Conceptualization, context, and comparison are key to understanding the evolution of fear.
The fearful ape hypothesis proposes that heightened fearfulness in humans is adaptive. However, despite its attractive anthropocentric narrative, the evidence presented for greater fearfulness in humans versus other apes is not sufficient to support this claim. Conceptualization, context, and comparison are strongly lacking in Grossmann's proposal, but are key to understanding variation in the fear response among individuals and species.


Structure and organization of the mitochondrial genome of the canine heartworm, Dirofilaria immitis.
This study determined the complete mitochondrial (mt) genome sequence of the canine heartworm, Dirofilaria immitis, and compared its structure, organization and other characteristics with Onchocerca volvulus and other secernentean nematodes. The D. immitis mt genome is 13814 bp in size and contains 36 of the 37 genes typical of metazoan organisms, and lacks the ATP synthetase subunit 8 gene. All of the genes are transcribed in the same direction. For the entire genome, the nucleotide contents are approximately 55% (T), approximately 19% (each for A and G) and approximately 7% (C), which is very similar to those of the protein-coding genes. In the latter genes, most (approximately 69%) third codon positions have a T, but rarely (approximately 1-9%) have an A or a C. The C content (8-12%) is higher at the first and second codon positions compared with the third position (approximately 1%). These nucleotide biases have a significant effect on the codon usage patterns and, thus, on the amino acid composition of the proteins. The mt genome organization of D. immitis is essentially the same as that of O. volvulus, but is distinctly different from other secernentean nematodes sequenced thus far. Irrespective of transpositions of transfer RNA (trn) genes and the non-coding, AT-rich region, there are 4 gene- or gene block-translocations between the mt genome of D. immitis and those of Caenorhabditis elegans, Ascaris suum and the 2 human hookworms, Ancylostoma duodenale and Necator americanus. For D. immitis, the 22 trn genes have secondary structures typical of other secernentean nematodes, and possess a TV-replacement loop instead of a TpsiC arm and loop. Like O. volvulus, the mt trnK and trnP of D. immitis use the anticodons CUU and AGG, whereas in other nematodes, UUU and UGG are employed, respectively. Also, the secondary structures of the 2 ribosomal RNA (rrn) genes are similar to the models for other nematodes. Overall, the availability of the complete D. immitis mt genome sequence provides a resource for future studies of the comparative mt genomics and of the population genetics and/or phylogeny of parasitic nematodes.


Continuities, discontinuities and transformations in the psychotherapy of a psychotic adolescent during the time of coronavirus.
The author describes the evolution of the psychotherapy of a psychotic adolescent in the period when the pandemic induced their national authorities to impose lockdown. The difficulty of coming to terms with an ever-present reality that proved to be distressing for both the patient and the analyst, as well as with the violence and rapidity with which the external situation developed, leading to a change in the therapy setting, are at the heart of the reflections in this paper. The "choice" of whether to continue the sessions over the phone determined the emergence of some distinctive issues related to discontinuity and to the impossibility of relying on visual perception. However, to the analyst's surprise, it also favoured the possibility of working through the meaning of some autistic mental areas which, up to that moment, had never really been accessible to verbalization. Questioning the meaning of these changes, the author develops a broader reflection about the way that, for analysts and patients, modifications in the frames of our daily lives and clinical practice have enabled the deployment of undifferentiated parts of the personality which had previously been secretly deposited in the "body" of the setting and therefore were inaccessible.


Monocular cues are superior to binocular cues for size perception when they are in conflict in virtual reality.
Three-dimensional (3D) depth information is important to estimate object sizes. The visual system extracts 3D depth information using both binocular cues and monocular cues. However, how these different depth signals interact with each other to compute the object size in 3D space is unclear. Here, we aim to study the relative contribution of monocular and binocular depth information to size perception in a modified Ponzo context by manipulating their relations in a virtual reality environment. Specifically, we compared the amount of the size illusion in the following two conditions, in which monocular cues and binocular disparity in the Ponzo context can indicate the same depth sign (congruent) or opposite depth sign (incongruent). Our results show an increase in the amount of the Ponzo illusion in the congruent condition. In contrast, in the incongruent condition, we find that the two cues indicating the opposite depth signs do not cancel out the Ponzo illusion, suggesting that the effects of the two cues are not equal. Rather, binocular disparity information seems to be suppressed and the size judgment is mainly dependent on the monocular depth information when the two cues are in conflict. Our results suggest that monocular and binocular depth signals are fused for size perception only when they both indicate the same depth sign and top-down 3D depth information based on monocular cues contributes more to size perception than binocular disparity when they are in conflict in virtual reality.


Elucidating sources of mercury in the west coast of Korea and the Chinese marginal seas using mercury stable isotopes.
Nearshore systems play an important role as mercury (Hg) sources to the open ocean and to human health via fish consumption. The nearshore system along East Asia is of particular concern given the rapid industrialization, which contributes to significant anthropogenic Hg emissions and releases. We used Hg stable isotopes to characterize Hg sources in the sediment and fish along the west coast of Korea, located at the northeast of the East China Sea. The Hg isotope ratios of the west coast sediments (δ202Hg; -0.89 to -0.27‰, Δ199Hg; -0.04 to 0.14‰) were statistically similar with other nearshore sediments (δ202Hg; -0.99 to -0.30‰, Δ199Hg; -0.04 to 0.19‰) and overlapped with the industrial Hg source end-member (δ202Hg; -0.5‰, Δ199Hg; 0.01‰) estimated from the Chinese marginal seas. Using a ternary mixing model, we estimated that industrial Hg sources contribute 83-97% in the west coast of Korea, and riverine and atmospheric Hg sources play minor roles in the Korean west coast and the Chinese marginal seas. The comparison between Hg isotope ratios of the sediment and nearshore fish revealed that the fish in the most west coast sites are exposed to MeHg produced in the sediment. At a few southwest coast sites, external MeHg produced in rivers and the open ocean water column appears to be more important as a source in fish. This is supported by much higher δ202Hg (0.74‰; similar to oceanic fish) and lower δ202Hg (-0.71‰; similar to riverine sources) compared to fish collected from other west coast sites influenced by sedimentary MeHg. The substantial Hg contributions from industrial activities suggest the national policies regulating anthropogenic Hg releases can directly mitigate human Hg exposure originating via local fish consumption. This study contributes to the growing regional and global inventories of Hg fluxes and sources exported into coastal oceans.


The distance of visual targets affects the spatial magnitude and multifractal scaling of standing body sway in younger and older adults.
The spatial magnitude of standing body sway is greater during viewing of more distant targets and reduced when viewing nearby targets. Classical interpretations of this effect are based on the projective geometry of changes in visual stimulation that are brought about by body sway. Such explanations do not motivate predictions about the temporal dynamics of body sway. We asked whether the distance of visible targets would affect both the spatial magnitude and the multifractality of standing body sway. It has been suggested that the multifractality of movement may change with age. Separately, previous research has not addressed the effects of target distance on postural sway in older adults. For these reasons, we crossed our variation in target distance with variation in age. In an open-air setting, we measured standing body sway in younger and older adults while looking at visual targets that were placed at three distances. The distance of visual targets affected the spatial magnitude of body sway in younger adults, replicating past studies. Target distance also affected the spatial magnitude of sway in older adults, confirming that this relation persists despite other age-related changes. Target distance also affected the multifractality of body sway, but this effect was modulated by age. Finally, the width of the multifractal spectrum was greater for older adults than for younger adults, revealing that healthy aging can affect the multifractality of movement. These findings reveal similarities and differences between the spatial magnitude and the multifractality of human movement.


An uncommon cause of hemoptysis: aortobronchial fistula.
Hemoptysis is a frequent sign of respiratory and non-respiratory diseases. While in most cases the underlying cause is rapidly identified, sometimes the real etiology might be misdiagnosed with dramatic delay in treatment. A 46-year-old man with hiatal hernia and a history of aortic surgery for aortic coarctation presented with dramatic episodes of hemoptysis and subsequent severe anemia (6,9 g/dl). Digestive and respiratory endoscopy resulted not exhaustive, thus he underwent a contrast-enhanced computed tomography (CT) scan of the chest that showed an aneurysmal dilatation of the descending thoracic aorta with suspected aortobronchial fistula. He underwent cardiac surgery that confirmed the diagnosis and successfully treated the fistula. We briefly review the literature to raise clinical awareness on this uncommon cause of hemoptysis.


Free radical-mediated membrane depolarization in renal and cardiac cells.
Cell membrane potential was measured with a flow cytometer by quantitating the intracellular accumulation of a fluorescent cationic carbocyanine dye. We used this system to demonstrate depolarization upon the addition of hydrogen peroxide (10-1,000 microM) and ferrous chloride (25-100 microM) to cultures of either neonatal rat myocardial or LLC-PK1 renal epithelial cells. Ferrous chloride-induced depolarization was prevented by superoxide dismutase, catalase and dimethyl sulfoxide, suggesting roles for the superoxide anion, hydrogen peroxide and the hydroxyl radical in effecting this depolarization, possibly through a Fenton-type reaction mechanism. Supplementation of either cell type with 2 microM tocopherol acid succinate during growth in tissue culture, prior to exposure to the oxidizing agent, decreased the magnitude of the depolarization in both cell types. The results are consistent with a role for tocopherols in scavenging free radical species responsible for the depolarization of the cell membrane.


Analysis of organochlorine pesticides in coral (Porites evermanni) samples using accelerated solvent extraction and gas chromatography/ion trap mass spectrometry.
A gas chromatography/ion trap mass spectrometry method was developed for analysis of organochlorine pesticides (OCPs) in coral samples, which were extracted with accelerated solvent extraction (ASE) and cleaned up on a sulfuric acid-modified silica gel column. The optimal ASE conditions were found to be 100 degrees C and 2000 psi, with a mixture of acetone and methylene chloride (1:1, v/v). The target analytes include hexachlorocyclohexanes (HCHs, specifically, alpha-, beta-, gamma-, and delta-HCH isomers), heptachlor, and hexachlorobenzene (HCB), o,p'-, p,p'-dichlorodiphenyltrichloroethane (o,p'-, p,p'-DDT), o,p'-, p,p'-dichlorodiphenyl-dichloroethylene (o,p'-, p,p'-DDE), and o,p'-, p,p'-dichlorodiphenyldichloroethane (o,p'-, p,p'-DDD). Standard sand samples were used as an alternative matrix spiked with OCP standards to determine the method precision and accuracy. Average recoveries of OCPs ranged from 82% to 102%, with relative standard deviations (RSDs) of 3%-6%, at a level of 10 ng/g and from 50% to 68%, with RSDs of 13%-19% at a level of 2 ng/g. The developed method was applied for analysis of OCPs in coral samples collected from Tern Island and Bikini Atoll in the Pacific Ocean. The concentrations of HCB were 7-26 pg/g dry weight in the samples from Bikini Atoll and 3-45 pg/g in those from Tern Island, and heptachlor concentrations were 208-2200 and 44-104 pg/g in the coral samples from Bikini Atoll and Tern Island, respectively. (summation operator)HCH (sum of alpha-, beta-, gamma-, and delta-HCH) were 8-82 pg/g in Bikini Atoll coral and 86-629 pg/g in Tern island coral, and (summation operator)DDT (sum of o,p'-, p,p'-DDD, o,p'-, p,p'-DDE, and o,p'- p,p'-DDT) were 80-212 pg/g in Bikini Atoll coral and 593-3165 pg/g in Tern Island coral. The results suggest that coral is a viable indicator species for pollution monitoring, which pollutants and their concentrations may be related to dated carbonate layers.


Another look at the eigenvalues of a population matrix model.
Population matrix models are important tools in resource management, in part because they are used to calculate the finite rate of growth ("dominant eigenvalue"). But understanding how a population matrix model converts life history traits into the finite rate of growth can be tricky. We introduce interactive software ("IsoPOPd") that uses the characteristic equation to display how vital rates (survival and fertility) contribute to the finite rate of growth. Higher-order interactions among vital rates complicate the linkage between a management intervention and a population's growth rate. We illustrate the use of the software for investigating the consequences of three management interventions in a 3-stage model of white-tailed deer (Odocoileus virginianus). The software is applicable to any species with 2- or 3-stages, but the mathematical concepts underlying the software are applicable to a population matrix model of any size. The IsoPOPd software is available at: https://cwhl.vet.cornell.edu/tools/isopopd.


[Surgical treatment of the mammary carcinoma according to stage (author's transl)].
Improvement of the results of treatment was achieved only when an increased number of patients were diagnosed in stage I. The prerequisite for limitation of radical surgery is histomorphologic classification of the stages. The central axillary group of lymph nodes appears to be representative of lymph node involvement. Differentiated methods of operations range from local excision to mastectomy in case of precancer. In histologic stage I, modified radical mastectomy; is the treatment of choices; operations with further limitations are recommended only within the scope of controlled studies. In stage II, the classical ablation is still the safest procedure.


A seroepidemiological study to evaluate the role of passive maternal immunity to malaria in infants.
Parasitaemias and loss of natural antibody to Plasmodium falciparum were studied in 104 infants in a highly endemic area of Papua New Guinea. There were 4 cases of congenital infection. Most infants lost malaria-specific immunoglobulin G (IgG) between 4 and 7 months (median = 21 weeks). 73% of heavy infections developed in infants without detectable antimalarial IgG. Infections in the presence of antimalarial IgG were asymptomatic and had scanty parasitaemias.


An equivalent metal ion in one- and two-metal-ion catalysis.
Nucleotidyl-transfer enzymes, which synthesize, degrade and rearrange DNA and RNA, often depend on metal ions for catalysis. All DNA and RNA polymerases, MutH-like or RNase H-like nucleases and recombinases, and group I introns seem to require two divalent cations to form a complete active site. The two-metal-ion mechanism has been proposed to orient the substrate, facilitate acid-base catalysis and allow catalytic specificity to exceed substrate binding specificity attributable to the stringent metal-ion (Mg2+ in particular) coordination. Not all nucleotidyl-transfer enzymes use two metal ions for catalysis, however. The betabetaalpha-Me and HUH nucleases depend on a single metal ion in the active site for the catalysis. All of these one- and two metal ion-dependent enzymes generate 5'-phosphate and 3'-OH products. Structural and mechanistic comparisons show that these seemingly unrelated nucleotidyl-transferases share a functionally equivalent metal ion.


Genetic-deletion of Cyclooxygenase-2 Downstream Prostacyclin Synthase Suppresses Inflammatory Reactions but Facilitates Carcinogenesis, unlike Deletion of Microsomal Prostaglandin E Synthase-1.
Prostacyclin synthase (PGIS) and microsomal prostaglandin E synthase-1 (mPGES-1) are prostaglandin (PG) terminal synthases that function downstream of inducible cyclooxygenase (COX)-2 in the PGI2 and PGE2 biosynthetic pathways, respectively. mPGES-1 has been shown to be involved in various COX-2-related diseases such as inflammatory diseases and cancers, but it is not yet known how PGIS is involved in these COX-2-related diseases. Here, to clarify the pathophysiological role of PGIS, we investigated the phenotypes of PGIS and mPGES-1 individual knockout (KO) or double KO (DKO) mice. The results indicate that a thioglycollate-induced exudation of leukocytes into the peritoneal cavity was suppressed by the genetic-deletion of PGIS. In the PGIS KO mice, lipopolysaccharide-primed pain nociception (as assessed by the acetic acid-induced writhing reaction) was also reduced. Both of these reactions were suppressed more effectively in the PGIS/mPGES-1 DKO mice than in the PGIS KO mice. On the other hand, unlike mPGES-1 deficiency (which suppressed azoxymethane-induced colon carcinogenesis), PGIS deficiency up-regulated both aberrant crypt foci formation at the early stage of carcinogenesis and polyp formation at the late stage. These results indicate that PGIS and mPGES-1 cooperatively exacerbate inflammatory reactions but have opposing effects on carcinogenesis, and that PGIS-derived PGI2 has anti-carcinogenic effects.


Permethrin, a pyrethroid insecticide, regulates ERK1/2 activation through membrane depolarization-mediated pathway in HepG2 hepatocytes.
Permethrin is a pyrethroid insecticide that acts thru membrane depolarization and is known to disrupt calcium levels in neurons. Disrupted calcium homeostasis is linked to oxidative stress as well as many other cellular mis-functions and permethrin has been reported to disrupt lipid and glucose metabolism in animals and mammalian cell models. It is not known, however, if permethrin influences calcium levels and its associated cellular mechanisms in liver cells. Thus, the goal of the current study was to investigate the mechanisms of permethrin on calcium-mediated cellular signaling pathway, particularly on activation of extracellular signal-related kinase (ERK1/2 or p42/p44) using human hepatocytes, HepG2. The current results showed that permethrin treatment induced oxidative stress and phosphorylation of ERK1/2, which were dependent upon voltage-sensitive sodium channels (VSSC). It was further determined that permethrin-induced ERK1/2 activation was mediated by the metabotropic glutamate receptors (mGluRs)-phosphoinositide phospholipase C (PLC)-protein kinase C (PKC) pathway, but not by changes of intracellular calcium or ER stress-mediated mechanisms.


Electrolyte disorders in community subjects: prevalence and risk factors.
Electrolyte disorders have been studied mainly in hospitalized patients, whereas data in the general population are limited. The aim of this study was to determine the prevalence and risk factors of common electrolyte disorders in older subjects recruited from the general population. A total of 5179 subjects aged 55 years or more were included from the population-based Rotterdam Study. We focused on hyponatremia, hypernatremia, hypokalemia, hyperkalemia, and hypomagnesemia. Multivariable logistic regression was used to study potential associations with renal function, comorbidity, and medication. The adjusted mortality also was determined for each electrolyte disorder. A total of 776 subjects (15.0%) had at least 1 electrolyte disorder, with hyponatremia (7.7%) and hypernatremia (3.4%) being most common. Diabetes mellitus was identified as an independent risk factor for hyponatremia and hypomagnesemia, whereas hypertension was associated with hypokalemia. Diuretics were independently associated with several electrolyte disorders: thiazide diuretics (hyponatremia, hypokalemia, hypomagnesemia), loop diuretics (hypernatremia, hypokalemia), and potassium-sparing diuretics (hyponatremia). The use of benzodiazepines also was associated with hyponatremia. Hyponatremic subjects who used both thiazides and benzodiazepines had a 3 mmol/L lower serum sodium concentration than subjects using 1 or none of these drugs (P < .001). Hyponatremia and hypomagnesemia were independently associated with an increased mortality risk. Electrolyte disorders are common among older community subjects and mainly associated with diabetes mellitus and diuretics. Subjects who used both thiazides and benzodiazepines had a more severe degree of hyponatremia. Because even mild electrolyte disorders were associated with mortality, monitoring of electrolytes and discontinuation of offending drugs may improve outcomes.


Dexmedetomidine and ketamine for fiberoptic intubation in a child with severe mandibular hypoplasia.
A 6-year-old girl with Treacher Collins syndrome presented for implantation of a hearing device. The patient was developmentally delayed and had severe micrognathia. After induction of anesthesia with dexmedetomidine and ketamine, the patient tolerated the introduction of a flexible fiberoptic bronchoscope without any change in respiration, and intubation was achieved easily.


Effectiveness of presurgical orthodontics in cleft lip and palate patients with alveolar bone grafting: A systematic review.
Alveolar repair has become a routine part of treatment protocols for patients with non-syndromic cleft lip and/or palate, but there is no clear conclusion of whether the presurgical orthodontic treatment is necessary to alveolar bone grafting or not. The purpose was to determine the necessity of the presurgical orthodontics in cleft lip and palate patients. Electronic databases including PubMed, Ovid, Embase, Cochrane Library, Web of Knowledge, and China Biology Medicine disc (SinoMed) were searched. Only studies published in English or Chinese were included. The last search was updated on 1 May 2020. 1225 articles remaining after the exclusion of duplicates. Finally, there were 11 publications (five in English and six in Chinese) eligible for systematic review according to the previously established inclusion and exclusion criteria. A descriptive statistical method was used to present data. The methodological index for non-randomized studies (MINORS) was used to determine the risk of bias. Eleven articles were included in this review, of which seven publications were retrospective study and four articles were comparative study. The average success rate of reconstruction with the presurgical orthodontic treatment was approximately 70-97%, while the success rate of the non-presurgical orthodontics was 25-80%. The fixed and removable presurgical orthodontic methods were frequently performed, rather than a single treatment model. The incidence of the postoperative complications resulting from whether adopting the presurgical orthodontics was different from none to 75%. There are a higher postoperative bone formation rate and a lower complication rate after ABG with presurgical orthodontics. However, more studies with high methodological quality and with a longer follow-up are needed to offer more safety for practitioners and patients regarding the surgical method selected to repair the cleft alveolar.


Characteristics of upper limb mass, muscle CSA and stiffness in adolescent baseball players with and without elbow injury.
Since elbow injuries are common in adolescent baseball players, this study aimed to determine the relationship between musculoskeletal status and elbow injuries in 47 baseball players aged 12-14 years. Participants answered a questionnaire and had their general body measurements taken. Magnetic resonance imaging was used to evaluate muscle cross sectional areas (CSA) of the upper arm flexor and extensor muscles, and x-ray absorptiometry was used to determine the mass of the upper arm and the total mass of the forearm and hand. Shear wave elastography was used to determine muscle stiffness of the biceps brachii, brachialis, pronator teres, and brachioradialis. An orthopedic surgeon performed a clinical assessment and elbow ultrasonography for each participant to diagnose elbow injuries. The measured values were compared between the elbow injury and control groups using two-sample t-tests. The elbow injury group had significantly higher muscle stiffness in the brachialis (p < 0.001) and brachioradialis (p = 0.004) muscles and greater elbow flexor CSA of the distal upper arm (p = 0.004) than the control group. The total mass of the forearm and hand and the mass ratio of the forearm and hand to the upper arm were significantly greater in the elbow injury group than in the control group (p = 0.002 and p < 0.001). Thus, it may be necessary to increase flexibility of the brachialis and brachioradialis flexible by stretching and massaging in addition to evaluating the mass distal to the elbow and the elbow flexor muscle size of the distal upper arm to manage elbow injury in youth baseball players. Characteristics of Upper Limb Mass, Muscle Cross-Sectional Area and Stiffness in Adolescent Baseball Players with and without Elbow Injury.


A Call for Conscious Changes to Counter COVID-19.
This article lays out the contours of a novel approach to social change and interactions, based on the organic interplay of individuals, institutions, countries and the global society. This approach is based on the POZE paradigm, which posits that change starts inside and is nurtured from the outside in - both for individuals and for durable social change. Such a holistic perspective is crucial to build society as it emerges from the Pandemic. COVID-19 is a reminder that humans around the World are fundamentally all the same; the result of 4 dimensions - soul, heart, mind and body, which find their expression in aspirations, emotions, thoughts and sensations. These 4 dimensions constantly interact and influence each other in ways that reflect the 4-dimensional dynamic that shapes our collective existence. Individuals are the micro dimension that stands at the center of everything else. Forming part of various institutions, from families to parties, individuals are constitutive components of the meso dimension. Individuals and institutions form countries and economies, the macro-dimension. These dimensions in addition to nature and supra-national institutions form the meta-dimension. A constant interplay connects and determines what happens in each dimension and what derives from it. To thrive in the post-pandemic world, we must understand and optimize this interplay. This is the point of departure for the argumentation laid out in this article. The prevailing systemic imbalance in which many lack the means to cover their basic needs can only be addressed by planting the C-Core (completion, compassion, creativity, cooperation) at the center of human interactions. When we bring risks, responsibility and real opportunities together in one coherent framework whilst applying the proposed twice 4-dimensional paradigm-shift a set of concrete recommendations appears. Looking at individuals, and institutions, the article concludes with suggestions to seize this moment and shape not merely a response to the crises, but to lay the ground for a new social contract. In the past the C in C-Suite stood for Chief, the upper part of the leadership ladder in an institution. In the future that C must represent C-Core qualities. The online version contains supplementary material available at 10.1007/s42413-021-00110-0.


SIRT1 reduction contributes to doxorubicin-induced oxidative stress and meiotic failure in mouse oocytes.
Impaired fertility is the major side effect of chemotherapy for female cancer patients, accumulated evidence indicates this is associated with damage on oocyte quality, but the underlying mechanisms remain unclear. Previously we reported that doxorubicin (DXR) exposure, one of the most widely used chemotherapy drugs, disrupted mouse oocyte meiotic maturation in vitro. In the current study, we identified that SIRT1 expression was remarkably reduced in DXR exposure oocytes. Next, we found that increasing SIRT1 expression by resveratrol partially alleviated the effects of DXR exposure on oocyte maturation, which was counteracted by SIRT1 inhibition. Furthermore, we revealed that increasing SIRT1 expression mitigated DXR induced oocyte damage through reducing ROS levels, increasing antioxidant enzyme MnSOD expression, and preventing spindle and chromosome disorganization, lowering the incidence of aneuploidy. Importantly, by performing in vitro fertilization and embryo transfer assays, we demonstrated that increasing SIRT1 expression significantly improved the fertilization ability, developmental competence of oocytes and early embryos. In summary, our data uncover that SIRT1 reduction represents one mechanism that mediates the effects of DXR exposure on oocyte quality.


Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways.
Rapamycin prevents experimental autoimmune encephalomyelitis (EAE) and activates the MAPK/ERK pathway in EAE. Thus, we hypothesized combining rapamycin and fingolimod treatments would have synergistic effects in EAE. We show that combination therapy ameliorated EAE and regulated spinal cord IL-17 and TGF-β levels in EAE mice. Combination therapy also modulated IL-17 and TGF-β concentration, RoRγt and Foxp3 mRNA levels, and Th17 cell and Treg frequencies in the spleen. Moreover, rapamycin decreased ps6k and increased pAkt and pERK, while combination therapy downregulated pAkt, ps6 k and pERK in EAE mice. Our findings provide insight into using this drug combination to treat EAE.


Accumulation of 3H-(-)noradrenaline in the rabbit aorta not related to uptake1 and uptake2, but sensitive to 3,4-dihydroxy-2-methylpropiophenone (U-0521) and oxytetracycline.
1. Some of the extraneuronal accumulation of 3H-(-)noradrenaline in the rabbit aorta was resistant to uptake2 inhibitors (corticosterone, normetanephrine, phenoxybenzamine). Even combined treatment of the tissue with the competitive inhibitor corticosterone (87 mumol . l-1) and the irreversible inhibitor phenoxybenzamine (90 mumol . l-1) was not more effective than was corticosterone alone. 2. The corticosterone-resistant extraneuronal accumulation of 3H-(-)noradrenaline (0.12 mumol . l-1) was reduced by about 30% by the COMT inhibitor U-0521 (1000 mumol . l-1) and by oxytetracycline (100 mumol . l-1). Combined treatment with U-0521 and oxytetracycline was not more effective than was U-0521 alone. Already 1 mumol . l-1 U-0521 had a half-maximal effect, i.e., it reduced accumulation by 15%. This effect of U-0521 was not related to its known ability to block uptake2. The catechol U-0521 probably inhibited binding of noradrenaline to a catechol-specific site. Furthermore, the accumulation was sensitive to the two iron-chelating agents deferoxamine and phenanthroline but not to ascorbic acid and N-ethylmaleimide. 3. A relatively high formation of 3,4-dihydroxymandelic acid (DOMA) took place in the corticosterone-resistant extraneuronal compartment of the mechanically denervated aorta. This formation of DOMA was probably a consequence of tissue injury brought about by removing the adventitia.


Wave-packet study of H2 formation on a graphite surface through the Langmuir-Hinshelwood mechanism.
We have studied the formation of the H2 molecule on a graphite surface, when both H atoms are initially physisorbed. The graphite surface is assumed to be planar. The interaction potential is modeled to reproduce the experimental properties of H physisorption on graphite. Extending our previous work [S. Morisset, F. Aguillon, M. Sizun, and V. Sidis, J. Chem. Phys. 121, 6493 (2004)], full-dimensionality quantum calculations are presented for collision energies ranging from 4 to 50 meV. It is shown that the reaction occurs with a large cross section and produces the H2 molecule with a considerable amount of vibrational energy. The mechanism is either direct or involves the formation of an intermediate complex.


Unaltered diabetes presentation in NOD mice lacking the vitamin D receptor.
Vitamin D deficiency increases risk for type 1 diabetes in genetically predisposed individuals, while high doses of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] prevent insulitis and diabetes in NOD mice. Since 1,25(OH)(2)D(3) regulates gene transcription through the vitamin D receptor (VDR), we investigated the role of VDR in diabetes development by creating NOD mice without functional VDR. VDR(-/-) NOD mice are rachitic and have lower numbers of putative regulator cells [TCR-alpha/beta(+)CD4(-)CD8(-) (natural killer T-cells) and CD4(+)CD25(+) T-cells [in central and peripheral immune organs compared with VDR(+/+) NOD littermates. Lipopolysaccharide-stimulated VDR(-/-) NOD macrophages expressed lower interleukin (IL)-1, IL-6, and CC chemokine ligand 2 mRNA, correlating with less nuclear translocation of p65 nuclear factor-kappaB compared with VDR(+/+) NOD macrophages. Thymic and lymph node dendritic cells from VDR(-/-) NOD mice displayed an even less mature CD11c(+)CD86(+) phenotype than VDR(+/+) NOD mice. Despite this immune phenotype linked to diabetes in NOD mice, VDR(-/-) NOD mice developed insulitis and diabetes at the same rate and incidence as VDR(+/+) NOD littermates. Despite aggravating known immune abnormalities in NOD mice, disruption of VDR does not alter disease presentation in NOD mice in contrast to the more aggressive diabetes presentation in vitamin D-deficient NOD mice.


Competition between Coiled-Coil Structures and the Impact on Myosin-10 Bundle Selection.
Coiled-coil fusions are a useful approach to enforce dimerization in protein engineering. However, the final structures of coiled-coil fusion proteins have received relatively little attention. Here, we determine the structural outcome of adjacent parallel and antiparallel coiled coils. The targets are coiled coils that stabilize myosin-10 in single-molecule biophysical studies. We reveal the solution structure of a short, antiparallel, myosin-10 coiled-coil fused to the parallel GCN4-p1 coiled coil. Surprisingly, this structure is a continuous, antiparallel coiled coil where GCN4-p1 pairs with myosin-10 rather than itself. We also show that longer myosin-10 segments in these parallel/antiparallel fusions are dynamic and do not fold cooperatively. Our data resolve conflicting results on myosin-10 selection of actin filament bundles, demonstrating the importance of understanding coiled-coil orientation and stability.


Vibrational circular dichroism in general anisotropic thin solid films: measurement and theoretical approach.
In this study, the measurement of the true vibrational circular dichroism (VCD) spectrum is considered from an experimental and theoretical approach for any general anisotropic thin solid sample exhibiting linear as well as circular birefringence (LB, CB) and dichroism (LD, CD) properties. For this purpose, we have made use of a simple model alpha-helix polypeptide, namely, the poly(gamma-benzyl-L-glutamate) or PBLG, reference sample possessing a well-known VCD spectrum and giving rise to slightly oriented films by deposition onto a solid substrate. Also, we have used a different Fourier transform infrared modulation of polarization (PM-FTIR) optical setup with two-channel electronic processing in order to record the PM-VLD and PM-VCD spectra for various sample orientations in its film plane. All the corresponding general relations of the expected intensities in these experiments and the related properly designed calibration measurements were established using the Stokes-Mueller formalism; in addition, the residual birefringence of the optical setup and the transmittance anisotropy of the detector were estimated. From a comparative study of the results obtained in solution and in the solid state, we then propose a simple new experimental procedure to extract the true VCD spectrum of an oriented PBLG thin film: its consists of calculating the half-sum of two spectra recorded at theta and at theta +/- 90 degrees sample orientations. Moreover, the complete linear and circular birefringence and dichroism properties of the ordered PBLG thin film are estimated in the amide I and amide II vibrational regions. This allows us to establish for any sample orientation various theoretical simulations of the VCD spectra that agree nicely with the observed experimental results; this confirms that the measurement of LD and LB is in this case a prerequisite in simulating the true VCD spectrum of a partly oriented anisotropic sample. This validates our combined experimental and theoretical approach and opens the route to promising future vibrational CD studies on other macroscopic anisotropic thin film samples.


Radiotherapy DICOM packet sniffing.
The Digital Imaging and Communications in Medicine (DICOM) standard is meant to allow communication of medical images between equipment provided by different vendors, but when two applications do not interact correctly in a multi-vendor environment it is often first necessary to demonstrate non-compliance of either the sender or the receiver before a resolution to the problem can be progressed. Sometimes the only way to do this is to monitor the network communication between the two applications to find out which one is not complying with the DICOM standard. Packet sniffing is a technique of network traffic analysis by passive observation of all information transiting a point on the network, regardless of the specified sender or receiver. DICOM packet sniffing traps and interprets the network communication between two DICOM applications to determine which is non compliant. This is illustrated with reference to three examples, a radiotherapy planning system unable to receive CT data from a particular CT scanner, a radiotherapy simulator unable to print correctly on a DICOM printer, and a PACS unable to respond when queried about what images it has in its archive by a radiotherapy treatment planning system. Additionally in this work it has been proven that it is feasible to extract DICOM images from the intercepted network data. This process can be applied to determine the cause of a DICOM image being rendered differently by the sender and the receiver.


Alveolar epithelial cell plasminogen activator. Characterization and regulation.
Intra-alveolar fibrin deposition is one of the pathological hallmarks of acute lung injury. Because alveolar epithelial cells play a central role in the repair process following acute lung injury, this study was undertaken to examine their potential to produce a plasminogen activator (PA). We now report the synthesis and secretion of PA by rat alveolar epithelial cells with the catalytic properties of a urokinase-type (u-PA) rather than tissue-type plasminogen activator. Studies of regulation of epithelial cell u-PA revealed: 1) phorbol myristate acetate (PMA) but not the inactive structural analog 4 alpha-PMA upregulated u-PA synthesis, putatively via the protein kinase C pathway; 2) PMA induction of u-PA activity was substantially inhibited by dexamethasone and completely inhibited by cycloheximide; 3) unstimulated alveolar epithelial cells had no detectable u-PA mRNA, whereas PMA exposure led to activation of the u-PA gene and accumulation of a 2.5-kilobase u-PA mRNA; and 4) cycloheximide did not abolish this induction of u-PA mRNA suggesting that intermediate protein synthesis was not necessary for the activation of transcription. In light of their capacity to promote fibrinolysis and their strategic anatomic location, alveolar epithelial cells are likely to play a key role in the extensive remodelling process that follows acute lung injury.


Dynamic heart phantom for the quality control of SPECT equipment.
A nuclear imaging of heart is a noninvasive procedure that reveals the cardiac structure and physiology enabling evaluation of cardiac function. According to the regulations published by the Polish Government and the Polish Ministry of Health, the nuclear medicine departments must follow the new legislation which has imposed quality assurance (QA) and quality control (QC) of equipment and medical testing procedures as compulsory. The foremost reason to perform QC tests of medical imaging equipment, using ionizing radiation, is to assure the provision of the best possible diagnostic service to the patient with the least radiological hazard. One of the most common ways of testing in nuclear medicine is using phantoms. The aim of this study was to design and perform a dynamic heart phantom. The heart phantom was designed according to directive of the ICRU Report 48. It consists of a pump, tubes, cardiac volume and a membrane simulating left ventricle. The pump compresses and decompresses membrane. The pumping frequency can be changed from 60 to 200 bpm. The phantom cardiac volume should be filled with radiopharmaceutical. The elaborated dynamic heart phantom is used for QC of imaging system in nuclear medicine department. The QC measurements were performed with the phantom filled with 45-50 MBq of (99m)Tc-MIBI solution and placed in water filled anthropomorphic torso phantom. The dynamic heart phantom can also be used to simulate all types of the myocardial infarctions and help to choose the best geometry of the measurement.


Self-Optimized Computational Method Calculating Robust b Values for Earthquake Catalogs Containing Small Number of Events.
In the Gutenberg-Richter relation that describes the frequency-magnitude distribution of earthquakes, the b value represents the distribution's slope. Since b values can be used for mapping the dynamic response of earthquake source, methodologies for calculating robust b values are of great importance. Although nowadays software which is meant for statistical analysis of earthquake data can determine b values with high accuracy, in occasions where catalogs that contain small number of earthquake events, the produced results are not satisfactory. In this paper we present a new self-optimized algorithm for a more efficient calculation of the b value. The algorithm's results are compared with two widely known software for statistical analysis of earthquake data, showing a better performance in evaluating b values for earthquake catalogs containing small number of events.


Brain biopsies for neurodegenerative disease in children.
Brain biopsies for neurodegenerative disease performed at The Hospital for Sick Children, Toronto, over a 12-year period (1964 to 1976) were reviewed. Of 64 biopsies, major histologic abnormalities with diagnostic or prognostic significance comprised 39% of the total cases, minor abnormalities represented 13%, and 48% appeared normal. The procedure failed to provide prognostic assistance in 41%. With the advent for newer diagnostic techniques (enzyme assays and muscle, skin, peripheral nerve, rectal, and appendix biopsies) for neurodegenerative disease in childhood, a much lower yield is noted (15 to 20%). Only two progressive degenerative childhood conditions remain in which cerebral tissue is necessary for diagnosis--Alexander disease and Canavan spongy degeneration.


A quantitative assessment of the eating capability in the elderly individuals.
Ageing process implies physiologically weakened muscles, loss of natural teeth and movement coordination, causing difficulties in the eating process. A term "eating capability" has been proposed to measure objectively how capable an elderly individual is in overall food management. Our objectives were to establish feasible methodologies of eating capability assessment, examine correlations between hand and oro-facial muscle strengths and grade elderly subjects into groups based on their eating capabilities. This study was performed with 203 elderly subjects living in the UK (n=103, 7 community centres, 2 sheltered accommodation) and Spain (n=100, 3 nursing homes, 1 community centre). Hand gripping force, finger gripping force, biting force, lip sealing pressure, tongue pressing pressure and touching sensitivity were measured for elderly subjects. Measured parameters were normalised and scored between 1 and 5, with 1 being the weakest. Subjects were then grouped into 4 groups based on their eating capability scores, being participants of cluster 1 the weakest group and 4 the strongest. Perception of oral processing difficulty was assessed by showing food images. Hand gripping force showed a strong linear correlation with tongue pressure (UK: 0.35; Spain: 0.326) and biting force (UK: 0.351; Spain: 0.427). Biting force was strongly dependent on the denture status. Elderly of the first three groups perceived food products with more hardness and/or fibrous structure as difficult to process orally. The objective measurements of various physiological factors enabled quantitative characterisation of the eating capabilities of elderly people. The observed relationship between hand and oro-facial muscle strengths provides possibility of using non-invasive hand gripping force measurement for eating capability assessment.


Fluoride supplements and changes in tooth decay on the Island of Tristan da Cunha: 1966-1996.
The island of Tristan Da Cunha is one of the few examples in the world of a remote enclosed community. The inhabitants of the island were transported to England in 1961 as a result of a volcanic eruption and during their time in England they received a detailed dental health examination. They were later examined back on the island in 1966 by Dr John Fisher and in 1982 a school fluoride supplementation programme was introduced. The present paper reports the results of the first dental health survey to be carried out on the island since the introduction of a regular school fluoride supplementation programme in 1982. A cohort of 6-19-year-old subjects on the island were examined in 1996 using a similar protocol to that which was used by Fisher in the 1966 examination. Comparing the 6-12-year-olds who were caries free in 1966 with those caries free in 1996 using the Chi-squared statistic reveals a statistically significant greater number caries free in the more recent cohort (X2 - 6.0, P- 0.014). For the older age group (13-19 years), a similar comparison reveals a highly statistically significant difference(Z2 - 12.26, P 0.005). A significant increase in the number of caries free 6-19-year-old children in Tristan Da Cunha between 1966 and 1996 was noted: 1) This is a significant finding in the light of the school fluoride supplementation programme that was introduced on the island in 1982; and 2) Appropriate fluoride supplementation regimes may have conferred a protective effect in a group of children with a cariogenic diet. The paper discusses the significance of this study in the support of fluoridation as a method of reducing the prevalence of dental caries a nd also discusses possibilities for future research on the island of Tristan Da Cunha.


Evolution and challenges in the design of computational systems for triage assistance.
Compared with expert systems for specific disease diagnosis, knowledge-based systems to assist decision making in triage usually try to cover a much wider domain but can use a smaller set of variables due to time restrictions, many of them subjective so that accurate models are difficult to build. In this paper, we first study criteria that most affect the performance of systems for triage assistance. Such criteria include whether principled approaches from machine learning can be used to increase accuracy and robustness and to represent uncertainty, whether data and model integration can be performed or whether temporal evolution can be modeled to implement retriage or represent medication responses. Following the most important criteria, we explore current systems and identify some missing features that, if added, may yield to more accurate triage systems.


Characterization of seven novel mutations on the HEXB gene in French Sandhoff patients.
Sandhoff disease (SD) is an autosomal recessive lysosomal storage disease caused by mutations in the HEXB gene encoding the beta subunit of hexosaminidases A and B, two enzymes involved in GM2 ganglioside degradation. Eleven French Sandhoff patients with infantile or juvenile forms of the disease were completely characterized using sequencing of the HEXB gene. A specific procedure was developed to facilitate the detection of the common 5'-end 16kb deletion which was frequent (36% of the alleles) in our study. Eleven other disease-causing mutations were found, among which four have previously been reported (c.850C>T, c.793T>G, c.115del and c.800_817del). Seven mutations were completely novel and were analyzed using molecular modelling. Two deletions (c.176del and c.1058_1060del), a duplication (c.1485_1487dup) and a nonsense mutation (c.552T>G) were predicted to strongly alter the enzyme spatial organization. The splice mutation c.558+5G>A affecting the intron 4 consensus splice site led to a skipping of exon 4 and to a truncated protein (p.191X). Two missense mutations were found among the patients studied. The c.448A>C mutation was probably a severe mutation as it was present in association with the known c.793T>G in an infantile form of Sandhoff disease and as it significantly modified the N-terminal domain structure of the protein. The c.171G>C mutation resulting in a p.W57C amino acid substitution in the N-terminal region is probably less drastic than the other abnormalities as it was present in a juvenile patient in association with the c.176del. Finally, this study reports a rapid detection of the Sandhoff disease-causing alleles facilitating genetic counselling and prenatal diagnosis in at-risk families.


SIR1, an upstream component in auxin signaling identified by chemical genetics.
Auxin is a plant hormone that regulates many aspects of plant growth and development. We used a chemical genetics approach to identify SIR1, a regulator of many auxin-inducible genes. The sir1 mutant was resistant to sirtinol, a small molecule that activates many auxin-inducible genes and promotes auxin-related developmental phenotypes. SIR1 is predicted to encode a protein composed of a ubiquitin-activating enzyme E1-like domain and a Rhodanese-like domain homologous to that of prolyl isomerase. We suggest a molecular context for how the auxin signal is propagated to exert its biological effects.


Corticotropin releasing hormone stimulation test and nocturnal cortisol levels in normal children.
This study examined hypothalamic-pituitary-adrenal axis functioning in a group (n = 25) of very carefully screened normal children with considerable attention to issues of adaptation and procedural stress. The subjects (mean age 10.3 +/- 1.6 y) were selected as "supernormal" controls as a part of a large psychobiologic study of childhood depression. After careful acclimatization over 24 h, the subjects underwent all-night sampling of plasma cortisol every 20 min, then the following evening had a corticotropin releasing hormone (CRH) stimulation test (using human CRH). Human CRH resulted in a rapid stimulation of adrenocorticotropin and cortisol. Adrenocorticotropin levels increased from 6.8 +/- 3.5 (+/- SD) pmol/L (30.7 +/- 16.1 pg/dL) to a peak of 11.6 +/- 5.5 pmol/L (52.9 +/- 24.8 pg/mL) at 15 min with return to baseline levels by 60 min. Cortisol levels increased from 131.4 +/- 59.7 nmol/L (4.8 +/- 2.2 micrograms/dL) to a peak of 427.0 +/- 113.5 nmol/L (15.5 +/- 4.1 micrograms/dL) at 30 min with return to baseline by 120 min. The cortisol peak was significantly greater (p less than 0.05) in boys [474.6 +/- 129.7 nmol/L (17.2 +/- 4.7 micrograms/dL)] than in girls [366.9 +/- 52.4 nmol/L (13.3 +/- 1.9 micrograms/dL, p less than 0.05)]. Age, body mass index, and pubertal status were not significantly related to hypothalmic-pituitary-adrenal axis measures. Nocturnal cortisol reached a nadir at 160 +/- 60 min after sleep onset (0102 h) and a peak 480 +/- 60 min after sleep onset (0612 h). Nocturnal cortisol levels were significantly (positively) correlated with human CRH-stimulated cortisol (r = 0.56, p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)


Dietary supplementation with pioglitazone hydrochloride and chromium methionine manipulates lipid metabolism with related genes to improve the intramuscular fat and fatty acid profile of yellow-feathered chickens.
Intramuscular fat (IMF) and polyunsaturated fatty acids (PUFAs) have been thought to play a crucial role in improving meat quality. Considering the ability of pioglitazone hydrochloride (PGZ) to deposit fat, and the anti-stress capability of chromium methionine (CrMet), we combined these compounds to produce higher quality meat in poultry. A total of 3000 female chickens were divided into four groups (five replicates, each with 150 chickens): control, control plus15 mg·kg-1 PGZ, control plus 200 μg·kg-1 CrMet, and control plus15 mg·kg-1 PGZ plus 200 μg·kg-1 CrMet. The experiment lasted for 28 days. Compared to the control group and the PGZ group, the average daily gain (ADG) was significantly increased in the PGZ plus CrMet group, whereas the feed-to-gain ratio (F/G) was decreased from 0 to 14 days. Meanwhile, the redness value of breast muscle and IMF of thigh muscle increased in the PGZ plus CrMet group compared with the control group and these detections in the PGZ plus CrMet group exhibited highest value among the four groups. The cooking loss decreased in the breast muscle and thigh muscle after PGZ combined with CrMet in diets. The percentages of C16:1, C18:2n-6 and PUFAs increased in the PGZ plus CrMet group. The mRNA abundance of peroxisome proliferator activated receptor (PPAR) γ, PPAR coactivator 1 α, and fatty acid binding protein 3 was significantly enhanced with PGZ plus CrMet supplementation. Collectively, dietary supplementation with PGZ plus CrMet improved growth performance and meat quality by decreasing the cooking loss and increasing the IMF and PUFA levels. © 2019 Society of Chemical Industry.


False-negative findings in chorionic villus sampling. An experimental approach and review of the literature.
61 fetuses/newborns who had an aberrant karyotype in amniocentesis (AC) or percutaneous umbilical blood sampling (PUBS) were followed-up by chorionic villus sampling (CVS) at birth or after interruption. The overall rate of discrepancies is surprisingly high. Among 46 cases with a non-mosaic numerical aberration an AC or PUBS three had a discrepant finding in placental tissue. This was also true in one of seven cases with non-mosaic structural aberrations and in three of five cases with mosaic structural aberrations. All three cases with a mosaic numerical aberration in AC or PUBS were not represented by CVS and/or lymphocytes or fibroblasts, demonstrating the general problem of the unpredictable prognostic value of mosaicism. Our data suggest, that in case of prenatal diagnosis by CVS, using a combined procedure of short-term (STC) and long-term culture (LTC), in our sample we would have missed one case of 45,X (1.6 per cent). When relying only on STC another two cases, one with 47, +21 and one with 46,XX,der(22) would not have been recognized (4.9 per cent, n = 3). All other chromosome aberrations would have been detected by STC alone. On the other hand, one case of 45,X was 'nearly missed' because of low-grade mosaicism in AC (45,X[1]/46,XX[19]), whereas in placental tissues and PUBS only 45,X was represented. This study mimics a false-negative rate of about 1:3000 (STC plus LTC) or about 1:1000 (STC alone) for an a priori risk group of two per cent (e.g., advanced maternal age).


Long-term Outcomes of Adults With Tricuspid Regurgitation Following Transcatheter Atrial Septal Defect Closure.
Functional tricuspid regurgitation (TR) is a common pathophysiologic condition in adults with ostium secundum atrial septal defect (ASD). The aim of this study was to evaluate long-term outcomes following transcatheter ASD closure, which have not been well studied among patients with significant TR. We reviewed consecutive adult patients who underwent transcatheter ASD closure at Toronto General Hospital, Ontario, Canada, from 1998 to 2016. We linked our hospital registry with Ontario population-based health administrative databases to collect longitudinal data on inpatient and outpatient health care utilisation and vital status. In this cohort study of 949 patients, 199 (22%) had moderate to severe TR before transcatheter ASD closure. A significant proportion of patients (61%) showed improvement in TR severity to at least mild TR after ASD intervention. At a median follow-up of 10.9 years, patients with baseline mild or no TR, compared with those with greater than moderate TR, had significantly lower rates of all-cause mortality (6.8 vs 22.5 per 1000 person-years [PY]; P < 0.001), composite hospitalisation for atrial fibrillation (AF) or heart failure (HF) (22.3 vs 49.1 per 1000 PY; P < 0.001), and new onset of AF (10.4 vs 20.2 per 1000 PY; P = 0.002) and HF (5.0 vs 9.2 per 1000 PY; P = 0.039). Preprocedural TR was independently associated with higher all-cause mortality (adjusted hazard ratio 1.69, 95% confidence interval 1.08-2.62). TR severity was independently associated with a higher risk of mortality and morbidity. Further investigation of earlier device closure or concomitant tricuspid valve intervention may be of interest.


Use of immunosorbent-purified antigens of Fasciola hepatica in enzyme immunoassays.
A monoclonal antibody specific for the T1 tegumental antigen of Fasciola hepatica was used as a solid-phase immunosorbent for the purification of T1 antigen from homogenised mature F hepatica. Material fractionated by this technique was successfully used in enzyme-linked immunoassays to detect antibodies to F hepatica in sera from sheep and cattle. Species differences in response to infection by F hepatica were demonstrated.


[Urbach-Wiethe syndrome: hyalinosis and lipoidosis of the skin and mucous membranes as a neuroectodermosis].
The author reports a case of Wiethe-Urbach syndrome (dermal and mucosal hyalinosis). The diagnosis was based on characteristic clinical findings in the skin and mucosal membranes and microscopic examination of the skin. Coexistent central nervous system dysplasia was characterized by brain atrophy, especially atrophy of the subcortical layers and two horn-like calcifications on the floor of the middle cranial fossa derived, most likely, from the dura.


Eigenvalue sensitivity-based analysis for evaluation of biological network stability versus disturbances.
Network modeling is an effective tool for understanding the properties of complex systems. Networks are widely used to help us gain insight into biological systems. In this way, the cell, gene, and protein are denoted as nodes, and the connection elements are regarded as links or edges. In this paper, a novel stochastic strategy is developed for identifying the most influential edges on the stability of biological networks. Regarding the principles of networks and control-theory basics like Jacobian and eigenvalue sensitivity-based analysis, a new criterion is proposed, called "random sensitivity index matrix" (RSIM). RSIM evaluates the eigenvalue sensitivity of all edges in a network in the presents of stochastic disturbances based on the Monte Carlo algorithm. Through the values of RSIM elements, the sensitive edges are identifiable. In addition, the contribution of each edge in network instability has been compared through different percentages of disturbances. Different percentages of disturbances did not change the results. The performance of the proposed method was verified by simulation results for Lac (lactose) operon and MAPK (Mitogen-activated protein kinases) as two sample biological networks.


Airborne Bacterial Diversity from the Low Atmosphere of Greater Mexico City.
Greater Mexico City is one of the largest urban centers in the world, with an estimated population by 2010 of more than 20 million inhabitants. In urban areas like this, biological material is present at all atmospheric levels including live bacteria. We sampled the low atmosphere in several surveys at different points by the gravity method on LB and blood agar media during winter, spring, summer, and autumn seasons in the years 2008, 2010, 2011, and 2012. The colonial phenotype on blood agar showed α, β, and γ hemolytic activities among the live collected bacteria. Genomic DNA was extracted and convenient V3 hypervariable region libraries of 16S rDNA gene were high-throughput sequenced. From the data analysis, Firmicutes, Proteobacteria, and Actinobacteria were the more abundant phyla in all surveys, while the genera from the family Enterobacteriaceae, in addition to Bacillus spp., Pseudomonas spp., Acinetobacter spp., Erwinia spp., Gluconacetobacter spp., Proteus spp., Exiguobacterium spp., and Staphylococcus spp. were also abundant. From this study, we conclude that it is possible to detect live airborne nonspore-forming bacteria in the low atmosphere of GMC, associated to the microbial cloud of its inhabitants.


The influence of respiratory state on monoamine oxidase activity in rat liver mitochondria.
Changes in the respiratory state of rat liver mitochondria caused significant changes (up to 10-fold) in the rates of oxidative deamination of tyramine, indicating interactions between the inner coupling membrane and the monoamine oxidase sites in the outer membrane, and suggesting the possibility that monoamine oxidase is regulated by the thermodynamic state of the mitochondria.


Cord Haploidentical Non-In Vitro T Cell Depletion Allogeneic Hematopoietic Stem Cell Transplantation Reduces Relapse of Refractory Acute Leukemia.
Whether a graft-versus-graft (GVG) response in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) is associated with an enhanced graft-versus-leukemia (GVL) effect remains highly controversial. Furthermore, it is unknown if the GVG response overwhelms the impact of refractory acute leukemia. We aimed to compare the characteristics and therapeutic outcomes between patients undergoing a modified haploidentical cord blood (cord-haplo) HSCT protocol (n = 97) and those undergoing haploidentical HSCT (n = 42) for refractory acute leukemia. A reliable and stable predominant haploidentical donor chimerism was established. The 2-year relapse rate was more favorable in patients undergoing cord-haplo HSCT than in those undergoing haploidentical HSCT (25.9% versus 53.2%; P = .007), as was progression-free survival (PFS; 35.5% versus 17.9%; P = .049). Meanwhile, nonrelapse mortality at 2 years was not significantly different (38.0% versus 24.6%; P = .367). We also found that a higher number of mutual haploidentical donor-mismatched antigens, a concept similar to HLA mismatching, was associated with better disease control. Multivariate analysis identified cord-haplo HSCT as an independent significant predictor of reduced relapse (hazard ratio [HR], .44; P = .028) and improved PFS (HR, .58; P = .033), as was chronic graft-versus-host disease (GVHD) (relapse: HR, .42; P = .013; PFS: HR, .63: P = .052). However, the incidences of neutrophil and platelet engraftment, GVHD, and virus reactivation were comparable in the 2 groups. This study demonstrates that cord-haplo HSCT significantly enhances the GVL effect and improves PFS, providing a reliable and efficient therapeutic platform for patients with refractory acute leukemia.


Amelogenin gene similarity in vertebrates: DNA sequences encoding amelogenin seem to be conserved during evolution.
Mouse amelogenin cDNA was used in hybridization assays with genomic DNA, cut with the restriction enzyme Eco RI, from the edentulous chicken (Gallus domesticus), the monophyodont mouse (as control), diphyodont man, and the polyphyodont fishes Atlantic salmon (Salmo salar) and seawolf (Anarrhichas lupus). The hybridization assay was performed under stringent conditions with non-radioactive probes. Hybridization was obtained with mouse (6.4-kb band), man (9-kb and 13-kb bands), and seawolf (18-kb band) genomic DNA. This demonstrates DNA sequence similarities between these species, and supports the theory that DNA sequences encoding enamel proteins appear to be highly conserved during the evolution of vertebrates. Lack of hybridization in salmon and chicken may be due to sequence divergences or structural differences in an amelogenin gene analog, or it may be that no amelogenin gene is present in these animals.


The maize abnormal chromosome 10 meiotic drive haplotype: a review.
The maize abnormal chromosome 10 (Ab10) haplotype encodes a meiotic drive system that converts heterochromatic knobs into centromere-like bodies that are preferentially segregated through female meiosis. Ab10 was first described in the 1940s and has been intensively studied. Here I provide a comprehensive review of the literature, starting from the discovery of knobs and Ab10, preceding through the classic literature, and finishing with molecular structure and mechanisms. The defining features of the Ab10 haplotype are its two specialized kinesins, Kinesin driver and TR-1 kinesin, that activate neocentromeres at knobs containing different classes of the tandem repeat. In most Ab10 haplotypes, the two kinesin/knob systems cooperate to promote maximum meiotic drive. However, recent interpretations suggest that each kinesin/knob system can function as an independent meiotic driver and that in some cases they compete with each other. Ab10 is present at low frequencies throughout the genus Zea and has significantly expanded genome size by promoting the formation of knobs throughout the genome.


Suicidal ideation among Bangladeshi university students early during the COVID-19 pandemic: Prevalence estimates and correlates.
Lockdown, social isolation, and interruption of daily life during the COVID-19 period have impacted many lives. University students are particularly vulnerable to such disruptions and may be particularly disposed to suicidal ideation, potentially creating a new public health crisis. This study aimed to assess suicidal ideation and associated factors among university students in Bangladesh during the early stages of the COVID-19 pandemic. A cross-sectional online survey was conducted using the Google form (Google survey tool) from April to May 2020. Initially, 3366 respondents voluntarily completed the survey form. Finally, 3331 surveys were included in the final analyses after removing incomplete surveys. The data ware reviewed, rechecked, and analyzed with SPSS (25.0 version) software. A total of 1979 (59.4%) males and 1352 (40.6%) females participated. Respondents were between the ages of 18 to 28 years (mean age 21.4 years [SD = 1.9]). The prevalence estimate of suicidal ideation was 12.8%. Potential risk factors included less sleep, excess sleep, cigarette smoking, past suicidal thoughts, suicide attempt history, family history of suicidality, depression, anxiety, and stress. Potential protective factors included being male, having lower SES, living in rural areas, regular physical exercise, and satisfactory study. Suicidal ideation was prevalent among Bangladeshi university students during the onset of the COVID-19 pandemic. Understanding the correlates of suicidal ideation may aid to develop targeted strategies to support students during and after the COVID-19 pandemic.


Decreased stable transfection frequencies of six X-ray-sensitive CHO strains, all members of the xrs complementation group.
Six X-ray-sensitive strains (xrs) of the Chinese hamster ovary (CHO) cell line, all of which have a defect in double-strand break (dsb) rejoining, have been investigated for their proficiency in DNA transfection assays. All 6 strains and clonal isolates derived from them, show a decreased stable transfection frequency using the plasmids pSV2neo and pSV2gpt after transfection by either the CaPh method or the polybrene method. The magnitude of this effect is DNA concentration dependent and is more marked after transfection with higher DNA concentrations (5-20 micrograms DNA). A spontaneous X-ray-resistant reactivant (or revertant) of one xrs strain also acquired the elevated transfection frequency of the wild-type strain providing evidence for a causal relationship between the decreased transfection frequency and the xrs phenotype. In contrast, the strains show no defect when transfection is assayed using a transient transfection system. Since the transient transfection assay only depends on the uptake and transcriptional activity of foreign DNA, and does not necessitate DNA integration, this suggests that the xrs strains do not have a defect in the uptake of foreign DNA, but might have a defect in integration or the processing of DNA molecules prior to integration.


Evaluation of heavy metals in hazardous automobile shredder residue thermal residue and immobilization with novel nano-size calcium dispersed reagent.
This study was conducted to synthesize and apply a nano-size calcium dispersed reagent as an immobilization material for heavy metal-contaminated automobile shredder residues (ASR) dust/thermal residues in dry condition. Simple mixing with a nanometallic Ca/CaO/PO4 dispersion mixture immobilized 95-100% of heavy metals in ASR dust/thermal residues (including bottom ash, cavity ash, boiler and bag filter ash). The quantity of heavy metals leached from thermal residues after treatment by nanometallic Ca/CaO/PO4 was lower than the Korean standard regulatory limit for hazardous waste landfills. The morphology and elemental composition of the nanometallic Ca/CaO-treated ASR residue were characterized by field emission scanning election microscopy combined with electron dispersive spectroscopy (FE-SEM/EDS). The results indicated that the amounts of heavy metals detectable on the ASR thermal residue surface decreased and the Ca/PO4 mass percent increased. X-ray diffraction (XRD) pattern analysis indicated that the main fraction of enclosed/bound materials on ASR residue included Ca/PO4- associated crystalline complexes, and that immobile Ca/PO4 salts remarkably inhibited the desorption of heavy metals from ASR residues. These results support the potential use of nanometallic Ca/CaO/PO4 as a simple, suitable and highly efficient material for the gentle immobilization of heavy metals in hazardous ASR thermal residue in dry condition.


Suicide mortality among patients treated by the Veterans Health Administration from 2000 to 2007.
We sought to examine rates of suicide among individuals receiving health care services in Veterans Health Administration (VHA) facilities over an 8-year period. We included annual cohorts of all individuals who received VHA health care services from fiscal year (FY) 2000 through FY 2007 (October 1, 1999-September 30, 2007; N = 8,855,655). Vital status and cause of death were obtained from the National Death Index. Suicide was more common among VHA patients than members of the general US population. The overall rates of suicide among VHA patients decreased slightly but significantly from 2000 to 2007 (P < .001). Male veterans between the ages of 30 and 64 years were at the highest risk of suicide. VHA health care system patients are at elevated risk for suicide and are appropriate for suicide reduction services, although the rate of suicide has decreased in recent years for this group. Comprehensive approaches to suicide prevention in the VHA focus not only on recent returnees from Iraq and Afghanistan but also on middle-aged and older Veterans.


Effectiveness of home-based telerehabilitation in mild to moderate Alzheimer's disease: A randomised controlled study.
The COVID-19 pandemic has made it necessity that rehabilitation services are provided remotely to patients. These process required a transformation in healthcare. The aim of this study was investigate the effectiveness of the home-based online supervised exercise program in Alzheimer's disease (AD). To our knowledge, this is the first study to report the results of real-time supervised physical exercise telerehabilitation program in AD. Eighteen subjects with early-middle stage of AD were randomised into 2 group as telerehabilitation group (TG; mean age: 77.7 ± 5.29 years; 7 Female, 3 Male) and control group (CG; mean age: 78.5 ± 7.07 years; 5 Female, 3 Male). Our primary outcome was Mini-Mental State Examination (MMSE), seconder outcomes were Timed Up&Go (TUG), One-leg Balance Test (OLBT), Functional Independence Measure (FIM), Geriatric Depression Scale-Short Form (GDS). The 6-week motor-cognitive dual-task exercise training was performed online and under the supervision of physiotherapist through videoconference. No physical or cognitive intervention was applied to the control group for 6 weeks. Subjects were assessed before and after the treatment. In statistical analysis, the change in the outcome scores was calculated (∆ = last measurement-first measurement), the difference between the groups was performed with the Mann Whitney-U Test in SPSS 22.0. Trial's protocol is registered with Clinicaltrials.gov under number NCT04606251. There was a significant difference between TG and CG in favor of TG in MMSE, TUG, FIM and GDS (p<0,05); There was no significant difference between groups in OLBT (p>0,05). Statistical results have been showed in Table 1. No safety problem was observed during the treatment. All subjects were completed the study, there was a high adherence to treatment. Physical exercise treatment with telerehabilitation was feasible, safe and well-accepted by people with early-middle stage of AD. Online-supervised exercise program can improve cognitive function, functional mobility, independence and reduce depressive symptoms.


New treatment of cerebral vasospasm with Fluosol-DA 20%: protective effect on cerebral ischemia and change of cerebral blood flow (CBF).
It was found that Fluosol-DA 20% relieves human acute cerebral ischemia resulting from vasospasm in 62% of the cases. However, several problems were encountered during the investigation. The efficacy of the solution was temporary, that is, within 24 hours. This is considered logical because perfluorochemical particles are eliminated fairly rapidly from the circulating blood. Successive administrations should be necessary until cerebral vasospasm is remitted. Another problem is that it is not clear whether the doses of the solution given in this study (10 ml/kg/day) are sufficient or not, since the depth of the cerebral ischemia is considered to vary depending on the case. It might be necessary to change the volume of the solution given in accordance with the depth of the ischemia of each patient.


HLA genotypes and variant alleles in Sudanese families of Arab-Negroid tribal origin.
The indigenous population of the Blue Nile Province, Sudan, is an Arab-Negroid admixture, although some isolates of west African origin (Fallata) have begun to intermix with the indigenous population. Consanguineous marriages are common in these Muslim families. Members of 22 nuclear families were typed for HLA class I and II antigens using complement-dependent microcytotoxicity with Ninth International Workshop (9th WS) and local reagents. Considerable polymorphism was observed at each locus with a majority of the World Health Organization (WHO)-recognized alleles represented in the parental sample, albeit at low frequency. Seven parental haplotypes carried A locus alleles which were not identical to WHO-recognized specificities. All appeared to be Aw19-related specificities. Five B locus serologic variants were observed; all appeared distinct from WHO-recognized specificities. In one family we observed a new DR-DQ association; DR4 segregated with DQw2, rather than with DQw3. As has been observed for several other genetic systems in these tribes, considerable polymorphism was found for all class I and class II gene products in spite of a high level of consanguinity. Tribal admixture and/or a selective advantage in protecting the population against disease may account for this unexpectedly high level of heterozygosity.


Sex-determining region Y-related high mobility group box (SOX)-2 is overexpressed in cervical squamous cell carcinoma and contributes cervical cancer cell migration and invasion in vitro.
Sex-determining region Y-related high mobility group box 2 (SOX-2) is a key pluripotency-associated transcription factor and may be implicated in the pathogenesis of cervical squamous cell carcinoma (SCC). The aim of this study was to explore SOX-2 expression in cervical SCC tissues and to examine whether and how SOX-2 regulates the malignant behaviors of cervical SCC cells in vitro. We here found that SOX-2 expression in the examined cervical SCC tissues was higher than that in the normal cervical and cervical intraepithelial neoplasia (CIN) tissues. Higher protein level of SOX-2 (nuclear positive staining cells ≥50 %) was detected in 34.9 % (29 out of 83 cases) of cervical SCC patients. We also noted that 100 % of well-differentiated and 66.7 % of moderately differentiated cervical SCCs showed lower SOX-2 expression (nuclear positive staining cells <50 %), while 58.8 % of poorly differentiated tumors had higher SOX-2 expression (P < 0.05). Furthermore, the migratory and invasive capabilities of SiHa cervical cancer cells were enhanced when SOX-2 was upregulated whereas suppressed when SOX-2 was downregulated. Also, the phosphorylation levels of protein kinase B (Akt) and extracellular regulated protein kinases (ERK) 1/2 were increased in SOX-2-overexpressed cancer cells but decreased in SOX-2-depleted cells. Additionally, LY294002 (Akt pathway inhibitor) or U0126 (ERK pathway inhibitor) significantly suppressed SOX-2-overexpression-induced migration and invasion in SiHa cells. Our results indicate that differentially expressed SOX-2 is associated with tumor differentiation (P < 0.05) and that SOX-2 contributes to the migratory and invasive behaviors of cervical SCC in vitro.


Occult primary malignant melanoma: factors influencing survival.
Seventy-six patients with occult primary malignant melanoma were studied in order to detect features which would help to determine prognosis. It was found that the 5-year survival rate of these patients was: (a) no worse than in patients first presenting with one known primary lesion and metastases; (b) just as poor for women as for men; (c) more favourable if only a single lymph node was involved with secondary deposits; (d) similar whether the manner of spread of the disease was lymphatic or haematogenous; (e) similar whether there was or was not a history of a pre-existing lesion. The prognosis for occult primary malignant melanoma, although bad, is not hopeless.


The structure of the Plasmodium falciparum EBA175 ligand domain and the molecular basis of host specificity.
Erythrocyte-binding antigen 175 (EBA175) is one of the best-characterized Plasmodium falciparum merozoite ligands; the recently solved crystal structure of EBA175 reveals that terminal sialic acids on the erythrocyte glycoprotein glycophorin A are a crucial factor for erythrocyte recognition by EBA175 because they lock into pockets on its surface. Comparison with Plasmodium reichenowi EBA175 indicates that these interactions have a pivotal role in the host-specific adaptations of parasite ligands.


Posterior Prosthetic Teeth Size Selection for Edentulous Egyptian Patients: A Radiographic Assessment.
The aim of this study was to correlate the location of the mental foramen and overlying teeth and apply these observations to posterior prosthetic teeth selection in a group of Egyptian edentulous patients. Retrospective cone beam computed tomography data from 40 dentate and 40 edentulous patients scanned with radiopaque denture duplicates were compared in relation to mental foramen position. The probability of locating the mental foramen opposite the first premolar was higher in dentate patients, while finding it opposite the first molar was higher in edentulous patients. Selected posterior teeth size for the selected Egyptian edentulous patients might be slightly smaller than for dentate patients.


Unique Hemoglobinopathy Pattern Following Treatment with Voxelotor.
Voxelotor, a FDA-approved drug for the treatment of patients with sickle cell disease (SCD), inhibits hemoglobin S (HbS) polymerization and increases total hemoglobin via hemolysis reduction. This drug has shown unique patterns in hemoglobin fractionation, affecting its interpretation. We aimed to evaluate whether these voxelotor-induced changes can be linked to improvement of hemolysis markers in pediatric patients on voxelotor. A total of 15 patients (age 12 to 20 years; 40% females) on voxelotor were evaluated to compare changes in the hemoglobin fractionation by capillary electrophoresis, total hemoglobin, reticulocyte percentage (retic%), lactate dehydrogenase (LDH), and bilirubin measurements before and after the recorded date of voxelotor prescription. Hemoglobin fractionation showed changes in the profile of 60% (9/15) of the patients studied. Out of the 9 patients for which voxelotor showed changes in the hemoglobin fractionation, 44% (4/9) had an increase of >1 g/dL in their total hemoglobin after voxelotor treatment was started. Assessment of other hemolysis markers available showed decreased LDH (4/4), retic % (6/8), and bilirubin (3/4). Unique pattern of hemoglobin fractionation analysis following therapy with voxelotor has potential as a tool for the assessment of response and/or compliance to voxelotor for the treatment of SCD.


A modified technique (using polyester tape) of skin surface biopsy. Its interest for the investigation of athlete's foot.
A technical modification of skin surface biopsy has been introduced by using plastic tape instead of glass as holder, mainly to investigate mycological infections of skin folds. Among various brands of plastic sheets, a polyester film (Melinex O UCB-SIDAC) has been demonstrated as the most suitable. A direct microscopic comparison has been made between our modified technique and conventional scraping as procedures for collecting material from interdigital spaces in 30 patients with bilateral athlete's foot. It has been shown that the skin surface biopsy gives a slightly greater number of positive results (presence of dermatophytes or Candida species) than the conventional scraping technique, although the difference between both techniques is not statistically significant at the 0-05 level (0-05 less than P less than 0-10). Some advantages of the modified skin surface biopsy are emphasized.


Determination of phenobarbital by radioimmunoassay.
A radioimmunoassay for phenobarbital has been studied. Antiphenobarbital antisera were obtained by repeated immunization of rabbits with p-succinamidophenobarbital conjugated to bovine serum albumin. Less than 0.2 pmol of phenobarbital could be measured by this procedure. The specificity of the antibodies was directed to substituents on the nitrogen atoms of the barbituric ring as well as to substituents at the carbon 5-position of the ring.


Biomechanical correlates of symptomatic and asymptomatic neurophysiological impairment in high school football.
Concussion is a growing public health issue in the United States, and chronic traumatic encephalopathy (CTE) is the chief long-term concern linked to repeated concussions. Recently, attention has shifted toward subconcussive blows and the role they may play in the development of CTE. We recruited a cohort of high school football players for two seasons of observation. Acceleration sensors were placed in the helmets, and all contact activity was monitored. Pre-season computer-based neuropsychological tests and functional magnetic resonance imaging (fMRI) tests were also obtained in order to assess cognitive and neurophysiological health. In-season follow-up scans were then obtained both from individuals who had sustained a clinically-diagnosed concussion and those who had not. These changes were then related through stepwise regression to history of blows recorded throughout the football season up to the date of the scan. In addition to those subjects who had sustained a concussion, a substantial portion of our cohort who did not sustain concussions showed significant neurophysiological changes. Stepwise regression indicated significant relationships between the number of blows sustained by a subject and the ensuing neurophysiological change. Our findings reinforce the hypothesis that the effects of repetitive blows to the head are cumulative and that repeated exposure to subconcussive blows is connected to pathologically altered neurophysiology.


Analysis of the cell-free amniotic fluid transcriptome expressed during the euploid mid-trimester of pregnancy.
The amniotic fluid (AF) contains cell-free RNAs (cfRNAs), which are considered to reflect the fetal status in utero. However, there are limited numbers of data to examine the AF cell-free transcriptome because amniocentesis is an invasive procedure. In this study, the AF transcriptome expressed during the euploid mid-trimester of pregnancy was characterized. Fourteen AF samples were collected. RNA was extracted from AF supernatant, hybridized to Affymetrix GeneChip Human arrays, and the transcriptome was analyzed by using the DAVID toolkit. We detected 1069 genes in the 14 AF samples. The GNF atlas mapping showed that genes present in the AF were annotated with endocrine organs and blood components, including the pancreas, adrenal gland, thyroid, ovary and monocytes. The proteins encoded by the transcriptome were localized to several organs, which are directly in contact with the AF, including the placenta, lung, skin, epithelium, and kidney. During the early fetal period, there is a bi-directional diffusion between the fetus and AF. Therefore, the AF composition is similar to that of the fetal plasma. In addition, fetal urine, swallowing, pulmonary secretion, and diffusion across the placenta contribute to produce amniotic fluid by directly excreting fluid. The KEGG pathway analysis with placenta specific genes revealed that focal adhesion and extracellular matrix receptor interaction pathways were enriched. These pathways are important for the placental development. cfRNA in the amniotic fluid originates from placenta and fetal organs directly contacting the amniotic fluid as well as from diffusion of the fetal plasma across the placenta. AF transcriptome may reflect not only fetal development, but also placental development.


Regional variation in home care use in Manitoba.
Previous studies report geographic variation in the use of home care services. In the province of Manitoba, home care is a core service that Manitoba's twelve regional health authorities (RHAs) are obligated to deliver. Manitoba's RHAs range from remote northern and rural southern regions to a major city, resulting in different challenges for delivering home care. Given this potential for inconsistent delivery and the previous findings of regional variation in other settings, the objective of this study was to measure and assess variation in the use of home care across Manitoba's RHAs. We used data from the Provincial Home Care Program's client registry, other health care administrative databases, and Vital Statistics. Home care use was measured using multiple indicators, including rates of population use, use after hospitalization, before entry to a long-term care facility, and before death. While some important differences emerged, overall we found comparable use of home care across Manitoba.


[The clinical value of endoscopic ultrasonography in early diagnosis of pancreatic tumor].
To investigate the clinical value of endoscopic ultrasonography (EUS) and intraductal ultrasonography (IDUS) compared with the other imaging examination in the early diagnosis of pancreatic tumor. Retrospect studied of 188 cases of small pancreatic lesions (less than 3 cm in diameter) detected by EUS, IDUS and the other imaging examination at Changhai hospital from October 1992 to September 2006. (1) The accurate rate of small pancreatic cancer diagnosed by EUS was 95.6%, and it is better compared with US (58.6%), CT (77.4%), MRI (76.2%) and ERCP (85.3%). The most common endosonographic features of small pancreatic cancer were alike round, irregular edge, hypoechoic mass with uniformity internal echo. (2) IDUS was performed in 25 cases of small pancreatic lesions, the accurate rate of diagnosis was 100% (25/25), and it is better compared with US 32.0% (8/25), CT 52.9% (9/17) and MRI 57.9% (11/19). (3) EUS guided FNA (EUS-FNA) was performed in 18 cases of small pancreatic lesions, the accurate rate of diagnosis was 66.7% (12/18). (4) The accurate rate of pseudocyst diagnosis by EUS was 100.0% (27/27), it is better compared with US 52.0% (13/25), CT 66.7% (12/18), MRI 82.4% (14/17) and ERCP 78.9% (15/19); and the overall accurate rate of diagnosis of cystic pancreatic tumors by EUS was 57.7% (15/26), it is better compared with US 19.2% (5/26), CT 36.4% (8/22), MRI 37.5% (6/16) and ERCP 50.0% (7/14). EUS and IDUS were better than the other imaging examinations in the detection of small pancreatic tumors.


Primary intracranial myxoma of the parietal region. Illustrated case report.
An extremely rare case of primary intracranial myxoma mimicking an intraaxial parenchymal tumour is reported. A 25 year old male presented with complaints of headache and right sided hemiparesis. A gross total resection of the tumour was achieved. Histology confirmed that the tumour was a myxoma. Investigations did not reveal any underlying cardiac focus. Following surgery, the patient had rapid recovery from his symptoms and on a follow up at 3 months was asymptomatic. Primary intracranial myxomas are extremely rare and this is the fifth reported case in neurosurgical literature and third report of supratentorial myxoma. Though metastatic myxomas from atrial myxomas are known to occur primary intracranial myxomas are extremely rare. Surgical resection provides an excellent prognosis and the surgical aim should be to achieve total resection.


Oxidative stress induces claudin-2 nitration in experimental type 1 diabetic nephropathy.
Renal complications in diabetes are severe and may lead to renal insufficiency. Early alterations in tight junction (TJ) proteins in diabetic nephropathy (DN) have not been explored and the role of oxidative stress in their disassembly has been poorly characterized. We investigated the expression and distribution of TJ proteins: claudin-5 in glomeruli (GL), occludin and claudin-2 in proximal tubules (PTs), and ZO-1 and claudin-1, -4, and -8 in distal tubules (DTs) of rats 21 days after streptozotocin injection. Redox status along the nephron segments was evaluated. Diabetes increased kidney injury molecule-1 expression. Expression of sodium glucose cotransporters (SGLT1 and SGLT2) and facilitative glucose transporter (GLUT2) was induced. Increased oxidative stress was present in GL and PTs and to a lesser extent in DTs (measured by superoxide production and PKCβ2 expression), owing to NADPH oxidase activation and uncoupling of the endothelial nitric oxide synthase-dependent pathway. Claudin-5, occludin, and claudin-2 expression was decreased, whereas claudin-4 and -8 expression increased. ZO-1 was redistributed from membrane to cytosol. Increased nitration of tyrosine residues in claudin-2 was found, which might contribute to decrement of this protein in proximal tubule. In contrast, occludin was not nitrated. We suggest that loss of claudin-2 is associated with increased natriuresis and that loss of glomerular claudin-5 might explain early presence of proteinuria. These findings suggest that oxidative stress is related to alterations in TJ proteins in the kidney that are relevant to the pathogenesis and progression of DN and for altered sodium regulation in diabetes.


Recognition of familial dyslipidemias in 5-year-old children using the lipid phenotypes of parents. The STRIP project.
Adult dyslipidemias may reveal familial and, therefore, offspring dyslipidemias. We evaluated the prevalences of the adult-offspring dyslipidemias in 441 general population families composed of both parents and one 5-year-old child. Family members were classified using the 90th or 10th percentiles for hypercholesterolemia (IIA), hypertriglyceridemia (IV), combined hyperlipidemia (IIB), and low high density lipoprotein cholesterol concentration without hyperlipidemia (hypoHDL). In familial combined hyperlipidemia (FCHL), the IIB-phenotype was in one generation and one of the three hyperlipidemias in the other generation. Finally, the parental dyslipidemia phenotypes and elevated lipids (>80th percentile) that reveal offspring dyslipidemia were selected by stepwise logistic regression. Either the IIA-, IV- or hypoHDL phenotype was found in both generations in 2.8, 2.0 and 1.4% of the families, respectively. FCHL was seen in 1.8% of the families, which confirms the earlier views. The predictive values of the elevated parental cholesterol, type IV or hypoHDL parents to find type IIA, IV and hypoHDL children were low for systematic screening: 16, 13 and 15%, respectively. However, 44% of the children of IIB parents expressed hyperlipidemia (odds ratio 4.7, P=0.006). The IIB phenotype of the parent is a good predictor of the child's hyperlipidemia, and when encountered, it indicates that the lipids of the child should be studied. This would be as important as selective screening of familial hypercholesterolemia.


Structure of the phosphosaccharide-inositol core of the Leishmania donovani lipophosphoglycan.
The phosphosaccharide-inositol core of the lipophosphoglycan of Leishmania donovani was generated by treatment of the glycoconjugate with mild acid and digestion with phosphatidylinositol-specific phospholipase C. The core was purified and examined by one- and two-dimensional 1H-1H NMR and by methylation analysis. From the results, the carbohydrate core was elucidated as a phosphosaccharide attached to the inositol residue of the lyso-alkylphosphatidylinositol anchor of lipophosphoglycan as follows: PO4----6GalP(alpha 1----6)GalP(alpha 1----3)Galf(alpha 1----3)ManP(alpha 1----3)ManP(alpha 1----4)GlcNP(alpha 1----6)myo-inositol. The presence of an internal galactofuranose residue is highly unusual and the ManP(alpha 1----4)GlcNP(alpha 1----6)myo-inositol sequence is homologous to the respective portion of the glycosylphosphatidylinositol anchors reported for both the Trypanosoma brucei variant surface glycoprotein and the rat brain Thy-1 glycoprotein.


Culture scale-up and immobilisation of a mixed methanotrophic consortium for methane remediation in pilot-scale bio-filters.
Robust methanotrophic consortia for methane (CH4) remediation and by-product development are presently not readily available for industrial use. In this study, a mixed methanotrophic consortium (MMC), sequentially enriched from a marine sediment, was assessed for CH4 removal efficiency and potential biomass-generated by-product development. Suitable packing material for bio-filters to support MMC biofilm establishment and growth was also evaluated. The enriched MMC removed ∼7-13% CH4 under a very high gas flow rate (2.5 L min-1; 20-25% CH4) in continuous-stirred tank reactors (∼10 L working volume) and the biomass contained long-chain fatty acids (i.e. C16 and C18). Cultivation of the MMC on plastic bio-balls abated ∼95-97% CH4 in pilot-scale non-sterile outdoor-operated bio-filters (0.1 L min-1; 1% CH4). Contamination by cyanobacteria had beneficial effects on treating low-level CH4, by providing additional oxygen for methane oxidation by MMC, suggesting that the co-cultivation of MMC with cyanobacterial mats does not interfere with and may actually be beneficial for remediation of CH4 and CO2 at industrial scale.


Diosmetin inhibits apoptosis and activates AMPK-induced autophagy in myocardial damage under hypoxia environment.
Inhibition of hypoxia-induced cardiomyocyte apoptosis is considered as an important treatment method for ischemic heart diseases, but related drugs are still insufficient. The present study aims to explore the protective function and mechanism of the key Chinese medicine monomer diosmetin (DIOS) on the injury of cardiomyocytes induced by hypoxia. Here, AC16 and HCM-a cells were treated with 40 μM of DIOS under hypoxic environment and a hypoxic rat model was built to study the role of DIOS. The viability and autophagy of cardiomyocytes were increased, but the apoptosis of cells was suppressed by 40 μM DIOS, under hypoxic environment. Intriguingly, 10 mM 3-methyladenine, an inhibitor of autophagy, reversed the effect of DIOS on autophagy and apoptosis of the cardiomyocytes under hypoxia. Furthermore, DIOS induced AMP-activated protein kinase (AMPK) activation and Compound C (5 μM), an AMPK inhibitor, attenuated the inhibition of DIOS on the apoptosis of cardiomyocytes under hypoxia environment. In isoprenaline-induced hypoxic rats, it was verified that DIOS inhibited apoptosis, accelerated autophagy, and activated AMPKα pathway in vivo. Our findings indicated that DIOS alleviated hypoxia-induced myocardial apoptosis via inducing the activation of AMPK-induced autophagy. In summary, the study suggested that DIOS inhibited the apoptosis and induced the autophagy of hypoxia-induced cardiomyocytes through AMPK activation.


Malakoplakia of urinary bladder following cadaveric renal transplantation.
Malakoplakia of the urinary bladder following cadaveric renal transplantation in a twenty-two-year-old woman is reported. Urinary tract infection with Escherichia coli persisted postoperatively. Three years later, gross hematuria and fever occurred. Yellow-tan mucosal plaques or nodules were observed cystoscopically, and histologic examination revealed malakoplakia of the urinary bladder with characteristic foamy histiocytes containing Michaelis-Gutmann bodies.