Tissue specific trisomy 15 mosaicism associated with urogenital malformations.
We describe a boy born with hypospadias and later diagnosed with vesicoureteral reflux and mild cognitive disability. Routine diagnostic investigation by karyotyping, chromosomal microarray (CMA) and trio analysis with whole exome sequencing was normal. However, later CMA performed on DNA from genital tissue showed trisomy 15, which prompted further analysis. Fluorescent in situ hybridization was performed to verify the CMA result and delineate the mosaic rate. Methylation specific MLPA was performed to investigate the parent of origin of the extra chromosome 15. Further medical examination of the boy identified fine Blaschko's lines, indicative of mosaicism, but earlier unnoticed. CMA on genital tissue showed 80% mosaicism for trisomy 15. Bladder mucosa and muscle showed a high degree of trisomy 15 (56% and 45% respectively), while buccal mucosa and abdominal skin showed low-grade or no trisomy 15. The extra chromosome 15 was of maternal origin. This case report describes a boy with two different malformations in the same organ region that carries a high degree of trisomy 15 mosaicism. Hence, the clinical implication is that there is no recurrence risk for sibs, but the boy in his turn risks producing gametes with an extra chromosome 15. Tissue restricted mutations are not commonly described but may cause congenital malformations that affects the information to the family.


Auditory Hallucinatory Beliefs in Patients With Schizophrenia: Association of Auditory Hallucinations With Social Interactions, Characteristics and Emotional Behaviors Over 3 Months.
The aims of this study were to explore social interactions, characteristics, and emotional behaviors to detect changes in auditory hallucinatory beliefs in patients with schizophrenia over a 3-month period. Participants (n=189) were evaluated using the Auditory Hallucinations Assessment Scale (AHAS) and the Assessment of Communication and Interaction Skills (ACIS). The characteristics and emotional behaviors measured by the AHAS showed improvements, while auditory hallucinatory beliefs became less influential. Social interaction scores increased regardless of changes in auditory hallucinatory beliefs. Psychiatric professionals need to train those who hear voices to react to them with indifference.


Developmental changes in membrane proteins from baboon erythrocytes.
1. Total membrane proteins from freshly isolated erythrocytes of fetal, newborn, and adult baboons were analyzed by electrophoresis. 2. The electrophoretic patterns of proteins from newborns and adults were similar but those from adults and fetuses were different. 3. Four proteins, P165, P155, P75, and P49, with approximate mol. wts of 165,000, 155,000, 75,000, and 49,000, respectively, were present in adult but not in fetal samples. 4. P155 and P49, were glycoproteins; P49 was a cell-surface protein. 5. The membrane protein characteristics of the adult erythrocyte differ from those of the fetal erythrocytes and at least four polypeptides are associated with development of the adult phenotype.


Evaluation of mobile applications focused on the care of patients with anxiety disorders: A systematic review in app stores in Brazil.
To identify and evaluate the quality of mobile apps available in Brazil focused on the care of patients with anxiety disorders. A comprehensive search was conducted until October 2021 on Play Store (Android) and Apple Store (iOS) in Brazil, using the terms "anxiety," "phobia," "panic attack," and "social phobia." Two independent authors identified the apps and performed data extraction and quality assessment using the Mobile App Rating Scale (MARS). Pearson's correlation was used to analyze the relationship between user star rating and the quality defined by the MARS instrument. A total of 3,278 potential apps were identified, of which 71 fully met the eligibility criteria. Most apps were made available on the Play Store (91.74%), in English (69.01%), and updated in the last two years (90.14%). Approximately half of the apps (50.70%) did not inform the developer's country and most of them did not report the user star rating (70.42%). The target population was indicated as free by most apps (85.92%), with generalized anxiety disorder being the most addressed disorder (74.65%), followed by panic disorder (33.80%). The three main purposes of the apps were education (83.10%), self-assessment (38.03%), and meditation/breathing (32.39%). Only 31 apps (43.66%) had acceptable quality (above 3.0) and the average total MARS quality score of 2.93 (2.20 to 3.90), with the functionality section receiving the highest score (3.90) and the lowest scoring sections being engagement (2.16). The apps that were rated stars by users (29.58%) showed a negative Pearson correlation (ρ = -0.100), evidencing a difference in the user's evaluation and that performed using the MARS instrument. Gaps in the quality of apps focused on the care of patients with anxiety disorders were evidenced since most were classified as having low quality through the MARS instrument. Thus, users are recommended to use these apps with caution.


Selective metabolism of E-3,4-bis(4-ethylphenyl)hex-3-ene in rat liver microsomes.
The synthetic stilbene derivative E-3,4-bis(4-ethylphenyl)hex-3-ene (E-DE-BPH) has been proposed as a potential anticancer drug with a new mode of action. We report here on the in vitro metabolism of E-DE-BPH in liver microsomes of rats and pigs. The formation of five metabolites, which could be separated on a reverse-phase HPLC column with UV detection, was observed in microsomal incubations. To facilitate the structural identification of these metabolites, two different deuterium-labeled forms of E-DE-BPH were synthesized. By comparing the mass spectra obtained for the metabolites of unlabeled E-DE-BPH and of the two deuterated forms, it could be demonstrated that E-DE-BPH was oxidized by liver microsomes exclusively at the benzylic positions of the molecule. The major metabolite was identified as E-3-(4-(1-hydroxyethyl)phenyl)-4-(4-ethylphenyl)hex-3-ene. Four minor metabolites were formed from the major metabolite, either by hydroxylation at the other benzylic position to yield a bishydroxylated metabolite, or by oxidation of the hydroxyl group to form E-3-(4-acetylphenyl)-4-(4-ethylphenyl)hex-3-ene. The latter compound was also obtained by chemical oxidation of the monohydroxylated metabolite of E-DE-BPH. Since no products containing hydroxyl groups at the aromatic rings or at other aliphatic sites of the molecule were detected, a surprisingly selective oxidative metabolism of E-DE-BPH appears to occur with rat and pig liver microsomes.


Focal dependent pleural thickening at MDCT: pleural lesion or functional abnormality?
To describe the characteristics of reversible focal pleural thickenings (PTs) mimicking real plaques, that firstly suggest asbestos exposure or pleural metastasis; to propose an imaging strategy and propose an explanation for their mechanism of formation. Retrospective review of data from 19 patients with PTs fitting the description of pleural plaques at chest computed tomography (CT) and presenting modifications (clearance or appearance) of at least one PT at an additional chest examination in prone position. A total of 152 PTs were recorded on the first chest CT examinations with a range of two to 19 pleural opacities per patient. All PTs had a posterior distribution in the lower lobes. On the additional acquisitions, 144 PTs disappeared. Seventeen patients presented complete regression of PTs and two patients presented persistence of eight PTs. Additional low dose acquisition in prone position should be performed in all patients presenting with focal PT in a dependent and basal location. This may allow to exclude a pleural plaque in case of asbestos exposure but also a pleural metastasis in oncologic patients. These reversible dependent PTs could be related to physiological focal accumulation of lymphatic fluid in subpleural area.


Increased interferon-γ levels and risk of severe malaria: a meta-analysis.
Interferon (IFN)-γ contributes to the pathogenesis of severe malaria; however, its mechanism remains unclear. Herein, differences in IFN-γ levels between patients with severe and uncomplicated malaria were evaluated using qualitative and quantitative (meta-analysis) approaches. The systematic review protocol was registered at PROSPERO (ID: CRD42022315213). The searches for relevant studies were performed in five databases, including PubMed, Scopus, Embase, MEDLINE and Web of Science, between 1 January and 10 July 2022. A meta-analysis was conducted to pool the mean difference (MD) of IFN-γ levels between patients with severe malaria and those with uncomplicated malaria using a random-effects model (DerSimonian and Laird method). Overall, qualitative synthesis indicated that most studies (14, 58.3%) reported no statistically significant difference in IFN-γ levels between patients with severe malaria and those with uncomplicated malaria. Meanwhile, remaining studies (9, 37.5%) reported that IFN-γ levels were significantly higher in patients with severe malaria than those in patients with uncomplicated malaria. Only one study (4.17%) reported that IFN-γ levels were significantly lower in patients with severe malaria than those in patients with uncomplicated malaria. The meta-analysis results indicated that patients with severe malaria had higher mean IFN-γ levels than those with uncomplicated malaria (p < 0.001, MD: 13.63 pg/mL, 95% confidence interval: 6.98-20.29 pg/mL, I2: 99.02%, 14 studies/15 study sites, 652 severe cases/1096 uncomplicated cases). In summary, patients with severe malaria exhibited higher IFN-γ levels than those with uncomplicated malaria, although the heterogeneity of the outcomes is yet to be elucidated. To confirm whether alteration in IFN-γ levels of patients with malaria may indicate disease severity and/or poor prognosis, further studies are warranted.


Identification of emerging safety and sustainability issues of advanced materials: Proposal for a systematic approach.
The EU Chemicals Strategy for Sustainability is a first step to achieve the Green Deal ambition for a toxic-free environment, and ensure that chemicals are produced and used in a way that maximises their contribution to society while avoiding harm to our planet and to future generations. Advanced materials are predicted to play a pivotal role in achieving this ambition and the underlying sustainability goals, and considerable efforts are invested in designing new classes of materials. Examples of such materials are metamaterials, artificially architectured materials designed to have material properties beyond those of the individual ingredient materials, or active materials at the boundary between materials and devices (e.g., new biomedical soft materials). Such innovative advanced materials raise concern about possible future safety and sustainability issues and would benefit from appropriate risk governance that promotes innovation, while pushing for safety and sustainability. To balance these aspects, a methodology is proposed for the early-stage identification of emerging safety and sustainability issues of advanced materials. As exemplified by two case studies, the methodology aims to be of use for innovators, risk assessors, and regulators. Extension of the methodology is highlighted, as well as implementation in broader initiatives like the EU's industrial policy approach.


Profiling of energy compartmentalization in photosystem II (PSII), light harvesting complexes and specific energy fluxes of primed maize cultivar (P1429) under salt stress environment.
Photosystem II efficiency is the most important aspect of stress physiology to keep photosynthetic momentum operative under stress conditions. In the last few decades effect of priming on the germination growth and physiology of plants were highlighted. Profiling energy compartmentalization in PSII using chlorophyll fluorescence kinetics and specific energy fluxes of primed seeds and plants has not been documented. It is crucial to discover the changes associated with the light-harvesting complexes, PSII functionality, and photochemical modulations occurring in the biochemical thylakoid membrane in response to priming and salt stress. The present study mainly focuses on photosystem II efficiency leading to physiological tolerance by seed priming. We grow the plants after seed priming with the solution of sodium chloride (75 and 150 mM), salicylic acid (1 and 2 mM), and calcium chloride (34 mM) and nitrate (20 mM). All the primed plants were subjected to salt stress 10 days after germination @ 0, 75, and 150 mM NaCl. Later germination, growth, morphology, physiology, PS II functionality and photochemical yield were evaluated. NaCl priming did more promising effects on energy compartmentalization, light-harvesting ability, and specific energy fluxes of photosystem II compared to salicylic acid and calcium salts under a stress environment. Maximum quantum yield (FV/FM), active reaction centers with higher efficiency of water splitting complex (FV/FO), restored electron flow, higher photochemical quenching (qP), oxygen evolution (SMT-phase), and almost negligible heat dissipation are associated with better osmotic adjustment and higher water uptake (RWC) under stress condition.


Association studies of cholesterol metabolism genes (CH25H, ABCA1 and CH24H) in Alzheimer's disease.
Recent studies have demonstrated that cholesterol metabolism has an important role in Alzheimer's disease (AD) pathogenesis, suggesting that cholesterol-related genes may be significant genetic risk factors for AD. Based on the results of genome-wide screens, along with biological studies, we selected three genes as candidates for AD risk factors: ATP-binding cassette transporter A1 (ABCA1), cholesterol 25-hydroxylase (CH25H) and cholesterol 24-hydroxylase (CH24H). Case-control of North American Caucasians and AD families of Caribbean Hispanic origin were examined. Although excellent biological candidates, the case-control dataset did not support the hypothesis that these three genes were associated with susceptibility to AD. Similarly, no association was found in the Caribbean Hispanic families for CH25H. However, we did observe a possible interaction between ABCA1 and APOE in the Hispanics.


Possible mechanisms of acute pancreatitis induced by ethanol.
We investigated the effect of intravenous and intragastric ethanol on pancreatic duct pressure, duct permeability to dextran molecules (20,000 molecular weight), and on the development of acute pancreatitis in an experimental model of the disease. Intragastric ethanol caused a small increase in pancreatic duct pressure (6 to 7 mm Hg) and an increase in duct permeability to dextran. Intravenous ethanol with exclusion of the sphincter of Oddi did not increase pancreatic duct pressure or permeability. Intravenous ethanol and intragastric normal saline solution altered neither pressure nor permeability. Artificial elevation of pancreatic duct pressure alone with no ethanol had no effect on duct permeability. However, when intravenous ethanol was given to produce similar systemic concentrations as achieved in the intragastric experiments (250 mg/dl) and duct pressure was artificially raised, duct permeability was increased. Ethanol concentrations similar to those found in peripheral blood were detected in secretin-stimulated pancreatic juice. Perfusion of the pancreatic duct with activated pancreatic enzymes after intragastric but not intravenous ethanol (that is, only in animals with increased duct permeability) caused acute edematous pancreatitis. Our results confirmed that increased duct permeability was necessary to produce acute pancreatitis in this model, and that this increase in permeability resulted from both a small increase in duct pressure and probably from the toxic metabolic effects of ethanol.


Estrogen and Myc negatively regulate expression of the EphA2 tyrosine kinase.
Estrogen receptor and c-Myc are frequently overexpressed during breast cancer progression but are downregulated in many aggressive forms of the disease. High levels of the EphA2 tyrosine kinase are consistently found in the most aggressive breast cancer cells, and EphA2 overexpression can increase metastatic potential. We demonstrate, herein, that estrogen and Myc negatively regulate EphA2 expression in mammary epithelial cells. These data reveal EphA2 as a downstream target of estrogen and Myc and suggest a mechanism by which estrogen and Myc may regulate breast cancer.


Long-term follow-up of patients with multiple myeloma treated with total body irradiation-Melphalan conditioning.
Since a study published in 2002 showed a survival advantage of melphalan-only conditioning for stem cell transplantation (HSCT) over melphalan-total body irradiation (mel-TBI) in patients with multiple myeloma (MM), most centers abandoned mel-TBI. Mel-TBI causes more early toxicity and is more complicated to administer, but we speculated it may result in longer term survival with radiation as an independent treatment modality. Therefore, we analyzed the long-term outcome of patients with MM who received mel-TBI as part of conditioning at our center. From 1995 to 2013, 50 patients with MM underwent autologous HSCT at Tulane University Medical Center using mel-TBI conditioning. We used Kaplan-Meier survival analysis and compared our patients with data available from the Louisiana Tumor Registry. The mean survival of our patients was 70.98 months from time of transplant and 84.2 months from time of initial diagnosis. No differences were observed according to gender, ethnicity, or age at transplant. The expected median survival in a population-based registry (matched for age and year of treatment) was 27 months (P<.001). Total body irradiation in conjunction with melphalan as conditioning is feasible and can lead to long-term survival. More research is necessary to determine which patients benefit most. Mel-TBI should also be explored in conjunction with immunotherapy.


Natural defenses and autoprotection: naturotherapy, an old concept of healing in a new perspective.
Recent molecular-biological and molecular-genetic research has shown that important cellular-based autoprotective mechanisms are mediated by heat-shock proteins (HSPs) or stress-response proteins, also called 'chaperones'. This can happen because cells react to extracellular stimuli by activating signal transduction pathways which result in activating the genetic program. Molecular biologists and cardiologists are tempted to evaluate these phenomena in respect to their potential meaning for a better understanding of the complex notions of health and disease. When molecular geneticists or cardiologists talk about autoprotective or natural defense mechanisms, and physicians talk about salutogenesis, they all mean something very specific. The phenomenon seen here belongs to the body's own defense mechanisms which make it capable of reacting to harmful influences and allow it to stabilize a structure and/or function of the body for a certain period. Here we see a connecting link to the historically grounded term self-healing forces, which has challenged medical doctors in the different historical periods of medical science. They tried to explain these effects based on the current model of the organism. Their understanding of this phenomenon played a role in defining the concept of health and disease. Thus, it seems very fitting to look back into history, since the phenomena discussed here as well as the insights into autoprotective mechanisms will continue to influence medical understanding of health and disease.


4-Chloro-5-(di-methyl-amino)-2-[(5-phenyl-1,3,4-oxa-diazol-2-yl)meth-yl]pyridazin-3(2H)-one.
In the structure of the title compound, C15H14ClN5O2, the terminal phenyl ring and the adjacent furan ring subtend a dihedral angle of 6.77 (17)°. The 4-chloro-5-(di-methyl-amino)-pyridazin-3(2H)-one group is linked to the oxa-diazole ring by a methyl-ene bridge, and the dihedral angle between the pyridazine and oxa-diazole rings is 88.66 (14)°. In the crystal, C-H⋯O and C-H⋯N hydrogen bonds extend the structure into a three-dimensional network.


Protective role of collaterals in patients with coronary artery occlusion.
We reviewed the clinical, hemodynamic and angiographic data of 105 patients with right coronary artery occlusion and 82 patients with left anterior descending coronary artery occlusion, subdivided into 3 groups by the presence and quality of collaterals to the occluded coronary (absent, poor or good collaterals). We found that patients with right coronary artery occlusion and good collaterals had a lower frequency of diaphragmatic myocardial infarction (60%) than patients with absent collaterals (100%) (P less than 0.01). In addition, in patients with old diaphragmatic myocardial infarction, both poor and good collaterals were associated with a lower frequency of severe asynergy of the diaphragmatic left ventricular segments at left ventriculography (54% and 14%, respectively), compared to patients with no collaterals to the right coronary artery (92%, P less than 0.02 vs. poor collaterals, P less than 0.001 vs. good collaterals). In contrast, in patients with left anterior descending coronary artery occlusion, the presence of either poor or good collaterals to the left anterior descending coronary artery was not associated with a lower frequency of old anterior myocardial infarction, or, in patients with old anterior myocardial infarction, with a less severe asynergy of the anterior left ventricular segments. Our results suggest that collaterals are effective in protecting the diaphragmatic left ventricular wall in patients with right coronary artery occlusion, but not the anterior left ventricular wall in patients with left anterior descending coronary artery occlusion.


Chronic abdominal pain caused by heterotopic ossification with functioning bone marrow: a case report and review of the literature.
Heterotopic ossification is rarely seen after midline abdominal surgery. The etiology of heterotopic ossification is unknown. Although it is well recognized that heterotopic ossification may contain osteogenic cells and/or hematopoietic cells, to our knowledge, no case has ever been reported to have histologic evidence of hematopoiesis. We report the occurrence of heterotopic bone with bone marrow showing normal trilineage hematopoiesis in the incision scar of a woman who underwent gastric reduction surgery for the treatment of obesity. The literature regarding heterotopic ossification and extramedullary hematopoiesis is reviewed in this report, and discussion focuses on the mechanism of this pathophysiologic process.


Changes of visual evoked potential induced by lateral geniculate nucleus kindling in rats.
The present study was undertaken to investigate the changes of visual evoked potential (VEP) induced by lateral geniculate nucleus (LGN) kindling in comparison with those induced by amygdala (AMG) and hippocampus (HPC) kindling in rats. Under pentobarbital anesthesia, the rats were fixed to a stereotaxic apparatus, and stainless steel electrodes were implanted into the LGN, AMG, HPC and the occipital cortex (OCOR). Bipolar stimulation was applied to the LGN, AMG or HPC every day until generalized seizure was obtained. VEP was recorded from the OCOR before the first day of electric stimulation (pre-kindled) and after the development of kindling (post-kindled). After the development of LGN kindling, the amplitudes of early VEP components (P(1)-N(1) and N(1)-P(2)) were significantly augmented in comparison with those of pre-kindled rats. In addition, the duration of the photically evoked after-discharge burst (duration of VEP) was significantly prolonged by LGN kindling. On the other hand, in AMG and HPC kindling, no significant changes were observed in VEP between pre-kindled and post-kindled rats. The changes of VEP observed in patients with photosensitive epilepsy are also demonstrated in animal study using LGN kindling.


Evaluation of in vitro tests to assess the efficacy of formulations as topical skin protectants against organophosphorus compounds.
Prevention of exposure to the neurotoxic organophosphorus compounds (OP) is a major concern both for pesticide users and soldiers. Skin barrier creams are being developed to complement or replace uncomfortable chemical protective suits. Quick evaluation of formulations efficacy mainly relies on in vitro tests which lead to consistent, complementary and relevant results. The objectives of this work were to determine the consistency of results from in vitro tests and importance of the formulation composition in the skin protective efficacy. The efficacy of three formulations, i.e. oil-in-water and water-in-oil emulsions and perfluorinated compounds-based cream, was evaluated against the OP paraoxon in vitro. Our results indicated that the least effective formulations could be quickly identified by performing in vitro permeation tests with silicone membrane and by evaluating interfacial interactions between formulations and OP. Among the tested formulations, the perfluorinated compounds-based cream could have a broader spectrum of efficacy than emulsions against OP and other toxic chemicals.


Human triacylglycerol-rich lipoprotein subfractions as substrates for lipoprotein lipase.
In order to test the hypothesis that lipoprotein lipase (LPL) acts preferentially on larger lipoprotein particles, we determined the susceptibility of triacylglycerol-rich lipoprotein (TRL) subfractions to hydrolysis by LPL in vitro. Chylomicrons (Sf > 400), very low density lipoproteins (VLDL)1 (Sf 60-400) and VLDL2 (Sf 20-60) were isolated from six subjects with a range of plasma-triacylglycerol (TAG) concentrations following an overnight fast and for up to 6 h after the consumption of a mixed meal (41% fat). The percent of TRL-TAG hydrolysed by LPL in subfractions isolated following overnight fast was VLDL1 > VLDL2 (46.8 +/- 10.2 vs. 25.9 +/- 7.4%, P = 0.006) and 3 h after the meal it was chylomicrons > VLDL1 > VLDL2 (81.0 +/- 12.6 vs. 52.8 +/- 10.2 vs. 27.7 +/- 6.2%, chylomicrons vs. VLDL1 and VLDL1 vs. VLDL2, both P < or = 0.005). The percent of VLDL1-TAG hydrolysed increased both within and between subjects as VLDL1-TAG concentrations increased. This relationship could be explained by the positive correlation observed between VLDL1-TAG and VLDL1-TAG:apolipoprotein B. In conclusion, increasing the size and TAG content of a lipoprotein particle increases its susceptibility to hydrolysis by LPL.


Neural mechanisms affecting pressor responses to angiotensins in the Pekin duck, Anas platyrhynchos.
1. Administration of SQ20881 diminished pressor responses to intravenous (i.v.) injections of angiotensin I (AI), but not those to injections of angiotensin II (AII), in Pekin ducks, indicating the occurrence of a mechanism similar to the mammalian angiotensin-converting enzyme reaction. 2. Pressor responses to AII were enhanced by general anaesthesia with phenobarbital, pentobarbital, or a combination of both phenobarbital and pentobarbital. 3. Ganglionic blockade with mecamylamine enhanced the pressor responses to AII and NE, but not those to tyramine, in anaesthetized ducks. 4. It is proposed that the potentiating effects of general anaesthesia and ganglionic blockade on pressor responses were due both to a lowering of baseline blood pressure (BP) and an inhibition of the neural reflexes which normally buffer BP. Furthermore, it is suggested that the augmented responsiveness of anaesthetized, ganglion-blocked ducks shows that the pressor effect of AII is predominantly of peripheral, rather than central nervous system (CNS), origin.


A Deletion Downstream of the CHCHD7 Gene Is Associated with Growth Traits in Sheep.
In sheep, the coiled-coil-helix-coiled-coil-helix domain containing 7 (CHCHD7) gene and the pleiomorphic adenoma gene 1 (PLAG1) are on the same growth-related major quantitative trait locus, positioned head-to-head approximately 420 bp apart on chromosome 9. PLAG1 affects sheep growth, but the effects of CHCHD7 have not been determined. In this study, an 8-bp deletion downstream of CHCHD7 was analyzed in 2350 sheep from seven breeds. The associations between the deletion and growth traits of Tan sheep were also determined. Both genotypes (homozygous wild-type and heterozygous) for the 8-bp deletion were found in Tan (TS), Luxi Blackhead (LXBH), Small-Tail Han (STHS), and Lanzhou Fat-Tail (LFTS) sheep. However, there were no polymorphic sites for the mutation in Hu (HS), Sartuul (SS), and Australian White (AUW) sheep. In TS, LXBH, STHS, and LFTS sheep, the deletion genotype was less frequent than the wild-type genotype, and the allele frequencies of the deletion variant were 0.007 (TS), 0.011 (LBXH), 0.008 (STHS), and 0.010 (LFTS). The 8-bp deletion was significantly associated with body length (p = 0.032), chest depth (p = 0.015), and chest width (p = 0.047) in Tan sheep. Thus, the 8-bp deletion downstream of the CHCHD7 gene might be associated with growth and development traits of sheep.


Effective population size for culturally evolving traits.
Population size has long been considered an important driver of cultural diversity and complexity. Results from population genetics, however, demonstrate that in populations with complex demographic structure or mode of inheritance, it is not the census population size, N, but the effective size of a population, Ne, that determines important evolutionary parameters. Here, we examine the concept of effective population size for traits that evolve culturally, through processes of innovation and social learning. We use mathematical and computational modeling approaches to investigate how cultural Ne and levels of diversity depend on (1) the way traits are learned, (2) population connectedness, and (3) social network structure. We show that one-to-many and frequency-dependent transmission can temporally or permanently lower effective population size compared to census numbers. We caution that migration and cultural exchange can have counter-intuitive effects on Ne. Network density in random networks leaves Ne unchanged, scale-free networks tend to decrease and small-world networks tend to increase Ne compared to census numbers. For one-to-many transmission and different network structures, larger effective sizes are closely associated with higher cultural diversity. For connectedness, however, even small amounts of migration and cultural exchange result in high diversity independently of Ne. Extending previous work, our results highlight the importance of carefully defining effective population size for cultural systems and show that inferring Ne requires detailed knowledge about underlying cultural and demographic processes.


Evaluation of effects of ultrasound-assisted curing on the flavor of Chinese bacon.
The curing stage is of great importance in flavor formation during Chinese bacon processing. Ultrasound-assisted curing plays an essential role in the Lipid oxidation of meat products. In this study, GC-MS and electronic nose were used to analyze the influence of different power ultrasonic-assisted curing on the flavor formation of Chinese bacon. Through the analysis of phospholipid and lipase, the fundamental precursors of ultrasonic on the flavor of Chinese bacon were determined. It was found that there were differences in the flavor contour description of Chinese bacon between the ultrasonic treatment group, mainly due to the change in the W1W sensor. A total of 28 volatile compounds were detected by GC-MS, and the aldehyde content increased with ultrasonic power. PC and PE are the main flavor precursors in the curing process. This study provides a theoretical basis for improving the curing technology of Chinese bacon.


Post-operative re-irradiation with hyperthermia in locoregional breast cancer recurrence: Temperature matters.
To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia. In this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4-5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into 'low' (n = 56) and 'high' TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 °C (Best CEM43T50) < 7.2 min and ≥7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed. TD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1-107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2-60.2), lymph node involvement (HR 2.9; 95%CI 1.2-7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8-11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4-11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018). High thermal dose (best CEM43T50 ≥ 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity.


Hyperglycemia raises the threshold of levosimendan- but not milrinone-induced postconditioning in rat hearts.
The authors examined whether milrinone and levosimendan could exert cardiac postconditioning effects in rats under normoglycemia and hyperglycemia, and whether the effects could be mediated by mitochondrial permeability transition pore (mPTP). Wistar rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received milrinone or levosimendan just before reperfusion under normoglycemic or hyperglycemic conditions with or without atractyloside, an mPTP opener. Under normoglycemia, both 30 μg/kg milrinone (29 ± 12%) and 10 μg/kg levosimendan (33 ± 13%) reduced infarct size compared with that in the control (58 ± 7%). Under hyperglycemia, milrinone (34 ± 13%) reduced infarct size at the same dose as under normoglycemia. In contrast, neither 10 nor 30 μg/kg levosimendan protected hyperglycemic hearts, and only 100 μg/kg levosimendan (32 ± 9%) reduced infarct size compared with that in the hyperglycemic control (58 ± 13%). All of these cardioprotective effects under normoglycemia and hyperglycemia are abolished by atractyloside. Milrinone and levosimendan exert postconditioning effects via inhibition of mPTP opening. Hyperglycemia raises the threshold of levosimendan-induced postconditioning, while milrinone-induced postconditioning is not influenced by hyperglycemia.


Antibiotics use and risk of colorectal neoplasia: An updated meta-analysis.
Accumulating evidence indicate that antibiotic use could induce microbiome dysbiosis, which was a critical driver to the onset and progression of colorectal cancer (CRC). But the relationship between antibiotics use and CRC was still disputed. Hence, we conducted this systematic review and meta-analysis to appraise and synthesize the present available evidence to clarify the association. PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for relevant observational studies from inception to June 5, 2020. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to explore the association between antibiotics use and CRC using random-effects model. Subgroup analyses, sensitive analyses, and publication bias were conducted to assess the robust reliability of pooled results. A total of 15 observational studies containing 5,164,138 patients were included in this meta-analysis. The pooled analysis indicated that the total antibiotic use was correlated with increased risk of CRC (OR, 1.11; 95% CI, 1.05-1.18). The subgroup analyses suggested that antibiotic use significantly elevated risk of colon cancer, but not rectal cancer. Furthermore, we found that penicillin, cephalosporin, anti-anaerobic, and anti-aerobic antibiotics increased the risk of CRC, in particular metronidazole but no significant associations were identified in macrolide, tetracycline, sulfonamides, nitrofurans, and quinolone use. The results of sensitive analyses and publication bias indicated the conclusions were robust. The findings showed that antibiotics use may be associated with the onset of CRC. Policy-makers and clinicians should adequately assess possible benefits and harms of antibiotics use, especially in some high-risk populations. Also, for high-risk patients with previous antibiotics use, it was suggested to perform early colonoscopy screening to find or even eliminate early-stage CRC.


Cardiac effects of halofantrine in children suffering from acute uncomplicated falciparum malaria.
The cardiac effects of halofantrine were assessed in 42 children with acute symptomatic uncomplicated Plasmodium falciparum malaria by electrocardiographic (ECG) and clinical monitoring over a period of 14 d. The children were treated with oral halofantrine 8 mg/kg body weight every 6 h for 3 doses. There was significant prolongation of the P-R interval (compared with the pre-treatment value) only at 8 h after drug administration. However, first degree auriculoventricular (AV) block occurred in 2 children at 8 h or 8 and 48 h, and second degree AV block in another child at 48 h. There was significant prolongation of the Q-Tc interval at 8, 16, 24, 48 and 72 h after treatment; the proportions of children with Q-Tc interval > 0.44 s were also significantly higher at all these times except 72 h. Rhythm disturbance was rare. There was no significant ECG change at 168 or 336 h. Despite the ECG abnormalities, there was no clinical symptom. These findings indicate that, in children, the currently recommended dose of halofantrine for the treatment of falciparum malaria may produce serious cardiac side effects.


Iris ischaemic changes and visual outcome after acute primary angle closure.
Ischaemic changes in the iris occur frequently after an episode of acute primary angle closure (APAC). The aim of this study was to investigate the significance of such changes with regards to visual outcome. Acute primary angle closure cases were treated with medical therapy followed by laser peripheral iridotomy after resolution of the acute episode. Subjects were examined at 1, 4, 8, 12 and 16 weeks post laser peripheral iridotomy. Eyes were examined for signs of iris ischaemic changes (IIC), defined as the presence of iris whorling or stromal atrophy. Iris photographs were also taken at weeks 1, 8 and 16. Subjects requiring glaucoma medication or filtering surgery during the follow-up period were excluded. The visual acuity and visual field (using automated white-on-white threshold perimetry) at week 16 were used in the assessment of visual outcome. Sixty-one subjects with APAC completed the study. The majority of subjects were female (82%) and Chinese (92%), and the mean age was 59 +/- 8.8 years. More than half the subjects (52.5%) were found to have developed IIC during the study, 65% of whom already had signs of IIC by the first week. Only 13 subjects (41%) with IIC and 6 subjects (21%) without IIC had an abnormal visual field defect at week 16 (P = 0.09). There was also no difference in visual acuity at week 16, the majority of subjects in both groups having visual acuity of 6/12 or better. The development of iris ischaemic changes after a single episode of APAC may not be associated with an adverse visual outcome.


The indirect nature of interaction of glucose transport with the system transporting galactosides.
The membrane transport systems for galactosides and glucose derivatives interact in enteric microorganisms. Stop-flow experiments with a double wavelength spectrophotometer and a flow-through cuvette (designed to minimize light-scattering effects) were used to measure the speed of interaction in Escherichia coli. The in vivo hydrolysis of ortho-nitrophenol-beta-D-galactopyranoside was measured by comparing the light transmitted by cell suspensions at 420 nm with that at 500 nm. Measurements at the latter wavelength corrected for residual scattering effects. The stop-flow experiment allowed the study of the early kinetics of transport and hydrolysis. It was found with strain ML308 that there was a significant lag in the achievement of steady-state inhibition by glucose and its derivative methyl-alpha-D-glucopyranoside (alpha MG). This strain constitutively produces high levels of permease and beta-galactosidase. The absorbancy increases at 420 nm are limited by transport because the beta-galactosidase is present inside the cells in excess. From earlier results, it was not surprising that inhibition is delayed with low concentrations of the glucose compounds, but the new double wavelength technique showed no kinetic component of rapid inhibition. This result therefore excludes competition for some membrane-bound component and is consistent with the production of the dephosphorylated form of the soluble Enzyme IIIglu that binds and inhibits the permease system in the membrane.


A pseudoencephalitis presentation of a pediatric non-intentional intoxication.
We report a case of a pseudo encephalitis presentation of pediatric intoxication - Case report - a 7 year-old girl was admitted to our pediatric emergency unit after she developed sudden agitation, visual and tactile hallucinations. She was febrile (38.3 °C). She had not experienced any recent head trauma, infection or toxic ingestion; she did not take any medication for ADD. Her physical exam revealed tachycardia, normal pupils, reflexes and normal plantar responses. Laboratory investigations (complete blood count, basic metabolic panel, plasma lactate level, ammonia level) produced normal results. Lumbar puncture and computed tomography of the brain were normal. A serum and urine drug screening (benzodiazepines, barbiturates, cocaine, cannabis, amphetamines, methadone, ethanol) was negative. An electroencephalogram, performed during an episode of hallucinations, was compatible with benzodiazepine intoxication. A larger toxic detection by liquid chromatography/diode array detector (LC-DAD) detected promethazine and its metabolites. Symptoms lasted 20 h and she finally said she drank syrup from an over-the-counter cough suppressant medication. Comments - Anticholinergic syndrome is not well recognized or evoked in children presenting hallucinations. Promethazine is still present in several over-the-counter medications, alone or in combination with acetaminophen, carbocisteine or opiates. Medications containing promethazine should not be prescribed in children. Such intoxication can mimic encephalitis.


Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY).
To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies. Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3-6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5' noncoding region, detecting essentially all enterovirus serotypes. Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical type 1 diabetes in the sample interval following detection of enteroviral RNA in serum (three diabetes cases diagnosed among 17 intervals) was significantly increased compared with that in intervals following a negative serum enteroviral RNA test (33 cases diagnosed among 1,064 intervals; hazard ratio 7.02 [95% CI 1.95-25.3] after adjusting for number of autoantibodies). Results remained significant after adjustment for ZnT8-autoantibodies and after restriction to various subgroups. Enteroviral RNA in rectal swabs was not predictive of progression to type 1 diabetes. No evidence for viral persistence was found. This novel observation suggests that progression from islet autoimmunity to type 1 diabetes may increase after an enterovirus infection characterized by the presence of viral RNA in blood.


Concurrent Use of Thyroid Hormone Therapy and Interfering Medications in Older US Veterans.
Thyroid hormone management in older adults is complicated by comorbidities and polypharmacy. Determine the prevalence of concurrent use of thyroid hormone and medications that can interfere with thyroid hormone metabolism (amiodarone, prednisone, prednisolone, carbamazepine, phenytoin, phenobarbital, tamoxifen), and patient characteristics associated with this practice. Retrospective cohort study between 2004 and 2017 (median follow-up, 56 months). Veterans Health Administration Corporate Data Warehouse. A total of 538 137 adults ≥ 65 years prescribed thyroid hormone therapy during the study period. Concurrent use of thyroid hormone and medications interfering with thyroid hormone metabolism. Overall, 168 878 (31.4%) patients were on at least 1 interfering medication while on thyroid hormone during the study period. In multivariable analyses, Black/African-American race (odds ratio [OR], 1.25; 95% CI, 1.21-1.28, compared with White), Hispanic ethnicity (OR, 1.12; 95% CI, 1.09-1.15, compared with non-Hispanic), female (OR, 1.11; 95% CI, 1.08-1.15, compared with male), and presence of comorbidities (eg, Charlson/Deyo Comorbidity Score ≥ 2; OR, 2.50; 95% CI, 2.45-2.54, compared with 0) were more likely to be associated with concurrent use of thyroid hormone and interfering medications. Older age (eg, ≥ 85 years; OR, 0.48; 95% CI, 0.47-0.48, compared with age 65-74 years) was less likely to be associated with this practice. Almost one-third of older adults on thyroid hormone were on medications known to interfere with thyroid hormone metabolism. Our findings highlight the complexity of thyroid hormone management in older adults, especially in women and minorities.


Chin Advancement, Augmentation, and Reduction as Adjuncts to Rhinoplasty.
Chin deformities are commonly encountered defects in patients seeking rhinoplasty. Careful preoperative evaluation may identify patients who could benefit from concurrent augmentation or reduction mentoplasty. Alloplastic chin implants and sliding genioplasty represent the main accepted methods of chin augmentation. Although both procedures may be used for retrognathia or microgenia, the sliding genioplasty may also be used in chin asymmetry, prognathia, and vertical height discrepancies. This article outlines the methods to analyze the chin, and discusses the treatment options available for correction of chin deformities as an adjunct to rhinoplasty.


[Outpatient psychiatric and substance abuse help in the Republic of Ingushetia].
Psychiatric service regards the "Home hospital" model as one of the optimal methods for organization of therapeutic and prophylactic work under present-day day socio-economic conditions and migration processes in the Republic. Prospects for further development of this model are outlined.


Safety and tolerability of a 90-minute rapid infusion of Sandoz biosimilar rituximab in B-cell lymphoproliferative disorders in a real-world setting.
Although rituximab is generally well-tolerated, infusion-related reactions (IRRs) are common with the initial dose when administered intravenously according to standard recommendations. To prevent IRRs, premedication and low-speed infusion rates have been recommended. Consequently, intravenous (i.v.) infusion of rituximab can become a labor-intensive process. Rapid i.v. rituximab infusion over 90 min has demonstrated a favorable safety profile for the second and subsequent infusions during the course of therapy. The aim of this study was to investigate the safety and tolerability of 90-min rapid infusion of Sandoz rituximab biosimilar (SDZ-RTX) for patients with CD20+ lymphoma or chronic lymphocytic leukemia (CLL). We retrospectively reviewed all patients with CD20+ lymphoma or CLL who received SDZ-RTX infusions in 90 min from July 2019 to July 2021 at seven Spanish hospitals. The primary end point was the incidence of IRRs. We identified 124 patients and 576 rapid administrations of SDZ-RTX, with an average of five rapid infusions per patient. Most rapid infusions of SDZ-RTX were in combination with CHOP/CHOP-like therapy (48.4%), followed by SDZ-RTX alone (15.1%), in combination with bendamustine (14.5%), or with other regimens (22%). The 90-min SDZ-RTX infusion schedule was well-tolerated with no grade 3/4 IRRs. The incidence of any grade IRR during the first rapid infusion was 1% (5 grade 1 IRRs and 1 grade 2 IRR). In conclusion, rapid 90-min i.v. administration of SDZ-RTX for the second and subsequent infusions during the course of therapy is well-tolerated in patients with CD20+ lymphoma or CLL.


Treatment of hypoxemia during one-lung ventilation using intravenous almitrine.
We performed this prospective randomized double-blinded study to assess the ability of almitrine to treat hypoxemia during one-lung ventilation (OLV). Twenty-eight patients were anesthetized with propofol, sufentanil, and atracurium; lung separation was achieved with a double-lumen tube. A transesophageal Doppler probe was inserted to evaluate cardiac index. If SpO(2) was equal to or decreased to <95% during OLV (inspired fraction of oxygen of 0.6), patients were included in the study and received a placebo or almitrine (12 microg x kg(-1) x min(-1) for 10 min followed by 4 microg x kg(-1) x min(-1)) infusion until SpO(2) reached 90% or decreased to <90% (exclusion from the study). Eighteen of the 28 patients were included and received either almitrine (n = 9) or a placebo (n = 9). Treatment was discontinued in 1 patient in the almitrine group and 6 in the placebo group (P < 0.05). Treatment was successful (SpO(2) remaining >or=95% during OLV) in 8 patients in the almitrine group and 1 in the placebo group (P < 0.01). Heart rate, arterial blood pressure, and cardiac index did not change throughout the study, but we could obtain an adequate aortic blood flow signal in only half of the patients. Almitrine could be used to treat hypoxemia during OLV. IV almitrine improves oxygenation during one-lung ventilation without hemodynamic modification. Such treatment could be used when conventional ventilatory strategy fails to treat hypoxemia or cannot be used.


R,R,R-alpha-tocopherol potentiates prostacyclin release in human endothelial cells. Evidence for structural specificity of the tocopherol molecule.
Human umbilical vein endothelial cells (HUVEC) in culture synthesize prostacyclin (PGI2) as the predominant metabolite of arachidonic acid which is derived from the deacylation of phospholipids. Under basal-unstimulated condition, PGI2 release from HUVEC is extremely low; however, when endothelial monolayers were preincubated with the natural vitamin E (R,R,R-alpha-tocopherol), we found a dose-dependent potentiation of basal PGI2 release. When HUVEC were stimulated with arachidonate or ionophore A23187, there was a dose-dependent increase of PGI2 release in response to tocopherol enrichment. When HUVEC were labelled with [Me-3H]choline followed by A23187 stimulation, a significantly higher lysophosphatidylcholine was found in the tocopherol-enriched cells, suggesting a change in enzymes involved in phosphatidylcholine metabolism. Analysis of these enzymes revealed that phospholipase A2 activity was enhanced by tocopherol enrichment, whereas lysophospholipase and acyl-CoA acyltransferase were unaffected. To determine the specificity of the tocopherol molecule, different analogues were tested for their PGI2 potentiating activity. Results showed that the free hydroxyl group on the chromanol ring as well as the phytyl side-chain are absolutely required to stimulate PGI2 release, whereas, different methyl locations and substituents on the chromanol ring had no effect. These studies demonstrated that tocopherol potentiates basal PGI2 release in HUVEC and in contrast to its reported inhibitory role in rat platelets, myocardium and neutrophils, tocopherol stimulates phospholipase activity in HUVEC.


Bibliometric data based on the Pharm.D. and Ph.D. degree in United States research-intensive colleges of pharmacy.
The objective of this work was to compare bibliometrics based on doctoral degrees within United States colleges of pharmacy to understand productivity differences. Secondary objectives were to provide quantitative data based on degree that could be utilized by individual faculty, administration and other key stakeholders in academic pharmacy. Bibliometric indices were obtained from Scopus and Web of Science for faculty from research-intensive United States pharmacy schools. Scholarly metrics that included publication number, total citations, highest cited article and H-index were compared between degrees using multivariate regression adjusted for academic rank and years since first publication. A correction for multiple testing was applied. All collected scholarly metrics were higher for Ph.D.-only and Pharm.D./Ph.D. faculty when compared to Pharm.D.-only faculty. Ph.D.-only faculty significantly differed compared to Pharm.D./Ph.D. faculty for Web of Science average citations per document. Differences are apparent between the major doctoral degrees at research-intensive, federally funded colleges of pharmacy; however, these differences were primarily identified for Pharm.D.-only compared to the other doctoral degree types Future work should analyse the potential variables that explain the scholarly metrics differences between degrees and aim to analyse other areas of faculty impact beyond scholarly metrics.


Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation.
CD4+ T cells specific for the diabetes-associated autoantigen GAD65 were analyzed using peripheral blood samples after pancreas transplantation in subjects with T1D with clinical evidence of recurrent autoimmune diabetes. MHC class II tetramers facilitated the identification and cloning of antigen-specific autoreactive cells, which were found at several time points over a multiyear span, in spite of chronic immunosuppression of the subjects. Comparisons of TCR clonotypes by cDNA sequencing revealed that identical T cells were present in the circulation, separated by long time intervals, consistent with a persistent memory response associated with recurrent autoimmunity.


Targeted Mutagenesis of Mycobacterium Strains by Homologous Recombination.
Targeted mutagenesis by homologous recombination (TMHR) is an efficient allelic exchange mutagenesis for bacterial genome engineering in synthetic biology. Unlike other allelic exchange methods, TMHR does not require a heterologous recombinase to insert or excise a selectable marker from the genome. In contrast, positive and negative selection is achieved solely by suicide vector-encoded functional and host cell proteins. Here we describe a concise protocol to knock out and knock in a 3-ketosteroid-1,2-dehydrogenase gene (kstd) in Mycobacterium neoaurum HGMS2 using TMHR approach. The homology arms flanking the kstd gene are amplified by PCR in vitro and then subcloned into a common homologous recombination vector. The vector is then electroporated into the HGMS2 competent cells. The replacement of the kstd gene by homologous recombination produces antibiotic-resistant single-crossover recombination via the first allelic exchange. Double-crossover markerless mutants are directly separated using sucrose-mediated counterselection. These two steps can generate seamless mutations down to a single DNA base pair. The whole process takes less than 2 weeks.


Driveway crush injuries in young children: a highly lethal, devastating, and potentially preventable event.
The aim of this study was to investigate driveway-related injuries in children, identify associated risk factors, and evaluate outcome compared with other mechanisms of blunt trauma. A 6-year review (1991 to 1996) of pediatric (age less than 18 years) pedestrian injuries treated at two urban trauma centers was conducted: one regional pediatric trauma center and one level I trauma center with pediatric commitment. Five hundred twenty-seven children injured in pedestrian accidents were identified from the trauma registry; 51 children (10%) sustained traumatic injuries as a result of being struck in their driveway. Data are reported as mean +/- SEM. Children less than 5 years of age (n = 41) had an injury severity score (ISS) of 12.3+/-2.3, 15 (37%) sustained closed head injury, 13 (37%) had torso trauma, 19 (46%) skeletal trauma, and eight (20%) died. Children > or = 5 years old (n = 10) had an ISS of 10.7+/-2.4, three (30%) sustained closed head injury, four (40%) torso trauma, six (60%) skeletal trauma, and none died. In contrast, all other pediatric pedestrian accidents analyzed over the same time period had a mortality rate of only 2% (11 of 476). Pediatric driveway trauma carries a significant risk of head injury and a 10-fold increase in mortality in children under 5 years of age when compared with all other pediatric pedestrian accidents. More emphasis must be placed on injury prevention and public education to prevent this devastating mechanism of injury in these young, vulnerable children.


[Histological Study on Integumentary and Digestive System of Hirudo nipponica].
The integumentary and digestive system of Hirudo nipponica were studied,in order to protect the precious Chinese herbal medicine. The histological study of integumentary and digestive system of Hirudo nipponica by histological methods were carried out by microscopical method. The body wall of Hirudo nipponica could be divided into five layers, including cuticular layer, epithelial layer, dermis layer, muscle layer and grape-like tissue. The digestive system was composed ofmouth,pharyngeal,esophagus,crop,intestine,rectum and anus. This study can provide the basic data for the artificial breeding, research in pathology and physiological functions of Hirudo nipponica.


Cancer mortality among relatives of children with soft-tissue sarcoma: a national survey in Italy.
Information was obtained on the living status or cause of death of 2223 close relatives of 195 children with soft-tissue sarcomas (STS) diagnosed under age 15. Three-hundred nine relatives had died, from all causes, before STS diagnosis in the index child. The expected figure estimated from age- and sex-specific mortality rates in Italy was 293.3. Cancer was reported as cause of death in 76 relatives (75.1 expected). Seven grandmothers, 2 aunts, 1 uncle and 0 mothers died from breast cancer vs. 4.6, 0.9, 0.0 and 0.2 expected. Three siblings died from cancer (0.2 expected, P less than 0.01), i.e. STS, ependymoma and non-Hodgkin lymphoma. These results confirm and expand previous observations that STS in children are associated with other cancers, particularly childhood and breast cancer, in members of the same family.


The mouse as a model for neuropsychiatric drug development.
Much has been written about the validity of mice as a preclinical model for brain disorders. Critics cite numerous examples of apparently effective treatments in mouse models that failed in human clinical trials, raising the possibility that the two species' neurobiological differences could explain the high translational failure rate in psychiatry and neurology (neuropsychiatry). However, every stage of translation is plagued by complex problems unrelated to neurobiological conservation. Therefore, although these case studies are intriguing, they cannot alone determine whether these differences observed account for translation failures. Our analysis of the literature indicates that most neuropsychiatric treatments used in humans are at least partially effective in mouse models, suggesting that neurobiological differences are unlikely to be the main cause of neuropsychiatric translation failures.


Increased expression of T cell immunoglobulin- and mucin domain-containing molecule-3 on natural killer cells in atherogenesis.
Atherosclerosis (AS) has many features of a chronic inflammatory disease in which both adaptive and innate immune cells play roles. Increasing evidence has demonstrated the impairment of circulating natural killer (NK) cells in atherosclerosis. However, the mechanisms of this impairment remain unclear. We previously reported the suppression of NK cell functions by T cell immunoglobulin- and mucin domain-containing molecule (Tim)-3. Here, we investigated the expression of Tim-3 on NK cells and assessed its possible roles in NK loss during atherogenesis. Flow cytometry analysis showed increased Tim-3 expression on peripheral NK cells from patients with AS. This increased expression of Tim-3 was significantly related to the levels of serum lipids and inflammation markers, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α, which are risk factors for atherogenesis. We detected decreased peripheral NK cell number in patients with AS. The NK cell number showed significant inverse correlations with Tim-3 expression levels on NK cells and the level of serum TNF-α. Consistently, Tim-3 overexpression reduced NK92 cell number. Blockade of Tim-3 protected NK92 cells from TNF-α-induced cell death. Similar results were obtained with peripheral NK cells from patients with AS. To the best of our knowledge, for the first time, the data from our study provide evidence that augmented Tim-3 expression on NK cells plays an important role in NK cell loss in atherosclerosis. The augmented Tim-3 expression on NK cells might be used as an indicator for disease progression.


Electrophysiological study of the excitatory parafascicular projection to the subthalamic nucleus and evidence for ipsi- and contralateral controls.
The activity of subthalamic neurons was recorded extracellularly in anaesthetized rats after stimulation, inhibition or lesioning of the parafascicular nucleus. Electrical stimulation of the parafascicular nucleus evoked a complex response with two excitatory phases. The first response was correlated with a monosynaptically-driven excitation via a parafascicular input to the subthalamic nucleus. Since the second phase was observed even when the early excitation was not recorded and was eliminated by lesion of the globus pallidus, we suggest that it is not generated by a mechanism intrinsic to the subthalamic nucleus and is due to a disinhibitory effect originating from the globus pallidus. Microinjection of carbachol into the parafascicular nucleus enhanced by 119% the discharge rate of the neurons in the ipsilateral subthalamic nucleus and that of muscimol decreased the discharge rate by 91%. Opposite changes, a decrease of the discharge rate of 49% after microinjection of carbachol and an increase of 47% after muscimol, occurred in the contralateral subthalamic nucleus. In contrast to the above results, the unilateral excitotoxic lesion of the parafascicular nucleus, performed one week before recording, decreased the discharge rate by 69% of the ipsilateral subthalamic nucleus neurons and by 34% that of the contralateral neurons. We suggest that the parafascicular input to the subthalamic nucleus is an excitatory pathway which can tonically drive the neuronal activity in this structure. The opposite changes recorded in the ipsi- and contralateral subthalamic nucleus during unilateral microinjection of excitatory or inhibitory drugs in the parafascicular nucleus emphasize the importance of this thalamic structure in the bilateral regulation of basal ganglia activity via the subthalamic nucleus.


Ileal penetration by a Multiload-Cu 375 intrauterine contraceptive device. A case report with review of the literature.
A case of a 28-year-old gravida 3 para 2 woman with an ileal penetration by an intrauterine device (IUD) is reported. Four weeks following insertion of a Multiload-Cu 375, the woman underwent laparotomy due to persistent vague abdominal pain and translocation of the IUD. The device had perforated the fundal uterine wall and the two flexible side arms and the copper-bearing rod had completely eroded into the wall of the ileum with only the strings protruding outside the small bowel mesentery. Resection of an ileal segment with end-to-end anastomosis was performed. The woman made an uneventful recovery. It appears that a translocated Multiload-Cu 375 IUD body can penetrate and be entirely embedded within the bowel wall as early as 4 weeks following translocation. This report documents the shortest interval between insertion and proven bowel injury by an IUD.


Targeting the Parasite to Suppress Malaria Transmission.
This article attempts to draw together current knowledge on the biology of Plasmodium and experience gained from past control campaigns to interpret and guide current efforts to discover and develop exciting new strategies targeting the parasite with the objective of interrupting transmission. Particular note is made of the advantages of targeting often unappreciated small, yet vital, bottleneck populations to enhance both the impact and the useful lifetime of hard-won interventions. A case is made for the standardization of methods to measure transmission blockade to permit the rational comparison of how diverse interventions (drugs, vaccines, insecticides, Genetically Modified technologies) targeting disparate aspects of parasite biology may impact upon the commonly used parameter of parasite prevalence in the human population.


Coils and tubes releasing heparin. Studies on a new vascular graft prototype.
Coiled metallic guidewires find widespread use, for instance in interventional cardiology. It is known that release of heparin from the surface of guidewires is advantageous to prevent formation of thrombotic emboli. New coiled tubular structures, having larger inner and outer diameter as compared to guidewires, are presented. In theory these tubes can be used as interposition vascular grafts. Ten coiled tubes with an internal diameter of 690 microm were made. Five different adherent polymeric coatings with increasing hydrophilicity were used. Five tubes contained heparin in the coating and the other five were unheparinised controls. The five tubes containing heparin were studied with respect to heparin release in vitro (amount released, kinetics), and immobilised heparin that is exposed at the surface. All tubes were studied with a direct cell contact assay using 3T3 mouse fibroblast cells, a dynamic thrombin generation test, and endothelial cell growth onto the coils. It was found that the heparinised tubes lead to very little thrombin formation. It is argued that this is due to heparin that is immobilised and exposed at the inner surface of such tubes. Furthermore the coils showed to be cytocompatible and endothelial cells adhere and proliferate well onto the coils. This concept is believed to hold promise for further development of small vascular grafts.


Perinatal MSG treatment attenuates fasting-induced bradycardia and metabolic suppression.
We studied the effect of arcuate nucleus (ARC) lesions induced pharmacologically by the perinatal treatment of monosodium l-glutamate (MSG) on the cardiovascular, metabolic, and behavioral responses to fasting. Saline and MSG-treated male Sprague-Dawley rats were instrumented with telemetry devices for measurement of mean arterial pressure (MAP) and heart rate (HR) and housed in room calorimeters at an ambient temperature (T(a)) of 23 degrees C for assessment of oxygen consumption (VO(2)). At baseline, controls and MSG-treated rats had similar MAP (control=95+/-4; MSG=91+/-2 mmHg), HR (control=323+/-4; MSG=324+/-2 bpm), and VO(2) (control=8.7+/-0.3; MSG=8.6+/-0.2 ml/min). There were no differences in fasting-induced reductions in body weight or in food intake upon refeeding. MSG-treatment significantly attenuated fasting-induced reductions in HR and VO(2). This effect was specific to reduced caloric availability, as MSG-treated rats exhibited intact capacity to both increase and decrease HR and VO(2) in response to cold (T(a)=15 degrees C) and to thermoneutrality (T(a)=30 degrees C). Additional studies were performed in saline- and MSG-treated rats chronically treated with beta(1)-adrenergic receptor blockade (atenolol) prior to and during fasting. In controls, the cardiovascular responses to fasting during beta(1)-blockade were blunted and generally mimicked the effects of MSG-treatment, while beta(1)-blockade had no additional effect on MSG-treated rats. The results are consistent with the hypothesis that ARC neuronal signaling is requisite for intact homeostatic responses to fasting and may participate in fasting-induced withdrawal of cardiac sympathetic activity.


Regenerated keratin-encapsulated gold nanorods for chemo-photothermal synergistic therapy.
Gold nanorods (AuNRs) have been widely applied to photothermal therapy against cancer. However, the chemically synthesized AuNRs such as that via seed-mediate method usually demonstrated a high cytotoxicity due to the existence of cetyltrimethylammonium bromide (CTAB) coating. In this work, keratin, a family of cysteine-rich structural fibrous proteins was used for the first time to encapsulate AuNRs by a simple mixing method. Compared with CTAB-AuNRs, the keratin-encapsulated AuNRs (AuNRs@Kr) showed an improved colloid stability and good biocompatibility including low cytotoxicity and hemolytic effect. Moreover, AuNRs@Kr exhibited great potential as drug carriers with redox-responsive drug release behavior, due to the high concentration of disulfide crosslinking in keratin coating, and the DOX-loaded AuNRs@Kr demonstrated higher chemo-photothermal synergistic therapy efficiency against 4T1 cells compared with either free DOX or AuNRs@Kr alone, suggesting a promising nanoplatform for cancer therapy.


The safety and efficacy of intrathecal diamorphine.
One hundred and seventy-eight patients undergoing total hip replacement and 67 patients undergoing spinal surgery were given diamorphine intrathecally in varying doses. Doses in mg/kg were plotted against duration of analgesia and the absence of retention and emetic symptoms in each type of surgery. Analysis showed that these were not dose dependent within the therapeutic range of 0.005-0.015 mg/kg.


Insights into the contemporary management of heart failure in specialized multidisciplinary ambulatory clinics.
Heart failure (HF) clinics are associated with improved outcomes in randomized trials, however, there is substantial heterogeneity in the service models of HF clinics in practice. Our objective was to evaluate the effect of this clinic level heterogeneity on HF patient management in Ontario, Canada. Charts were abstracted from 9 HF clinics, chosen at random from the 34 HF clinics in operation in Ontario in 2011. From each clinic, approximately 100 patient charts were randomly selected for detailed abstraction on patient demographic characteristics, comorbidities, diagnostic tests, medication use, and referrals, over a 1-year period from the first clinic visit. Significant heterogeneity was observed in patient baseline profiles, pharmacological therapies, diagnostic testing, clinic personnel, and referrals across 9 clinics. The mean age of patients was 66.1 ± 15.7 years and was significantly different between the clinics. Most patients were male (65%), and mean left ventricular ejection fraction was 33%. There was significant variation in the utilization of echocardiography (42%-94%) and coronary angiography (19%-62%). Overall, approximately 88% of patients were prescribed angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, and 85% were prescribe β-blockers. The rates of referral to cardiac rehabilitation programs were overall low at 10.4% of patients, with substantial variation (1%-28%). Specialized HF clinics have wide variation in the health personnel involved and the care provided; in addition, patients treated at these HF clinics have important differences in clinical characteristics. Strategies should be considered at the appropriate level (eg, province-wide in Ontario) to standardize HF management and provide best evidence-based care to patients.


Mother-infant feeding interaction in full-term small-for-gestational-age infants.
Maternal and infant behavior during feeding was assessed in 30 mother-infant dyads: 15 small-for-gestational-age (SGA) infants (birth weights below the 10th percentile) and 15 appropriate-for-gestational-age (AGA) infants (birth weights between the 25th and 90th percentiles). The groups were balanced for gestational age, sex, neonatal risk factors, and maternal age, parity, socioeconomic status, and race. Behaviors indicative of infant feeding difficulties were coded for mother and infant. The SGA mothers had higher frequencies of these behaviors than did their AGA counterparts. Qualitative ratings of interactive behavior were recorded for mother and infant: SGA infants had ratings indicative of less optimal interactions than those of the AGA group. Infant caloric intake (calories per kilogram per feeding) was calculated by first dividing the change in infant weight in grams before feeding and immediately after feeding by the infant's weight before feeding and then converting it to calories. Although no difference in caloric intake was observed between the two groups, infant behaviors and ratings were associated with caloric intake. These data suggest the importance of including neonatal behavior during feeding in the risk assessment of potential growth failure in SGA infants.


PDE4D gene variants and haplotypes are associated with asthma and atopy in Brazilian children.
PDE4D (Phosphodiesterase 4D) gene encodes a hydrolase of cyclic AMP. PDE4D genetic variants have been associated with asthma susceptibility. Therefore, this study aimed to investigate the association between PDE4D variants (and haplotypes) with asthma and atopy in a Brazilian population. The study comprised 1,246 unrelated participants from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was performed using the Illumina 2.5 Human Omni bead chip. Multivariate logistic regression was used to investigate the association between PDE4D variants and asthma/atopy phenotypes in PLINK 1.09 software. Twenty-four SNVs in PDE4D were associated with atopy or asthma. The rs6898082 (A) variant increased asthma susceptibility (OR 2.76; CI 99% 1.26-6.03) and was also related to a greater PDE4D expression in the GTEx database. Also, the variant rs6870632 was further associated with asthma in meta-analysis with a replication cohort. In addition, the variants rs75699812 (C), rs8007656 (G), and rs958851 (T) were positively associated with atopy. Moreover, these variants formed an atopy risk haplotype (OR 1.82; CI 99% 1.15-2.88). Also, these variants were related to lower levels of IL-10. Functional in silico assessment showed that some PDE4D SNVs may have an impact on gene regulation and expression. Variants in the PDE4D are positively associated with asthma and allergy markers. It is possible that these variants lead to alteration in PDE4D expression and therefore impact immunity and pulmonary function.


Evaluation of the synergistic effect of chitosan metal ions (Cu2+/Co2+) in combination with antibiotics to counteract the effects on antibiotic resistant bacteria.
The effectiveness of antibiotics that save millions of lives is in danger due to the increasing rise of resistant bacteria around the world. We proposed chitosan-copper ions (CSNP-Cu2+) and chitosan-cobalt ion nanoparticles (CSNP-Co2+) as biodegradable nanoparticles loaded with metal ions synthesized via an ionic gelation method for treatment of antibiotic resistant bacteria. The nanoparticles were characterized using TEM, FT-IR, zeta potential and ICP-OES. The MIC was evaluated for the NPs in addition to evaluating the synergetic effect of the nanoparticles in combination with cefepime or penicillin for five different antibiotic resistant bacterial strains. In order to investigate the mode of action, MRSA, DSMZ 28766 and Escherichia coli E0157:H7 were selected for further evaluation of antibiotic resistant genes expression upon treatment with NPs. Finally, the cytotoxic activities were investigated using MCF7, HEPG2 and A549 and WI-38 cell lines. The results showed quasi spherical shape and mean particle size of 19.9 ± 5 nm, 21 ± 5 nm and 22.27 ± 5 for CSNP, CSNP-Cu2+ and CSNP-Co2+ respectively. FT-IR showed slight shifting of the hydroxyl and amine group's peaks of chitosan indicating the adsorption of metal ions. Both nanoparticles had antibacterial activity with MIC ranging between 125 and 62 μg ml-1 for the used standard bacterial strains. Moreover, the combination of each of the synthesized NP with either cefepime or penicillin not only showed a synergetic effect as antibacterial activity of each NP or antibiotics alone, but also decreased the fold of antibiotic resistance genes expression. The NPs showed potent cytotoxic activities for MCF-7, HepG2 and A549 cancer cell lines with lower cytotoxic values for the WI-38 normal cell line. The NPs' antibacterial activity may be due to penetration and rupture of the cell membrane and the outer membrane of Gram negative and Gram positive bacteria causing bacterial cell death, in addition to, penetration into the bacterial genes and blocking gene expression that is vital to bacterial growth. The fabricated nanoparticles can be an effective, affordable and biodegradable solution to challenge antibiotic resistant bacteria.


HSF4 regulates lens fiber cell differentiation by activating p53 and its downstream regulators.
Cataract refers to opacities of the lens that impede the passage of light. Mutations in heat shock transcription factor 4 (HSF4) have been associated with cataract; however, the mechanisms regarding how mutations in HSF4 cause cataract are still obscure. In this study, we generated an hsf4 knockout zebrafish model using TALEN technology. The mutant zebrafish developed an early-onset cataract with multiple developmental defects in lens. The epithelial cells of the lens were overproliferated, resulting in the overabundance of lens fiber cells in hsf4null zebrafish lens. Consequently, the arrangement of the lens fiber cells became more disordered and irregular with age. More importantly, the terminal differentiation of the lens fiber cell was interrupted as the organelles cannot be cleaved in due time. In the cultured human lens epithelial cells, HSF4 could stabilize and retain p53 in the nucleus to activate its target genes such as fas cell surface death receptor (Fas) and Bcl-2-associated X apoptosis regulator (Bax). In the hsf4null fish, both p53 and activated-caspase3 were significantly decreased. Combined with the finding that the denucleation defect could be partially rescued through microinjection of p53, fas and bax mRNA into the mutant embryos, we directly proved that HSF4 promotes lens fiber cell differentiation by activating p53 and its downstream regulators. The data we presented suggest that apoptosis-related genes are involved in the lens fiber cell differentiation. Our finding that HSF4 functions in the upstream to activate these genes highlighted the new regulatory modes of HSF4 in the terminal differentiation of lens fiber cell.


Microarray analysis of gene expression in olive flounder liver infected with viral haemorrhagic septicaemia virus (VHSV).
The most fatal viral pathogen in olive flounder Paralichthys olivaceus, is viral hemorrhagic septicemia virus, which afflicts over 48 species of freshwater and marine fish. Here, we performed gene expression profiling on transcripts isolated from VHSV-infected olive flounder livers using a 13 K cDNA microarray chip. A total of 1832 and 1647 genes were upregulated and down-regulated over two-fold, respectively, after infection. A variety of immune-related genes showing significant changes in gene expression were identified in upregulated genes through gene ontology annotation. These genes were grouped into categories such as antibacterial peptide, antigen-recognition and adhesion molecules, apoptosis, cytokine-related pathway, immune system, stress response, and transcription factor and regulatory factors. To verify the cDNA microarray data, we performed quantitative real-time PCR, and the results were similar to the microarray data. In conclusion, these results may be useful for the identification of specific genes or for the diagnosis of VHSV infection in flounder.


Blastocoel fluid removal and melatonin supplementation in the culture medium improve the viability of vitrified bovine embryos.
In this study, we investigated the effects of melatonin supplementation in the culture medium and blastocoel fluid removal (BFR) before vitrification on the quality and viability of in vitro-derived bovine embryos. After fertilization, presumptive zygotes were assigned to one of the following treatments: control, in vitro standard culture (IVC) medium; IVC + M10-9, IVC medium supplemented 10-9 M melatonin; or IVC + M10-9 BFR, IVC medium supplemented with 10-9 M melatonin plus BFR on day 7 (D7) of culture. D7 blastocysts were vitrified by the Cryotop method and, after 5 mo of storage, were warmed and incubated for an additional 72 h. The re-expansion rate was evaluated after 2 and 24 h, and the hatching rate was evaluated after 24, 48, and 72 h. At 72 h, the total number of cells (TNC); number of apoptotic cells (NAC); and expression of genes related to oxidative stress (HSPA5), cell metabolism (SLC2A3), cell repair (MSH6), placentation (KRT8 and PLAC8), and implantation (FOSL1) were assessed in the blastocysts. Less than 30% of the control blastocysts re-expanded until 2 h, whereas more than 85% of the IVC + M10-9 and IVC + M10-9 BFR blastocysts re-expanded (P < 0.05). The hatching rate of IVC + M10-9 BFR blastocysts increased at all time points (P < 0.05), reaching 66.8% at 72 h of incubation. The TNC was similar among treatments (P > 0.05), regardless of vitrification/warming and re-cultivation. The NAC:TNC was smaller for melatonin-treated blastocysts (P < 0.05). BFR increased HSPA5 (P = 0.0118) expression and did not affect SLC2A3, MSH6, KRT8, and FOSL1 expression (P > 0.05). In conclusion, melatonin (10-9 M) supplementation in the culture medium and BFR on D7 of culture increased the hatching rate 24, 48, and 72 h after warming of the vitrified embryos, indicating an improvement in cryotolerance.


Normal pace walking is beneficial to young participants' executive abilities.
Exercise can improve cognitive function. The impact of acute exercise on cognition is related to exercise intensity. This study aimed to explore whether normal walking had a beneficial effect on cognition. Compared with standing still, thirty healthy young men walked on a treadmill at a normal pace, and completed the Stroop test. Near-infrared spectroscopy was used to monitor the hemodynamic changes of the prefrontal cortex during the entire experiment. Studies showed that normal walking did not stimulate higher average cerebral oxygen in the PFC, but the peak cerebral oxygen in cognitive tests during walking was higher (Stroop Word: 2.56 ± 0.43 and 3.80 ± 0.50, P < 0.01, Stroop Color: 2.50 ± 0.37 and 3.66 ± 0.59, P < 0.05, Stroop Color-Word: 4.13 ± 0.55 and 5.25 ± 0.66, P < 0.01, respectively), and better results were achieved in the Stroop Color-Word test, which was reflected in faster reaction times (49.18 ± 1.68 s, 56.92 ± 2.29 s, respectively, P < 0.001) and higher accuracies (46.19 ± 0.69, 44.15 ± 0.91, respectively, P = 0.018). For healthy young people, even a normal walk is therefore good for cognition.


Biochemical aspect of HMG CoA reductase inhibitors.
Subsequent to the discovery of compactin (ML-236B) as a specific inhibitor of HMG CoA reductase, a series of compactin analogs have been either isolated or synthesized. Several of these compounds, which include compactin, mevinolin (monacolin K) and CS-514, have been extensively studied. The inhibition of HMG CoA reductase by these compounds is reversible and competitive (Ki = approximately 1 nM). The 3', 5'-dihydroxypentanoic acid portion of the acid form of compactin analogs, which resembles the HMG portion of HMG CoA, plays a crucial role in inhibitory activity. These inhibitors block sterol synthesis both in cultured mammalian cells and in animals. Strong inhibition of sterol synthesis results in a marked increase in HMG CoA reductase activity both in vitro and in vivo. These compounds strongly lower plasma LDL-cholesterol levels in animals and humans. The lowering of LDL-cholesterol levels occurs by an inhibition of LDL synthesis and/or by an elevation of the receptor-mediated LDL catabolism in the liver.


The kinetics of baculovirus adsorption to insect cells in suspension culture.
The influence of various culture parameters on the attachment of a recombinant baculovirus to suspended insect cells was examined under normal culture conditions. These parameters included cell density, multiplicity of infection, and composition of the cell growth medium. It was found that the fractional rate of virus attachment was independent of the multiplicity of infection but dependent on the cell density. A first order mathematical model was used to simulate the adsorption kinetics and predict the efficiency of virus attachment under the various culture conditions. This calculated efficiency of virus attachment was observed to decrease at high cell densities, which was attributed to cell clumping. It was also observed that virus attachment was more efficient in Sf900II serum free medium than it was in IPL-41 serum-supplemented medium. This effect was attributed to the protein in serum which may coat the cells and so inhibit adsorption. A general discussion relating the observations made in-these experiments to the kinetics of recombinant baculovirus adsorption to suspended insect cells is presented.


Chlamydia pneumoniae in vascular tissue.
This review summarizes the evidence for the presence of Chlamydia pneumoniae organisms in atherosclerotic lesions. A total of 17 publications are mentioned concerning this topic. In all but two, both from the same group, evidence is presented by means of various techniques for the existence of the organisms in atherosclerotic tissue. Thus, they have been found in the aorta and in coronary, carotid, pulmonary, femoral and iliac arteries. In the first study in the UK, the aorta, femoral and iliac arteries were found to be positive for C. pneumoniae. In a recent study on autopsy specimens undertaken in conjunction with South African investigators, 71% of atheromatous arteries were positive for C. pneumoniae compared with only 9% of non-atheromatous arteries. Interestingly, the organisms were detected in 67% of the vessels showing only early atherosclerotic lesions (fatty streaks). The relationship between the age of the subject and the probability of detecting C. pneumoniae organisms is discussed; the youngest subjects with arteries positive for these organisms were aged 15 and 20 years. It is concluded that the presence of chlamydiae within atherosclerotic lesions is now beyond doubt, but as yet there is no conclusive evidence for a causal role in atherosclerosis.


Differential effects of diazepam treatment and withdrawal on recombinant GABAA receptor expression and functional coupling.
Prolonged exposure to benzodiazepines, drugs known to produce tolerance and dependence and also to be abused, leads to adaptive changes in GABA(A) receptors. To further explore the mechanisms responsible for these phenomena, we studied the effects of prolonged diazepam treatment on the recombinant alpha(1)beta(2)gamma(2S) GABA(A) receptors, stably expressed in human embryonic kidney (HEK) 293 cells. The results demonstrating that long-term (48 and 72 h) exposure of cells to a high concentration of diazepam (50 microM) enhanced the maximum number (B(max)) of [(3)H]flunitrazepam, [(3)H]muscimol and [(3)H]t-butylbicycloorthobenzoate ([(3)H]TBOB) binding sites, without changing their affinity (K(d)), suggested the up-regulation of GABA(A) receptors. As demonstrated by cell counting and WST-1 proliferation assay, the observed increase in receptor expression was not a consequence of stimulated growth of cells exposed to diazepam. Semi-quantitative RT-PCR and Western blot analysis, showing elevated levels of alpha(1) subunit mRNA as well as beta(2) and gamma(2) subunit proteins, respectively, suggested that prolonged high dose diazepam treatment induced de novo receptor synthesis by acting at both transcriptional and translational levels. The finding that the number of GABA(A) receptor binding sites returned to control value 24 h following diazepam withdrawal, makes this process less likely to account for the development of benzodiazepine tolerance and dependence. On the other hand, the results demonstrating that observed functional uncoupling between GABA and benzodiazepine binding sites persisted after the termination of diazepam treatment supported the hypothesis of its possible role in these phenomena.


Intermodal stimulated Brillouin scattering in two-mode fibers.
Characterization of stimulated Brillouin scattering (SBS) in an elliptic-core two-mode fiber is experimentally demonstrated. The LP(01) or LP(11) mode is selectively launched to a fiber under test by a mode-selective coupler as a Brillouin pump, and the Brillouin gain spectra are analyzed for different mode pairs of the pump and probe waves. Intermodal SBS between counterpropagating LP(01) and LP(11) modes is observed, and the efficiency is measured to be about 58% of that of the SBS between the LP(01) modes.


[Trial of replacement of ABC cement with the preparation Evicrol in fusing metal alloys used in prosthetic to the enamel].
The fusion strength was compared of the main metal alloys (Wiron 88, Wironit, Spal, Super Fluid) to the enamel by means of the ABC cement (Vivadent) and the preparation Evicrol (Spofa Dental). The obtained samples of metal alloys were subjected to abrasive blasting processing, defatted, and covered with the preparation "metal primer" from the ABC set, and fused to the pickled enamel with ABC cement and Evicrol preparation. The strength of the fusion was tested with the Instrom testing device. The fusion strength was greater in the case of Evicrol.


Small calcification indicator in ultrasonography using correlation of echoes with a modified Wiener filter.
The purpose of this study is to improve the calcification depiction ability in ultrasonography using correlation of echoes with a modified Wiener filter. The waveform of an ultrasound pulse changes when it passes through the location of a calcification. Since the change in echo waveform caused by a calcification decreases the correlation of waveforms in adjacent scan lines, we have proposed a calcification depiction method using the decorrelation of echoes. However, the low signal-to-noise ratio of echoes also decreases the correlation of the echoes. In this study, we employ the correlation of echoes with a modified Wiener filter to suppress the effect of noise, as an indicator of a calcification. The proposed calcification indicator depicted copper cylindrical rods 0.2 mm in size at a depth of 2 cm with a sensitivity of 80% and a positive predictive value of 80%, despite being hardly depicted at all on B-mode ultrasound imaging. This study suggests the potential of the proposed method to improve the performance of calcification depiction by ultrasound devices.


Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury.
Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.


[C5 collaterals of the internal carotid siphon: embryology, angiographic anatomical correlations, pathological radio-anatomy (author's transl)].
Since Parkinson's original description, the C5 collaterals are always presented as originating from a common trunk (meningo-hypophyseal). This is the least frequent anatomical variation. In fact, the posterior (C5) group of collaterals corresponds to the remnant of two transient embryonic vessels (primitive maxillary and trigeminal arteries), branches of which will give rise to the two main groups of collaterals originating from this area: medially, the inferior hypophyseal and the medial clival arteries; laterally, the basal tentorial and lateral clival arteries, which are constantly anastomosed with the ascending pharyngeal artery. Only in some cases (10%) do these two groups arise in common from the C5 carotid siphon. Apart from these branches the so-called Bernasconi's artery may originate from eight different pedicles, the C5 siphon representing only one of them.


Extracellular matrix and pathogenic mechanisms in osteoarthritis.
Osteoarthritis (OA) is a heterogeneous condition of joint degeneration characterized by structural changes in extracellular matrices such as subchondral bone and cartilage. Research has identified many diverse ways of initiating OA, varying from mechanical disruption to gene mutations in structural proteins. A frequent end point is cartilage loss, which can occur irrespective of the initiating mechanism. Of the mechanisms responsible for cartilage matrix damage, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 was identified as of key importance in knockout mice, but work with human cartilage has suggested that ADAMTS-4 was also involved. A transgenic mouse expressing aggrecan lacking a key aggrecanase site clearly showed that loss of aggrecan from cartilage was an important step in both inflammatory and trauma-induced joint degeneration. In OA, cartilage chondrocytes show changes in gene expression, and it remains to be resolved if this reflects adaptive responses to changes in biological, physical, and mechanical signaling rather than any form of differentiation.


Direct C-H alkylation and indole formation of anilines with diazo compounds under rhodium catalysis.
The rhodium(III)-catalyzed direct functionalization of aniline C-H bonds with α-diazo compounds is described. These transformations provide a facile construction of ortho-alkylated anilines with diazo malonates or highly substituted indoles with diazo acetoacetates.


Enhanced cytostatic activity of the sesquiterpene lactone eupatoriopicrin by glutathione depletion.
Eupatoriopicrin (EUP), a sesquiterpene lactone from Eupatorium cannabinum L., possesses cytostatic activity. This was demonstrated for FIO 26 cells in vitro with the aid of a clonogenic assay and in vivo by tumour growth delay in FIO 26 and Lewis lung tumour-bearing mice. In vitro the IC50 for 1 h exposure to EUP was 1.5 microgram ml-1 (4.1 nmol ml-1). This concentration depleted about 25% of its cellular GSH concentration. Pretreatment of FIO 26 cells with BSO, resulting in greater than 99%. GSH depletion, enhanced the cytotoxic effect of EUP. The dose-enhancement factor at the level of 10% cell survival was 2.3. Growth inhibition of the Lewis lung carcinoma and the FIO 26 fibrosarcoma, solidly growing in C57Bl mice, was found after i.v. injection of 20 or 40 mg kg-1 EUP, at a tumour volume of about 500 microliters. Pretreatment with BSO at a dose of 4 mmol kg-1 i.p., 6 h before EUP administration, resulted in a significantly stronger growth delay of both tumours compared with EUP only. At the time of EUP treatment, cellular GSH in the tumours was reduced by BSO treatment to about 60%. It is concluded that EUP possesses antitumour activity in vivo and that chemosensitisation of EUP may be accomplished by pretreatment with BSO, indicating that endogenous GSH protects against the cytostatic action of EUP.


Unruptured 32-week rudimentary horn pregnancy presenting as right upper quadrant pain.
An unruptured third trimester rudimentary horn pregnancy is rare, life threatening, and can go undetected until the onset of symptoms. Given the high risk of uterine rupture, conservative management after viability is controversial. A 21 year-old with a 32-week rudimentary horn pregnancy, diagnosed via exploratory laparotomy five days earlier, presented with acute right upper quadrant pain. The patient underwent cesarean delivery. The rudimentary horn was noted to be intact, but so thin it was transparent. Advanced ectopic pregnancy or rudimentary horn pregnancy should be considered in cases of unusual or undiagnosed abdominal pain in pregnancy. When surgical exploration is performed, an incision allowing optimal visualization and exposure is recommended.


Experimental datasets on compliance level to minimum standard requirements among sandcrete block manufacturers in South Western Nigeria.
The data in this article are related to "Assessment of Sandcrete Blocks Manufacturers 'Compliance to Minimum Standard Requirements by Standard Organisation of Nigeria in Southwest, Nigeria" (Ajao et al., 2018). The data shows the compliance level of Sandcrete Block Manufacturers to Minimum Standard Requirement in Southwest, Nigeria. Experimental procedures carried out on aggregates and sandcrete blocks included sieve analysis to determine grading distribution sizes and bulk density and compressive strength to determine the strength parameters. The results of the experiment were presented in charts and graphs.