission information. To increase the accuracy of localization, we propose a confidence value for each anchor node to indicate its credibility for participating in the estimation. An automatic calibration device is designed to help acquire the values. The acceleration sensor and unscented Kalman filter (UKF) are also introduced to reduce the influence of measuring noise in the application. Energy control is another key point in WSN systems and may prolong the lifetime of the system. Thus, a quadtree structure is constructed to describe the region correlation between neighboring areas, and the unnecessary anchor nodes can be detected and set to sleep to save energy. The localization system is implemented on real-time Texas Instruments CC2430 and CC2431 embedded platforms, and the experimental results indicate that these mechanisms achieve a high accuracy and low energy cost.


Combined modality treatment: Outcome in patients with Hodgkin's lymphoma.
Hodgkin's lymphoma (HL) can be treated with combined modality treatment (CMT) to limit long-term toxicities in the early favorable stage. Early unfavorable and advanced stage HL is mainly treated with chemotherapy followed by radiation to the bulky site. This study examines the impact of CMT in early as well as advanced stage HL. From 2001 to 2011, 125 patients with Stage I to IV HL were analyzed. Median age of the patients was 25 years (range 12-68 years). CMT, chemotherapy, and radiation alone were given to 51, 64, and 10 patients, respectively. Chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was given to 100 patients, 6 patients received ABVD-like regimen, and 9 patients received cyclophosphamide, vincristine, procarbazine, and prednisone regimen. Radiotherapy (RT) was given to 61 (49%) patients, involved field RT to 55 (90%), and extended-field RT to 6 (10%) patients, respectively. Median radiation dose was 30 Gy (18-40 Gy). All 25 patients with early-stage achieved complete response (CR) with CMT. At a median follow-up of 70 months (range 12-230 months), relapse was seen in two patients (1 local and 1 distant). Of 26 patients with advanced stage, 25 achieved a CR and 1 had stable disease with CMT. Relapse occurred in one patient (distant). In patients with early-stage treated with chemotherapy only ( n = 30, 24%), 9 patients had relapse (4 local and 5 distant) while in those with RT only ( n = 10, 8%), 4 developed distant relapse. In patients with advanced stage treated with chemotherapy only ( n = 34, 27%), 8 relapsed (5 local and distant, 3 distant only). Patients with relapse were salvaged with CMT ( n = 6), chemotherapy ( n = 15), or RT ( n = 3). Two patients have died. Five years' disease-free survival (DFS) in patients with early favorable stage, early unfavorable stage, and advanced stage was 91%, 82%, and 73%, respectively ( P = 0.026). DFS was significantly better with CMT than chemotherapy or radiation alone. Five years' overall survival (OS) was 93%, 92%, and 84%, respectively ( P = 0.139). Second malignancy occurred in 3 (2.4%) patients; carcinoma of the tongue, pseudomyxoma peritonei, and non-HL each, respectively. None of these patients had received prior radiation. CMT improved DFS in patients with HL. OS was similar in all patients irrespective of treatment combinations. The incidence of second malignancy was 2.4%.


The relationship between proximal pole blood flow and the subjective assessment of increased density of the proximal pole in acute scaphoid fractures.
The cause and importance of increased density of the proximal pole of the scaphoid seen in radiographs after an acute fracture were investigated. Blood flow to the proximal poles of 32 nonsurgically treated scaphoid fractures were assessed 1 to 2 weeks after injury by measuring their uptake of gadopentetate dimeglumine with dynamic magnetic resonance imaging and calculating its steepest slope and percentage of enhancement values. Initial (week 0) and week 8 scaphoid series radiographs were independently assessed by 2 observers for increased proximal pole density; both agreed that the density had increased during treatment in 9 fractures. All 9 fractures united, suggesting that increased proximal pole density is not a major determinant of fracture outcome. Increased density of the proximal pole was associated with low proximal pole blood flow, but this relationship was not absolute, suggesting that other factors contribute to the appearance of increased density.


COVID-19 Risk Prediction for Diabetic Patients Using Fuzzy Inference System and Machine Learning Approaches.
Individuals with pre-existing diabetes seem to be vulnerable to the COVID-19 due to changes in blood sugar levels and diabetes complications. As observed globally, around 20-50% of individuals affected by coronavirus had diabetes. However, there is no recent finding that diabetic patients are more prone to contract COVID-19 than nondiabetic patients. However, a few recent findings have observed that it could be at least twice as likely to die from complications of diabetes. Considering the multifold mortality rate of COVID-19 in diabetic patients, this study proposes a COVID-19 risk prediction model for diabetic patients using a fuzzy inference system and machine learning approaches. This study aimed to estimate the risk level of COVID-19 in diabetic patients without a medical practitioner's advice for timely action and overcoming the multifold mortality rate of COVID-19 in diabetic patients. The proposed model takes eight input parameters, which were found as the most influential symptoms in diabetic patients. With the help of the various state-of-the-art machine learning techniques, fifteen models were built over the rule base. CatBoost classifier gives the best accuracy, recall, precision, F1 score, and kappa score. After hyper-parameter optimization, CatBoost classifier showed 76% accuracy and improvements in the recall, precision, F1 score, and kappa score, followed by logistic regression and XGBoost with 75.1% and 74.7% accuracy. Stratified k-fold cross-validation is used for validation purposes.


Novel linkage mapping approach using DNA pooling in human and animal genetics. II. Detection of quantitative traits loci in dairy cattle.
Selective DNA pooling is an advanced methodology for linkage mapping of quantitative trait loci (QTL) in farm animals. The principle is based on densitometric estimates of marker allele frequency in pooled DNA samples of phenotypically extreme individuals from half-sib, backcross and F(2) experimental designs in farm animals. This methodology provides a rapid and efficient analysis of a large number of individuals with short tandem repeat markers that are essential to detect QTL through the genome - wide searching approach. Several strategies involving whole genome scanning with a high statistical power have been developed for systematic search to detect the quantitative traits loci and linked loci of complex traits. In recent studies, greater success has been achieved in mapping several QTLs in Israel-Holstein cattle using selective DNA pooling. This paper outlines the currently emerged novel strategies of linkage mapping to identify QTL based on selective DNA pooling with more emphasis on its theoretical pre-requisite to detect linked QTLs, applications, a general theory for experimental half-sib designs, the power of statistics and its feasibility to identify genetic markers linked QTL in dairy cattle. The study reveals that the application of selective DNA pooling in dairy cattle can be best exploited in the genome-wide detection of linked loci with small and large QTL effects and applied to a moderately sized half-sib family of about 500 animals.


Substance P injected into the medial preoptic area inhibits sodium, potassium and water urinary excretion. Putative modulation of the cholinergic system.
Substance P (SP, 1.5 nmol) injected into the medial preoptic area (MPOA) of conscious, unrestrained, water-loaded male rats induced a significant decrease in urinary sodium, potassium and water excretion. In contrast, a significant natriuretic effect was observed after injection of 0.3 nmol of a specific competitive SP antagonist [( D-Pro2, D-Trp7,9]-substance P). SP partially blocked the carbachol-induced natriuresis in a time-dependent manner. These data indicate a tonic inhibitory action of SP on sodium excretion and suggest a putative modulatory action of SP on the cholinergic system.


[Psychopathological alteration of the auditory structure in schizophrenia; "the experience of no-sounds"].
According to recent cognitive theories, the greater part of the perceptional meaning and representative meaning are both pre-determined, or pre-organized as a set of meaning, which has a biophysiological and socio-cultural origin. Humans however, drive some kind of sensational Gestalt from each sense organ, and this is incapable of being transformed into language (representative pre-meaning), this enabling us to experience the possibility of truly private meaning in our own right. The author has emphasized this two moments of the meaning, that is, private moments of meaning vs. institutional moments. The author has offered the phenomenological hypothesis of auditory experience and elaborated the relation between these two moments in it. Then, the author has testified its validity in the process of describing and analysing the pathological alteration of auditory sensation in schizophrenia. Auditory space is thought to be differentiated into a three-dimensional structure. That is, a dimension of background, a dimension of signs, and a dimension of symbols, and we accept environmental-sounds, event-sounds, symbolic sounds in each level. Close investigations about 5 schizophrenics revealed that these patients undergo a strange silent experience before the onset of delusional ideas, descriptively and phenomenologically, this phenomenon appeared to be initiated by the deprivation of the dimension of background sounds (referred to as "the experience of no-sounds"). This experiences often occurred especially when they are eager to listen to the surrounding sounds (for example, noises in the neighborhood, classroom chatter), in order to solve their own interpersonal difficulties. Furthermore, the author described the ambivalent nature of patients' thinking in this pathological auditory situation, in which one idea of the polarity of dichotomy was forced to switch to the another one, influenced by an attribute of surrounding sounds. With regard to this aspect, the patients experienced both the physiological changes in the auditory structure as well as the psychological turmoil. The author has emphasized the need to appreciate this ambiguous nature of the psychological context mixed with the physiological context, which is supposed to be very important from psychotherapeutical viewpoint.


Alternate splicing of transcripts shape macrophage response to Mycobacterium tuberculosis infection.
Transcriptional reprogramming of macrophages upon Mycobacterium tuberculosis (Mtb) infection is widely studied; however, the significance of alternate splicing (AS) in shaping cellular responses to mycobacterial infections is not yet appreciated. Alternate splicing can influence transcript stability or structure, function and localization of corresponding proteins thereby altering protein stoichiometry and physiological consequences. Using comprehensive analysis of a time-series RNA-seq data obtained from human macrophages infected with virulent or avirulent strains of Mtb, we show extensive remodeling of alternate splicing in macrophage transcriptome. The global nature of this regulation was evident since genes belonging to functional classes like trafficking, immune response, autophagy, redox and metabolism showed marked departure in the pattern of splicing in the infected macrophages. The systemic perturbation of splicing machinery in the infected macrophages was apparent as genes involved at different stages of spliceosome assembly were also regulated at the splicing level. Curiously there was a considerable increase in the expression of truncated/non-translatable variants of several genes, specifically upon virulent infections. Increased expression of truncated transcripts correlated with a decline in the corresponding protein levels. We verified the physiological relevance for one such candidate gene RAB8B; whose truncated variant gets enriched in H37Rv infected cells. Upon tweaking relative abundance of longer or shorter variants of RAB8B transcripts by specialized transduction, mycobacterial targeting to lysosomes could be promoted or blocked respectively, which also resulted in corresponding changes in the bacterial survival. Our results show RAB8B recruitment to the mycobacterial phagosomes is required for phagosome maturation. Thus the abundance of truncated RAB8B variant helps virulent Mtb survival by limiting the RAB8B levels in the cells, a mechanism which we subsequently verified in human primary macrophages. Taken together we demonstrate alternate splicing as a new locus of intervention by Mtb and provide attractive alternative to exploit for novel drug targets against Mtb.


Factors associated with adequate pain control in hospitalized postsurgical patients diagnosed with cancer.
The inadequate management of pain continues to be a significant problem for persons with cancer. Experts suggest that contributing factors include discrepancies in pain assessment, inadequate administration of opiate therapy, and insufficient documentation of the patient's pain experience. This study, part of a multidepartmental investigation into the adequacy of pain management in hospitalized patients, describes the pain experience of surgical oncology patients. Its correlational ex post facto design (n = 34) was guided by Loeser's model of pain. Randomly selected surgical oncology patients were interviewed using a structured format. The patient's primary nurse and physician simultaneously completed brief assessments of their perceptions of the patient's pain intensity. Data were analyzed using descriptive and correlational statistics, and implications for nursing practice and future nursing research are discussed.


A simultaneous assessment of CYP3A4 metabolism and induction in the DPX-2 cell line.
The DPX-2 cell line, a derivative of HepG2 cells, harbors human PXR and a luciferase-linked CYP3A4 promoter. These cells were used in a panel of cell-based assays for a parallel assessment of CYP3A4 induction, metabolism, and inhibition at the cellular level. CYP3A4 induction in the DPX-2 cell line by various agents was monitored in 96-well plates by a luciferase-based transcriptional activation assay. Of the prototypical CYP3A4 inducers examined, all exhibited elevated luciferase activity in DPX-2 cells. CYP3A4 enzyme activity in noninduced and rifampicin-induced DPX-2 cells was also assessed using Vivid fluorogenic substrates. Significantly elevated CYP3A4 activity levels (2.8-fold +/- 0.2-fold above DMSO-treated cells) were found in DPX-2 cells after 48 hours of exposure to rifampicin, but were undetectable in parental HepG2 cells. Rifampicin-induced activity levels were found to be suitable for assessing the inhibitory potential of new chemical entities in downstream CYP3A4 inhibition assays. The elevated CYP3A4 activity was inhibited 85% by 10 microM ketoconazole. In addition, a cytotoxicity assay to correct for possible toxic effects of compounds at the cellular level was applied. The comparative data obtained with a combination of the above assays suggests that the application of several independent in vitro technologies used in DPX-2 cells is the best possible strategy for the assessment of the complex phenomena of CYP3A4 induction and inhibition.


Tissue distribution of HRF20, a novel factor preventing the membrane attack of homologous complement, and its predominant expression on endothelial cells in vivo.
A 20,000 molecular weight (MW) homologous restriction factor (HRF20), detected by 1F5 monoclonal antibody (mAb), is present on blood cell surfaces and inhibits the terminal stage of the formation of membrane attack complexes by homologous complement activation. The tissue distribution of HRF20 was studied by immunohistochemical analysis using 1F5. HRF20 was predominantly expressed on endothelial cells of systemic arteries, veins and capillaries, as well as on the surface of cultured human umbilical vein endothelial cells. HRF20 was also detected, to a lesser extent, on the Schwann sheath of peripheral nerve fibres, ependymal cells and certain epithelial cells such as acinar cells of the salivary gland, bronchial epithelium, renal tubules and squamous epithelium. The distribution pattern of HRF20 differed somewhat from that of decay-accelerating factor (DAF), which is another membrane inhibitor of homologous complement activation.


Predicting cesarean section and uterine rupture among women attempting vaginal birth after prior cesarean section.
There is currently no validated method for antepartum prediction of the risk of failed vaginal birth after cesarean section and no information on the relationship between the risk of emergency cesarean delivery and the risk of uterine rupture. We linked a national maternity hospital discharge database and a national registry of perinatal deaths. We studied 23,286 women with one prior cesarean delivery who attempted vaginal birth at or after 40-wk gestation. The population was randomly split into model development and validation groups. The factors associated with emergency cesarean section were maternal age (adjusted odds ratio [OR] = 1.22 per 5-y increase, 95% confidence interval [CI]: 1.16 to 1.28), maternal height (adjusted OR = 0.75 per 5-cm increase, 95% CI: 0.73 to 0.78), male fetus (adjusted OR = 1.18, 95% CI: 1.08 to 1.29), no previous vaginal birth (adjusted OR = 5.08, 95% CI: 4.52 to 5.72), prostaglandin induction of labor (adjusted OR = 1.42, 95% CI: 1.26 to 1.60), and birth at 41-wk (adjusted OR = 1.30, 95% CI: 1.18 to 1.42) or 42-wk (adjusted OR = 1.38, 95% CI: 1.17 to 1.62) gestation compared with 40-wk. In the validation group, 36% of the women had a low predicted risk of caesarean section (< 20%) and 16.5% of women had a high predicted risk (> 40%); 10.9% and 47.7% of these women, respectively, actually had deliveries by caesarean section. The predicted risk of caesarean section was also associated with the risk of all uterine rupture (OR for a 5% increase in predicted risk = 1.22, 95% CI: 1.14 to 1.31) and uterine rupture associated with perinatal death (OR for a 5% increase in predicted risk = 1.32, 95% CI: 1.02 to 1.73). The observed incidence of uterine rupture was 2.0 per 1,000 among women at low risk of cesarean section and 9.1 per 1,000 among those at high risk (relative risk = 4.5, 95% CI: 2.6 to 8.1). We present the model in a simple-to-use format. We present, to our knowledge, the first validated model for antepartum prediction of the risk of failed vaginal birth after prior cesarean section. Women at increased risk of emergency caesarean section are also at increased risk of uterine rupture, including catastrophic rupture leading to perinatal death.


Fatigue and Discomfort During Spatially Distributed Sequential Stimulation of Tibialis Anterior.
Neuromuscular electrical stimulation is conventionally applied through a single pair of electrodes over the muscle belly, denominated single electrode stimulation (SES). SES is limited by discomfort and incomplete motor-unit recruitment, restricting electrically-evoked torque and promoting premature fatigue-induced torque-decline. Sequential stimulation involving rotation of pulses between multiple pairs of electrodes has been proposed as an alternative, denominated spatially distributed sequential stimulation (SDSS). The present aim was to compare discomfort, maximal-tolerated torque, and fatigue-related outcomes between SES and SDSS of tibialis anterior. Ten healthy participants completed two experimental sessions. The self-reported discomfort at sub-maximal torque, the maximal-tolerated torque, fatigue-induced torque-decline during, and doublet-twitch torque at 10- and 100-Hz before and after, 300 intermittent (0.6-s-ON-0.6-s-OFF) isokinetic contractions were compared between SES and SDSS. SDSS stimulation improved fatigue-related outcomes, whereas increased discomfort and reduced maximal-tolerated torque. SDSS holds promise for reducing fatigue. However, limited torque production and associated discomfort may limit its utility for rehabilitation/training.


[Effect of intravenous diazepam (Faustan) on EEG focal disturbances].
The influence of intravenous administration of diazepam (Faustan) on focal e.e.g. changes was checked in 34 patients. Bioelectric functional disturbances may remain unchanged, may be provoked or abolished; apparently etiological aspects are not decisive. According to the authors' results, the value of this provocation method for the differentiation of space-occupying intracranial processes and cerebrovascular disturbances should be regarded with caution.


[Recent data on the radiation exposure to the patient in diagnostic radiology (author's transl)].
As a consequence of the x-ray decree (GFR 1973) data are obligatory to assess the radiation exposure to the patient. These data can easily be obtained with an additional device for recording the dose surface product. The value of the fluoroscopy time for calculating the radiation exposure of different organs is discussed. By a high standard of technical equipment and training of the technical personnel, radiation exposure to the patient may be kept low. Recent data on the exposure to the patient in diagnostic radiology and the corresponding somatic and genetic hazards are summarized in this review.


[The physiological-biochemical properties of Klebsiella pneumoniae strains of different origins].
While comparatively analyzing the properties of Klebsiella pneumoniae from three studied sources (patients, healthy people, environment), no reliable differences between the comparable strains have been revealed. No differences have been found in the toxin formation, hemagglutinating and antilysozymic activity, adhesivity and invasive properties as well as in the peculiarities of gas exchange, while growing on media with different nitrogen and carbon sources. The studied microorganisms differed only in antibiotic resistance: strains isolated from the environment were sensitive to antibiotics, whereas strains of human origin were resistant to them.


Ischemia of the Penis and Fingertips Secondary to Calcifying Uremic Arteriolopathy.
Calcifying uremic arteriolopathy (CUA), also called calciphylaxis, refers to the calcification of the walls of the arteries of medium and small caliber, causing ischemic skin lesions. Diagnosis should be made if ischemic lesion develops in a patient with chronic renal failure (CRF), and it is confirmed based on clinical, radiological, and histological criteria. Generalized CUA characterized by ischemia of the penis (IP) along with other localizations of cutaneous ischemia is exceptional, and the morbidity and high mortality rate associated with this entity most often warrant multidisciplinary and conservative management.


Childhood Sexual Abuse, Spirituality/Religion, Anxiety and Depression in a Jewish Community Sample: the Mediating Role of Religious Coping.
Childhood sexual abuse (CSA) is a pervasive problem impacting a broad range of mental health outcomes. Previous research has shown that spiritual and religious (S/R) factors both positively and negatively relate to mental health issues among survivors of CSA, but mediating mechanisms of effect are unclear. The present study examined CSA, anxiety, depression, and positive/negative religious coping among 372 Jewish community members with and without CSA histories. Individuals who experienced CSA endorsed significantly higher anxiety and depression as well as negative religious coping than those without CSA. Negative religious coping mediated the relationship between CSA and anxiety and depression. We discuss clinical and social implications of these findings, including the need to address S/R factors in treatment of CSA, especially within religious communities. Further research examining abuser identity, survivors' disclosure experience, and other S/R mediators of effect is warranted.


Studies on the subsite structure of amylases. IV. Tryptophan residues of glucoamylase from Rhizopus niveus studied by chemical modification with N-bromosuccinimide.
Chemical modification of glucoamylase [EC 18.104.22.168] from Rhizopus niveus by N-bromosuccinimide was carried out to investigate the role of tryptophan residues in the enzyme-catalyzed reaction and their location in the enzyme subsites. Of the ten tryptophan residues of the enzyme four could be modified. The two more reactive residues were confirmed not be essential for the catalytic activity for the hydrolysis of maltodextrin and phenyl alpha-maltoside. Complete loss of the catalytic activity, however, was brought about by modifying the two less reactive residues, and the modification of these residues was prevented by the substrates. The characteristic difference spectrum produced by maltose (7) disappeared in parallel with the loss of the catalytic activity. These results suggest that the tryptophan residue(s) responsible for the maltose-induced difference spectrum may be located at one of the subsite near the catalytic site and plays an important role in the catalytic activity of the enzyme.


Preconcentration and determination of tellurium in garlic samples by hydride generation atomic absorption spectrometry.
A procedure for the determination of traces of total tellurium (Te) in garlic (Allium sativa) is described that combines hydride generation atomic absorption spectrometry with preconcentration of the analyte by coprecipitation. The samples, each spiked with lanthanum nitrate (20 mg/L), are introduced into an Amberlite XAD-4 resin and mixed with ammonium buffer (pH 9.1). Te is preconcentrated by coprecipitation with the generated lanthanum hydroxide precipitate. The precipitate is quantitatively collected in the resin, eluted with hydrochloric acid, and then transferred into the atomizer device. Considering a sample consumption of 25 mL, an enrichment factor of 10 was obtained. The detection limit (3sigma) was 0.03 microg/L, and the precision (relative standard deviation) was 3.5% (n = 10) at the 10 microg/L level. The calibration graph using the preconcentration system for Te was linear with a correlation coefficient of 0.9993. Satisfactory results were obtained for the analysis of Te in garlic samples.


Work-related treatment for major depressive disorder and incapacity to work: preliminary findings of a controlled, matched study.
The aim of this study was to compare the effectiveness of work-related cognitive-behavioral treatment (W-CBT) with that of cognitive-behavioral treatment as usual (CBT-AU) for employees on sick leave as a result of a major depressive disorder (MDD). We collected data for 26 matched outpatients at pre- and posttreatment, as well as at 1-year follow-up. Outcome measures were the days of incapacity to work (DIW) as well as self-report measures (Beck Depression Inventory [BDI], Symptom Checklist 90-R [GSI], Life Satisfaction Questionnaire [FLZ]). We analyzed data with hierarchical linear modeling in a 2-level model. Therapy effects were defined in 3 ways: effect size (ES), response (based on the reliable change index), and remission compared with the general population's symptom level. The DIW were reduced significantly after both types of treatment, but employees showed even fewer DIW after W-CBT. At follow-up, significantly more employees were working as a result of W-CBT than with CBT-AU. Significant improvements on scores of self-rating measures corresponded with moderate-to-large effect sizes for both treatment types. Approximately 2 thirds of the treated employees were categorized as unimpaired on BDI scores at posttreatment and at follow-up. At least 1 half of the employees were classified as unimpaired on GSI scores at both assessment points. In future research, a randomized controlled trial should be conducted using a larger sample size to investigate the impact of moderators (e.g., employees at different branches of the company). Findings provided support for using common CBT techniques to enhance return to work without losing expected improvements at the symptom level.


Assessing regimen adherence of adolescents with type 1 diabetes.
The purpose of this study is to evaluate two updated measures of diabetes regimen adherence. The Diabetes Self-Management Profile (DSMP) is a widely used, structured interview. Limitations include a substantial interviewer and respondent time burden and the need for well-trained interviewers to use appropriate prompts and score the open-ended responses. The Diabetes Behavior Rating Scale (DBRS) is a self-administered, fixed-choice survey. Both measures were administered to 146 youth with type 1 diabetes (aged 11-18 years) and their parents. Items were added to the DBRS to allow for both flexible and conventional regimens, and the DSMP was modified to use standardized wording across items, accommodate flexible regimens, and permit administration by nonmedical interviewers. Both measures had good evidence of internal consistency (for the DSMP: parent 0.75 and youth 0.70; for the DBRS: parent 0.84 and youth 0.84). Scores on the DSMP and the DBRS were significantly related (r = 0.72 for parents and 0.74 for youth). There was moderate agreement between parent and youth (DSMP, r = 0.51; DBRS, r = 0.48). The measures were correlated with HbA1c for both parent (DSMP, r = -0.35; DBRS, r = -0.35) and youth (DSMP, r = -0.36; DBRS, r = -0.34) reports. Both measures exhibit good psychometric properties and good criterion validity but varied in terms of respondent and interviewer burden, issues that should be considered in selecting assessment procedures.


Post-treatment alpha fetoprotein and platelets predict hepatocellular carcinoma development in dual-infected hepatitis B and C patients after eradication of hepatitis C.
We investigated the long-term risk of hepatocellular carcinoma (HCC) in dual-infected hepatitis B and C patients after eradication of hepatitis C virus (HCV). A total of 164 (62% male, median age, 50.5 years) hepatitis B and C dual-infected patients who achieved HCV sustained virological response were recruited. Half the patients were HCV genotype 1 with a median viral load of 5.5 log10 IU/mL, and 22.6%had an HBV DNA level ≥ 2000 IU/mL before therapy. HCC developed in 14 patients (8.5%), with an annual incidence of 1.38% per person-year. The 3-year, 5-year, 10-year, and 15-year cumulative probabilities were 2.5%, 5.1%, 12.6%, and 22.7%, respectively. Six months after treatment, a Cox regression hazard analysis revealed platelet level (HR: 0.98, 95% CI: 0.957-0.999, P = 0.038) and AFP level (HR: 1.20, 95% CI: 1.031-1.400, P = 0.019) to be independent factors in HCC. A higher 10-year cumulative risk of HCC was detected in patients with 6-month post-treatment AFP levels > 5.0 ng/mL and platelet levels < 130 x1000/µL (54.9%), compared to patients with neither (8.6%). Although the risk of HCC is low, surveillance of HCC is encouraged in dual-infected patients after eradication of HCV. Post-treatment AFP and platelet levels predict HCC development.


Portal vein arterialization following a radical left extended hepatectomy for Klatskin tumor: A case report.
Portal vein arterialization (PVA) has been attracting attention for its role as a salvage inflow technique in various clinical applications. Initially performed in shunt surgery for portal hypertension, with the aim of preventing a decreased hepatic inflow, it is largely used in case of hepatic artery thrombosis in the transplantation domain or in the enlarged radical operations in case of hilar cancer invading the hepatic artery. A 62-year-old man underwent a left extended hepatectomy with hepatic bile duct resection and right Roux-en-Y hepaticojejunostomy for hilar cholangiocarcinoma. Computed tomography scan on postoperative day (POD) 5 revealed right hepatic artery pseudo-aneurysm, which was confirmed by an angiography. Stent placement was infeasible. Coiling of the pseudoaneurysm was associated with a risk of complete occlusion inducing critical liver failure. Since his general conditions were deteriorated, the patient underwent an emergency laparotomy. Hepatic artery reconstruction was impossible. Thus, a PVA was performed by anastomosing the ileocecal artery and vein. The intraoperative ultrasound showed satisfactory patency of the PVA with good portal flow in the absence of arterial flow. Doppler ultrasound on POD 15 showed that the cross-sectional area and blood flow of the portal vein were increased. The patient was discharged on POD 54 in good general condition. Hepatic artery disruption represents potentially lethal complications of hepatic, biliary, and pancreatic surgery. PVA may be a feasible therapeutic strategy to guarantee arterial inflow to the remnant liver. Although PVA is a salvage surgical procedure, increased portal flow should be controlled to avoid portal hypertension and liver fibrosis.