Cerebral endothelium-dependent function and reactivity to hypercapnia: the role of α1-adrenoreceptors.
We assessed hypercapnic cerebrovascular reactivity (CVR) and endothelium-dependent function [cerebral shear-mediated dilation (cSMD)] in the internal carotid artery (ICA) with and without systemic α1-adrenoreceptor blockade via Prazosin. We hypothesized that CVR would be reduced, whereas cSMD would remain unchanged, after Prazosin administration when compared with placebo. In 15 healthy adults (3 female, 26 ± 4 years), we conducted ICA duplex ultrasound during CVR [target +10 mmHg partial pressure of end-tidal carbon dioxide ([Formula: see text]) above baseline, 5 min] and cSMD (+9 mmHg [Formula: see text] above baseline, 30 s) using dynamic end-tidal forcing with and without α1-adrenergic blockade (Prazosin; 0.05 mg/kg) in a placebo-controlled, double-blind, and randomized design. The CVR in the ICA was not different between placebo and Prazosin (P = 0.578). During CVR, the reactivities of mean arterial pressure and cerebrovascular conductance to hypercapnia were also not different between conditions (P = 0.921 and P = 0.664, respectively). During Prazosin, cSMD was lower (1.1 ± 2.0% vs 3.8 ± 3.0%; P = 0.032); however, these data should be interpreted with caution due to the elevated baseline diameter (+1.3 ± 3.6%; condition: P = 0.0498) and lower shear rate (-14.5 ± 23.0%; condition: P < 0.001). Therefore, lower cSMD post α1-adrenoreceptor blockade might not indicate a reduction in cerebral endothelial function per se, but rather, that α1-adrenoreceptors contribute to resting cerebral vascular restraint at the level of the ICA.NEW & NOTEWORTHY We assessed steady-state hypercapnic cerebrovascular reactivity and cerebral endothelium-dependent function, with and without α1-adrenergic blockade (Prazosin), in a placebo-controlled, double-blind, and randomized study, to assess the contribution of α1-adrenergic receptors to cerebrovascular CO2 regulation. After administration of Prazosin, cerebrovascular reactivity to CO2 was not different compared with placebo despite lower blood flow, whereas cerebral endothelium-dependent function was reduced, likely due to elevated baseline internal carotid arterial diameter. These findings suggest that α1-adrenoreceptor activity does not influence cerebral blood flow regulation to CO2 and cerebral endothelial function.


The cost of implementing two small media interventions to promote HPV vaccination.
To estimate the cost of implementing lay health worker delivered print-based photonovella intervention and iPad-based tailored interactive multimedia intervention (TIMI) to promote Human Papillomavirus (HPV) vaccine uptake and completion among Hispanic parents of daughters 9-17years old. We recruited 301 participants in control, 422 in photonovella, and 239 in TIMI clinics. Intervention costs were estimated using micro-costing from the societal perspective. Cost included time spent planning, training the promotoras, recruiting study participants, and delivering the interventions. Overhead for utilities and project administration was estimated at 30% of direct costs. The total cost per person for the photonovella and TIMI interventions were $88 and $108, respectively. Less than 10% of costs were fixed and therefore the average cost estimates were insensitive to the size of the target groups. The electronic medium for HPV vaccine education was 23% more costly than the standard low-tech print based approach. The cost difference should be considered relative to the effectiveness of these methods in achieving increases in immunization rates. The cost estimates provide information for cost-effectiveness and budget impact assessments of new HPV immunization intervention programs.


Menstrual cycle-related changes in HPA axis reactivity to acute psychosocial and physiological stressors - A systematic review and meta-analysis of longitudinal studies.
Sex disparities are evident in the biological response to acute stressors, with a suggested influence of ovarian hormones on hypothalamic-pituitary-adrenal (HPA) axis functioning. This systematic review and meta-analysis investigates differences in HPA axis reactivity to acute psychosocial or physiological stressors between menstrual cycle phases. A systematic literature search of six databases resulted in 12 longitudinal studies (n = 182) examining HPA axis reactivity in healthy, naturally-cycling, non-breastfeeding participants aged between 18 and 45 years in at least two cycle phases. The quality of cortisol and menstrual cycle assessment was rated and a descriptive synthesis and meta-analysis of HPA axis reactivity between two broader and five more precise cycle phases was conducted. Three studies provided sufficient data for the meta-analysis and showed a significant, small-sized effect, indicating higher cortisol reactivity in the luteal than in the follicular cycle phase. More primary studies with high-quality menstrual cycle and cortisol assessment are needed. The review did not receive funding and was pre-registered (PROSPERO; CRD42020181632).


Inhibition of natural killer cell lysis by natural killer-inhibitory substance: mechanism of suppression.
The mechanism of suppression of NK-mediated lysis by a soluble product of peritoneal cells (NK-IS, natural killer-inhibitory substance) was investigated. Pretreatment of effector cells resulted in depressed NK lysis while pretreatment of targets had no effect, indicating suppression is due to alterations in effector cell function rather than changes in target cells. NK-IS had no effect on the formation of conjugates between effectors and NK-susceptible targets. When NK-IS was added to effector-target cell mixtures after the binding step had been successfully completed, ensuing lysis was significantly depressed, confirming that NK-IS inhibited a postbinding lytic event. The degree of suppression caused by NK-IS was directly related to the duration of exposure to the inhibitory molecule. In addition, a preliminary temperature-dependent step of binding to and/or intracellular entry of NK-IS into effectors is required before suppression can occur. NK-IS prevents the activation of NK cell lysis by interferon and Corynebacterium parvum and effectively inhibits lysis mediated by already activated effectors. The potent suppression of NK lysis and prevention of interferon and C. parvum-mediated activation of NK lysis by a soluble product of peritoneal cells may explain the extremely low level of NK effector cell function within the peritoneal cavity.


Effects of a newly synthesized kappa-opioid receptor agonist, TRK-820, on the discriminative stimulus and rewarding effects of cocaine in rats.
We previously demonstrated that the prototypical kappa-opioid receptor agonist U-50,488H did not affect the discriminative stimulus effects of cocaine, and the dose of U-50,488H which significantly induced aversive effects attenuated the rewarding effects of cocaine. In the present study, the effects of a newly synthesized kappa-opioid receptor agonist, TRK-820, on the discriminative stimulus and rewarding effects of cocaine were examined in rats. In the drug discrimination procedure, the effects of TRK-820 on the discriminative stimulus effects of cocaine were examined in rats that had been trained to discriminate between 10 mg/kg cocaine and saline. TRK-820-induced place preference or place aversion and the effects of TRK-820 on the cocaine (4 mg/kg)-induced place preference were examined using a conditioned place preference procedure in rats. TRK-820 did not engender cocaine-like responding in rats trained to discriminate between 10 mg/kg cocaine and saline. In combination tests, low doses of TRK-820, which did not affect the response rate, significantly attenuated the discriminative stimulus effects of cocaine, and these effects of TRK-820 were reversed by a kappa-opioid receptor antagonist, nor-BNI. In the conditioned place preference procedure, low doses of TRK-820, which did not affect the response rate in the drug discrimination, did not produce either place preference or place aversion, whereas, higher dose (80 microg/kg) of TRK-820 slightly but significantly induced a place aversion. Under these conditions, the cocaine-induced place preference was completely attenuated by low doses of TRK-820. These results may prompt further investigation of the effectiveness of the new kappa-opioid receptor agonist TRK-820 as a novel pharmacotherapeutic compound for the treatment of cocaine addiction.


"Crack lung and heart" presenting after chemotherapy in a 65-year-old man with non-Hodgkin lymphoma.
Crack cocaine can cause a variety of pulmonary and cardiac complications. Pulmonary findings in a 65- year-old man with non-Hodgkin lymphoma who presented with shortness of breath not resolving with antibiotics are presented here. The usual manifestation of "crack lung" in an unusual clinical circumstance underlines the importance of a clinical history in such cases. The finding of "crack lung" preceded the diagnosis of probable "crack heart." No other similar published case reports could be identified in the literature.


Skin temperature in lower hind limb subjected to distal vein arterialization in rats.
Vascular surgery for distal vein arterialization (DVA) has been adopted clinically as a strategy for saving arteriosclerotic lower limbs from amputation. To gain more detailed information on DVA, the present study investigated the procedure in hind limbs of rats under isoflurane anesthesia. Since successful DVA requires destruction of venous valves, a coronary angioplasty catheter guidewire was used to destroy valves either solely in the femoral vein or in both femoral and popliteal veins. The femoral artery was then anastomosed to the femoral vein with sutures under binocular microsopic control. Changes in the distribution of skin blood flow in the hind limbs were studied with a thermal camera. Skin temperature increased in the thigh and knee after femoral venous valve destruction, but hyperthermia was observed in the distal leg and foot only when the valves in the popliteal vein were also disrupted. These results showed that increased arterial blood flow could be established by DVA surgery in both the proximal and distal regions of the hind limbs.


Meiotic indices in the oligospermic male.
Thirty-four oligospermic males were evaluated by determining the meiotic index in testicular biopsy specimens. Only 1 patient of 10 with a meiotic index of less than 15 achieved pregnancy, whereas 16 of 24 patients with a meiotic index of more than 15 had a successful outcome. Corresponding increases in the semenogram were also noted to be related to the meiotic index.


How many mechanosensory organs in the bushcricket leg? Neuroanatomy of the scolopidial accessory organ in Tettigoniidae (Insecta: Orthoptera).
The subgenual organ and associated scolopidial organs are well studied in Orthoptera and related taxa. In some insects, a small accessory organ or Nebenorgan is described posterior to the subgenual organ. In Tettigoniidae (Ensifera), the accessory organ has only been noted in one species though tibial sensory organs are well studied for neuroanatomy and physiology. Here, we use axonal tracing to analyse the posterior subgenual organ innervated by the main motor nerve. Investigating seven species from different groups of Tettigoniidae, we describe a small group of scolopidial sensilla (5-9 sensory neurons) which has features characteristic of the accessory organ: posterior tibial position, innervation by the main leg nerve rather than by the tympanal nerve, orientation of dendrites in proximal or ventro-proximal direction in the leg, and commonly association with a single campaniform sensillum. The neuroanatomy is highly similar between leg pairs. We show differences in the innervation in two species of the genus Poecilimon as compared to the other species. In Poecilimon, the sensilla of the accessory organ are innervated by one nerve branch together with the subgenual organ. The results suggest that the accessory organ is part of the sensory bauplan in the leg of Tettigoniidae and probably Ensifera.


Hippocampal neurogenesis: a biomarker for depression or antidepressant effects? Methodological considerations and perspectives for future research.
Whereas animal models of depression are associated with decreased adult hippocampal neurogenesis, antidepressant treatments, including pharmacotherapy but also electroconvulsive therapy, have the opposite action, as they stimulate cell proliferation and the survival and maturation of newborn dentate gyrus neurons. Although the lack of these new cells is not causally involved in depression, as their absence does not trigger a depressive-episode per se, their loss has been shown to be causally involved in the ability of chronic monoaminergic antidepressants to achieve remission. However, the process by which the stimulation of hippocampal neurogenesis can elicit recovery after a depressive-like episode is poorly understood. The accepted view is that hippocampal newborn neurons integrate into the hippocampal network and thus participate in hippocampal cognitive functions crucial for remission. The hippocampus is associated with a wide range of such functions, including spatial navigation, pattern separation, encoding of new contextual information, emotional behavior and control over the hypothalamic-pituitary-adrenal axis. The present review aims at discussing each of these functions and tries to identify the process by which newborn cells participate in remission after successful therapy. Finally, future directions are proposed for a better understanding of these mechanisms.


Fruit ripening in Vitis vinifera: apoplastic solute accumulation accounts for pre-veraison turgor loss in berries.
In Vitis vinifera L. berries, the onset of ripening (known as "veraison") involves loss of turgor (P) in the mesocarp cells. We hypothesized that P loss was associated with an accumulation of apoplastic solutes in mesocarp tissue prior to veraison. Apoplastic sap was extracted from the mesocarp by centrifugation at the appropriate gravity to measure the apoplast solute potential (Psi (s) (A) ) and assay the sap composition. The Psi (s) (A) was about -0.2 MPa early in development, decreased about 1.0 MPa by veraison, and continued to decrease during ripening to almost -4.0 MPa by the end of berry development. Potassium, malate, tartrate, proline, glucose, fructose, and sucrose were quantified in apoplastic sap. The calculated contribution of these solutes was about 50% of the total Psi (s) (A) preveraison, but increased to about 75% as fructose and glucose accumulated during ripening. The contribution of the estimated matric potential to apoplast water potential decreased during development and was only 1.5% postveraison. We conclude that high concentrations of solutes accumulated in the mesocarp apoplast prior to veraison, and that P loss was a direct result of decreased Psi (s) (A) . Because Psi (s) (A) decreased before veraison, our findings suggest that apoplast solutes play an important role in the events of cellular metabolism that lead to the onset of ripening.


The noneffect of a large linear hydrocarbon, squalene, on the phosphatidylcholine packing structure.
The interaction of squalene with liposomes and monolayers of dipalmitoyl phosphatidylcholine (DPL) has been studied by differential scanning calorimetry, Raman spectroscopy, and surface potential measurements. Mole ratios of squalene to DPL up to 9 to 1 were studied. In contrast to small, nonpolar molecules, which profoundly influence the structure of lipid bilayers as detected by changes in both their thermodynamic phase transition parameters and membrane fluidity, this large, nonpolar, linear hydrocarbon is devoid of such influences. It is clear from our data that a large nonpolar molecule such as squalene, having no polar group that might anchor it to the aqueous interface, cannot intercalate between the acyl chains either below or above the phase transition of DPL. This behavior is not compatible with models that treat the bilayer interior as a bulk hydrocarbon, and suggests that great caution should be exercised in extrapolating partition coefficients based on bulk hydrocarbon measurements to lipid bilayers.


A high-throughput screening platform to identify nanocarriers for efficient delivery of RNA-based therapies.
RNA-based therapies are highly selective and powerful regulators of biological functions. Non-viral vectors such as nanoparticles (NPs) are very promising formulations for the delivery of RNA-based therapies but their cell targeting, cell internalization and endolysomal escape capacity is rather limited. Here, we present a methodology that combines high-throughput synthesis of light-triggerable NPs and a high-content imaging screening to identify NPs capable of efficiently delivering different type of RNAs. The NPs were generated using polymers synthesized by Michael type addition reactions and they were designed to: (i) efficiently complex coding (mRNAs) and non-coding (miRNAs and/or lncRNAs) RNA molecules, (ii) allow rapid cell uptake and cytoplasmic release of RNA molecules and (iii) target different cell types based on their composition. Furthermore, light-responsive domains were attached to the polymers by distinctive methods to provide diverse disassembly strategies. The most efficient formulations were identified using cell-based assays and high-content imaging analysis. This strategy allows precise delivery of RNA-based therapies and provides an effective design approach to address critical issues in non-viral gene delivery.


Plasma inhibitor of glomerular fibrinolysis in the hemolytic-uremic syndrome.
To detect an inhibitor of glomerular fibrinolysis, dilutions of human plasma were incubated on microscope slides with two frozen sections of normal human kidney. The slides were studied by the fibrin slide technique. The lysis inhibitory titer was defined as the highest dilution completely inhibiting glomerular fibrinolysis. Of 27 children without renal disease, none had a lysis inhibitory titer greater than 1:2. Defining an elevated lysis inhibitory titer as 1:8 or greater, we found an elevated lysis inhibitory titer in plasma from all 17 children with hemolytic-uremic syndrome. No correlation was found between the lysis inhibitory titer and the hematocrit, white blood cell or platelet counts, serum creatinine level, or levels of the antiplasmins alpha 1-antitrypsin, alpha 2-macroglobulin, C1-esterase inhibitor, or alpha 2-antiplasmin. The inhibitor was found to have a molecular weight of less than 12,000. A close correlation was discovered between the duration of lysis inhibitory titer elevation and the clinical course; removal of the inhibitor from the plasma by peritoneal dialysis was associated with improvement in renal function. Results suggest that the inhibitor may play an important role in the pathogenesis and persistence of glomerular fibrin deposition.


Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study.
Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development. We conducted a case-control study of 304 TGCT cases, aged 18-45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants' mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son's birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80-2.01) or herbicides (OR = 1.15, CI = 0.67-2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04-2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26-4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06-5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12-3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype. Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.


Quantification of femtomolar concentrations of the CYP3A substrate midazolam and its main metabolite 1'-hydroxymidazolam in human plasma using ultra performance liquid chromatography coupled to tandem mass spectrometry.
The benzodiazepine midazolam is a probe drug used to phenotype cytochrome P450 3A activity. In this situation, effective sedative concentrations are neither needed nor desired, and in fact the use of very low doses is advantageous. We therefore developed and validated an assay for the femtomolar quantification of midazolam and 1'-hydroxymidazolam in human plasma. Plasma (0.25 mL) and 96-well-based solid-phase extraction were used for sample preparation. Extraction recoveries ranged between 75 and 92% for both analytes. Extracts were chromatographed within 2 min on a Waters BEH C18 1.7 μm UPLC® column with a fast gradient consisting of formic acid, ammonia, and acetonitrile. Midazolam and 1'-hydroxymidazolam were quantified using deuterium- and (13)C-labeled internal standards and positive electrospray tandem mass spectrometry in the multiple reaction monitoring mode, which yielded lower limits of quantification of 50 fg/mL (154 fmol/L) and 250 fg/mL (733 fmol/L) and a corresponding precision of <20%. The calibrated concentration ranges were linear for midazolam (0.05-250 pg/mL) and 1'-hydroxymidazolam (0.25-125 pg/mL), with correlation coefficients of >0.99. Within-batch and batch-to-batch precision in the calibrated ranges for both analytes were <14% and <12%. No ion suppression was detectable, and plasma matrix effects were minimized to <15% (<25%) for midazolam (1'-hydroxymidazolam). The assay was successfully applied to assess the kinetics of midazolam in two human volunteers after the administration of single oral microgram doses (1-100 μg). This ultrasensitive assay allowed us to quantify the kinetics of midazolam and 1'-hydroxymidazolam for at least 10 h, even after the administration of only 1 μg of midazolam.


Differential effects of antioxidants and indomethacin on compound 48/80 induced histamine release and Ca2+ uptake in rat mast cells.
The effect of nordihydroguaiaretic acid (NDGA), vitamin E, butylated hydroxytoluene (BHT) and indomethacin on histamine release and Ca2+ uptake in rat mast cells stimulated with compound 48/80 was studied. NDGA inhibited both the release of histamine and Ca2+ uptake in stimulated cells; however, there was no correlation between inhibition of Ca2+ uptake and the amount of histamine release. At a concentration of 5 microM, NDGA completely inhibited Ca2+ uptake, while histamine release was decreased by less than 50%. BHT (50 microM) inhibited both the Ca2+ uptake and histamine release. On the other hand, vitamin E (50 microM) inhibited histamine release by 70% without impairment in Ca2+ uptake. In the absence of the stimulus, vitamin E increased the cell-associated Ca2+; however, it had no effect on spontaneous release of histamine. Indomethacin (3 microM) inhibited Ca2+ uptake in stimulated cells by 50%, but did not affect the release of histamine. The results suggest that a part of Ca2+-influx may not be related to the coupled activation--secretion response and that lipid peroxidation through the lipoxygenase pathway may be involved in secretion of histamine from mast cells.


Carbon dioxide assimilation of hardwood seedlings in relation to community dynamics in central illinois : I. Field measurements of photosynthesis and respiration.
Field measurements of net assimilation and respiration for seedlings of four hardwood species were made periodically over a growing season with soil moisture tension maintained between 0 and 0.75 bar. Total net assimilation per day was significantly greater for Acer saccharum than either Quercus rubra or Quercus alba and for Quercus macrocarpa as compared with Q. rubra, when measurements were made under natural shade conditions and light intensity varied from 80 to 120 ft-c. Mean light compensation points determined under canopy shade were 50.3, 53.5, 87.2, and 102.5 ft-c., respectively, for Acer saccharum, Quercus macrocarpa, Q. rubra, and Q. alba. In a 0.04-hectare canopy opening, total net assimilation per day was not significantly different between Q. rubra, Q. alba, and A. saccharum but was significantly greater for Q. macrocarpa than Q. alba and A. saccharum. Relationships between photosynthetic efficiency and successional characteristics of these species are inferred from the data.


Safety of multiple bolus loading of intravenous disopyramide.
Although a single intravenous bolus of disopyramide is an effective antiarrhythmic, side effects occur in some patients. We tested the safety of multiple bolus loading for intravenous disopyramide in 10 patients with frequent premature ventricular beats. Concurrent with a 1.0 mg/kg/hr infusion, a bolus of 0.5 mg/kg of disopyramide was given over 5 minutes. Up to three additional boluses were given 5 minutes after the first bolus unless a 50% reduction in premature ventricular beats or side effects occurred. The infusion was continued for 3 hours and was then decreased to 0.4 mg/kg/hr for 15 hours. All patients had a 50% reduction in premature ventricular beats and attained therapeutic blood levels. Three patients with a history of controlled congestive heart failure developed either hypotension or pulmonary edema. Hypotension and pulmonary edema following intravenous disopyramide is more related to the pharmacology of the drug than to the loading scheme employed.


Accuracy of enzyme-linked immunosorbent assays for quantification of antibodies against Aleutian mink disease virus.
There is a growing interest among mink ranchers to select their stock for tolerance to the Aleutian mink disease virus (AMDV). Enzyme-linked immunosorbent assays (ELISA) are used to identify mink which have low anti-AMDV antibody titres and are expected to tolerate the AMDV infection. The objective of this study was to calculate the accuracy of three ELISA systems which were performed on blood or serum of AMDV-inoculated American mink (Neovison vison) at five laboratories in Canada, USA, Finland, the Netherlands and Denmark. The accuracy was determined by comparing the ELISA results with antibody titres measured by the counter-immunoelectrophoresis (CIEP) using 10 two-fold serial dilutions of the plasma. Antibody titres of 880 black mink which were inoculated with a spleen homogenate from a naturally infected mink were measured between 16 and 176 weeks post-inoculation. Each ELISA result from every laboratory covered a wide range of antibody titres and the Spearman's rank correlation coefficients between CIEP and ELISA results from different laboratories varied between 0.41 and 0.83, indicating a low to moderate accuracy of ELISA systems for ranking mink by antibody titre. The recombinant VP2-based ELISA used in the Netherlands and Finland ranked the mink by antibody titres more accurately than did the AMDV-G-based ELISA platforms developed in Denmark and the USA, suggesting that the source of antigen was one of the factors affecting the accuracy of ELISA results. It was concluded that the ELISA systems, particularly those based on AMDV-G antigen, require further refinement to improve their accuracy for ranking mink by antibody titre.


Red emitting human serum albumin templated copper nanoclusters as effective candidates for highly specific biosensing of bilirubin.
In this paper, we report a new type of human serum albumin (HSA) stabilized red emissive copper nanoclusters (HSA-CuNCs) were prepared at room temperature and HSA-CuNCs were applied to identify the bilirubin in human urine and blood serum samples. The emission characteristics of synthesized HSA-CuNCs were pH responsive to that the intensity of emission enhanced quickly with varying the pH range from 12 to 6. Emission spectral signal of HSA-CuNCs was found as reduced well with the raise in the amounts of bilirubin attributed to strong binding attraction leads to the non-fluorescent complex formation of HSA-CuNCs with bilirubin. Due to the strong affinity between the nanoprobe and analyte, the red emissive HSA-CuNCs illustrates more specific for the detection bilirubin over the different potential interfering molecules. Two good linear relationships were distinguished the relative emission intensity of HSA-CuNCs versus bilirubin concentrations range from 1.25 × 10-6 to 7.50 × 10-6 M and 5.00 × 10-6 to 2.875 × 10-5 M with lowest limit of detection was determined as 35.00 × 10-9 M and 145.00 × 10-9 M (S/N = 3), respectively. Furthermore, this methodology was effectively used in the quantification of bilirubin in clinical (real) samples. In addition, this fluorometric method offers cost-effective, easy, highly specific and ultrasensitive optical platform for the determination of bilirubin.


Malonaldehyde formation in intact platelets is catalysed by thromboxane synthase.
Imidazole and compound L8027 (selective inhibitors of thromboxane synthase) produced parallel inhibition of malonaldehyde and thromboxane B2 secretion induced by collagen or thrombin in gel-filtered suspensions of human platelets. Comparing the effects of these inhibitors and aspirin on secretion of granule constituents indicated that platelet degranulation depends mainly on thromboxane production; prostaglandin endoperoxides contributed little.


Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity.
Lung cancer is the first leading cause of cancer deaths. Chemotherapy toxicity is one of factors that limited the efficacy of platinum-based chemotherapy in lung cancer patients. Transporters and DNA repair genes play critical roles in occurrence of platinum-based chemotherapy toxicity. To investigate the relationships between transporter and DNA repair gene polymorphisms and platinum-based chemotherapy toxicity in lung cancer patients, we selected 60 polymorphisms in 14 transporters and DNA repair genes. The polymorphisms were genotyped in 317 lung cancer patients by Sequenom MassARRAY. Logistic regression was performed to estimate the association of toxicity outcome with the polymorphisms by PLINK. Our results showed that polymorphisms of SLC2A1 (rs3738514, rs4658, rs841844) were significantly related to overall toxicity. XRCC5 (rs1051685, rs6941) and AQP2 (10875989, rs3759125) polymorphisms were associated with hematologic toxicity. AQP2 polymorphisms (rs461872, rs7305534) were correlated with gastrointestinal toxicity. In conclusion, genotypes of these genes may be used to predict the platinum-based chemotherapy toxicity in lung cancer patients.


[Preparation of armored RNA containing M gene of influenza H3N2].
To prepare the armored RNA containing M gene of influenza H3N2. The vector pAR-1 was constructed from expression vector pET30b in which the bacteriophage MS2 DNA fragment, containing the genes for maturase and coat protein and the pac site, was inserted. The M gene fragment of influenza A was inserted into the HindIII site downstream of the pac site on the pAR-1, which formed a new recombinant plasmid pAR-2. After the prokaryotic expression was carried out, armored RNA AR-2 containing M gene was obtained. AR-2 was purified, and then was quantified by real time RT-PCR. Moreover, the stability of AR-2 was checked. AR-2 was expressed successfully. AR-2 remained stable under various storage environments. Approximately 8.9 x 10(11) copies of AR-2 particles can be purified from one milliliter of culture. It showed that AR-2 was stable and RNase-resistant, which, as a virus surrogate, would be used as RT-PCR standards, controls and training or proficiency samples.


Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1alpha and oxidative phosphorylation.
The transcriptional coactivator PGC-1alpha is a potent regulator of several metabolic pathways, including, in particular, the activation of oxidative phosphorylation and mitochondrial biogenesis. Recent evidence suggests that increasing PGC-1alpha activity may have beneficial effects in various conditions, including muscular dystrophy, diabetes, and neurodegenerative diseases. We describe here a high-throughput screen to identify small molecules that induce PGC-1alpha expression in skeletal muscle cells. A number of drug classes are identified, including glucocorticoids, microtubule inhibitors, and protein synthesis inhibitors. These drugs induce PGC-1alpha mRNA, and the expression of a number of genes known to be regulated by PGC-1alpha. No induction of these target genes is seen in PGC-1alpha -/- cells, demonstrating that the drugs act through PGC-1alpha. These data demonstrate the feasibility of high-throughput screening for inducers of PGC-1alpha. Moreover, the data identify microtubule inhibitors and protein synthesis inhibitors as modulators of PGC-1alpha and oxidative phosphorylation.


Phenotypical, physiological and biochemical analyses provide insight into selenium-induced phytotoxicity in rice plants.
The present study investigated the phenotypical, physiological and biochemical changes of rice plants exposed to high selenium (Se) concentrations to gain an insight into Se-induced phytotoxicity. Results showed that exposure of rice plants to excessive Se resulted in growth retardation and biomass reduction in connection with the decreased levels of chlorophyll, carotenoids and soluble proteins. The reduced water status and an associated increase in sugar and proline levels indicated Se-induced osmotic stress in rice plants. Measurements of Se contents in roots, leaf sheaths and leaves revealed that Se was highly accumulated in leaves followed by leaf sheaths and roots. Se also potentiated its toxicity by impairing oxidative metabolism, as evidenced by enhanced accumulation of hydrogen peroxide, superoxide and lipid peroxidation product. Se toxicity also displayed a desynchronized antioxidant system by elevating the level of glutathione and the activities of superoxide dismutase, glutathione-S-transferase and glutathione peroxidase, whereas decreasing the level of ascorbic acid and the activities of catalase, glutathione reductase and dehydroascorbate reductase. Furthermore, Se triggered methylglyoxal toxicity by inhibiting the activities of glyoxalases I and II, particularly at higher concentrations of Se. Collectively, our results suggest that excessive Se caused phytotoxic effects on rice plants by inducing chlorosis, reducing sugar, protein and antioxidant contents, and exacerbating oxidative stress and methylglyoxal toxicity. Accumulation levels of Se, proline and glutathione could be considered as efficient biomarkers to indicate degrees of Se-induced phytotoxicity in rice, and perhaps in other crops.


Jingfang granules exert anti-psoriasis effect by targeting MAPK-mediated dendritic cell maturation and PPARγ-mediated keratinocytes cell cycle progression in vitro and in vivo.
Jingfang granules (JFG), derived from JingFangBaiDu San (JFBDS), are a traditional herbal formulas used for the treatment of respiratory tract infections. They were initially prescribed to treat skin disease, such as psoriasis in Chinese Taiwan, but are not widely used for psoriasis treatment in mainland China because of the lack of anti-psoriasis mechanism research. The present study was designed to evaluate the anti-psoriasis effect of JFG and reveal the correlated mechanisms of JFG in vivo and in vitro using network pharmacology, UPLC-Q-TOF-MS technology and molecular biotechnology methods. An imiquimod-induced psoriasis-like murine model was used to verify the anti-psoriasis effect in vivo, with inhibition of lymphocytosis and CD3+CD19+B cell proliferation in the peripheral blood and prevention of the activation of CD4+IL17+T cells and CD11c+ MHC Ⅱ+ dendritic cells (DCs) in the spleen. Network pharmacology analysis demonstrated that the targets of the active components were significantly enriched in pathways involved in cancer, inflammatory bowel disease and rheumatoid arthritis, which were closely related to cell proliferation and immune regulation. The drug-component-target networks and molecular docking analysis demonstrated the active ingredients to be luteolin, naringin and 6'-feruloylnodakenin, which had a good binding affinity to PPARγ, p38a MAPK and TNF-a. Finally, UPLC-Q-TOF-MS analysis to validate the active ingredients in drug-containing serum and in vitro experiments showed that JFG inhibited the maturation and activation of BMDCs via the p38a MAPK signaling pathway and translocation of the agonist PPARγ into the nuclei to reduce the activity of NF-κB/STAT3 inflammatory signaling pathway in keratinocytes. Our study demonstrated that JFG improved psoriasis by inhibiting the maturation and activation of BMDCs and proliferation and inflammation of keratinocytes, which may facilitate the applications of JFG in anti-psoriasis therapy in clinical settings.


[Changes in the protein level in rat hippocampal neurons during development of the alimentary conditioned reflex under normal conditions and after treatment with iproniazid].
The protein content in neurons of areas CA-1 and CA-3 of the dorsal hippocampus has been determined by means of cytointerferometry in rats during elaboration of unlocal alimentary instrumental reflex (ULAIR) and local alimentary instrumental reflex (LAIR) on the background of increased and normal serotonine content in the brain. It has been found that during the ULAIR elaboration the hippocampal neurons react by an increase of dry mass, during the LAIR elaboration-by its decrease. Under condition of serotonine excess in the brain the changes of dry mass in hippocampal neurons during elaboration of the two reflexes are opposite to these observed during the ULAIR and LAIR elaboration with normal serotonine content.


The relation between the resultant moments at a joint and the moments measured by an isokinetic dynamometer.
Isokinetic dynamometers have frequently been used to determine in vivo properties of human skeletal muscles. In these investigations the moments recorded by the dynamometer were often (implicitly) assumed to be the same as the joint moments produced by muscles. This assumption may have contributed to the conflicting results about in vivo muscle properties of human skeletal muscles that are reported in the literature. The purpose of this paper is to present a method for calculating the resultant joint moments from the moments recorded using a Cybex II dynamometer and to determine the differences between these two moments for some typical exercise conditions. The differences between these these moments are shown to be due to (a) gravitational effects, (b) inertial effects, and (c) non-rigidity of the Cybex arm/shank-foot system. The results obtained suggest that the moments recorded using the dynamometer should not be used to derive muscle properties without taking into account the relationship between the resultant joint moments and the moments measured using an isokinetic dynamometer.


Systemic corticosteroid therapy of oral vesiculoerosive diseases (OVED). An open trial.
We report the preliminary findings from our open study on how to optimize the doses and the response times to systemic corticosteroid therapy for three forms of oral vesiculoerosive diseases (OVED). All twenty-one patients enrolled in the study were affected with OVED (10 OLP, 6 MMP, 5 EM) and received different doses of prednisone in relation to the type of disease and its severity. Daily mouthwashes with 0.12% chlorhexidine and application of miconazole gel were added to the therapy; its response time to treatment varied individually, the doses were reduced only after 75% of lesions had cleared. The average response time to treatment was 28 days. Clinical assessment showed that 95% of the patients had improved, whereas 71% had complete remission of oral signs and 48% experienced side effects. The degree of clinical resolution was: 70% complete remission after 26 days of therapy in patients with OLP, 33% complete remission after 38 days in patients with MMP, and 100% complete remission after ten days in patients with EM. Although a preliminary study, initial results showed different types and times of response to systemic corticosteroid treatment for the three diseases. Our findings strongly suggest that a unified therapeutic protocol for different OVED is not advisable, nor can systemic treatment be considered the first therapeutic approach.


Activity measurements with radionuclide calibrators in the Czech Republic.
Since radionuclide calibrators are used in nuclear medicine for the determination of the activity of radiopharmaceuticals administered to patients, it is important to ensure their long-term accuracy. Results of the checks performed in the Czech Republic during the year 2002 are given, together with a short overview of previous years. For the CMI 4pigamma ionization chamber, against which all the calibrators are checked, we calculated the response function and basic characteristics by a Monte Carlo method, using the MCNP4C code.


Analogue separates biological effects of salmon calcitonin on brain and renal cortical membranes.
The conformation-activity relationship of salmon calcitonin in kidney and brain was investigated with regard to effects on membrane binding and adenylate cyclase activity. Since an amphipathic alpha-helical conformation on the calcitonin molecule is associated with high potency in lowering serum calcium, the activity of the parent peptide was compared to that of [Gly8, D-Arg24]des-Leu16-salmon calcitonin, a calcitonin analogue (CTA) with less helix forming potential. The results indicate that while salmon calcitonin possesses similar potency in brain and kidney, CTA is effective only in brain. Furthermore, CTA did not inhibit the binding of 125I-labeled human calcitonin gene-related peptide (HCGRP) to brain membranes. Our findings suggest that the specific binding and effects of salmon calcitonin on adenylate cyclase activity in brain do not depend on conformational features in the middle region of the molecule, although the alpha-helical structure in this region does appear to be an important property for salmon calcitonin binding to renal cortical membranes.


Characterization and evolution of the sediments of a Mediterranean coastal lagoon located next to a former mining area.
Coastal lagoons are ecosystems that are relatively enclosed water bodies under the influence of both the terrestrial and the marine environment, being vulnerable to human impacts. Human activities, such as mining extraction, are significant anthropogenic coastal stressors that can negatively affect ecosystems and communities. In light of the above, the objective of this research is to examine the influence of metal mining activities on the composition of sediments of a Mediterranean coastal lagoon, named Mar Menor. This paper presents a comprehensive characterization for grain size, mineralogy, geochemistry and organic matter of sediments of this coastal lagoon, investigating their variation along space and time. Sedimentation dynamics are ruling clearly the grain size predominant in each area of the Mar Menor coastal lagoon, determining the existence of entrainment, transport and sedimentation areas. For minerals, elements and organic matter, sedimentation dynamics are also determining their distribution.


Effects of barbiturates and ethanol on muscimol-induced release of [3H]-D-aspartate from rodent cerebellum.
The K+-stimulated release of [3H]-D-aspartate and [14C]-GABA from synaptosomal (P2) fractions prepared from rat cerebellum was studied. Muscimol enhanced the release of [3H]-D-aspartate by 60-75% and the release of [14C]-GABA by 20-35%. Muscimol also enhanced the release of [3H]-D-aspartate from P2 fractions prepared from swine and mouse cerebellum. Pentobarbital, an anesthetic barbiturate, had no effect on basal or K+-stimulated release of [3H]-D-aspartate or [14C]-GABA but potentiated the enhancement of [3H]-D-aspartate release by muscimol. The EC50 was approx. 50 microM. The S(-)-isomer of pentobarbital was more potent than the R(+)-isomer in potentiating the action of muscimol, in agreement with the anesthetic potencies of the isomers. Phenobarbital, an anticonvulsant barbiturate, enhanced release of [3H]-D-aspartate and [14C]-GABA in the absence of muscimol. In contrast, the convulsant barbiturate 5-ethyl-5-(2'-cyclohexylidene-ethyl)barbituric acid (CHEB) caused a significant increase in basal release of [3H]-D-aspartate and [14C]-GABA in the absence of muscimol. Diazepam and ethanol had no effect on the release of [3H]-D-aspartate and did not potentiate the action of muscimol. These experiments provide biochemical evidence for an enhancement of the action of GABA by anesthetic barbiturates. This effect appears to be mediated through a benzodiazepine-insensitive presynaptic GABA receptor.


Update on chronic hepatitis C.
Strategies for the diagnosis and treatment of chronic hepatitis C continue to evolve. Liver biopsy is now used selectively rather than routinely, and the combination peginterferon plus ribavirin is the treatment of choice for the majority of patients.


[Correlations between dietary salt intake and 24-h urine sodium excretion in a sample of the urban population of Cáceres].
Excessive salt intake is associated with higher levels of AHT and prevalence of cardiovascular diseases. WHO recommends consuming less than 5 g/day of salt (equivalent to 2 g Na+/day). Identifying foods and behaviours with greater contribution to excess intake would facilitate preventive dietary advice. Observational study. SITE: Urban Health Center in Cáceres. We estimated salt consumption using two food consumption frequency (FFQ) questionnaires, one generic and one with high Na+ content, and a 24 h follow-up survey. We use the Evalfinut program for nutritional evaluation of the diet. We analyzed correlations between estimated salt intake and 24-h urine sodium elimination (gold standard). 92% of the population had consumption higher than the recommendations with intakes equivalent to 9.5 g/day of salt (3.7 g/d of Na+). When sodium intake is determined by the Na+/K+ ratio, 79.54% have high intakes. Sodium elimination follows a slightly increasing trend with BMI. The perception of salt consumption is low, 56.3% consider it "adequate". 32.4% add salt to food once served. FFQ underestimate Na+ intake and targeted surveys provide higher values. The correlation between FFQ and Na+ urinary elimination is weak. We must reduce salt intake by increasing the perception of consumption, improving knowledge about the salt content in food and identifying target patients of the health council.


Cane molasses and oligofructose in the diet of laying hens improves the mineral content of eggs and meat.
Poultry-based foods contribute to human health due to their high nutrient value. Previously, it was shown that short-chain fatty acids (SCFAs) produced by in vitro intestinal fermentation of a molasses and oligofructose mixture (M-O) stimulated iron and calcium transport through the colonic epithelium of laying hens. However, the real impact of including M-O mixture in the diet on the mineral content of poultry products had not yet been demonstrated. In this study, Hy-Line W-36 leghorn hens were assigned into two groups that either received a conventional diet or a diet supplemented with cane molasse and oligofructose, over a period of 42 days. The weight of the animals and their eggs, blood parameters and intestinal epithelium integrity were determined. Intestinal bacteria, their fermentation products, and the mineral content of eggs, bones and muscles were also assessed. The experimental diet proved to be safe, favored the proliferation of SCFA producing bacteria in the intestines, led to higher concentration of acids (mainly SCFA) in the digesta, and induced the elongation of microvilli at the apical tip of enterocytes. Mineral content of eggs and meat were improved after four weeks of feeding with the experimental diet compared to the conventional one. Higher iron content was observed in the edible portion of eggs and leg muscle, and higher calcium content was observed in the egg edible portion and shell in hens fed the supplemented diet. This feeding strategy could be useful to improve the mineral content of poultry products and therefore human nutrition, while diversifying molasses applications.


Tuberous sclerosis and polycystic kidney disease in a 3-month-old infant.
Tuberous sclerosis (TSC) is an autosomal dominantly inherited multisystemic disease characterized by the development of hamartomas predominantly in brain and kidneys. The TSC2 gene for tuberous sclerosis is localized on chromosome 16p13.3 immediately adjacent to PKD1, the gene for autosomal dominant polycystic kidney disease (ADPKD). A TSC2-PKD1 contiguous gene syndrome caused by chromosomal microdeletions disrupting both the TSC2 and PKD1 genes has been identified in patients with TSC and early-onset severe ADPKD. We report a 3-month-old Caucasian girl of non-consanguineous parents with TSC and early manifestation of ADPKD. She presented with right-sided focal seizures, two small hypopigmented areas on the left flank, and elevated blood pressure requiring antihypertensive treatment. Brain magnetic resonance imaging revealed typical signs of tuberous sclerosis and abdominal ultrasonography showed bilaterally enlarged kidneys with multiple cysts resembling those seen in ADPKD. There was no family history of renal disease or of tuberous sclerosis. Findings were highly suspicious of TSC2-PKD1 contiguous gene syndrome. Using fluorescence in situ hybridization and plasmid probe CW23, which spans the adjacent 3' regions of TSC2 and PKD1 genes, we identified a submicroscopic deletion on only one of the chromosomes 16p13.3, thus permitting the diagnosis of the TSC2-PKD1 contiguous gene syndrome.


Lactate causes changes in gonococci including increased lipopolysaccharide synthesis during short-term incubation in media containing glucose.
Gonococci (strain BS4(agar)), emerging from lag-phase during 1-1.5 h incubation in a medium containing glucose (28 mM) and either 5 microM or 50 microM sodium lactate, show enhanced capacity for their lipopolysaccharide (LPS) to be sialylated by cytidine 5'-monophospho-N-acetyl neuraminic acid. The sialyltransferase content of the lactate-treated gonococci was not greater than that of control organisms and showed no differences in LPS components. However, the total LPS content of the lactate-treated gonococci was 10-20% higher than that of control organisms, so lactate enhancement may be due to more sialyl receptors becoming available due to an overall stimulation of LPS synthesis. The protein and pentose contents of the lactate-treated gonococci were also higher than those of controls, indicating stimulation of protein synthesis and ribosome production. Electron microscopy showed hair-like external appendages on control but not on lactate-treated gonococci. The above growth conditions are unnatural. However, when concentrations of glucose and lactate were adjusted to values akin to those occurring in vivo (glucose 5 mM alone and with either 1 mM or 10 mM lactate), and gonococcal multiplication occurred during the short incubation period (1-1.5 h), lactate again induced greater contents of LPS, protein and pentose. A high content of LPS, which will contribute to pathogenicity, should be a constant feature of gonococci growing in human urogenital tissues, where lactate is ever present with glucose.


Point-of-Care Ultrasound for the Diagnosis of Pediatric Foreign Body Ingestion: A Narrative Review and Illustrative Case Report.
Foreign body ingestion (FBI) is a frequent concern in emergency departments. Clinical guidelines recommend performing plain x-rays as the primary modality of diagnosis. Although point-of-care ultrasound (PoCUS) has increasingly been integrated into the daily practice of emergency medicine, it has been poorly investigated in the diagnostic approach for FBI.This review aims to highlight the current state of PoCUS use for pediatric FBI.The following research question was considered in this narrative review: Is PoCUS useful for FBI management? A literature search was conducted to identify articles reporting PoCUS use for the management of FBI. All articles were assessed for quality by 2 reviewers. The 14 selected articles reported 52 FBI cases in which PoCUS successfully identified and located the ingested FB. Point-of-care ultrasound was used either as the primary imaging technique or after positive or negative x-ray findings. In 5 cases (9.6%), PoCUS was the only modality used for the diagnosis. Of these cases, 3 (60%) underwent a successful procedure to remove the FB and 2 (40%) received conservative treatment without complications. This review suggests that PoCUS might be a reliable modality for the initial management of FBI. PoCUS can locate, identify, and evaluate the size of the FB in a wide range of materials and gastrointestinal locations. Point-of-care ultrasound could eventually become the go-to modality in the case of radiolucent FB, thus avoiding the use of radiation. Further studies are nevertheless required to validate PoCUS use for FBI management.


Evolution of minimally invasive surgery for donor nephrectomy and outcomes.
Laparoscopic donor nephrectomy was introduced into Australia in 1997 by this unit. However, some donors may be considered unsuitable, and few modifications to the existing technique can tailor this procedure for an individual donor. Recently, further changes including clustering of ports and single-port methods have been investigated. The laparoscopic method was offered to all but 3 donors from May 1997 to October 2009. Data were collected on all 289 donors who underwent laparoscopic procedures. All but 5 donor procedures were completed laparoscopically, and in 4 of them conversion to open was necessary due to hemorrhage. The fifth was a planned conversion in our first right LDN. Delayed graft function was seen in 7 recipients and 5 required dialysis postoperatively. Two kidneys were lost due to arterial thrombosis, and 5 patients underwent segmental infarction with decreased renal function. Mean hospital stay was 2.35±1.67 days. There were no donor deaths or serious morbidity. Although the benefits to the donor of the laparoscopic method are well recognized, our modifications will benefit those who may be precluded from this method.


Role of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and classification of lymphomas.
endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe and effective technique in the diagnosis of mediastinal and abdominal masses. However, the usefulness of EUS-FNA in the diagnosis and classification of lymphomas is controversial. The aim of this study was to determine the yield of EUS-FNA in the diagnosis and classification of lymphomas. a retrospective case series was performed in a tertiary referral center. All consecutive patients referred for EUS-FNA with a suspected diagnosis of lymphoma from March 2013 to June 2019 were included. thirty-five patients (54.3 % women, median age 72 years) were included. The most frequent location of the node was the abdomen (67.9 %). Nodes were punctured using a 22-gauge (85.7 %) and 19-gauge needle (14.3 %) with a slow-pull technique. The number of passes performed were three or more in 82.9 % of patients. The samples were processed by the cellblock method. Adequate samples for immunohistochemical and molecular biological study were obtained in 33 (94.3 %) patients. EUS-FNA correctly diagnosed lymphoma in 30 out of 35 patients (85.7 %), and subclassification was determined in 23 patients (65.7 %). The most frequent diagnosis was non-Hodgkin lymphoma (85.7 %). There was one moderate adverse event (bleeding), which was resolved during the procedure. EUS-FNA may be a valuable technique in the evaluation of suspected lymphomas with an adequate diagnostic yield and a very low rate of adverse events.


The pathology of wildebeest-associated malignant catarrhal fever in hamsters, rats and guinea-pigs.
Lesions typical of malignant catarrhal fever were found in hamsters, rats and guinea-pigs inoculated with a rabbit-passaged strain (C-500) of alcelaphine herpesvirus-1. Lesions found during primary passage included proliferation of lymphoid tissues, multisystemic mononuclear cell infiltrates, vasculitis and necrosis, especially in the alimentary tract. The character, severity and distribution of lesions remained stable in affected hamsters during serial passage of disease, whereas lympho-proliferation became dominant in rats. The lesions in rats typically affected lymph nodes, heart and kidney and appear similar to those caused by oncogenic herpesviruses. Because rodents are susceptible to malignant catarrhal fever, the prospect is advanced that they can be used to elucidate the pathogenesis of both lymphoproliferative and cytolytic aspects of the disease.


Predictors of remaining in foster care after age 18 years old.
The Fostering Connections to Success and Increasing Adoptions Act of 2008 created the option for U.S. states to extend the foster care age limit up to the 21 st birthday. The law provides foster youth extra protections while they transition to adulthood. To inform states' efforts to better design and implement extended foster care (EFC), we examine the impact of the policy change on length of EFC stay and factors associated with youth's time in EFC. We use two samples of foster youth in California that extended the foster care age limit to 21 in 2012: 37,827 youths who turned 18 between the years 2008 and 2014 and 711 youths who participated in an interview-based panel study. Leveraging California's child welfare administrative data and California Youth Transitions to Adulthood Study's (CalYOUTH) survey data, we investigated predictors of months youths remained in EFC with linear regression and Cox proportional hazard regression. Almost half of youth eligible for EFC remained in care until their 21 st birthday. These cohorts stayed in foster care up to 16 months longer (p < .001) than previous cohorts without an EFC option. Multiple individual factors were associated with youths' length of stay in EFC. However, a youth's county of placement made a greater difference on their time in EFC-up to 16 months (p < .05). Our findings underscore the importance that placement location has on how long youth remain in EFC, and expands our understanding of how county and state context shape EFC participation.


Interferon-delta: the first member of a novel type I interferon family.
We have recently described a novel type I interferon (IFN) co-expressed with IFN-gamma by the trophectoderm of the pig conceptus between day 12 and day 18 of gestation, a development stage that corresponds to implantation in the uterus. This IFN, now officially named IFN-delta, is recognized as the first member of a novel type I IFN family. This paper reviews the main published data on IFN-delta, together with some new data, showing that IFN-delta, while being a true type I IFN, has some very specific structural and biological properties. Sequences related to IFN-delta coding sequence were found in the genome of man and other ungulates but the only other potentially functional gene was found, so far, in the horse. The pig IFN-delta mature protein, with 149 amino acids, is the smallest of all known type I IFNs. It is unusually rich in cysteines (seven residues), and has a very basic isoelectric point. Recombinant IFN-delta expressed in insect cells is glycosylated and has a high antiviral activity on porcine cells, but not on human cells. It has high antiproliferative activity, which is significantly enhanced in the presence of IFN-gamma. This new IFN was shown to bind on pig cells to the same type I receptor as IFN-alpha. IFN-delta and IFN-gamma genes are co-regulated in the pig trophectoderm, whose cells on day 14-16 of development simultaneously secrete both IFN proteins. The biological role of porcine IFN-delta in early pregnancy has been found unrelated to the known antiluteolytic effect of trophoblastic IFN-tau in ruminants.


Flow of a single magnetic vortex in a submicron-size superconducting Al disk controlled by radio-frequency currents.
We report the first observation of a single-vortex flow in a mesoscopic superconductor. A flow of a single vortex is successfully controlled by an rf current superimposed on a dc current, evidence of which is provided by voltage steps in current-voltage (I-V) characteristics. Irrespective of the number of vortices confined to the disk, we unambiguously observe that when a single vortex inside the disk is driven out of the disk, another vortex enters the disk similarly to two balls colliding in billiards: only one vortex passes through the Al disk at the same time in mesoscopic systems.


Variability in nutrient intake in a 28-day period.
This study of food logs showed that although individual intake varied widely, there were no significant differences in the intake of energy or seven selected nutrients from week to week over a four-week period. With the exception of protein, there was no difference attributable specifically to the day of the week. Thus, it is concluded that 7-day records most accurately reflect intake over periods of up to 28 days. A 4-day record, covering a weekend (Friday through Monday), also correlates well with information collected for 7, 14, and 28 days.


Amiodarone-induced thyrotoxicosis: is there a place for surgery?
Amiodarone-induced hyperthyroidism has on most instances been reported as mild, and thyroid functions return to normal after discontinuation of the drug. Nevertheless, life-threatening amiodarone-induced thyrotoxicosis has also been described. Conventional treatments such as antithyroid drugs (thionamide) and corticosteroids are essentially ineffective or fail to alter the dramatic course of the thyroid crisis. This limited effectiveness of medical therapy, particularly in patients with previously neglected or unknown thyroid disease, prompted us to intervene surgically. We report a series of nine patients who underwent total or near-total thyroidectomy as a first-line therapy for five of them. Surgery resulted in rapid resolution of thyrotoxicosis with an uneventful postoperative course. This approach has the advantage of immediate effectivity, low risk of relapse, and appears to be the only treatment that permits continued therapy with amiodarone when the drug appears needed to control a life-threatening arrhythmia.


A genotoxicological study of the new local anaesthetic carbamate derivatives carbisocaine, heptacaine and pentacaine.
The potential mutagenic activity of three carbamate derivatives with local anaesthetic activity was investigated. Genotoxic activity was observed after application of Carbisocaine on Euglena gracilis, whereas no activity was detected by Carbisocaine, Heptacaine and Pentacaine on Salmonella typhimurium, Escherichia coli and Drosophila melanogaster.


Association of complete recovery from acute kidney injury with incident CKD stage 3 and all-cause mortality.
There is a gap of knowledge in the long-term outcomes of patients who have complete recovery of kidney function after an episode of acute kidney injury (AKI). We sought to determine whether complete recovery of kidney function after an episode of AKI is associated with the development of incident stage 3 chronic kidney disease (CKD) and mortality in patients with normal baseline kidney function. Retrospective cohort study. 3,809 patients from an integrated health care delivery system who had a hospitalization between January 1, 1999, and December 31, 2009, with follow-up through March 31, 2010. AKI defined by International Classification of Diseases, Ninth Revision (ICD-9) codes and using the AKI Network (AKIN) definition, with complete recovery defined as a decrease in serum creatinine level to less than 1.10 times the baseline value. Incident stage 3 CKD persistent for 3 months and all-cause mortality. After a median follow-up of 2.5 years, incident stage 3 CKD occurred in 15% and 3% of those with and without AKI, respectively, with an unadjusted HR of 5.93 (95% CI, 4.49-7.84) and HR of 3.82 (95% CI, 2.81-5.19) in propensity score-stratified analyses. Deaths occurred in 35% and 24% of those with and without AKI, respectively, with an unadjusted HR of 1.46 (95% CI, 1.27-1.68). In propensity score-stratified analyses, HR decreased to 1.08 (95% CI, 0.93-1.27). Measurements of albuminuria were not available. Complete recovery of kidney function after an episode of AKI in patients with normal baseline kidney function is associated with increased risk of the development of incident stage 3 CKD, but not all-cause mortality.


Cyclooxygenase inhibition prior to ventricular fibrillation induced ischemia reperfusion injury impairs survival and outcomes.
Nonsteroidal anti-inflammatory medications (NSAIDs) are one of the most commonly used analgesics in the world. NSAIDs decrease prostaglandin synthesis through cyclooxygenase inhibition (COX-1 or COX-2). The effects of NSAIDs on survival and outcomes from global ischemia reperfusion events and specifically from cardiac arrest (CA) remain controversial. We hypothesized that NSAIDs prior to global whole-body ischemia reperfusion (I/R) injury impairs survival and outcomes. We explored this hypothesis in our swine model of Cardiac Arrest (CA) which involves global I/R with pretreatment using a predominantly COX-1 inhibitor (Indomethacin [COX-1/min COX-2 Inh], a COX-2 Inhibitor [COX-2-Inh, (Celecoxib)] or placebo control. We determined the effects of each inhibitor on a) survival, b) myocardial injury biomarker (Troponin 1), and c) Autonomic Nervous System (ANS) injury marker (heart rate variability [HRV]) up to 3 h after resuscitation. There were no survivals in COX-1/min COX-2-Inh pretreated animals and, 87% survived in both COX-2 Inhibited and control animals. COX-2 Inh pretreated animals had an 1800 fold increase of Troponin 1 compared to baseline whereas control animals had a 90 fold increase (p < 0.001). These results along with literature review of focal I/R in animal models with COX-2 overexpression, human studies of CA, and post myocardial infarction treatment with NSAIDs, support the hypothesis that NSAIDs prior to an I/R event impairs survival and outcomes. Specifically, predominantly COX-1 inhibition impairs survival, and COX-2 inhibition induces myocardial damage, autonomic nervous system dysfunction, and increases the risk for all-cause mortality and morbidity in humans post-MI which has significant implications for the nearly 10% of the population who are taking NSAIDs.


Prematurity and fetal lung response after tracheal occlusion in fetuses with severe congenital diaphragmatic hernia.
To evaluate the independent association of fetal pulmonary response and prematurity to postnatal outcomes after fetal tracheal occlusion for congenital diaphragmatic hernia. Fetal pulmonary response, prematurity (<37 weeks at delivery) and extreme prematurity (<32 weeks at delivery) were evaluated and compared between survivors and non-survivors at 6 months of life. Multivariable analysis was conducted with generalized linear mixed models for variables significantly associated with survival in univariate analysis. Eighty-four infants were included, of whom 40 survived (47.6%) and 44 died (52.4%). Univariate analysis demonstrated that survival was associated with greater lung response (p=0.006), and the absence of extreme preterm delivery (p=0.044). In multivariable analysis, greater pulmonary response after FETO was an independent predictor of survival (aOR 1.87, 95% CI 1.08-3.33, p=0.023), whereas the presence of extreme prematurity was not statistically associated with mortality after controlling for fetal pulmonary response (aOR 0.52, 95% CI 0.12-2.30, p=0.367). Fetal pulmonary response after FETO is the most important factor associated with survival, independently from the gestational age at delivery.


Vasopressin inhibition via combined head-out water immersion and a prostaglandin E-1 precursor in the treatment of male reproductive failure due to chronic alcohol abuse.
Male reproductive failure and infertility are quite common in alcoholics. There are very high correlations between elevated vasopressin levels and male infertility on the one hand, and probable deficiencies of prostaglandin E1 which may raise levels of PGE2 and endorphins which, in turn, release vasopressin on the other. Since head-out water immersion rapidly decreases vasopressin levels, a suggested joint protocol of head-out water immersion and a prostaglandin E-1 precursor is proposed for male reproductive failure in alcoholics.


The Association between Tea Consumption and the Risk of Fracture: A Dose-Response Meta-Analysis of Prospective Cohort Studies.
Inconsistent results exist on the role of tea consumption on subsequent risk of fracture. A dose-response meta-analysis was therefore conducted to assess the association of tea consumption with the risk of fracture based on prospective cohort studies. The electronic databases of PubMed, Embase, and the Cochrane library were systematically searched to identify prospective cohort studies from inception until September 2020. The categories of high versus low and dose-response meta-analyses for tea consumption on the risk of fracture were calculated using the random-effects model. Eight prospective cohort studies recruited 774,134 individuals selected for the final meta-analysis. An increment of 1 cup in tea consumption was not associated with the risk of fracture [relative risk (RR), 0.98; 95% confidence interval (CI), 0.96-1.00; P = 0.102]. Moreover, the highest tea consumption category was associated with a reduced risk of fracture (RR, 0.93; 95% CI, 0.88-0.98; P = 0.005). Furthermore, heavy (RR, 0.91; 95% CI, 0.85-0.98; P = 0.008) and mild (RR, 0.97; 95% CI, 0.94-1.00; P = 0.046) tea consumption were associated with lower risk of fracture. However, moderate tea consumption was not associated with the risk of fracture (RR, 0.98; 95% CI, 0.94-1.02; P = 0.281). This study found that increased tea consumption may provide a protective role in the risk of fracture. The benefits of tea consumption should be further explored according to the characteristics of the individuals.


Construction of a p-coumaric and ferulic acid auto-regulatory system in Pseudomonas putida KT2440 for protocatechuate production from lignin-derived aromatics.
Lignin is a robust and underutilized aromatic heteropolymer on earth. The effective valorization of lignin into value-added products is an attractive research topic in lignocellulosic biorefineries. However, a low bioconversion rate, high process cost, low yield, and high toxicity of substrates hinder its further applications. In this study, an auto-regulatory system was developed and identified as an effective solution to diminish these challenging bottlenecks. First, a lignin-derived standard model aromatic p-coumaric acid (p-CA)-responsive biosensor was successfully developed through a series of rational engineering approaches in Pseudomonas putida KT2440. Furthermore, an auto-regulatory system was established, which rapidly coexpressed key rate-limiting enzymes, 4-hydroxybenzoate hydroxylase, vanillate-O-demethylase, and transporter HcnK under the biosensor element, to convert the mixture of p-CA and ferulic acid into a value-added platform chemical protocatechuate with a titer of 12.7 g/L. This study demonstrated that the constructed auto-regulatory platform is effective and economical for lignin valorization.


Factors affecting bilateral tourism flows.
This paper examines the structure of bilateral tourism and identifies five broad categories of factors that may affect the overall size of tourism flows. Such analysis of tourism is important because diplomacy and trade continues to be conducted on a nation-to-nation basis despite a growing shift towards multilateralism in free trade blocks such as the European Union and the North American Free Trade Agreement. Further, Bilateralism is important because countries have reduced abilities to control tourism imports in an era of growing globalization. A framework that may be employed to analyze problems in bilateral tourism flows is also outlined.


Genetic activity in Saccharomyces cerevisiae of compounds found in effluents of pulp and paper mills.
20 compounds identified in pulp mill effluents were screened for genetic activity in growing cells using Saccharomyces cerevisiae strains D7 and XV185-14C without and with S9. Nine compounds were positive in one or the other yeast strain (7 in D7; 2 in XV185-14C). One additional compound showed weak effects and two others showed elevated frequencies/survivor without absolute increases of mutants. The presence of S9 enabled detection of one positive and two weak effects, it enhanced the genetic activity of one compound in each strain, and it reduced the mutagenic effects of 4 others in strain D7. 7 of the 20 chemicals tested have been shown previously to be mutagenic in the Salmonella/mammalian-microsome assay. Of the 7 bacterial mutagens, 6 were positive and 1 had a weak effect in yeast.


Humoral responses during wound healing in Holothuria tubulosa (Gmelin, 1788).
Wounds in living organisms trigger tissue-repair mechanisms. The sea cucumber (Holoturia tubulosa) is an excellent model species for achieving a better understanding of the humoral and cellular aspects involved in such healing processes. Consequently, this study assesses data on its morphometric, physiological and humoral responses 1, 2, 6, 24 and 48h after wound induction. In particular, morphometric data on the weight, width, length and coelomic-fluid volume of the species were estimated at different times during our experiments. In addition, the humoral aspects related to the enzymatic activity of esterase, alkaline phosphatase and peroxidase, as well as the cytotoxic activity of cell lysates (CL) and cell-free coelomic fluids (CfCf) are evaluated for the first time. Our results reveal a significant decrease in body length and weight, along with time-dependent, significant changes in the esterase, alkaline phosphatase, peroxidase and cytotoxic activity in both the CL and CfCf. The data obtained lead to the pioneering finding that there is an important time-dependent involvement of morphometric (changes in weight and length) and humoral (enzymatic and cytotoxic) responses in wound healing.


[Fight against maternal mortality in rural areas: decentralization of emergency obstetric cares in Burkina Faso].
In order to cover the shortage of midwives (MWs) in the health district of Tougan, Burkina Faso, a strategy for the decentralization of emergency obstetric cares, based on ad hoc interventions undertaken by MW to manage obstetric complications in health centers (HCs), has been developed in rural areas. This study aimed to describe this experience and to analyze the achieved results. We conducted a cross-sectional, analytical, intervention study based on a review of routine data from all the parturients treated from 2013 to 2015. Data collection took place from 5 to 20 January 2016. Chi-square Test, odds ratios (ORs) and their 95% confidence intervals were calculated. A total of 416 parturients with obstetric complications were treated by zonal MW. The average age of patients was 26.4 years. The median distance travelled to treat parturients was 15 km, with an average intervention period of 21.1 minutes (standard deviation = 7.13 minutes). Dystocias accounted for half (50.7%, CI95%= 45.8-55.6) of treated complications followed by hemorrhage (26.4%, CI95%= 22.3%-31.0%). More than 77% of interventions resulted in local resolution of obstetric complications. Finally, the intervention outcome was subject to the pathology treated (OR=5.88; p < 0.001). This strategy was an answer to the shortage of MWs in the perypheral HCs in the health district of Tougan. In this particular context, this intervention could provide an alternative solution to the shortage of human resources for health in rural areas.


The epidemiology of concurrent infection in patients with pyogenic spine infection and its association with early mortality: A nationwide cohort study based on 10,695 patients.
Generally, a sufficient duration of relevant antibiotics based on an appropriate culture combined with proper surgical treatment guarantees a favorable clinical outcome in patients with pyogenic spine infections. However, a patient's condition often deteriorates as concurrent infections occur in other organs, leading to mortality. Therefore, this study aimed to investigate the epidemiology of concurrent infections in patients with a pyogenic spine infection and estimate the rates and risks of early mortality. Patients with a pyogenic spine infection were identified using a national claims database that includes the entire population. The epidemiology of the six types of concurrent infections was investigated, and the corresponding early mortality rates and risks were estimated. The results were validated internally by bootstrapping and externally by defining two additional cohorts for sensitivity analysis. Among 10,695 patients with a pyogenic spine infection, the prevalence of the six types of concurrent infections was 11.3 % for urinary tract infections, 9.4 % for intra-abdominal infections, 8.5 % for pneumonia, 4.6 % for septic arthritis or osteomyelitis of the extremities, 0.7 % for central nervous system infections, and 0.5 % for cardiac infections. Patients with a concurrent infection had approximately 4-fold greater mortality than those without (3.3 % vs. 0.8 %). The early mortality rates were particularly higher in patients with multiple or specific types of concurrent infections, including central nervous system infections, cardiac infections, and pneumonia. In addition, the mortality trends differed significantly according to the number and type of concurrent infections. These data on six types of concurrent infection among patients with pyogenic spinal infection can be used as a source of reference by clinicians.


Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients.
Immune checkpoint inhibitors (ICIs) cause thyroid immune-related adverse effects (irAEs). However, associations between each type of thyroid immune-related adverse effect (irAE) and the anti-tumor effect of ICI remains unknown. This study aimed to determine the effects of each type of thyroid dysfunction on patient survival. Patients who initiated ICI treatment from January 2015 to December 2019 in Seoul St. Mary's Hospital were retrospectively analyzed. Thyroid dysfunction was classified into four types: newly developed overt or subclinical hypothyroidism, thyrotoxicosis, worsened hypothyroidism, and subclinical hyperthyroidism. Patients were divided into two groups according to the presence or absence of thyroid dysfunction. Among the 191 patients, 64 (33.5%) developed thyroid irAEs. There was no significant difference in age, sex, or cancer type between the two groups. The overall survival in patients with thyroid irAEs was significantly higher than that in patients without thyroid irAEs (25 months vs. 18 months, respectively, p = 0.005). After adjusting for confounding factors, the hazard ratio for mortality in the thyroid irAE group compared to the no thyroid irAE group was 0.480 (p = 0.006). Newly developed overt or subclinical hypothyroidism patients showed a significantly lower hazard ratio for mortality of 0.324 (p = 0.002). Patients with thyrotoxicosis showed a worse hazard ratio for mortality than those without thyroid irAE, although the difference was not statistically significant. It was verified that ICI treatment-induced thyroid dysfunction was associated with better survival, even in the real-world practice. Thus, endocrinologists should cooperate with oncologists to monitor patients treated with ICIs.


Brief report on the clinical characteristics of patients whose samples generate small cell lung cancer circulating tumour cell derived explants.
Small cell lung cancer (SCLC) has a dismal prognosis. Circulating tumour cells (CTCs) can be used to generate CTC derived explants (CDX) for the study of SCLC biology and the development of novel therapeutics. We investigated whether there are demographic or clinical predictors of the success of CDX generation, and whether CDX models are representative of the SCLC patient population. This was a single centre, retrospective analysis of SCLC patients who had participated in the CHEMORES Study. Paired blood samples were donated for CTC enumeration and CDX generation attempt at pre-treatment baseline, disease progression and intervening timepoints. Clinical and demographic data was collected from electronic records, and analysed for differences between patients whose samples did and did not generate a CDX. 231 paired blood samples were taken from 147 patients. 45 CDX were generated from 34 patients. CTC number was significantly higher in blood samples which successfully generated a CDX than those which didn't, at both baseline (p=<0.0001) and progression (p = 0.0001). The group with successful blood samples had a poorer performance status (p = 0.0067), and a higher proportion of patients with chemorefractory disease (p = 0.0077). Both progression free survival (PFS) (p = 0.0132) and overall survival (p=< 0.0001) were significantly shorter for patients with successful samples. Patients whose samples generate CDX models may have a higher disease burden and more aggressive disease. Thus, insights gained by study of SCLC CDX may have a significant impact, particularly in the SCLC subpopulation with the greatest clinical need.


Alpha-synuclein is expressed in different tissues during human fetal development.
Alpha-synuclein is a small presynaptic protein associated with both normal synaptic plasticity and neurodegenerative processes. Its normal cellular function, however, remains unknown. Even though it is highly enriched in the brain, its presence was reported in other human adult tissues. In the present study, we examined tissue expression of alpha-synuclein in human and rat prenatal development. Using Western blot analysis, various peripheral tissues from 15 to 23 gestational weeks, human and E19 rat fetuses, along with human and rat adult tissues, were assayed. alpha-Synuclein expression was observed in all fetal human organs examined. In adult human tissues the high expression of alpha-synuclein was maintained in the brain, whereas in other organs the expression was greatly reduced. In contrast, both in fetal and adult rat tissues, alpha-synuclein was only detected in the brain. In addition to a 19-kDa alpha-synuclein band, 36- and 52-kDa immunoreactive bands were observed in all fetal and adult human organs, with the exception of the brain, but their identity remains to be determined. These findings suggest that apart from its function in development of the nervous system, alpha-synuclein has an important function in peripheral tissues as well during normal human prenatal development.


Factors associated with loneliness in immigrant and Canadian-born older adults in Ontario, Canada: a population-based study.
While loneliness is common in older adults, some immigrant groups are at higher risk. To inform tailored interventions, we identified factors associated with loneliness among immigrant and Canadian-born older adults living in Ontario, Canada. We conducted a cross-sectional analysis of 2008/09 data from the Canadian Community Health Survey (Healthy Aging Cycle) and linked health administrative data for respondents 65 years and older residing in Ontario, Canada. Loneliness was measured using the Three-Item Loneliness Scale, with individuals categorized as 'lonely' if they had an overall score of 4 or greater. For immigrant and Canadian-born older adults, we developed separate multivariable logistic regression models to assess individual, relationship and community-level factors associated with loneliness. In a sample of 968 immigrant and 1703 Canadian-born older adults, we found a high prevalence of loneliness (30.8% and 34.0%, respectively). Shared correlates of loneliness included low positive social interaction and wanting to participate more in social, recreational or group activities. In older immigrants, unique correlates included: widowhood, poor health (i.e., physical, mental and social well-being), less time in Canada, and lower neighborhood-level ethnic diversity and income. Among Canadian-born older adults, unique correlates were: female sex, poor mental health, weak sense of community belonging and living alone. Older immigrant females, compared to older immigrant males, had greater prevalence (39.1% vs. 21.9%) of loneliness. Although both groups had shared correlates of loneliness, community-level factors were more strongly associated with loneliness in immigrants. These findings enhance our understanding of loneliness and can inform policy and practice tailored to immigrants.


Understanding potential barriers and enablers to a perioperative early phase cell therapy trial.
Early-phase cell therapy clinical trials depend on patient and physician involvement, yet barriers can impede their participation. To optimize engagement for a planned cell therapy trial to prevent perioperative cardiac complications, the authors conducted semi-structured interviews with at-risk patients and physicians who could potentially be involved in the study. The authors used the theoretical domains framework to systematically identify potential barriers and enablers. Forty-one interviews were conducted to reach data saturation, and four overall potential barriers to participation (themes) were identified. Theme 1 emphasizes that patients and physicians need accessible information to better understand the benefits and risks of the novel therapy and trial procedures and to address misconceptions. Theme 2 underscores the need for clarity on whether the trial's primary purpose is safety or efficacy, as this may influence patient and physician decisions. Theme 3 recognizes the resource and logistic realities for patients (e.g., convenient follow-up appointments) and physicians (e.g., personnel to assist in trial procedures, competing priorities). Theme 4 describes the importance of social influences (e.g., physicians and family, peers/colleagues) that may affect decisions to participate and the importance of patient preferences (e.g., availability of physicians to discuss the trial, including caregivers in discussions). Prospectively addressing these issues may help optimize feasibility prior to conducting an expensive, resource-intensive trial.


Effect of mesenchymal stem cells on anti-Thy1,1 induced kidney injury in albino rats.
To evaluate the effect of mesenchymal stem cells (MSCs) in rats with anti-Thy1,1 nephritis. Female albino rats were divided into three groups, control group, anti-Thy1,1 group and treatment with i.v. MSCs group. MSCs were derived from bone marrow of male albino rats, Y-chromosome gene was detected by polymerase chain reaction in the kidney. Serum urea and creatinine were estimated for all groups. Kidney of all studied groups was examined histologically and histochemically (total carbohydrates and total proteins). DNA fragmentation and expression of α-SMA were detected. Kidney of animals injected with anti-Thy1,1 showed inflammatory leucocytic infiltration, hypertrophied glomeruli, tubular necrosis and congestion in the renal blood vessels. The kidney tissue also showed reduction of carbohydrates and total proteins together with increase in apoptosis and in expression of α-SMA. Moreover, the levels of urea and creatinine were elevated. Treating animals with MSCs revealed that kidney tissue displayed an improvement in the histological and histochemical changes. Apoptosis and α-SMA expression were decreased, and the levels of urea and creatinine decreased. The obtained results demonstrated the potential of MSCs to ameliorate the structure and function of the kidney in rats with anti-Thy1,1 nephritis possibly through the release of paracrine growth factor(s).


Loss of function of Ywhah in mice induces deafness and cochlear outer hair cells' degeneration.
In vertebrates, 14-3-3 proteins form a family of seven highly conserved isoforms with chaperone activity, which bind phosphorylated substrates mostly involved in regulatory and checkpoint pathways. 14-3-3 proteins are the most abundant protein in the brain and are abundantly found in the cerebrospinal fluid in neurodegenerative diseases, suggesting a critical role in neuron physiology and death. Here we show that 14-3-3eta-deficient mice displayed auditory impairment accompanied by cochlear hair cells' degeneration. We show that 14-3-3eta is highly expressed in the outer and inner hair cells, spiral ganglion neurons of cochlea and retinal ganglion cells. Screening of YWHAH, the gene encoding the 14-3-3eta isoform, in non-syndromic and syndromic deafness, revealed seven non-synonymous variants never reported before. Among them, two were predicted to be damaging in families with syndromic deafness. In vitro, variants of YWHAH induce mild mitochondrial fragmentation and severe susceptibility to apoptosis, in agreement with a reduced capacity of mutated 14-3-3eta to bind the pro-apoptotic Bad protein. This study demonstrates that YWHAH variants can have a substantial effect on 14-3-3eta function and that 14-3-3eta could be a critical factor in the survival of outer hair cells.


The impact of instructing management skill to managers on the obstetrician's efficiency.
The importance of efficiency and improvement of health service for resolving people's health requirement and meeting their expectation is increasing. In addition, it considers as a priority for making decision and manager's activity in health officials. Manager's control on the management principle and the proper use of their management skill and creating a sense of trust and commitment are the tools that were providing a good condition for working and catching the organization's goals. In this quasi-experimental study, before beginning the research, the non-teaching hospitals that are affiliated to the Kurdistan's medical science university were randomly divided into 2 groups. Three hospitals from 3 cities considered as a control group, and three hospitals from 3 cities considered as an intervention group.80 person of hospital's obstetrician staff classified in these 2 group by quota method and the hospital's nurses and obstetrician's manager of case-control involved by census method. The research's tool was Hersi and Gold Smith's standard efficiency questionnaire, which was filled out at the beginning of the study by the obstetricians of both groups and then it gave to the hospital's nurses and obstetrician's managers of the case group's instructing management skills for 16 hours. The efficiency's questionnaire was filled out, compared, and evaluated again by the obstetricians of both groups, 12 weeks after intervention. The data analyzed by the independent T-test, variance analysis, paired T-test, and SPSS 22. The findings showed that the average of the obstetrician's efficiency mainly developed in the intervention team after the instruction of management skills to the managers (P < 0.001). The instruction of the management skill to the nurses and obstetrician's managers caused the efficiency's promotion. Therefore, the instruction of the management skills has suggested as a method of increasing efficiency in hospitals.


Hemangiopericytoma of the uterus: report of a case with a comprehensive review of the literature.
A case of locally recurrent and metastatic uterine hemangiopericytoma successfully treated with surgery, radiotherapy and chemotherapy is presented. The patient is alive without evidence of detectable tumor, 13 years after the initial diagnosis. Review of the literature revealed 64 reported cases of uterine hemangiopericytoma. The clinical features are not sufficiently characteristic to enable the diagnosis to be made preoperatively. However, with the help of histological and ultrastructural studies a definite diagnosis of hemangiopericytoma can be made. The primary treatment is radical surgery which usually involved total hysterectomy and bilateral salpingo-oophorectomy. The prognosis of uterine hemangiopericytoma is better than that of other sites. However, long follow-up of these patients is necessary because of the tendency to local and distant recurrence many years after the initial treatment. The recurrent tumor should be treated aggressively with surgery, radiotherapy, and chemotherapy as long-term survival is not unusual.


Cholesteryl ester exchange protein in human plasma isolation and characterization.
A protein catalyzing the exchange of cholesteryl esters among the lipoproteins was found in human plasma. A rapid method for assaying this activity was developed based on the transfer of radioactive cholesteryl esters from low density lipoprotein with MnCl2 in the presence of phosphate. Fractionation of plasma through a combination of ammonium sulfate precipitation, ultracentrifugation at p = 1.25, and chromatography on Phenyl-Sepharose, CM-cellulose, and concanavalin A-Sepharose, yielded a preparation purified 3500-fold compared to the starting plasma. The exchange protein was found to be a glycoprotein with an isoelectric point of 5 and apparent molecular weight of 80 000. On the basis of these properties and its immunological characteristics the exchange protein was judged to be distinct from any of the known apolipoproteins. This protein could also be separated from plasma phosphatidylcholine cholesterol acyl-transferase on DEAE-cellulose. The exchange protein did not appear to influence cholesterol esterification in lipoproteins by phosphatidylcholine cholesterol acyl-transferase, and the latter had no effect on the transfer of low density lipoprotein cholesteryl esters to high density lipoprotein. The exchange protein did not esterify cholesterol or hydrolyze cholesteryl esters in lipoproteins.


The ultimate resignation: suicide and search activity.
This paper presents an integrative approach to suicidal behavior in terms of search activity concept. Search activity concept displays a broad and holistic approach to behavior, adaptation to environment, body resistance, brain amine metabolism, and REM-sleep functions. Search activity is defined as activity that is oriented to change the situation (or at least the subject's attitude to it) in the absence of a precise prediction of the outcome of such activity, but taking into consideration outcomes at all previous stages of activity. According to the proposed hypothesis, renunciation of search (a state opposed to search activity) leads to a feeling of helplessness, problem-solution deficits, inefficient coping, dreams that represent renunciation of search, and a drop in the activity of amines. All these factors further exacerbate the state of renunciation of search and elevate suicidal risk. In addition, the remnants of search activity are misdirected to self-defeating behaviors that increase mental pain and contribute to renunciation of search. This hypothesis integrates findings from a number of fields of study of suicidal behavior, resolves some paradoxes, suggests new lines of research, and raises suggestions for assessment and treatment of suicidal behavior.


3D ultrasound to quantify lateral hip displacement in children with cerebral palsy: a validation study.
To assess the validity of a new index, lateral head coverage (LHC), for describing hip dysplasia in a population of children with cerebral palsy (CP). LHC is derived from 3D ultrasound assessment. Twenty-two children (15 males, seven females; age 4-15y) with CP undergoing routine hip surveillance were recruited prospectively for the study. Each participant had both a planar radiograph acquired as part of their routine care and a 3D ultrasound assessment within 2 months. Reimer's migration percentage (RMP) and LHC were measured by the same assessor, and the correlation between them calculated using Pearson's correlation coefficient. The repeatability of LHC was investigated with three assessors, analysing each of 10 images three times. Inter- and intra-assessor variation was quantified using intraclass correlation coefficients. LHC was strongly correlated with RMP (Spearman's rank correlation coefficient=-0.86, p<0.001). LHC had similar inter-assessor reliability to that reported for RMP (intraclass correlation coefficient=0.97 and intra-assessor intraclass correlation coefficient=0.98). This is an initial validation of the use of 3D ultrasound in monitoring hip development in children with CP. LHC is comparable with RMP in estimating hip dysplasia with similar levels of reliability that are reported for RMP.


Detection of intranuclear clusters of Sm antigens with monoclonal anti-Sm antibodies by immunoelectron microscopy.
It has been shown that small nuclear RNA (snRNA) species U1, U2, U4, U5, and U6 are found in the nucleus in the form of small nuclear ribonucleoprotein particles (snRNPs), and that anti-Sm antibodies react with snRNP polypeptides, which are associated with all five snRNAs. We report here a novel intranuclear complex, denoted "Sm cluster," detected by immunostaining with monoclonal anti-Sm antibodies in HeLa cells.


Diagnosis and management of arterial mural thromboemboli.
If ischemic lesions or cerebral dysfunction appear without obvious cause, aneurysm, stenosing, or ulcerative plaques in proximal arteries are suspected. Diagnostic methods are outlined. Treatment by removal of the embolic source is preferred and exclusion of the lesion and bypass is reserved for inacessible lesions or poor operative risks.