Studies on the biosynthesis in vivo and excretion of 16-unsaturated C 19 steroids in the boar.
1. In one experiment [7alpha-(3)H]pregnenolone was infused continuously for 12min into the left spermatic artery of a sexually mature boar and blood was collected during this period by continuous drainage from the spermatic vein. After infusion, the testis was removed and immediately cooled to -196 degrees C. 2. From both the testicular tissue and the spermatic venous plasma, (3)H-labelled 16-unsaturated C(19) steroids were isolated and characterized and their radiochemical purity was established. 5alpha-Androst-16-en-3alpha- and 3beta-ol occurred mainly as sulphate conjugates and to a lesser extent as free steroids. Only traces of these alcohols occurred as glucosiduronate conjugates. 5alpha-Androst-16-en-3-one was found in the free (ether-extractable) fraction. 3. The isotope concentration of each of the (3)H-labelled 16-unsaturated C(19) steroids in testicular tissue was different from that in spermatic venous plasma. 4. The ratios of tritiated 5alpha-androst-16-en-3alpha- and 3beta-ol (free steroids) to their respective sulphate conjugates in the testicular tissue were less than the ratios of the same compounds in the spermatic venous plasma. The possibility that the sulphates are partially hydrolysed by testicular sulphatases before secretion is discussed. 5. In a second experiment, a continuous close-arterial infusion of [7alpha-(3)H]pregnenolone into the left testis was performed over a 200min period and all the urine that accumulated during the infusion was collected for analysis. 6. No (3)H-labelled 16-unsaturated C(19) steroids were detected in the urine as free steroids. Only a trace of 5alpha-androst-16-en-3alpha-ol was detected conjugated as glucosiduronate, whereas the corresponding 3beta-alcohol occurred mainly as glucosiduronate and to a lesser extent as sulphate. 7. The absence of 5alpha-androst-16-en-3beta-ol glucosiduronate in the spermatic venous blood and its presence in considerable amount in the urine may be attributed to hepatic glucuronyl transferase activity.


Managing the interface between medical schools, hospitals, and clinical research.
To review how academic health centers are coping with the changing environment of health care delivery with special emphasis on the impact of the changing health care system on clinical research. In response to Health and Human Services Secretary Donna Shalala's 1995 mandated review of the National Institutes of Health (NIH) Warren Grant Magnuson Clinical Center, an NIH review team visited 30 health facilities and government-owned organizations throughout the country. The review team determined what strategies are used by academic health centers to survive and thrive in the changing health care marketplace. The findings have implications for the NIH Clinical Center as well as academic health centers. Management strategies in successful academic health centers include streamlined governance structures whereby small groups of highly empowered group leaders allow institutions to move quickly and decisively; an active strategic planning process; close integration of hospital and medical school management; heavy investment in information systems; and new structures for patient care delivery. Successful centers are initiating discussions with third-party payers and are implementing new initiatives, such as establishing their own managed care organizations, purchasing physician practices, or owning hospitals. Other approaches include establishing revenue-generating centers for clinical research and new relations with industry. Attention to the infrastructure required to support the training and conduct of clinical research is essential for the future vitality of medical schools.


Effects of solvent exposure on testosterone levels and butyrylcholinesterase activity in mice.
In female and male mice the effect of exposure to trichloroethylene (TCE) seen at the lowest concentration is an increase in liver weight. The activity of plasma butyrylcholinesterase (BuChE) increases even more than the liver weight at corresponding concentrations, but only in the males. Depletion of testosterone through castration or destruction of the pituitary gland or hypothalamus, are the only other ways to experimentally induce corresponding increases in BuChE. Plasma BuChE activity increase was found to be a common reaction after exposure to TCE, perchloroethylene, chloroform, methylene chloride and carbon tetrachloride and also after exposure to ethanol. Other solvents such as toluene, xylene, benzene and 1,1,1-trichloroethane had little or no effect on BuChE activity. Normal and castrated male mice were continuously exposed for one month to 150 p.p.m. TCE. The increase in BuChE activity after the exposure was of the same magnitude as the increase seen after castration. BuChE activity in castrated males was not further increased by TCE exposure. Administration of testosterone with osmotic minipumps for 13 days almost restored the normal testosterone and BuChE levels in castrates. The effect of TCE exposure on BuChE activity in these animals was the same as on normal males. Testosterone levels were not influenced by the TCE exposure in normal males or in castrates given testosterone. No sex hormone binding globulins (SHBG) could be detected in the mice. BuChE activity changes induced through solvent exposure are therefore neither directly nor indirectly (through SHBG) due to effects on testosterone. The results from these animal experiments do not support the epidemiological findings of decreased testosterone levels in humans exposed to solvents.


The effects of individually ventilated cages on the respiratory systems of male and female Wistar rats from birth until adulthood.
To evaluate the respiratory systems of male and female rats maintained in individually ventilated cages (IVCs) from birth until adulthood. Female Wistar rats were housed in individually ventilated cages or conventional cages (CCs) and mated with male Wistar rats. After birth and weaning, the male offspring were separated from the females and kept in cages of the same type until 12 weeks of age. The level of food consumption was lower in male offspring (IVC=171.7±9; CC=193.1±20) than in female offspring (IVC=100.6±7; CC=123.4±0.4), whereas the water intake was higher in female offspring (IVC=149.8±11; CC=99.2±0) than in male offspring (IVC=302.5±25; CC=249.7±22) at 11 weeks of age when housed in IVCs. The cage temperature was higher in individually ventilated cages than in conventional cages for both male (IVCs=25.9±0.5; CCs=22.95±0.3) and female (IVCs=26.2±0.3; CCs=23.1±0.3) offspring. The respiratory resistance (IVC=68.8±2.8; CC=50.6±3.0) and elastance (IVC=42.0±3.9; CC=32.4±2.0) at 300 µm/kg were higher in the female offspring housed in ventilated cages. The ciliary beat values were lower in both the male (IVCs=13.4±0.2; CC=15±0.4) and female (IVC=13.5±0.4; CC=15.9±0.6) offspring housed in individually ventilated cages than in those housed in conventional cages. The total cell (IVC=117.5±9.7; CC=285.0±22.8), neutrophil (IVC=13.1±4.8; CC=75.6±4.1) and macrophage (IVC=95.2±11.8; CC=170.0±18.8) counts in the bronchoalveolar lavage fluid were lower in the female offspring housed in individually ventilated cages than in those housed in conventional cages. The environmental conditions that exist in individually ventilated cages should be considered when interpreting the results of studies involving laboratory animals. In this study, we observed gender dimorphism in both the water consumption and respiratory mechanics of rats kept in ventilated cages.


Covalently bound hole-injecting nanostructures. Systematics of molecular architecture, thickness, saturation, and electron-blocking characteristics on organic light-emitting diode luminance, turn-on voltage, and quantum efficiency.
Hole transporting materials are widely used in multilayer organic and polymer light-emitting diodes (OLEDs, PLEDs, respectively) and are indispensable if device electroluminescent response and durability are to be truly optimized. This contribution analyzes the relative effects of tin-doped indium oxide (ITO) anode-hole transporting layer (HTL) contact versus the intrinsic HTL materials properties on OLED performance. Two siloxane-based HTL materials, N,N'-bis(p-trichlorosilylpropyl)-naphthalen-1-yl)-N,N'-diphenyl-biphenyl-4,4'-diamine (NPB-Si(2)) and 4,4'-bis[(p-trichlorosilylpropylphenyl)phenylamino]biphenyl (TPD-Si(2)), are designed and synthesized. They have the same hole transporting triarylamine cores as conventional HTL materials such as 1,4-bis(1-naphthylphenylamino)biphenyl (NPB) and N,N-diphenyl-N,N-bis(3-methylphenyl)-1,1-biphenyl)-4,4-diamine (TPD), respectively. However, they covalently bind to the ITO anode, forming anode-HTL contacts that are intrinsically different from those of the anode to TPD and NPB. Applied to archetypical tris(8-hydroxyquinolato)aluminum(III) (Alq)-based OLEDs as (1) the sole HTLs or (2) anode-NPB HTL interlayers, NPB-Si(2) and TPD-Si(2) enhance device electroluminescent response significantly versus comparable devices based on NPB alone. In the first case, OLEDs with 36 000 cd/m(2) luminance, 1.6% forward external quantum efficiency (eta(ext)), and 5 V turn-on voltages are achieved, affording a 250% increase in luminance and approximately 50% reduction in turn-on voltage, as compared to NPB-based devices. In the second case, even more dramatic enhancement is observed (64 000 cd/m(2) luminance; 2.3% eta(ext); turn-on voltages as low as 3.5 V). The importance of the anode-HTL material contact is further explored by replacing NPB with saturated hydrocarbon siloxane monolayers that covalently bind to the anode, without sacrificing device performance (30 000 cd/m(2) luminance; 2.0% eta(ext); 4.0 V turn-on voltage). These results suggest new strategies for developing OLED hole transporting structures.


Partial purification from bovine pulmonary tissue of a protein capable of inhibiting in vivo DNA synthesis in mouse pulmonary cells.
This paper reports on partial purification and characterization of a natural (endogenous) factor capable of inhibiting in vivo DNA synthesis in mouse pneumocytes in a tissue-specific manner. By using a combination of ultrafiltration and various chromatographic techniques, the active agent has been partially purified from aqueous extracts of both bovine and rat pulmonary tissue. The factor responsible for the observed effect was found to be a heat labile compound, most likely a protein of approx. 40 000 molecular weight. Its chemical and physicochemical properties determined so far, and also the manner of its biological action implies that this lung tissue derived agent might be an endogenous proliferation inhibitor with a chalone-like character operating in the pulmonary epithelial cells.


Potential effects on human health of an ammonia rich atmospheric environment in an archaeologically important cave in southeast Asia.
This important cave is described together with an analysis of the potential health effects for humans inhabiting an ecosystem, albeit on a temporary basis, possessing an ammonia rich atmospheric environment. The work emphasises potential environmental hazards together with an evaluation of the range of clinical effects. The environmental pollution in this cave is generally unlikely to have marked adverse effects on temporary visitors who lack pre-existing respiratory impairments. It is suggested that ancient humans would, to avoid an unpleasant polluted environment, have confined most of their activities to the outer regions of the cave. Comparisons are made with other ammonia contaminated environments.


Physiologically Based Pharmacokinetic Modeling to Understand the Absorption of Risperidone Orodispersible Film.
The aim of the present study was to investigate the absorption routes as well as the potential application of the oral transmucosal delivery of risperidone orodispersible film (ODF) using physiologically based pharmacokinetic modeling. The pharmacokinetic study after intragastric (i.g.), supralingual, and sublingual administration of risperidone ODF was conducted in Beagle dogs. Then a mechanic absorption model which combined Oral Cavity Compartment Absorption and Transit (OCCAT) model with Advanced Compartment Absorption and Transit (ACAT) model for predicting the absorption routes of risperidone ODF in vivo was constructed using GastroPlus™. A sensitivity analysis was performed to investigate the impact of oral residence time on the in vivo absorption of risperidone ODF. Based on the fraction of intraoral absorption, the potential of the oral transmucosal delivery of risperidone were predicted. There were no statistical differences in the AUC0-t (P = 0.4327), AUC0-∞ (P = 0.3278), Cmax (P = 0.0531), and Tmax (P = 0.2775) values among i.g., supralingual, and sublingual administration of risperidone ODF in Beagle dogs. The predicted absorption percentage via oral mucosa at oral residence time of 2 min, 5 min, and 10 min was 7.0%, 11.4%, and 19.5%, respectively. No obvious difference was observed for the bioavailability of risperidone ODF within 10 min of oral residence time. The PBPK absorption model for risperidone could be simplified to include ACAT model solely. The main absorption route for risperidone ODF was the gastrointestine. The absorption percentage via oral mucosa was almost negligible due to the physicochemical properties of risperidone although ODF dissolved completely in the oral cavity of Beagle dogs within 2 min.


The mitochondrial genome of the tapeworm Taenia solium: a finding of the abbreviated stop codon U.
The complete nucleotide sequence of the tapeworm Taenia solium mitochondrial DNA (mtDNA) has been determined. The sequence is 13,709 base pairs in length and contains 36 genes (12 for proteins involved in oxidative phosphorylation, 2 for ribosomal RNAs, and 22 for transfer RNAs). The gene content and organization of the T. solium mtDNA are identical to those of other taeniid mtDNAs. All genes are transcribed in the same direction, and all protein-coding genes appear to initiate with the AUG or GUG codon. In a gene for NADH dehydrogenase subunit 1, the abbreviated stop codon U was confirmed for the first time in flatworm mtDNAs.


The legless lizard Anguis fragilis (slow worm) has a potent metal-responsive transcription factor 1 (MTF-1).
The metal-responsive transcription factor-1 (MTF-1) is a key regulator of heavy metal homeostasis and detoxification. Here we characterize the first MTF-1 from a reptile, the slow worm Anguis fragilis. The slow worm, or blind worm, is a legless lizard also known for its long lifespan of up to several decades. Anguis MTF-1 performs well and matches the strong zinc and cadmium response of its human ortholog, clearly surpassing the activity of rodent MTF-1s. Some amino acid positions critical for metal response are the same in humans and slow worm but not in rodent MTF-1. This points to a divergent evolution of rodent MTF-1, and we speculate that rodents can afford a less sophisticated metal handling than humans and (some) reptiles.


[Computerized tomography imaging of the anterior cardiophrenic angle].
The anterior cardiophrenic angle (ACA) is the lowermost anterolateral portion of the mediastinum. It is limited inferiorly by the diaphragm, anteriorly by the chest wall, posteriorly by the pericardium, and laterally by the parietal pleura. In 20% computed tomography (CT) of the normal ACA shows the diaphragm as a linear structure, and in 15% as a pseudotumorous structure that has to be differentiated from real tumours. The inferior sternopericardial ligament appears as a linear structure in 22%. In 3% nodular structures of up to 8 mm of diameter are visible in the normal ACA, probably corresponding to cardiophrenic angle nodes. These findings suggest that, exceptionally, normal cardiophrenic angle nodes may be demonstrated by CT.


Parent socialization of emotion in a high-risk sample.
The Socialization of Emotion (Eisenberg, Cumberland, & Spinrad, 1998; Eisenberg, Spinrad, & Cumberland, 1998) model creates a theoretical framework for understanding parents' direct and indirect influences on children's emotional development, including the influence of parent characteristics on subsequent emotion specific parenting. Large numbers of children live in families with fathers who have alcohol problems, setting the stage for cascading risk across development. For instance, fathers' alcohol problems are a marker of risk for higher family conflict, increased parental depression and antisociality, and less sensitive parenting, leading to dysregulated child emotion and behavior. We examined a conceptual model for emotion socialization in a community sample of alcoholic and nonalcoholic father families (N = 227) recruited in infancy (i.e., 12 months) with follow-ups to adolescence (i.e., 15-19 years), and examined if hypothesized paths differed by child sex or group status (alcoholic vs. nonalcoholic families). Results indicated significant indirect effects between parent psychopathology and sensitivity in early childhood to both adaptive (e.g., emotion regulation) and maladaptive (e.g., aggression and peer delinquency) outcomes in middle childhood to adolescence via child negative emotionality and supportive emotion socialization. There were significant differences by child sex and alcohol group status. Implications for intervention and prevention are discussed. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


[Laparoscopic treatment of hydatid liver cysts].
Laparoscopic hepatic hydatidectomy (LHE) was performed in 37 patients. Conversion to laparotomy in one case was caused by intrahepatic location of liver cyst. In 36 patients after LHE, the postoperative period was significantly easier than after standard operation. There were the following complications: bile efflux in abdominal cavity (1), bile efflux from residual cavity (2), suppuration of residual cavity (1). The complications were removed without laparotomy, all the patients recovered. The patients were discharged on day 5.6 on the average. LHE is a promising method of surgical treatment for uncomplicated liver echinococcosis.


Organized chronic subdural hematoma requiring craniotomy--five case reports.
Two child and three elderly patients underwent craniotomy for organized and/or partially calcified chronic subdural hematomas (CSHs). The characteristic feature of magnetic resonance imaging was a heterogeneous web-like structure in the hematoma cavity. Both children had undergone one side subduroperitoneal shunt for bilateral CSHs when infants. As a result, the opposite hematoma cavities persisted and developed into calcified CSHs after a couple of years. All three elderly patients with senile brain atrophy showed various systemic complications such as cerebral infarction, diabetes mellitus, leg ulceration, cirrhosis, and bleeding tendency. Craniotomy for removal of the hematoma and calcification achieved good results in all patients. Subdural space created by shunt, craniotomy, or brain atrophy and persisting for a certain period, and additional various brain damage such as microcirculatory disorder, meningitis, encephalitis, or premature delivery may be important in generating calcified or organized CSH.


Life-threatening airway obstruction as a complication to the management of mediastinal masses in children.
Life-threatening airway obstruction from large mediastinal masses in children poses a difficult diagnostic and therapeutic dilemma, requiring the close coordination of a pediatric surgeon, anesthesiologist, radiologist, and oncologist. To focus on this problem, the anesthetic and surgical management of 50 consecutive children with mediastinal masses treated between 1978 and 1984 were reviewed. Thirty children presented with respiratory symptoms; nine had life-threatening respiratory compromise with dyspnea, orthopnea, and stridor. Thirteen of these symptomatic children had marked compression of the trachea and/or mainstem bronchi on radiographic studies. The tracheal cross-sectional area which was measured by computed tomography was decreased by 35% to 93% of the normal tracheal dimensions in these children. Nonresectable malignant neoplasms including lymphoma, Hodgkin's disease, rhabdomyosarcoma, and neuroblastoma were the eventual diagnoses in 10 of these patients. The other 3 patients were less than 4 years old and had benign lesions. General anesthesia was judged to be prohibitively risky in 5 of 13 patients. The diagnosis was established by node or needle biopsy under local anesthesia, and general anesthesia was deferred until the compromised airway was alleviated by radiation and chemotherapy. General anesthesia with endotracheal intubation was administered to 8 patients, 5 of whom developed total airway obstruction. Using a variety of maneuvers, ventilation was reestablished in all 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma.
Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues by means of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intra-tumoral melanocytes. Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5-8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.


Increased lipid peroxidation of erythrocytes in blood stored in polyvinyl chloride blood storage bags plasticized with di-[2-ethyl hexyl] phthalate and effect of antioxidants.
Previous work in this laboratory has shown significant decrease in vitamin E in erythrocytes in blood stored in polyvinyl chloride (PVC) bags plasticized with di-[2-ethyl hexyl] phthalate (DEHP), and in erythrocytes incubated in vitro with DEHP. Since vitamin E is a major antioxidant, a study was carried out to find out whether this decrease observed in vitamin E has an effect on lipid peroxidation in blood stored in DEHP-plasticized PVC blood bags. Blood was collected in Penpol blood storage bags (which is a DEHP-plasticized PVC bag) and parameters of lipid peroxidation, i.e. activity of superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, concentration of malondialdehyde (MDA), conjugated dienes, hydroperoxides, glutathione and vitamin E studied in erythrocytes after various periods of storage as compared to glass bottles. Erythrocytes were also incubated in vitro with DEHP with and without vitamin E, and changes in lipid peroxidation studied. Blood stored in Penpol bags showed increased lipid peroxidation in erythrocytes as compared to that stored in glass bottles, as is evident from a greater increase in MDA and a greater decrease in glutathione and a significant decrease in vitamin E. The addition of vitamin E decreased the formation of MDA and conjugated dienes and prevented the decrease in vitamin E. However in spite of increased lipid peroxidation in the presence of DEHP, the release of K+ and hemoglobin from erythrocytes was lower. When there was an increase in DEHP taken up by erythrocytes, there was a corresponding decrease in vitamin E. More important, whenever there was an increase in vitamin E in erythrocytes (when RBCs in the presence of DEHP were incubated with vitamin E), there was a progressive decrease in DEHP. DEHP caused increased lipid peroxidation in erythrocytes. At the same time, it decreased the release of K+ and hemoglobin from erythrocytes. It is possible that the stabilizing effect of DEHP on the erythrocyte membrane may offset the detrimental effects of the increased lipid peroxidation it causes.


Quantitative assessment of microbes from samples of indoor air and dust.
Different types of house dust samples are widely used as surrogates of airborne inhalation exposure in studies assessing health effects of indoor microbes. Here we studied-in a quantitative assessment-the representativeness of different house dust samples of indoor air (IA) and investigated seasonality and reproducibility of indoor samples. Microbial exposure was measured five times over 1 year in four rural and five urban Finnish homes. Six sampling methods were used: button inhalable aerosol sampler (actively collected personal and indoor air sampling), settled dust, floor dust, mattress dust and vacuum cleaner dust bag dust; the latter three referred to herein as "reservoir dust samples". Using quantitative PCR, we quantified the fungal species Cladosporium herbarum, the fungal group Penicillium/Aspergillus/Paecilomyces variotii, total fungal DNA, and Gram-positive and Gram-negative bacteria. We observed significant differences in microbial levels between rural and urban homes, most pronounced for personal air samples. Fungal species and groups but not total fungal DNA in indoor air correlated moderately to well with reservoir dust and with personal air samples. For bacterial groups, the correlations between air and dust were generally lower. Samples of indoor air and settled dust reflected similarly seasonal variation in microbial levels and were also similar compositionally, as assessed by ratios of qPCR markers. In general, determinations from mattress dust and other reservoir samples were better reproducible in repeated assessments over time than from indoor air or settled dust. This study indicates that settled dust reflects the microbial composition of indoor air and responds similarly to environmental determinants. Reservoir dusts tend to predict better microbial levels in indoor air and are more reproducible. Sampling strategies in indoor studies need to be developed based on the study questions and may need to rely on more than one type of sample.


The usefulness of clinical-practice-based laboratory data in facilitating the diagnosis of dengue illness.
Alertness to dengue and making a timely diagnosis is extremely important in the treatment of dengue and containment of dengue epidemics. We evaluated the complementary role of clinical-practice-based laboratory data in facilitating suspicion/diagnosis of dengue. One hundred overall dengue (57 dengue fever [DF] and 43 dengue hemorrhagic fever [DHF]) cases and another 100 nondengue cases (78 viral infections other than dengue, 6 bacterial sepsis, and 16 miscellaneous diseases) were analyzed. We separately compared individual laboratory variables (platelet count [PC] , prothrombin time [PT], activated partial thromboplastin time [APTT], alanine aminotransferase [ALT], and aspartate aminotransferase [AST]) and varied combined variables of DF and/or DHF cases with the corresponding ones of nondengue cases. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) in the diagnosis of DF and/or DHF were measured based on these laboratory variables. While trade-off between sensitivity and specificity, and/or suboptimal PPV/NPV was found at measurements using these variables, prolonged APTT + normal PT + PC < 100 × 10(9) cells/L had a favorable sensitivity, specificity, PPV, and NPV in diagnosis of DF and/or DHF. In conclusion, these data suggested that prolonged APTT + normal PT + PC < 100 × 10(9) cells/L is useful in evaluating the likelihood of DF and/or DHF.


Perceptual decisions formed by accumulation of audiovisual evidence in prefrontal cortex.
To form perceptual decisions in our multisensory environment, the brain needs to integrate sensory information derived from a common source and segregate information emanating from different sources. Combining fMRI and psychophysics in humans, we investigated how the brain accumulates sensory evidence about a visual source in the context of congruent or conflicting auditory information. In a visual selective attention paradigm, subjects (12 females, 7 males) categorized video clips while ignoring concurrent congruent or incongruent soundtracks. Visual and auditory information were reliable or unreliable. Our behavioral data accorded with accumulator models of perceptual decision making, where sensory information is integrated over time until a criterion amount of information is obtained. Behaviorally, subjects exhibited audiovisual incongruency effects that increased with the variance of the visual and the reliability of the interfering auditory input. At the neural level, only the left inferior frontal sulcus (IFS) showed an "audiovisual-accumulator" profile consistent with the observed reaction time pattern. By contrast, responses in the right fusiform were amplified by incongruent auditory input regardless of sensory reliability. Dynamic causal modeling showed that these incongruency effects were mediated via connections from auditory cortex. Further, while the fusiform interacted with IFS in an excitatory recurrent loop that was strengthened for unreliable task-relevant visual input, the IFS did not amplify and even inhibited superior temporal activations for unreliable auditory input. To form decisions that guide behavioral responses, the IFS may accumulate audiovisual evidence by dynamically weighting its connectivity to auditory and visual regions according to sensory reliability and decisional relevance.


[Plasma fructosamine to evaluate metabolic control among women with gestational diabetes].
Metabolic control of diabetic pregnant women is assessed using glycated hemoglobin (HbAlc) levels and fasting blood sugar. Another glycated protein, namely fructosamine, can be an indicator of average glucose levels during the last three weeks. To evaluate plasma fructosamine as an indicator of glycemic control in women with gestational diabetes. Prospective cohort study of 41 pregnant women aged 30 to 37 years, with gestational and pre-gestational diabetes. Blood glucose, HbAlc, fructosamine were measured. Newborn weight, and other prenatal and postnatal variables, were used to evaluate the correlation between metabolic control and the presence or absence of macrosomia. The correlation observed between fructosamine and fasting blood glucose (r = 0.627, p < 0.001) was superior to that of HbA1c and blood glucose (r = 0.516, p < 0.001). No association was observed between macrosomia and levels of fructosamine, nor between the other studied variables. Fructosamine levels were not associated with macrosomia, but it could be better for the evaluation of glycemic control in patients with gestational diabetes since it allows short-term monitoring.


Metamizole sodium-induced severe aplastic anemia and its recovery with a short-course steroid therapy.
The authors treated a girl with severe aplastic anemia that developed following urinary tract infection. She was referred to our hospital for bone marrow transplantation. The detailed medical history of the patient revealed iatrogenic metamizole sodium overdose that was given during her infection. She responded to a 3-day, high-dose methylprednisolone therapy and consequent conventional dose steroid. The authors observed at first partial and subsequently complete remission of all the hematologic parameters of the patient within 30 days and 4 months, respectively. This case suggests that the history of drug use should be questioned carefully in the patients with aplastic features. Steroid treatment may be an appropriate alternative therapy for aplastic anemia if associated drug use is detected in the medical history.


Comparison between double-balloon and single-balloon enteroscopy in therapeutic ERC after Roux-en-Y entero-enteric anastomosis.
To compare the efficacy of double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE) in therapeutic endoscopic retrograde cholangiography (ERC) in patients with Roux-en-Y entero-enteric anastomosis. Retrospective analysis of our patient cohort revealed 4 patients with enterobiliary anastomosis and Roux-en-Y entero-enteric anastomosis who underwent repeated ERC with DBE and SBE because of recurrent cholangitis. A total of 38 endoscopic retrograde cholangiopancreatography procedures were performed in 25 patients with Roux-en-Y entero-enteric anastomosis. DBE was used in 29 procedures and SBE in 9. The 4 patients who underwent repeated ERC with DBE and SBE suffered from recurrent cholangitis due to stenosis of the enterobiliary anastomosis. ERC was performed repeatedly to achieve balloon dilation with/without biliary stone extraction and multiple stent placement at the level of the enterobiliary anastomosis. In all 4 patients DBE and SBE were equally successful. Compared to DBE, SBE was equally effective in passing the Roux-en-Y entero-enteric anastomosis, reaching the enterobiliary anastomosis and performing therapeutic ERC. This retrospective comparison shows that DBE and SBE are equally successful in the performance of therapeutic ERC at the level of the enterobiliary anastomosis after Roux-en-Y entero-enteric anastomosis.


Hypothesis/review: contribution of putrescine to 4-aminobutyrate (GABA) production in response to abiotic stress.
4-Aminobutyrate (GABA) accumulates in various plant parts, including bulky fruits such as apples, in response to abiotic stress. It is generally believed that the GABA is derived from glutamate, although a contribution from polyamines is possible. Putrescine, but not spermidine and spermine, generally accumulates in response to the genetic manipulation of polyamine biosynthetic enzymes and abiotic stress. However, the GABA levels in stressed plants are influenced by processes other than putrescine availability. It is hypothesized that the catabolism of putrescine to GABA is regulated by a combination of gene-dependent and -independent processes. The expression of several putative diamine oxidase genes is weak, but highly stress-inducible in certain tissues of Arabidopsis. In contrast, candidate genes that encode 4-aminobutyraldehyde dehydrogenase are highly constitutive, but not stress inducible. Changes in O(2) availability and cellular redox balance due to stress may directly influence the activities of diamine oxidase and 4-aminobutyraldehyde dehydrogenase, thereby restricting GABA formation. Apple fruit is known to accumulate GABA under controlled atmosphere storage and therefore could serve as a model system for investigating the relative contribution of putrescine and glutamate to GABA production.


Neurodegeneration after repeated noise trauma in the mouse lower auditory pathway.
High intensity noise exposure leads to a permanent shift in auditory thresholds (PTS), affecting both peripheral (cochlear) tissue and the central auditory system. Studies have shown that a noise-induced hearing loss results in significant cell loss in several auditory structures. Degeneration can be demonstrated within hours after noise exposure, particularly in the lower auditory pathway, and continues to progress over days and weeks following the trauma. However, there is limited knowledge about the effects of recurring acoustic trauma. Repeated noise exposure has been demonstrated to increase neuroplasticity and neural activity. Thus, the present study aimed to investigate the influence of a second noise exposure on the cytoarchitecture of key structures of the auditory pathway, including spiral ganglion neurons (SGN), the ventral and dorsal cochlear nucleus (VCN and DCN, respectively), and the inferior colliculus (IC). In the experiments, young adult normal hearing mice were exposed to noise once or twice (with the second trauma applied one week after the initial exposure) for 3 h, using broadband white noise (5 - 20 kHz) at 115 dB SPL. The cell densities in the investigated auditory structures significantly decreased in response to the initial noise exposure compared to unexposed control animals. These findings are consistent with earlier research, which demonstrated degeneration in the auditory pathway within the first week after acoustic trauma. Additionally, cell densities were significantly decreased after the second trauma, but this effect was only observed in the VCN, with no similar effects seen in the SGN, DCN, or IC. These results illustrate how repeated noise exposure influences the cytoarchitecture of the auditory system. It appears that an initial noise exposure primarily damages the lower auditory pathway, but surviving cellular structures may develop resistance to additional noise-induced injury.


Clinical and prognostic significance of radiographic pattern, distribution, and severity of thoracic radiographic changes in neonatal foals.
A total of 207 thoracic radiographs obtained from 128 foals were evaluated to assess the impact of pulmonary radiographic pattern, distribution, and severity of pulmonary changes on short-term survival of neonatal foals. The association between selected clinical variables and the radiographic manifestation of neonatal respiratory disease was also investigated. The evaluation of interstitial and alveolar-interstitial radiographic patterns within the caudodorsal, caudoventral, and cranioventral lung regions proved to be highly reliable between viewers in the study. A diagnosis of systemic inflammatory response syndrome was related to increased pulmonary infiltrates within the caudodorsal lung region. Dyspneic foals had more extensive pulmonary infiltrates within the cranioventral lung, advanced respiratory disease, and lower survival rates. A fibrinogen concentration >400 mg/dL was associated with increased cranioventral radiographic abnormalities. In addition, tachypnea most consistently related to diffuse (caudodorsal, caudoventral, and cranioventral) pulmonary changes. Neutropenia, milk reflux from the nares, upper airway pathology, abnormal respiratory sounds, failure of transfer of passive immunity (IgG concentration <400 mg/dL), immaturity, or fever, however, were not related to radiographic pattern, distribution, or severity of radiographic changes. Sixty-five percent of foals with radiographic pulmonary disease were discharged alive from our referral hospital. Concurrent caudodorsal and caudoventral radiographic disease was most frequently observed in this foal population. Increased caudodorsal radiographic scores retained statistical significance as a prognostic indicator for nonsurvival in a multiple stepwise logistic regression analysis.


Surface imprinting of pepsin via miniemulsion polymerization.
Surface imprinted polymers allow accessibility of the selective binding sites to large molecules such as proteins. In this work, small polymer particles offering a large surface area were prepared via miniemulsion polymerization in the presence of pepsin serving as a template molecule. The influence of four different functional monomers and of the amount of the template on the imprinting effect of pepsin was investigated. After the miniemulsion polymerization and a washing step, stable polymer suspensions with an average particle diameter of 400-600 nm and a specific surface area of 30-65 m2 g-1 were obtained. The results of detailed rebinding experiments revealed that the highest imprinting effect was achieved with (3-acrylamidopropyl)trimethylammonium chloride as a functional monomer and a high amount of the template. These polymer particles also showed selectivity for pepsin against various proteins. This approach provides a fundamental step towards the development of synthetic protein receptors and protein scavenger materials useful in biomimetic assays and for clean-up in biotechnology.


Do confounding or selection factors of residential wiring codes and magnetic fields distort findings of electromagnetic fields studies?
In contrast with several previous studies, our recent large case-control study found little association between childhood acute lymphoblastic leukemia (ALL) and electric-power-line wire codes. Here we examine internal evidence from our study to assess the possibility that selection bias and/or confounding may have affected the findings. We compared the relation between childhood ALL and wire codes and direct measurements of magnetic fields in subjects who participated in all phases of the study with the relation in all subjects, including those who declined to allow access inside the home. We found that the odds ratio for ALL among those living in homes with very high current configurations increased by 23% when 107 "partial participants" were excluded. We found similar, but slightly smaller, increases in the odds ratios when we performed the same comparisons using direct measurements of magnetic fields, excluding subjects who allowed only a measurement outside the front door. "Partial participants" tended to be characterized by lower socioeconomic status than subjects who participated fully, suggesting possible selection bias. We also examined the relation between a large number of potential confounding variables and both proxy and direct measurements of magnetic fields. Univariate adjustment for individual variables changed the odds ratio for ALL by less than 8%, while simultaneous adjustment for several factors reduced the estimate by a maximum of 15%. We conclude that while confounding alone is unlikely to be an important source of bias in our own and previous studies of magnetic fields, selection bias may be more of a concern, particularly in light of the generally low response rates among controls in case-control studies.


Liquid-crystal-deflector based variable fiber-optic attenuator.
A compact, low-component-count, no-moving-parts variable optical attenuator (VOA) is demonstrated for the first time by means of beam spoiling that is implemented via an electrically reconfigurable nonpixelated nematic liquid-crystal deflector. The VOA design features an in-line alignment polarization-insensitive design that does not use bulky polarization splitting and combining optics. The proof-of-concept VOA at 1550 nm demonstrates a 30-dB attenuation range, a 2.5-dB insertion loss, a < or = 0.8-dB polarization-dependent loss, and a 1-s maximum attenuation reset time. The VOA design can counter performance-reducing environmental effects such as excess-loss increases due to temperature variations.


In vitro diagnosis of allergy: how to interpret IgE antibody results in clinical practice.
The basis of any diagnosis of allergy requires a good history and examination, which should then provide a certain degree of confidence as to whether or not allergy is present. However, the diagnosis cannot be confirmed on the basis of symptoms alone, because both allergic and non-allergic conditions can present with similar symptoms. Based on prevalence figures, about half of the patients presenting with allergic symptoms in primary care may be non-allergic. Therefore, allergy testing in the form of specific IgE (sIgE) measurement and/or skin prick testing is an invaluable aid in demonstrating both the presence and severity of such an allergy. The usefulness of such tests extends beyond just the positive or negative result. Often, more information can be gleaned by using the test results in a form of a continuous variable in order to determine the likelihood that allergy can be attributed as an explanation for patients' symptoms and disease. In this review, we describe the rationale for utilising specific IgE antibody tests in diagnosing allergy. Furthermore, to optimize the information gained from allergy testing, we describe how to employ one particular well-validated IgE testing system for determining the likelihood that an individual patient's disease can be attributed to allergy.


BCL-6: a possible missing link for anti-inflammatory PPAR-delta signalling in pancreatic beta cells.
Inflammatory mediators contribute to pancreatic beta cell death in type 1 diabetes. Beta cells respond to cytokine exposure by activating gene networks that alter cellular metabolism, induce chemokine release (thereby increasing insulitis), and cause apoptosis. We have previously shown by microarray analysis that exposure of INS-1E cells to IL-1beta + IFN-gamma induces the transcription factor peroxisome proliferator-activated receptor (Ppar)-delta and several of its target genes. PPAR-delta controls cellular lipid metabolism and is a major regulator of inflammatory responses. We therefore examined the role of PPAR-delta in cytokine-treated beta cells. Primary beta cells that had been purified by fluorescence-activated cell sorting and INS-1E cells were cultured in the presence of the cytokines TNF-alpha, IL-1beta, or IL-1beta + IFN-gamma, or the synthetic PPAR-delta agonist GW501516. Gene expression was analysed by real-time PCR. PPAR-delta, monocyte chemoattractant protein (MCP-1, now known as CCL2) promoter and NF-kappaB activity were determined by luciferase reporter assays. Exposure of primary beta cells or INS-1E cells to cytokines induced Ppar-delta mRNA expression and PPAR-delta-dependent CD36, lipoprotein lipase, acyl CoA synthetase and adipophilin mRNAs. Cytokines and the PPAR-delta agonist GW501516 also activated a PPAR-delta response element reporter in beta cells. Unlike immune cells, neither INS-1E nor beta cells expressed the transcriptional repressor B-cell lymphoma-6 (BCL-6). As a consequence, PPAR-delta activation by GW501516 did not decrease cytokine-induced Mcp-1 promoter activation or mRNA expression, as reported for macrophages. Transient transfection with a BCL-6 expression vector markedly reduced Mcp-1 promoter and NF-kappaB activities in beta cells. Cytokines activate the PPAR-delta gene network in beta cells. This network does not, however, regulate the pro-inflammatory response to cytokines because beta cells lack constitutive BCL-6 expression. This may render beta cells particularly susceptible to propagating inflammation in type 1 diabetes.


Early debridement for necrotizing pancreatitis: is it worthwhile?
The timing for debridement of necrotizing pancreatitis is controversial. We reviewed our experience with early and delayed surgical debridement in patients with necrotizing pancreatitis. The records of patients diagnosed with acute necrotizing pancreatitis from January 1993 through June 2000 were reviewed retrospectively. Data were analyzed with respect to Ranson's, APACHE II, and multiple organ failure scores, etiology, presence of infection, overall and ICU length of stay, time to first debridement, number of debridements, fluid requirements, days to enteral feeding, transfusion requirements, complications, and mortality. Twenty-six patients (18 males, 8 females, mean age 51 years) were diagnosed with acute necrotizing pancreatitis. The admission Ranson's score was 4.8, the APACHE II score was 11.7, and multiple organ failure score was 4.2. All but one patient underwent pancreatic debridement (4.3 debridements per patient). Eighteen patients (69%) had infected pancreatic necrosis. The timing of debridement was based on patients' condition and surgeon's preference. The presentation and demographics of patients who underwent early (<2 weeks) or late (>2 weeks) debridement did not differ significantly. Patients debrided early had a trend toward higher mortality (29% versus 18%) and experienced a higher number of major complications (p < 0.05). The six patients (23%) who died were older, had multiple organ failure scores, and more often had Candida in the infected necrosis (p < .05). Early debridement for acute necrotizing pancreatitis might not improve survival and might even be associated with increased number of complications. Most patients diagnosed with necrotizing pancreatitis eventually need debridement, but it might be beneficial to delay debridement if the patient's condition allows for it.


Primary Spinal Epidural Diffuse Large B-cell Lymphoma: Case Report and Literature Review.
Primary spinal epidural lymphoma (PSEL) comprises a group of tumors present only in the spinal epidural space with a histopathological picture of lymphoma and negative diagnostic workup for lymphoma at other sites. We present the case of an older male adult with primary spinal diffuse large B-cell lymphoma (DLBCL) presenting with spinal cord compression who was treated with surgery followed by high dose methotrexate in combination with RCHOP (rituximab, cyclophosphamide, prednisone, vincristine, and doxorubicin). This case report and review of literature on DLBCL limited to the spine provide a novel chemotherapy regimen and a comprehensive perspective on the optimal management of these patients.


Olanzapine treatment in chronic drug-resistant childhood-onset schizophrenia: an open-label study.
The use of typical antipsychotics is limited in children with schizophrenia, owing to the high rate of response failure and early appearance of extrapyramidal syndromes as well as tardive and withdrawal dyskinesia. The aim of the present study was to examine the effectiveness of the atypical antipsychotic olanzapine in the treatment of childhood-onset schizophrenia. The study sample included nine children hospitalized for schizophrenia who had proven refractory to treatment with at least two antipsychotic drugs. Olanzapine was administered after a 2-week washout period in gradually increasing doses to a maximum of 5 mg/day on day 5 and 10 mg/day in week 3; six patients received up to 20 mg/day as of week 5. The duration of the study was 12 weeks. Patient psychiatric status was measured with three scales at onset of therapy and thereafter once weekly. Patients also underwent regular blood, laboratory, and liver function tests, and we also monitored their blood pressure and weight and performed electrocardiography and electroencephalography. A reduction in all psychopathology scores was obtained at 12 weeks from baseline. All extrapyramidal symptoms of previous medications resolved, and there were no new incidents. Side effects were mild. There were no adverse changes in blood chemistry, hematological tests, or electrocardiography parameters, but the treatment was associated with a significant weight gain (6.10 +/- 3.25 kg). At 1-year follow-up, the improvement in psychiatric symptoms was sustained in eight children. We conclude that olanzapine may have potential as a first-line drug in the treatment of drug-resistant childhood-onset schizophrenia. Large-scale, double-blind, placebo-controlled comparative studies are needed to clarify the role of the various atypical antipsychotics in both treatment-resistant and treatment-naïve populations with psychotic symptoms/disorders.


Polyphenol Polymerization by an Alternative Oxidative Microbial Enzyme and Characterization of the Biological Activity of Oligomers.
The recombinant catalase-peroxidase HPI from E. coli was used as an alternative enzyme in polymerization reactions for the production of (-) epicatechin oligomers and their biological activity was characterized. The enzyme was prepared in two forms: a purified and an immobilized form. Both were tested for their activity in oxidative polymerization reactions, and their stability and reusability were assessed. The polymerization reactions were followed by SEC-HPLC analyses, and the substrate was completely converted into one or more polymerization products depending on the reactions conditions. Results showed that the utilized conditions allowed for the isolation of some oligomers of different molecular weight: the oligomers containing 6 and 7 units of epicatechin substrate are the heaviest ones. Epicatechin was also used in reactions catalyzed by HRP in the same reaction conditions for comparison. In addition, one selected oligomer obtained by HPI enzyme catalysis was shown to act as in vitro inhibitor of tumor cell growth, like one oligomer deriving from epicatechin by HRP catalysis. These data confirm that epicatechin oligomeric form is more effective than its monomer in biological activity and suggest the use of HPI as an alternative enzyme in reactions for the production of epicatechin oligomers.


Management of chronic pain and control of long-term disability.
Chronic pain has become a major public health problem. Often, the availability of entitlement programs as well as psychosocial, occupational, and other nonmedical factors-rather than objective pathophysiology-are major contributors to disability. In this chapter, the authors discuss the relationship between impairment and disability and detail factors likely to predict or contribute to adverse clinical outcome and disability. Guidelines for disability prevention also are examined.


Identification of critical residues of influenza neuraminidase in viral particle release.
Influenza neuraminidase (NA) is essential for virus release from its host cells and it is one of the targets for structure-based antiviral drug design. In this report, we established a pseudoviral particle release assay to study NA function, which is based on lentiviral particles pseudotyped with influenza glycoproteins HA and NA as a surrogate system. Through an extensive molecular analysis, we sought to characterize important residues governing NA function. We identified five residues of NA, 234, 241, 257, 286 and 345, four of which (except 345) map away from the active site of NA when projected onto the three-dimensional structure of avian influenza H5N1 NA, and substitutions of these residues adversely affected the NA-mediated viral particle release, suggesting that these residues are critical for NA enzymatic activity. Through extensive chimeric and mutational analyses, we have identified several residues, which map away from the active site and are critical for NA function. These findings provide new insights into NA-mediated pseudoviral particle release and may have important implications in drug design and therapeutics against influenza infection.


Medication adherence in patients with asthma using once-daily versus twice-daily ICS/LABAs.
This real-world observational study compared medication adherence and persistence among patients with asthma receiving the once-daily inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fluticasone furoate/vilanterol (FF/VI) versus the twice-daily ICS/LABAs budesonide/formoterol (B/F) and fluticasone propionate/salmeterol (FP/SAL). This retrospective cohort study conducted using IQVIATM Health Plan Claims Data included patients with asthma ≥18 years of age initiating ICS/LABA therapy with FF/VI, B/F, or FP/SAL between January 1, 2014 and June 30, 2016 (index date). Patients had ≥12 months and ≥3 months of continuous eligibility pre- and post-index date, respectively. Patients receiving FF/VI were separately matched 1:1 with patients receiving B/F or FP/SAL using propensity score matching (PSM) and multivariable regression to balance baseline covariates between cohorts. The primary endpoint was medication adherence, measured by proportion of days covered (PDC). Secondary endpoints included proportion of patients achieving PDC ≥ 0.5 and PDC ≥ 0.8 and persistence with index medication, measured by time to discontinuation (>45-day gap in therapy). After PSM, 3,764 and 3,339 patients receiving FF/VI were matched with patients receiving B/F or FP/SAL, respectively. Mean PDC was significantly higher for FF/VI versus B/F (0.453 vs 0.345; adjusted p < 0.001) and FP/SAL (0.446 vs 0.341; adjusted p < 0.001). The proportion of patients achieving PDC ≥ 0.5 or PDC ≥ 0.8, and treatment persistence were significantly higher for FF/VI versus B/F and FP/SAL (all p < 0.001). In this real-world study, patients initiating FF/VI had better adherence and lower risk of discontinuing treatment versus B/F or FP/SAL, suggesting that once-daily ICS/LABA treatment might improve adherence and persistence compared with twice-daily alternatives.


[Absorption of fatty acids by the rat heart in arrhythmia].
Fifty-three white rat males were divided into 4 groups: intact, with arrhythmia, with arrhythmia treated with cordaron, with arrhythmia treated with cardiotron. The rats' diet was enriched with animal fats. Anesthesia was made with uretan (1,0-1,2 g/kg, i.p.). Arrhythmia was induced with akonitine (30-40 mg/kg, i.v.). The drugs were administered 12 and 25 days before arrhythmia induction which was registered on ECG at min 3, 5, 15 and 25 in 1, 11 and 111 standard leads. Total lipid fatty acids (TLFA) of plasma were detected in heart inflowing and outflowing blood with gas chromatography. Arrhythmia drastically changes qualitative characteristics of arterio-venous difference for fatty acids. Cordaron and cardiotron prevented arrhythmia in 63-75% cases. TLFA arterio-venous difference recovered by 55-69%. Cordaron and cardiotron may have a mediating mechanism of action on fatty acid absorption by the heart in normalization of normal heart rate in experimental arrhythmia.


Harassment in the headache field: a global web-based cross-sectional survey.
Matters of workplace harassment are an important issue. This issue needs to be recognized and studied to prevent occurrences. These important sensitive areas of effective workplace management are increasingly gaining more interest. We aimed to identify the prevalence of workplace sexual, verbal and physical harassment among headache professionals. We adopted a cross‑sectional exploratory survey approach with quantitative design. The survey was distributed electronically among headache healthcare and research professionals globally through the International Headache Society (IHS). Data were obtained from 579 respondents (55.3%; 320/579 women). A large percentage of respondents (46.6%; 270/579) had experienced harassment; specifically, 16.1% (93/578) reported sexual harassment, 40.4% (234/579) verbal harassment and 5.5% (32/579) physical harassment. Women were almost seven times more likely to experience sexual harassment compared to men (odds ratio = 6.8; 95% confidence interval = 3.5-13.2). Although women did also more frequently report other types of harassment, this was not statistically significant (odds ratio = 1.4; 95% confidence interval = 1.0-2.0). Lifetime exposure to workplace harassment is prevalent among headache professionals, especially in women. The present study uncovers a widespread issue and calls for strategies to be implemented for building a healthy and safe workplace environment.


IFN-gamma plays a dominant role in upregulation of Candida-specific IgE synthesis in patients with atopic dermatitis.
Although Candida albicans (CA) is known to induce Th1 clones that suppress IgE synthesis, serum IgE antibody against CA is often increased in atopic patients. This study aims to elucidate the mechanism of IgE synthesis against CA in atopic patients. We measured the production of IL-4 and IFN-gamma by peripheral blood mononuclear cells (PBMCs) from atopic patients upon stimulation with CA and examined the correlation with the level of serum IgE antibody against CA. The level of serum CA-specific IgE antibody (CA-IgE) was significantly higher in patients with atopic dermatitis (AD) than in patients with bronchial asthma (BA) (geometric mean = 3.6 vs. 0.27 U(A)/ml, p < 0.02) (U(A) = unit allergen), while there was no difference in the level of house dust mite-specific IgE antibody between them (67.6 vs. 87.1 U(A)/ml). Although IL-4 production by PBMCs upon stimulation with CA in patients with AD was not significantly different from that in patients with BA (mean = 359.1 vs. 515.3 fg/ml), IFN-gamma production was significantly lower in the former than in the latter group (8.1 vs. 56.2 pg/ml, p < 0.001). Consequently, the ratio of IL-4/IFN-gamma production was apparently higher in patients with AD than in those with BA, which corresponds to the difference between them in the level of serum CA-IgE. A significant negative correlation was seen in patients with AD between IFN-gamma production by CA-stimulated PBMCs and the level of serum CA-IgE (p < 0.05). IgE synthesis against CA in atopic patients may be precipitated not by enhancing IL-4 production, but by reducing IFN-gamma secretion.


Simultaneous editing of TCR, HLA-I/II and HLA-E resulted in enhanced universal CAR-T resistance to allo-rejection.
The major challenge for universal chimeric antigen receptor T cell (UCAR-T) therapy is the inability to persist for a long time in patients leading to inferior efficacy clinically. The objective of this study was to design a novel UCAR-T cell that could avoid the occurrence of allo-rejection and provide effective resistance to allogeneic Natural Killer (NK) cell rejection, together with the validation of its safety and efficacy ex vivo and in vivo. We prepared T-cell receptor (TCR), Human leukocyte antigen (HLA)-I/II triple-edited (TUCAR-T) cells and evaluated the anti-tumor efficacy ex vivo and in vivo. We measured the resistance of exogenous HLA-E expressing TUCAR-T (ETUCAR-T) to NK rejection by using an enhanced NK. Furthermore, we established the safety and efficacy of this regimen by treating Nalm6 tumor-bearing mice with a repeated high-dose infusion of ETUCAR-T. Moreover, we analyzed the effects of individual gene deficiency CAR-T on treated mice and the changes in the transcriptional profiles of different gene-edited T cells via RNA-Seq. Data showed that HLA-II editing didn't impair the anti-tumor efficacy of TUCAR-T ex vivo and in vivo and we found for the first time that HLA-II deficiency could facilitate the persistence of CAR-T. Contrastively, as the most commonly eliminated target in UCAR-T, TCR deficiency was found to be a key disadvantageous factor for the shorter-term anti-tumor efficacy in vivo. Our study demonstrated ETUCAR-T could effectively resist allogeneic NK rejection ex vivo and in vivo. Our research provided a potential and effective strategy for promoting the persistence of UCAR-T cells in clinical application. And it reveals the potential key factors of the poor persistence of UCAR-T along with new insights for future development.


Nationwide Outcomes of Pancreaticoduodenectomy for Pancreatic Malignancies: Center Volume Matters.
Complex surgeries such as pancreaticoduodenectomies (PD) have been shown to have better outcomes when performed at high-volume centers (HVCs) compared to low-volume centers (LVCs). Few studies have compared these factors on a national level. The purpose of this study was to analyze nationwide outcomes for patients undergoing PD across hospital centers with different surgical volumes. The Nationwide Readmissions Database (2010-2014) was queried for all patients who underwent open PD for pancreatic carcinoma. High-volume centers were defined as hospitals where 20 or more PDs were performed per year. Sociodemographic factors, readmission rates, and perioperative outcomes were compared before and after propensity score-matched analysis (PSMA) for 76 covariates including demographics, hospital factors, comorbidities, and additional diagnoses. Results were weighted for national estimates. A total of 19,810 patients were identified with age 66 ± 11 years. There were 6,840 (35%) cases performed at LVCs, and 12,970 (65%) at HVCs. Patient comorbidities were greater in the LVC cohort, and more PDs were performed at teaching hospitals in the HVC cohort. These discrepancies were controlled for with PSMA. Length of stay (LOS), mortality, invasive procedures, and perioperative complications were greater in LVCs when compared to HVCs before and after PSMA. Additionally, readmission rates at one year (38% vs 34%, P < .001) and readmission complications were greater in the LVC cohort. Pancreaticoduodenectomy is more commonly performed at HVCs, which is associated with less complications and improved outcomes compared to LVCs.


"The Story I Will Never Forget": Critical Incident Narratives in Surgical Residency.
We sought to better understand what defines a critical incident experience for the surgical trainee. Critical incidents are formative moments stamped indelibly on one's memory that shape professional identity. The critical incident technique-using participants' narratives to identify patterns and learn from their perceptions-has been explored in some healthcare settings, but there has been no inquiry within surgery. Surgical residents at 5 residency programs (1 community, 1 university-affiliated, 3 university) were surveyed using an online questionnaire from November to December 2020. Convenience sampling was used to identify the study population. Participants were invited to write about formative, impactful experiences in training. Interpretive description was the qualitative methodology used to locate information, analyze, and record patterns in the data. Individual responses were categorized and assessed for overlying themes. Overall, 28 narratives were collected from surgery residents in 3 specialties (general surgery, plastic surgery, and urology), with postgraduate year representation of post-graduate years 1 to 6. Respondents were 40% female. Nineteen of the narratives reported a negative experience. Four themes were identified from responses: 1) growth through personal self-reflection, 2) difficult interpersonal interactions, 3) positive team dynamics as a psychological safety net, and 4) supportive program cultures that promote learning. Critical incident narratives among surgical residents indicate that unforgettable and formative experiences-both positive and negative- occur in 4 domains: within the individual, within a relationship, among a team, and within a program. Further exploring these domains in surgical training will inform optimal educational programming to support trainee development and wellbeing.


SB-205384 is a positive allosteric modulator of recombinant GABAA receptors containing rat α3, α5, or α6 subunit subtypes coexpressed with β3 and γ2 subunits.
Many drugs used to treat anxiety are positive modulators of GABAA receptors, which mediate fast inhibitory neurotransmission. The GABAA receptors can be assembled from a combination of at least 16 different subunits. The receptor's subunit composition determines its pharmacologic and functional properties, and subunit expression varies throughout the brain. A primary goal for new treatments targeting GABAA receptors is the production of subunit-selective modulators acting upon a discrete population of receptors. The anxiolytic 4-amino-7-hydroxy-2-methyl-5,6,7,8,-tetrahydrobenzo[b]thieno[2,3-b]pyridine-3-carboxylic acid, but-2-ynyl ester (SB-205384) is widely considered to be selective for α3-containing GABAA receptors. However, it has been tested only on α1-, α2-, and α3-containing receptors. We examined the activity of SB-205384 at recombinant receptors containing the six different α subunits and found that receptors containing the α3, α5, and α6 subunits were potentiated by SB-205384, with the α6 subunit conferring the greatest responsiveness. Properties associated with chimeric α1/α6 subunits suggested that multiple structural domains influence sensitivity to SB-205384. Point mutations of residues within the extracellular N-terminal domain identified a leucine residue located in loop E of the agonist binding site as an important determinant of high sensitivity to modulation. In the α6 subunit the identity of this residue is species-dependent, with the leucine found in rat subunits but not in human. Our results indicate that SB-205384 is not an α3-selective modulator, and instead acts at several GABAA receptor isoforms. These findings have implications for the side-effect profile of this anxiolytic as well as for its use in neuronal and animal studies as a marker for contribution from α3-containing receptors.


Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor.
We have characterized platelet-derived growth factor (PDGF) C, a novel growth factor belonging to the PDGF family. PDGF-C is a multidomain protein with the N-terminal region homologous to the extracellular CUB domain of neuropilin-1, and the C-terminal region consists of a growth factor domain (GFD) with homology to vascular endothelial growth factor (25%) and PDGF A-chain (23%). A serum-sensitive cleavage site between the two domains allows release of the GFD from the CUB domain. Competition binding and immunoprecipitation studies on cells bearing both PDGF alpha and beta receptors reveal a high affinity binding of recombinant GFD (PDGF-CC) to PDGF receptor-alpha homodimers and PDGF receptor-alpha/beta heterodimers. PDGF-CC exhibits greater mitogenic potency than PDGF-AA and comparable or greater mitogenic activity than PDGF-AB and PDGF-BB on several mesenchymal cell types. Analysis of PDGF-CC in vivo in a diabetic mouse model of delayed wound healing showed that PDGF-CC significantly enhanced repair of a full-thickness skin excision. Together, these studies describe a third member of the PDGF family (PDGF-C) as a potent mitogen for cells of mesenchymal origin in in vitro and in vivo systems with a binding pattern similar to PDGF-AB.


Biochemical properties of the superficial masseter muscle in the aging rat.
In young (15 weeks) and senescent (2 years) rats, the metabolic enzyme activities and the composition of myosin heavy chain (MHC) isoforms of the superficial masseter muscle were assessed by biochemical analysis. The succinate dehydrogenase activity and phosphofructokinase activity of the masseter muscle were significantly lower in senescent rats than in young rats. A large portion of the masseter muscle was composed of MHC IIb and IId isoforms in both young and senescent rats. As compared with young rats, no significant change in the composition of MHC isoforms was found in the masseter muscle of the senescent rats. These findings indicate that aging has a significant effect on the energy supply of the superficial masseter muscle.


Trophic and protective effects of growth/differentiation factor 5, a member of the transforming growth factor-beta superfamily, on midbrain dopaminergic neurons.
Growth/differentiation factor 5 (GDF5) is a novel member of the transforming growth factor-beta (TGF-beta) superfamily of multifunctional cytokines. We show here that GDF5 is expresed in the developing CNS including the mesencephalon and acts as a neurotrophic, survival promoting molecule for rat dopaminergic midbrain neurons, which degenerate in Parkinson's disease. Recombinant human GDF5 supports dopaminergic neurons, dissected at embryonic day (E) 14 and cultured for 8 days under serum-free conditions, to almost the same extent as TGF-beta 3, and is as effective as glial cell line-derived neurotrophic factor (GDNF), two established trophic factors for midbrain dopaminergic neurons. In contrast to TGF-beta and GDNF, GDF5 augments numbers of astroglial cells in the cultures, suggesting that it may act indirectly and through pathways different from those triggered by TGF-beta and GDNF. GDF5 also protects dopaminergic neurons against the toxicity of N-methylpyridinium ion (MPP+), which selectively damages dopaminergic neurons through mechanisms currently debated in the etiology of Parkinson's disease (PD). GDF5 may therefore now be tested in animal models of PD and might become useful in the treatment of PD.


Microtubules self-repair in living cells.
Microtubule self-repair has been studied both in vitro and in vivo as an underlying mechanism of microtubule stability. The turnover of tubulin dimers along the microtubule has challenged the pre-existing dogma that only growing ends are dynamic. However, although there is clear evidence of tubulin incorporation into the shaft of polymerized microtubules in vitro, the possibility of such events occurring in living cells remains uncertain. In this study, we investigated this possibility by microinjecting purified tubulin dimers labeled with a red fluorophore into the cytoplasm of cells expressing GFP-tubulin. We observed the appearance of red dots along the pre-existing green microtubule within minutes. We found that the fluorescence intensities of these red dots were inversely correlated with the green signal, suggesting that the red dimers were incorporated into the microtubules and replaced the pre-existing green dimers. Lateral distance from the microtubule center was similar to that in incorporation sites and in growing ends. The saturation of the size and spatial frequency of incorporations as a function of injected tubulin concentration and post-injection delay suggested that the injected dimers incorporated into a finite number of damaged sites. By our low estimate, within a few minutes of the injections, free dimers incorporated into major repair sites every 70 μm of microtubules. Finally, we mapped the location of these sites in micropatterned cells and found that they were more concentrated in regions where the actin filament network was less dense and where microtubules exhibited greater lateral fluctuations.


Validity and Reliability of the Chronic Respiratory Disease Questionnaire in Elderly Individuals with Mild to Moderate Non-Cystic Fibrosis Bronchiectasis.
The chronic respiratory disease questionnaire (CRDQ) is designed to assess health-related quality of life (HRQOL) in chronic respiratory conditions, but its reliability, validity and responsiveness in individuals with mild to moderate non-cystic fibrosis (CF) bronchiectasis are unclear. This study aimed to determine measurement properties of the CRDQ in non-CF bronchiectasis. Participants with non-CF bronchiectasis involved in a randomised controlled trial of exercise training were recruited. Internal consistency was assessed using Cronbach's α. Over 8 weeks, reliability was evaluated using intra-class correlation coefficients and Bland-Altman analysis for measures of agreement. Convergent and divergent validity was assessed by correlations with the other HRQOL questionnaires and the Hospital Anxiety and Depression Scale (HADS). The responsiveness to exercise training was assessed using effect sizes and standardised response means. Eighty-five participants were included (mean age ± SD, 64 ± 13 years). Internal consistency was adequate (>0.7) for all CRDQ domains and the total score. Test-retest reliability ranged from 0.69 to 0.85 for each CRDQ domain and was 0.82 for the total score. Dyspnoea (CRDQ) was related to St George's respiratory questionnaire (SGRQ) symptoms only (r = 0.38), with no relationship to the Leicester cough questionnaire (LCQ) or HADS. Moderate correlations were found between the total score of the CRDQ, the SGRQ (rs = -0.49) and the LCQ score (rs = 0.51). Lower CRDQ scores were associated with higher anxiety and depression (rs = -0.46 to -0.56). The responsiveness of the CRDQ was small (effect size 0.1-0.24). The CRDQ is a valid and reliable measure of HRQOL in mild to moderate non-CF bronchiectasis, but responsiveness was limited.


Measles virus induces oncolysis of mesothelioma cells and allows dendritic cells to cross-prime tumor-specific CD8 response.
Despite conventional medical and surgical treatments, malignant pleural mesothelioma (MPM) remains incurable. Oncovirotherapy (i.e., the use of replication-competent virus for cancer treatment) is currently explored in clinical trials. In this study, we investigated the antineoplastic potential of a new oncolytic viral agent, a live-attenuated measles virus (MV) strain derived from the Edmonston vaccine lineage (Schwarz strain). We evaluated both oncolytic activity and immunoadjuvant properties of the MV vaccine strain on mesothelioma tumor cells. Infectivity, syncytium formation, and cytolytic activity of MV were studied on a panel of mesothelioma cells derived from pleural effusions of MPM patients. We observed that MV infected preferentially MPM cell lines in comparison with nontransformed mesothelial cells, leading to an efficient killing of a significant fraction of tumor cells. A cytoreductive activity was also evidenced through formation of multinuclear cellular aggregates (syncytia). The susceptibility of MPM cell lines to measles infection was assessed by the analysis of cell surface expression of the MV vaccine receptor (CD46). We also evaluated whether MV infection of mesothelioma cells could elicit an autologous antitumor immune response. We showed that MV Schwarz strain induced apoptotic cell death of infected mesothelioma cells, which were efficiently phagocytosed by dendritic cells (DC). Loading of DCs with MV-infected MPM cells induced DC spontaneous maturation, as evidenced by the increased expression of MHC and costimulatory molecules along with the production of proinflammatory cytokines. Priming of autologous T cells by DCs loaded with MV-infected MPM cells led to a significant proliferation of tumor-specific CD8 T cells. Altogether, these data strongly support the potential of oncolytic MV as an efficient therapeutic agent for mesothelioma cancer.


Different Raman spectral patterns of primary rat pancreatic β cells and insulinoma cells.
As a noninvasive and label-free analytical technique, Raman spectroscopy has been widely used to study the difference between malignant cells and normal cells. Insulinomas are functional β-cell tumors of pancreatic islet cells. They exhibit many structural and immunohistochemical features in common with normal pancreatic β cells; thus, they are typically difficult to distinguish under the microscope, especially in vivo. We investigated insulinoma and primary rat pancreatic β-cell populations using Raman spectroscopy. The details of the optical heterogeneity between these two populations were determined based on different Raman regions primarily involving nucleic acid and protein contents, which are the most distinct cellular contents in these two types of cells. Using principal component analysis–linear discriminant analysis, these two cell types can be readily separated. The results of this work indicate that Raman spectroscopy is a promising tool for the noninvasive and label-free differentiation of insulinoma cells and normal pancreatic β cells.


A prospective multi-site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis.
Shoulder pain is a common musculoskeletal complaint in the general population. Bone marrow concentrate (BMC) injections offer promising potential as a minimally invasive approach for treatment of shoulder pain in degenerative disease. In this study, we investigated the clinical outcomes of the BMC injections for treatment of shoulder pain and disability due to osteoarthritis (OA) and rotator cuff tears in a treatment registry population. A total of 115 shoulders in 102 patients were treated with autologous BMC injections for symptomatic OA at the glenohumeral joint and/or rotator cuff tears. Data were collected for factors potentially influencing outcome, including age, sex, body mass index, and the type of condition treated (ie, OA or rotator cuff tear). Clinical outcomes were assessed serially over time using the disabilities of the arm, shoulder and hand score (DASH), the numeric pain scale (NPS), and a subjective improvement rating scale. Baseline scores were compared to the most recent outcome scores at the time of the analysis and adjusted for demographic differences. We reported comparisons of pre- and post-treatment scores, the differences between osteoarthritis and rotator cuff groups, and the predictive effects on the clinical outcomes. At the most current follow-up assessment after treatment, the average DASH score decreased (improved) from 36.1 to 17.1 (P<0.001) and the average numeric pain scale value decreased (improved) from 4.3 to 2.4 (P<0.001). These changes were associated with an average subjective improvement of 48.8%. No differences were observed between outcomes among the shoulders treated for OA versus rotator cuff tears, nor did age, sex, or body mass index influence pain or functional outcomes. There were no significant treatment-related adverse events reported. We observed preliminarily encouraging results following BMC injections for shoulder OA and rotator cuff tears. These results serve as basis for the design of an adequately powered randomized controlled trial.


Expansion and contraction of ribosomal DNA repeats in Saccharomyces cerevisiae: requirement of replication fork blocking (Fob1) protein and the role of RNA polymerase I.
Saccharomyces cerevisiae carries approximately 150 copies of rDNA in tandem repeats. It was found that the absence of an essential subunit of RNA polymerase I (Pol I) in rpa135 deletion mutants triggers a gradual decrease in rDNA repeat number to about one-half the normal level. Reintroduction of the missing RPA135 gene induced a gradual increase in repeat number back to the normal level. Gene FOB1 was shown to be essential for both the decrease and increase of rDNA repeats. FOB1 was shown previously to be required for replication fork blocking (RFB) activity at RFB site in rDNA and for recombination hot-spot (HOT1) activity. Thus, DNA replication fork blockage appears to stimulate recombination and play an essential role in rDNA expansion/contraction and sequence homogenization, and possibly, in the instability of repeated sequences in general. RNA Pol I, on the other hand, appears to control repeat numbers, perhaps by stabilizing rDNA with the normal repeat numbers as a stable nucleolar structure.


The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma.
Pancreatic cancer (PC) is the seventh leading cause of cancer-related death. PC incidence has continued to increase by about 1% each year in both men and women. Although the 5-year relative survival rate of PC has increased from 3% to 12%, it is still the lowest among cancers. Hence, novel therapeutic strategies are urgently needed. Challenges in PC-targeted therapeutic strategies stem from the high PC heterogeneity and from the poorly understood interplay between cancer cells and the surrounding microenvironment. Signaling pathways that drive PC cell growth have been the subject of intense scrutiny and interest has been attracted by necroptosis, a distinct type of programmed cell death. In this review, we provide a historical background on necroptosis and a detailed analysis of the ongoing debate on the role of necroptosis in PC malignant progression.


Physical activity and self-reported symptoms of insomnia, restless legs syndrome, and depression: the comprehensive dialysis study.
Symptoms of sleep and mood disturbances are common among patients on dialysis and are associated with significant decrements in survival and health-related quality of life. We used data from the Comprehensive Dialysis Study (CDS) to examine the association of self-reported physical activity with self-reported symptoms of insomnia, restless legs syndrome (RLS), and depression in patients new to dialysis. The CDS collected data on physical activity, functional status, and health-related quality of life from 1678 patients on either peritoneal (n = 169) or hemodialysis (n = 1509). The Human Activity Profile was used to measure self-reported physical activity. Symptoms were elicited in the following manner: insomnia using three questions designed to capture difficulty in initiating or maintaining sleep, RLS using three questions based on the National Institutes of Health workshop, and depression using the two-item Patient Health Questionnaire. We obtained data on symptoms of insomnia and depression for 1636, and on symptoms of RLS for 1622 (>98%) patients. Of these, 863 (53%) reported one of three insomnia symptoms as occurring at a persistent frequency. Symptoms of RLS and depression occurred in 477 (29%) and 451 (28%) of patients, respectively. The Adjusted Activity Score of the Human Activity Profile was inversely correlated with all three conditions in models adjusting for demographics, comorbid conditions, and laboratory variables. Sleep and mood disturbances were commonly reported in our large, diverse cohort of patients new to dialysis. Patients who reported lower levels of physical activity were more likely to report symptoms of insomnia, RLS, and depression.


Equine granulocytic anaplasmosis in the Czech Republic.
Twelve confirmed cases of equine granulocytic anaplasmosis (EGA) and five additional suspected cases, showing a compatible clinical history and specific IgG titres of 1280 or above, were recorded in the Czech Republic during the period 2002 to 2008. The diagnosis was based on clinical signs, the detection of Anaplasma phagocytophilum morulae in neutrophils in blood smears, serology and molecular methods. Pyrexia (39.8 to 41.3 degrees C), depression, partial or total anorexia, limb oedema and icterus were the most frequently observed clinical abnormalities. Haematological examination revealed thrombocytopenia in all the horses, and mild anaemia and leucopenia in five of them. Several horses showed high titres of specific antibodies immediately after onset of the disease, suggesting that they had previously been exposed to A phagocytophilum. Genotyping of the A phagocytophilum strains distinguished two genetic variants, with divergence in the sequence of the ank gene of the bacterium, circulating in the Czech Republic.


[Current issues of mathematical modeling and advancement in radiology].
An analysis of certain issues in mathematical support and optimization of radiological procedures has pointed to many criteria involved in designing effective schedules of radiotherapy of neoplasms. TDF, CRE and ETD may be used for relevant evaluations. The greatest promise is held by such criteria as tumor tissue ablation (TTA) and radiation injury complications (RIC) in normal organs and tissue. This calls for development of suitable methods. Considering the high complexity of the body. It should be expected that body responses to radiation are determined by irradiation parameters and condition of target tissues. The report deals with a procedure for adapting mathematical models to on-line requirements. Newly-developed programming complexes are designed to help the medical radiologist integrate available data with his or her clinical findings.


Discrimination of Rhizobium japonicum, Rhizobium lupini, Rhizobium trifolii, Rhizobium leguminosarum and of bacteroids by uptake of 2-ketoglutaric acid, glutamic acid and phosphate.
Rhizobium strains (one each of Rh. japonicum, Rh. lupini, Rh. leguminosarum) take up 2-ketoglutaric acid in general much faster and from lower concentrations in the medium than strains of Escherichia coli, Bacillus subtilis and Chromobacterium violaceum. A strain of Enterobacter aerogenes, however, is more similar to some Rhizobium strains. The same strains of Rhizobium take up also phosphate much faster and from lower concentrations than the other bacteria tested. 4 strains of Rh. lupini proved to be significantly different from 4 strains of Rh. trifolii in taking up L-glutamic acid from three to ten times lower concentration within 5 h. A similar difference was noticed between 5 strains of Rh. leguminosarum and 2 strains of Rh. japonicum for the uptake of 2-ketoglutaric acid and of L-glutamic acid. Isolated bacteroids from nodules of Glycine max var. Chippeway have a reduced uptake capacity for glutamic acid and for 2-ketoglutaric acid during the first 10-12 h, but reach the same value after 24 h as free living Rh. japonicum cells. The differences in the uptake kinetics are independent of cell concentration. The group II Rhizobium strains (Rh. japonicum and Rh. lupini, slow growing Rhizobium) are characterized by a rapid uptake of glutamic acid to a low remaining concentration of 1-3 X 10(-7) M and an uptake of 2-ketoglutaric acid to a remaining concentration of 2-5 X 10(-7) M. The group I Rhizobium strains (Rh. trifolii and Rh. leguminosarum, fast growing Rhizobium), can be characterized by a much slower uptake of both substances with a more than ten times higher concentration of both metabolites remaining in the medium after the same time.


[Marfan syndrome and echocardiography].
We report the echocardiographic features of nine patients with Marfan syndrome. Six men and three women. Average age: twenty nine years. Sixty six per cent had aneurysmatic enlargement of the aortic root. One hundred per cent of the cases had aortic insufficiency, enlargement of the left ventricular diameter, decrease of the ejection fraction, and decrease in circunferential shortening; mitral prolapse, (in 6) and signs of high pulmonary artery pressure (in 4 cases). Hemodynamic studies performed in 46 per cent of the patients correlated well with the echocardiographic features. Autopsy performed in the patients who died, corroborated the cardiovascular abnormalities. We conclude that the use of the echocardiogram is a useful non-invasive technique for the early evaluation of the cardiovascular features in the Marfan syndrome.


In Vivo Selective Capture and Rapid Identification of Luteolin and Its Metabolites in Rat Livers by Molecularly Imprinted Solid-Phase Microextraction.
A method based on molecularly imprinted solid-phase microextraction (MIP-SPME) coupled with liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) was developed for the detection of luteolin and its metabolites in vivo. The MIP-SPME fibers were first fabricated by dopamine and silane, and then luteolin MIPs-coated fibers were successfully prepared using luteolin, acrylamide (AM), and ethylene glycol dimethacrylate (EGDMA) as the template, functional monomer and cross-linker, respectively. The characterizations of polymers were analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and the Brunauer-Emmett-Teller method (BET). The properties involving adsorption and selective experiments were evaluated, and these results revealed that MIP fibers presented high adsorption capacity and selectivity to luteolin. Furthermore, the developed MIP-SPME coupled with the LC-QTOF-MS/MS method was adopted to capture and identify luteolin and its metabolites in rat livers in vivo, and eventually, apigenin, chrysoeriol, and diosmetin were rapidly identified as metabolites.


Haptoglobin phenotyping from older bloodstains by enzyme immunoassay and haptoglobin phenotypes within a Nebraska Caucasian population.
Enzyme immunoassay and Western blotting (electrophoretic) techniques were used to determine haptoglobin (HP) phenotypes from older bloodstains. Serum was collected from liquid blood and the HP phenotypes were determined. Bloodstains were prepared from these specimens and stored at various temperatures for several months. The stains were extracted and applied to gradient polyacrylamide gels. The Western blotting technique was used to achieve the transfer of HP bands from the gels to the nitrocellulose membranes. Enzyme immunoassay with goat anti-HP antiserum and rabbit anti-goat immunoglobulin peroxidase were used to identify the HP bands from the extracted samples. Enzyme immunoassay was found to be clearly more sensitive than o-dianisidine or o-tolidine in detecting HP bands from diluted serum samples. The haptoglobin frequency in a Caucasian population in Nebraska was calculated. The frequencies of Phenotypes 1, 2-1, and 2 were found to be 15.8, 48.4, and 35.8%, respectively.


Nurses' perceptions of and factors promoting patient safety culture in Turkey.
This descriptive and cross-sectional study included 561 nurses in hospitals located in Istanbul, Turkey. The Patient Safety Questionnaire was used for data collection. The type of hospital and the amount of education nurses obtained about patient safety and quality improvement were positively associated with patient safety culture. Conversely, the type of work unit negatively affected workers' behaviors and adverse event reporting in terms of patient safety culture.


Bioactive Compounds and Their Influence on Postnatal Neurogenesis.
Since postnatal neurogenesis was revealed to have significant implications for cognition and neurological health, researchers have been increasingly exploring the impact of natural compounds on this process, aiming to uncover strategies for enhancing brain plasticity. This review provides an overview of postnatal neurogenesis, neurogenic zones, and disorders characterized by suppressed neurogenesis and neurogenesis-stimulating bioactive compounds. Examining recent studies, this review underscores the multifaceted effects of natural compounds on postnatal neurogenesis. In essence, understanding the interplay between postnatal neurogenesis and natural compounds could bring novel insights into brain health interventions. Exploiting the therapeutic abilities of these compounds may unlock innovative approaches to enhance cognitive function, mitigate neurodegenerative diseases, and promote overall brain well-being.


Effect of folic acid and zinc sulphate on endocrine parameters and seminal antioxidant level after varicocelectomy.
Varicocele is among the most common problems which may lead to male infertility. Spermatogenesis is impaired as a consequence of this vascular defect, through mechanisms that are not well described. This study aimed to evaluate serum hormonal level (inhibin B, FSH and testosterone) and seminal plasma antioxidant defence levels after folic acid and zinc sulphate administration in varicocelectomised patients. Participants were randomly allocated to four experimental groups. Our randomisation schedule was as follows: zinc sulphate/folic acid, folic acid, zinc sulphate and placebo. The patients underwent varicocelectomy, before which a blood and semen sample were obtained and also three and six months after varicocelectomy for evaluation of blood hormonal level (FSH, testosterone, inhibin B) and seminal oxidative stress status (nitric oxide, superoxide dismutase, total antioxidant capacity). Patients in different groups took orally one capsule per day after dinner following varicocelectomy for 6 months. A significant rise in peripheral blood inhibin B and seminal plasma activity was detected in the zinc sulphate/folic acid group after 6 months. The present clinical trial indicates a change in the hormonal status of varicocelectomised patients following long-term administration of zinc sulphate and folic acid.


Prognostic value of physical function tests and muscle mass in elderly hospitalized patients. A prospective observational study.
To determine the prognostic value for mortality of physical function tests, muscle mass loss, disability and frailty in elderly hospitalized patients. We prospectively included 298 hospitalized patients aged >60 years (152 men and 146 women). We assessed comorbidity using the Charlson Comorbidity Index; nutrition by body mass index, midarm muscle area and subjective nutritional score; physical muscle function by handgrip strength, gait speed, standing balance and stand up test; disability using the Barthel test and activities of daily living; frailty by the clinical frailty scale and Fried frailty index; and cognitive impairment by the Pfeiffer test. We assessed 100-day and long-term mortality. We found a high prevalence of malnutrition, comorbidity, cognitive impairment, physical function impairment, disability and frailty. Mortality at 100 days was 15.1%, with a long-term median survival of 989 days. Mortality was significantly related to age, comorbidity, nutritional status, physical function, disability and frailty. Serum vitamin D3 levels were not related to mortality. Independent prognostic value for long-term mortality was shown by: (i) incapacity to carry out any of the walking, stand up and standing balance tests; (ii) male sex; (iii) aged >80 years; (iv) impaired handgrip strength or gait speed; (v) Charlson Comorbidity Index ≥1; and (6) impaired muscle mass of subjective nutritional score. In elderly hospitalized patients, there is an important role of muscle regarding prognosis, mainly related to physical function, but also and independently regarding muscle mass. Geriatr Gerontol Int 2018; 18: 57-64.


Effect of spontaneous arousals on cardio-respiratory interaction in healthy children.
The aim of this paper was to study the effect of spontaneous arousals during night-time sleep on the interactions between R-R intervals and respiratory phases in healthy children. We collected overnight polysomnography data of 40 healthy children and investigated cardio-respiratory interaction before and after spontaneous arousals during stage 2 sleep using joint symbolic dynamics. The R-R time series were extracted from electrocardiograms (ECG) and respiratory phases were obtained from abdominal sensors using the Hilbert transform. Both the series were transformed into ternary symbol vectors based on the changes between two successive R-R intervals or respiratory phases, respectively. Subsequently, words of length '2' were formed and the correspondence between words of the two series was determined to quantify cardio-respiratory interaction for pre- and post-spontaneous arousal episodes. We observed a brief but significant shortening in R-R and respiratory intervals after arousal. There was also a significant short-term increase in cardio-respiratory interaction during the first 30-second post-arousal episode as compared to 30-second pre-arousal episode (7.5±3.4 vs. 5.2±3.7%, p<0.0001, respectively). In conclusion, spontaneous arousals in healthy children during night-time sleep are associated with a temporal but significant increase in cardio-respiratory interaction.