Cell-Type Specific Regulation of Cholesterogenesis by CYP46A1 Re-Expression in zQ175 HD Mouse Striatum.
Cholesterol metabolism dysregulation is associated with several neurological disorders. In Huntington's disease (HD), several enzymes involved in cholesterol metabolism are downregulated, among which the neuronal cholesterol 24-hydroxylase, CYP46A1, is of particular interest. The restoration of CYP46A1 expression in striatal neurons of HD mouse models is beneficial for motor behavior, cholesterol metabolism, transcriptomic activity, and alleviates neuropathological hallmarks induced by mHTT. Among the genes regulated after CYP46A1 restoration, those involved in cholesterol synthesis and efflux may explain the positive effect of CYP46A1 on cholesterol precursor metabolites. Since cholesterol homeostasis results from a fine-tuning between neurons and astrocytes, we quantified the distribution of key genes regulating cholesterol metabolism and efflux in astrocytes and neurons using in situ hybridization coupled with S100β and NeuN immunostaining, respectively. Neuronal expression of CYP46A1 in the striatum of HD zQ175 mice increased key cholesterol synthesis driver genes (Hmgcr, Dhcr24), specifically in neurons. This effect was associated with an increase of the srebp2 transcription factor gene that regulates most of the genes encoding for cholesterol enzymes. However, the cholesterol efflux gene, ApoE, was specifically upregulated in astrocytes by CYP46A1, probably though a paracrine effect. In summary, the neuronal expression of CYP46A1 has a dual and specific effect on neurons and astrocytes, regulating cholesterol metabolism. The neuronal restoration of CYP46A1 in HD paves the way for future strategies to compensate for mHTT toxicity.


A novel apparatus for interocular interaction evaluation in children with and without anisometropic amblyopia.
Dichoptic visual stimulation may be achieved using shutter goggles and mirror systems. These methods vary in their feasibility for use in children. This study aims to investigate the feasibility of use of a simple trial frame-based system to evaluate interactions in children. Low contrast acuity, contrast sensitivity and alignment sensitivity were measured in the non-dominant eye of 10 normally-sighted children, 14 anisometropic children without amblyopia and 14 anisometropic amblyopic children (aged 5-11 years) using goggles and a trial frame apparatus (TFA). The dominant eye was either fully or partially occluded. The difference in visual functions in the non-dominant eye between the full and partial occlusion conditions was termed the 'interaction index'. Agreement between the TFA and goggles in terms of visual functions and interactions was assessed in anisometropic children with and without amblyopia using the Bland-Altman method and t-test. Training sessions allowed subjects to become accustomed to the systems and tasks. The duration of training, the number of breaks requested by subjects and their willingness to attend further experiments were recorded in 10 subjects from each group and were compared between groups and between systems. Both Bland-Altman and t-test methods indicated acceptable agreement between the TFA and goggles in visual function and interaction measures (p > 0.05), except for contrast sensitivity measured in anisometropic children without amblyopia (p = 0.042). For all subject groups, contrast sensitivity training was significantly longer using goggles than using the TFA (p ≤ 0.001). Significantly more breaks were requested in acuity and contrast sensitivity testing, when goggles were used than when the TFA was used (p < 0.045). Anisometropic children without amblyopia showed a significantly greater willingness to attend more experiments using the TFA than using goggles (p = 0.025). The TFA may be a useful tool in studies of interactions in amblyopes, particularly in studies of children's vision.


Time and causation in studies of long-term exposure to environmental factors.
The various shortcomings of the prevalence study as an instrument for causal research are evaluated by comparing the prevalence design with the classical experimental design. On the basis of these shortcomings it is suggested that epidemiologists refine their research strategies in two respects, both related to time. (1) it is suggested that they include formerly exposed as well as presently exposed in their sampling frames and (2) that they avoid using present status with respect to causal factors as indicators of life-experience of these factors in analysis. On the basis of some studies of the relationship between long-term exposure to presumed noxae and chronic lung disease, numerical examples of the undesirable consequences of ignoring time are given.


From margin to center: An Asian Americanist psychology.
In the midst of a global pandemic and movements for racial justice, there is an opportunity to (re)imagine an Asian Americanist psychology that can bring about a more just society. The authors describe the contours of an Asian Americanist psychology that is grounded in historical context, an intersectional analysis, and representational ethics while focusing on community strengths and structural change. The article concludes with calls to action for Asian American psychologists, other psychologists of color, and White psychologists to envision a new era that centers Asian Americans in the multiracial pursuit of social justice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Effects of oral pretreatment with metoprolol on left ventricular wall motion, infarct size, hemodynamics, and regional myocardial blood flow in anesthetized dogs during thrombotic coronary artery occlusion and reperfusion.
To study the effects of oral pretreatment with metoprolol over 3 days on hemodynamics, left ventricular function, regional myocardial blood flow, and infarct size in an anesthetized dog model of thrombotic occlusion of the anterior descending coronary artery treated with thrombolysis. Ten dogs received 200 mg metoprolol (Selozok) orally and 8 dogs received placebo for 3 days twice daily and 1 hour before the experiment. Under general anesthesia, thrombotic occlusion was provoked by the copper-coil technique. Intracardiac pressures and their derivatives, cardiac output (thermodilution method), regional coronary blood flow (microspheres), global and regional left ventricular function (ventriculography), and infarct size (triphenyltetrazolium staining) were measured. Measurements were performed during control, after 60 minutes of occlusion, and after 30 and 90 minutes of reperfusion. Thrombolysis was performed in all dogs 60 minutes after occlusion by intravenous infusion of 10 micrograms/kg/min of rt-PA for 30 minutes. During control cardiac output was lower, total peripheral resistance higher, and Tau and the left ventricular isovolumic relaxation time greater in the metoprolol group. During occlusion and after reperfusion, there were no significant hemodynamic differences between both groups. Blood flow to the area at risk and circumflex territory during occlusion were, respectively, 12.8 +/- 5.80 ml/100 g/min versus 9.65 +/- 8.35 ml/100 g/min (p > 0.05) and 42.58 +/- 7.86 ml/100 g/min versus 61.52 +/- 20.43 ml/100 g/min (p = 0.01) in the metoprolol- and placebo-treated dogs. The ratios of flow area at risk/circumflex territories in the epicardial, midmyocardial, and endocardial layers were, respectively, 0.44 +/- 0.20, 0.19 +/- 0.09, and 0.20 +/- 0.13 in the metoprolol- versus 0.24 +/- 0.16, 0.08 +/- 0.06, and 0.06 +/- 0.07 (p > or = 0.04) in the placebo-treated dogs. The ratio of flow endocardium/epicardium was higher (p > or = 0.02) in the active treatment group during the control period, both in the area at risk and circumflex territory; this was also the case in the circumflex territory at the end of the experiment (p = 0.003). Thirty minutes after occlusion, blood flow to the three layers of the area at risk rose to 2-3 times control values in both groups; a significant increase above control values also occurred in the circumflex territory. After 90 minutes reperfusion, blood flow to both territories was similar in both groups but was comparable to the control; however, in necrotic tissue of the subendocardial layer of both groups, flow fell below control values (p < 0.05). End-systolic volume rose from 21.2 +/- 7.4 ml to 36.1 +/- 11.5 ml (p < 0.05), end-diastolic volume remained constant (46.0 +/- 13.8 vs. 47.9 +/- 12.1 ml; p > 0.05), and ejection fraction fell from 53.9 +/- 8.3% to 25.8 +/- 10.2% (p < 0.05) at the end of the experiment in the metoprolol group. Respective figures for the placebo group were 19.4 +/- 7.9 versus 27.9 +/- 10.9 (p < 0.05), 38.5 +/- 13.0 versus 42.1 +/- 11.0 (p > 0.05), and 50.6 +/- 5.7 versus 35.5 +/- 11.7 (p < 0.05). Fractional shortening of the chords analyzed was similar in both groups during the control period; it fell significantly at the end of the experiment in three chords of the metoprolol group and in five chords of the placebo group. The apical chord in the placebo, but not in the metoprolol, dogs was dyskinetic: fractional shortening was -0.86 +/- 9.7 versus 7.5 +/- 13.5% (p > 0.05). The area at risk was 41.6 +/- 10.6 cm2 in metoprolol- and 40.5 +/- 7.2 cm2 in placebo-treated dogs (p > 0.05); the infarct size, expressed as a percentage of the area at risk, was 29.0 +/- 22.5% and 45.3 +/- 23.6% (p = 0.02), respectively. Oral pretreatment with metoprolol limited infarct size and improved regional left ventricular function, probably due to its negative chronotropic and inotropic effects, and also due to an enhancement of collateral flow fr


Drug Prescription Patterns During Initial Treatment of Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: A Study Based on Health Insurance Review and Assessment Database.
To evaluate the drug prescription patterns for men diagnosed with benign prostatic hyperplasia (BPH) in Korea. We extracted the data of 3% of the national patient samples including men aged ≥ 40 years between 2012 and 2017 from the Health Insurance Review and Assessment database and investigated the drugs prescribed for men with the BPH code N40. Men with a diagnosis of BPH but not receiving treatment were excluded. The primary outcome was the drugs prescribed and the changes in drug prescription pattern over 6 years for men first diagnosed with BPH. Alpha blockers were the most commonly prescribed drugs in men with BPH, and tamsulosin was the most common. The proportion of prescriptions increased steadily. The number of prescriptions for anticholinergics (ACH) increased, but decreased with the start of mirabegron prescriptions in 2015. Prescriptions of mirabegron are increasing rapidly and replacing ACH. Based on the prescription pattern by drug category, alpha blocker monotherapy decreased, whereas combination therapies such as alpha blocker + 5-alpha-reductase inhibitors (5ARI), and alpha blocker + 5ARI + ACH increased steadily. As for the number of prescriptions by drug ingredient, tamsulosin monotherapy was the most common, and the combination therapy of tamsulosin and mirabegron increased. Alpha blockers were the most commonly prescribed drug for men first diagnosed with BPH in Korea from 2012 to 2017, and tamsulosin was the most common alpha blocker. Prescriptions of combination therapy and mirabegron are gradually increasing.


Variability of key biological parameters of round sardinella Sardinella aurita and the effects of environmental changes.
We examined growth rates and reproductive characteristics of Sardinella aurita off Senegal and other coastal areas over a 20 year period (1995-2014) to determine how they relate to variations in environmental characteristics of coastal waters. Based on fish length-frequency data and a coastal upwelling index, we found that S. aurita recruitment tends to occur during the periods of most intensive upwelling (March-April off Senegal). Peak reproduction corresponds to periods of low sea-surface temperature (in February or March). The sex ratio was remarkably consistent during the 30 year study period and so was not affected by environmental changes. We hypothesise that S. aurita takes advantage of the higher zooplankton productivity that occurs in coastal waters when upwelling brings nutrient-rich water to the surface (i.e., it increases its growth rate and accumulates energy reserves for spawning). Growth performance appears to be strongly dependent on environmental conditions. The timing of spawning seems to occur when food (zooplankton) is most available for supplying the energy requirements needed by adults for spawning and early development of larvae. Environmental changes seem to have a significant effect on S. aurita growth and reproduction, which endorses their high phenotypic plasticity.


Activation of JAK2-V617F by components of heterodimeric cytokine receptors.
The JAK2-V617F mutation is an important etiologic factor for the development of myeloproliferative neoplasms. The mechanism by which this mutated tyrosine kinase initiates deregulated signals in cells is not completely understood. It is believed that JAK2-V617F requires interactions with homodimeric cytokine receptors to elicit its transforming signal. In this study, we demonstrate that components of heterodimeric cytokine receptors can also activate JAK2-V617F. Expression of IL27Ra, a heterodimeric receptor component, enhanced the activation of JAK2-V617F and subsequent downstream signaling to activation of STAT5 and ERK. In addition, expression of components of the interleukin-3 receptor, IL3Ra and the common beta chain, activated JAK2-V617F as well as STAT5 and ERK. Importantly, expression of IL27Ra functionally replaced the requirement of a homodimeric cytokine receptor to promote the activation and transforming activity of JAK2-V617F in BaF3 cells. Tyrosine phosphorylation of IL27Ra was not required to induce activation of JAK2-V617F or STAT5, or to enhance the transforming activity of JAK2-V617F. Expression of IL3Ra or the common beta chain in BaF3 cells also enhanced the ability of JAK2-V617F to transform these hematopoietic cells. However, the heterodimeric receptor component IL12RB1 did not enhance the activation or transforming signals of JAK2-V617F in BaF3 cells. IL27Ra also activated the K539L and R683G JAK2 mutants. Together our data demonstrate that in addition to homodimeric receptors, some heterodimeric receptor components can support the activation and transforming signals of JAK2-V617F and other JAK2 mutants. Therefore, heterodimeric receptors may play unappreciated roles in JAK2 activation in the development of hematopoietic diseases including myeloproliferative neoplasms.


Structural, electronic, and optical properties of Eu-doped BiOX (X = F, Cl, Br, I): a DFT+U study.
In order to understand the photophysical properties and explain the experimental observations of Eu-doped BiOX (X = F, Cl, Br, I), the crystal structure, electronic structure, and optical properties of pure BiOX and Eu-doped BiOX have been calculated using the DFT+U method. By Eu doping, the band gap of BiOI is slightly narrowed, while the band gaps of others (BiOF, BiOCl, and BiOBr) are slightly broadened. Importantly, there is an isolated impurity energy band in the middle of the band gap, which is formed by seven spin-up energy levels of Eu-4f states. Furthermore, Eu doping enhances the internal electric fields of BiOX and makes the variation of band gaps and band widths become more outstanding, especially for the band widths of X-ns, O-2s, and Bi-6s related bands. Taking into account the energy level matching and band edge position, Eu-doped BiOCl is favorable not only for the photoluminescence application but also for the photocatalysis application. The findings in the present work could well explain the experimental observations in the literature and are helpful for the development of novel optoelectronic applications of BiOX-based materials.


Regulation of the growth rate of mouse fibroblasts by IL-3-activated mouse bone marrow-derived mast cells.
When mouse bone marrow-derived mast cells (BMMC) are cocultured with a confluent layer of mouse 3T3 fibroblasts in the presence of WEHI-3-conditioned medium, the mast cells undergo a phenotypic change toward that of a connective tissue mast cell, and the fibroblasts increase their synthesis of globopentaosylceramide. We now demonstrate that fibroblasts lose their contact inhibition and multiply such that by the 2nd and the 4th wk of coculture there are, respectively, approximately four-fold and six-fold more fibroblasts than in the cultures that are not exposed to BMMC. This in vitro increase in the number of fibroblasts is dependent on the number of mast cells (over the range of 6 x 10(4) to 1 x 10(6) BMMC/culture) initially seeded with the fibroblasts and on the concentration of WEHI-3-conditioned medium present during the coculture. That the fibroblasts also multiply in BMMC/fibroblast cocultures exposed to synthetic IL-3 or to purified IL-3 indicates that IL-3 is a component in WEHI-3-conditioned medium that induces mast cells to produce the fibroblast growth factor. The number of fibroblasts does not increase if fibroblasts are exposed to lysates of BMMC, or to BMMC-derived conditioned medium, or if the two cell types are separated from one another during the coculture with a 3-microns filter or a 0.4-microns filter. Thus, IL-3-activated BMMC must be in proximity to fibroblasts to induce them to multiply. Because of their increased numbers per culture dish, total fibroblasts that were cocultured with mast cells synthesized approximately two-fold more 35S-labeled proteoglycans, incorporated approximately 3-fold more [3H] proline into collagenase-sensitive proteins, and had substantially more alpha 2(I) collagen mRNA than fibroblasts that were maintained in the absence of mast cells. These is vitro studies reveal a sequence by which IL-3-activated mast cells may play a role in the induction of fibrosis.


Optimization of propofol dose shortens procedural sedation time, prevents resedation and removes the requirement for post-procedure physiologic monitoring.
To examine the effect of propofol dosing (total dose and number of doses) on patient sedation time and likelihood of resedation. This was a prospective, observational patient series in an urban district hospital ED with 42 000 attendances per annum. Patients undergoing an emergent procedure requiring procedural sedation were included. Titrated intravenous propofol was administered according to departmental procedure. Standardized consent and data collection forms were used. Time taken for the patient to become conversational after first administration was recorded and any resedation documented. Four hundred patients, undergoing 404 procedures, were enrolled for the period commencing August 2004 until March 2006. The mean initial propofol bolus was 0.8 mg/kg (SD 0.6), and mean total propofol dose was 1.8 mg/kg (SD 1.0), comprising a mean of 2.3 (SD 2.1) doses of 15.8 mg (SD 11.4). Mean sedation time was 11.8 min (SD 6.9), and increased sedation times were associated with higher total propofol dose and number of boluses (P < 0.0001). Resedation occurred in two patients (0.5%, 95% CI 0-1.6%). Shorter sedation times are seen with lower doses of propofol. Patients do not need prolonged post-procedure monitoring because the occurrence of spontaneous resedation associated with propofol use is a rare event. This has implications for patient flow and staff resource allocation in a busy ED.


Novel biomarkers for cardiac surgery-associated acute kidney injury: a skeptical assessment of their role.
Cardiac surgery-associated acute kidney injury (AKI) is common and is associated with a high mortality rate. Traditional biomarkers of AKI (creatinine and urea) increase slowly in response to renal injury, are insensitive to mild degrees of AKI, and are influenced by nonrenal factors. There is considerable interest in novel biomarkers of AKI such as neutrophil gelatinase-associated lipocalin that increase rapidly after renal injury, detect mild degrees of AKI, and are less subject to nonrenal factors. It has been postulated that the early diagnosis of cardiac surgery-associated AKI using novel biomarkers will result in improved outcomes. However, there is little evidence that interventions started early in the course of evolving AKI enhance renal recovery. Until effective therapies are developed that significantly improve the outcome from AKI, there is little benefit from early diagnosis using novel biomarkers.


Rapid Production of High-Purity Hydrogen Fuel through Microwave-Promoted Deep Catalytic Dehydrogenation of Liquid Alkanes with Abundant Metals.
Hydrogen as an energy carrier promises a sustainable energy revolution. However, one of the greatest challenges for any future hydrogen economy is the necessity for large scale hydrogen production not involving concurrent CO2 production. The high intrinsic hydrogen content of liquid-range alkane hydrocarbons (including diesel) offers a potential route to CO2 -free hydrogen production through their catalytic deep dehydrogenation. We report here a means of rapidly liberating high-purity hydrogen by microwave-promoted catalytic dehydrogenation of liquid alkanes using Fe and Ni particles supported on silicon carbide. A H2 production selectivity from all evolved gases of some 98 %, is achieved with less than a fraction of a percent of adventitious CO and CO2 . The major co-product is solid, elemental carbon.


[Long-term survival of a patient with locally advanced unresectable pancreatic cancer treated with gemcitabine after chemoradiation therapy].
We report a case of long-term survival of a patient with locally advanced unresectable pancreatic cancer treated with gemcitabine after chemoradiation therapy( CRTx). A 61-year-old woman was diagnosed as having locally advanced unresectable pancreatic cancer, 3.0 cm in diameter, which had invaded the superior mesenteric artery by computed tomography (CT). She was treated with CRTx( gemcitabine[ GEM] at 250 mg/m2/week for 6 weeks+liniac irradiation of 50.2 Gy) followed by systemic chemotherapy (gemcitabine (GEM) at 1,000 mg/m2). Reassessment after CRTx yielded a diagnosis of stable disease (according to the Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). To date, the patient has undergone 57 courses of chemotherapy in the outpatient clinic; however, she did require biliary stent placement because of occlusive jaundice.


Is Roux-en-Y gastric bypass advantageous?-surgical outcomes in obese patients with type-2 diabetes after gastric bypass versus sleeve gastrectomy, a matched retrospective study.
There are few comparative studies of the clinical outcomes after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). The aim of the study was to compare diabetes- and metabolic disorder-related outcomes following RYGB and SG, based on data for matched participants. This was a retrospective matched study using data from 2011-2018. Patients with type-2 diabetes undergoing RYGB (n=35) were matched with up to 2 RYGB participants (n=56) regarding age, sex, body mass index, hemoglobin A1c level, medication use, diabetes duration, and blood pressure. All surgeries were performed laparoscopically without complications or malnutrition during 24 months of follow-up. Both surgical procedures achieved excellent diabetes remission and weight loss. RYGB was associated with a significantly higher diabetes medication discontinuation rate 24 months postoperatively (RYGB: 87.5% vs. SG: 68.6%; P<0.05), better reduction in serum cholesterol and low-density lipoprotein-c levels, as well as better diabetes control compared with SG. The incidence of microvascular and macrovascular complications showed no significant difference between two groups. In this matched retrospective study, although RYGB and SG were both excellent surgeries for treating obesity in patients with type-2 diabetes, RYGB was associated with better results compared with SG regarding dyslipidemia remission and metabolic disorder-related medication reduction.


Randomized, controlled trial of coronary artery bypass surgery versus percutaneous coronary intervention in patients with multivessel coronary artery disease: six-year follow-up from the Stent or Surgery Trial (SoS).
The Stent or Surgery Trial is a randomized, controlled trial comparing percutaneous coronary intervention with coronary artery bypass grafting (CABG) for patients with multivessel disease. Initial results at a median follow-up of 2 years showed a survival advantage for patients randomized to CABG. This article reports survival outcome at a median follow-up of 6 years. A total of 988 (n=488 percutaneous coronary intervention, n=500 CABG) patients were randomized at 53 centers during the period from 1996 to 1999. Investigators established survival status from hospital or community medical records or national databases or by direct contact with patients and their relatives. All-cause mortality was compared with hazard ratios and confidence intervals calculated from Cox proportional hazards models. Prespecified subgroup analyses for diabetes mellitus, angina grade, and angiographic severity of coronary disease at baseline were performed with tests for interaction. At a median follow-up of 6 years, 53 patients (10.9%) died in the percutaneous coronary intervention group compared with 34 (6.8%) in the CABG group (hazard ratio 1.66, 95% confidence interval 1.08 to 2.55, P=0.022). Little evidence was found that the treatment effect on mortality differed between subgroups according to baseline angina grade (interaction test P=0.52), the severity of coronary disease (P=0.92), or diabetic status (P=0.15). At a median follow-up of 6 years, a continuing survival advantage was observed for patients managed with CABG, which is not consistent with results from other stent-versus-CABG studies.


Cloning of the cDNA of the heme-regulated eukaryotic initiation factor 2 alpha (eIF-2 alpha) kinase of rabbit reticulocytes: homology to yeast GCN2 protein kinase and human double-stranded-RNA-dependent eIF-2 alpha kinase.
We have cloned the cDNA of the heme-regulated eIF-2 alpha kinase (HRI) of rabbit reticulocytes. In vitro translation of mRNA transcribed from the HRI cDNA yields a 90-kDa polypeptide that exhibits eIF-2 alpha kinase activity and is recognized by a monoclonal antibody directed against authentic HRI. The open reading frame sequence of the HRI cDNA contains all 11 catalytic domains of protein kinases with consensus sequences of protein-serine/threonine kinases in conserved catalytic domains VI and VIII. The HRI cDNA also contains an insert of approximately 140 amino acids between catalytic domains V and VI. The HRI cDNA coding sequence has extensive homology to GCN2 protein kinase of Saccharomyces cerevisiae and to human double-stranded-RNA-dependent eIF-2 alpha kinase. This observation suggests that GCN2 protein kinase may be an eIF-2 alpha kinase in yeast. In addition, HRI has an unusually high degree of homology to three protein kinases (NimA, Wee1, and CDC2) that are involved in the regulation of the cell cycle.


Regional cerebral blood flow-SPECT in chronic alcoholism: relation to neuropsychological testing.
To determine the prevalence of central nervous system damage due to ethanol, we evaluated 40 asymptomatic chronic alcoholics and 20 age-matched controls. Studies included neuropsychological testing, brain 99mTc-HMPAO SPECT, and morphometric analysis by CT scan. In the qualitative analysis, 30 of the 40 alcoholics showed hypoperfused areas on SPECT scan. In the semiquantitative analysis, alcoholics exhibited significant reduction in regional cerebral blood flow (rCBF) ratio of all brain lobes compared to controls (p < 0.001). The rCBF ratio was mainly reduced in frontal lobes (65%). Only 11 alcoholics showed significant frontal lobe atrophy in the morphometric analysis; most also had abnormalities on SPECT scan. Alcoholics exhibited significant impairment of frontal tasks and visuospatial skills. Frontal test impairment was independently related to both frontal atrophy and hypoperfusion. In a group of ten alcoholics in whom another SPECT scan was performed after 2 mo of ethanol abstinence, rCBF ratio of the frontal lobes normalized in eight, without frontal atrophy. In patients without frontal atrophy, reduced rCBF ratio of the anterior portion of the frontal lobes correlated negatively with frontal test results (r = -0.6535, p < 0.001). A significant negative correlation between cerebral perfusion and the amount of ethanol consumed in the month prior to study was observed (r = -0.6289, p < 0.001). In conclusion, asymptomatic chronic alcoholics frequently showed reversible frontal lobe hypoperfusion, which is related to recent ethanol intake, reflects brain function impairment and is independent of brain atrophy.


Modified PCR-RFLP method for HLA-DPB1 and -DQA1 genotyping.
We previously developed a new technique for HLA class II genotyping by digestion of polymerase chain reaction-amplified genes with restriction endonucleases (PCR-RFLP method). This PCR-RFLP method is an efficient and convenient typing technique for class II alleles. However, small fragments or bands located close to each other on polyacrylamide gels sometimes prevent precise analysis of the RFLP bands. Furthermore, the restriction enzymes we have reported in the previous papers are not sufficient to identify the genotypes of all heterozygous individuals. Here, we report an improved PCR-RFLP method using some informative restriction enzymes which have either a single cleavage site or, alternatively, no cleavage site in the amplified DNA region, depending on the HLA alleles, making reading of RFLP band patterns much easier. Each second exon of the HLA-DQA1 or -DPB1 gene was selectively amplified from genomic DNAs of 70 HLA-homozygous B-cell lines and 100 healthy Japanese by PCR. Amplified DNAs were digested with restriction endonucleases and then subjected to electrophoresis assaying simply for cutting, or no cutting, of the DNA. ApaLI, HphI, BsaJI, FokI, MboII and Mn1I can discriminate eight alleles of the DQA1 gene. Similarly 19 alleles of the DPB1 gene can be discriminated with Bsp1286I, FokI, DdeI, BsaJI, BssHII, Cfr13I, RsaI, EcoNI, and AvaII enzymes. This modified PCR-RFLP method can be successfully applied to heterozygotes. Thus, the method is technically simpler and more practical for routine HLA typing work than our previous PCR-RFLP method.


Cost-effectiveness of Chloride-liberal versus Chloriderestrictive Intravenous Fluids among Patients Hospitalized in the United States.
Background: Patients developing acute kidney injury (AKI) during critical illness or major surgery are at risk for renal sequelae such as costly and invasive acute renal replacement therapy (RRT) and chronic dialysis (CD). Rates of renal injury may be reduced with use of chloride-restrictive intravenous (IV) resuscitation fluids instead of chloride-liberal fluids. Objectives: To compare the cost-effectiveness of chloride-restrictive versus chloride-liberal crystalloid fluids used during fluid resuscitation or for the maintenance of hydration among patients hospitalized in the US for critical illnesses or major surgery. Methods: Clinical outcomes and costs for a simulated patient cohort (starting age 60 years) receiving either chloride-restrictive or chloride-liberal crystalloids were estimated using a decision tree for the first 90-day period after IV fluid initiation followed by a Markov model over the remainder of the cohort lifespan. Outcomes modeled in the decision tree were AKI development, recovery from AKI, progression to acute RRT, progression to CD, and death. Health states included in the Markov model were dialysis free without prior AKI, dialysis-free following AKI, CD, and death. Estimates of clinical parameters were taken from a recent meta-analysis, other published studies, and the US Renal Data System. Direct healthcare costs (in 2015 USD) were included for IV fluids, RRT, and CD. US-normalized health-state utilities were used to calculate quality-adjusted life years (QALYs). Results: In the cohort of 100 patients, AKI was predicted to develop in the first 90 days in 36 patients receiving chloride-liberal crystalloids versus 22 receiving chloride-restrictive crystalloids. Higher costs of chloride-restrictive crystalloids were offset by savings from avoided renal adverse events. Chloride-liberal crystalloids were dominant over chloride-restrictive crystalloids, gaining 93.5 life-years and 81.4 QALYs while saving $298 576 over the cohort lifespan. One-way sensitivity analyses indicated results were most sensitive to the relative risk for AKI development and relatively insensitive to fluid cost. In probabilistic sensitivity analyses with 1000 iterations, chloride-restrictive crystalloids were dominant in 94.7% of iterations, with incremental cost-effectiveness ratios below $50 000/QALY in 99.6%. Conclusions: This analysis predicts improved patient survival and fewer renal complications with chloriderestrictive IV fluids, yielding net savings versus chloride-liberal fluids. Results require confirmation in adequately powered head-to-head randomized trials.


Amyand's hernia: a report of 18 consecutive patients over a 15-year period.
The presence of a vermiform appendix in an inguinal hernia sac is termed Amyand's hernia. It may present as a tender inguinal or inguino-scrotal swelling and is often misdiagnosed as an incarcerated or strangulated hernia. The purpose of this study was to review the management of Amyand's hernia at a single institution since 1991. A retrospective analysis was undertaken of 18 consecutive patients with an Amyand's hernia operated upon at our institution from 1991 to 2005. Patients' demographics, treatment and postoperative outcome were analysed. There were 17 men and one woman. Their median age was 42 years. None of the patients was diagnosed preoperatively. The commonest presenting symptom was painful inguinal or inguino-scrotal swelling (83%). All patients, therefore, underwent emergency surgery with a presumptive diagnosis of either incarcerated or strangulated inguinal hernia. Operative findings included 11 normal appendices, four inflamed appendices and three perforated appendices in the inguinal hernial sac. Patients with a normal appendix (n = 11) had a mesh hernia repair without an appendicectomy. The rest of the patients (n = 7) with an abnormal appendix underwent emergency open appendicectomy followed by Bassini's sutured hernia repair. One patient died in the postoperative period of pneumonia. Only one recurrent hernia has been detected, with a median follow-up time of 6.4 years. The inflammatory status of the appendix determines the type of hernia repair and the surgical approach. Incidental appendicectomy in the case of a normal appendix is not favoured.


[Malaria in the central highlands of Madagascar: control strategies].
The purpose of this article is to present data on malaria in the central highland plateaux of Madagascar and strategies to improve the national malaria control program. Use of rapid diagnosis strips, early home-based fever management with pre-packaged chloroquine treatment kits and proposed new therapeutic combination based on artemisinine are discussed for management of patients with high suspicion of malaria attack. Preventive measures including alternated targeted and full-house indoor spraying for vector control, use of insecticide-impregnated bednets, implementation of intermittent preventive treatment in risk groups, optimization of the epidemic early detection and warning system using the Lot Quality Assurance Sampling method for epidemiological investigation if the alert threshold is exceeded, and provision of rapid diagnosis strips are presented.


An Efficient Multilinear Optimization Framework for Hypergraph Matching.
Hypergraph matching has recently become a popular approach for solving correspondence problems in computer vision as it allows the use of higher-order geometric information. Hypergraph matching can be formulated as a third-order optimization problem subject to assignment constraints which turns out to be NP-hard. In recent work, we have proposed an algorithm for hypergraph matching which first lifts the third-order problem to a fourth-order problem and then solves the fourth-order problem via optimization of the corresponding multilinear form. This leads to a tensor block coordinate ascent scheme which has the guarantee of providing monotonic ascent in the original matching score function and leads to state-of-the-art performance both in terms of achieved matching score and accuracy. In this paper we show that the lifting step to a fourth-order problem can be avoided yielding a third-order scheme with the same guarantees and performance but being two times faster. Moreover, we introduce a homotopy type method which further improves the performance.


Media, Technology, and the Sins of Memory.
Human memory is prone to error and distortion. Schacter (1999, 2001) proposed that memory's misdeeds can be classified into seven categories or "sins". This article discusses the impact of media and technology on four memory sins, transience (forgetting over time), absent-mindedness (lapses in attention that produce forgetting), misattribution (attributing a memory to the wrong source), and suggestibility (implanted memories). Growing concerns have been expressed about the negative impact of media and technology on memory. With respect to transience, I review research regarding the impact of the Internet (ie, Google), GPS, and photographs. Studies have documented impaired memory following specific tasks on which people rely on media/technology (eg, poor memory for a route after using GPS), but have revealed little evidence for broader impairments (eg, generally impaired memory in GPS users), and have also documented some mnemonic benefits (eg, reviewing photos of past experiences). For absent-mindedness, there is strong evidence that media multitasking is associated with poor memory for a target task (eg, a lecture) because of attentional lapses, suggestive evidence that chronic media multitasking could be associated with broader memory problems, and emerging evidence that technology can help to reduce certain kinds of absent-minded errors. Regarding misattribution and suggestibility, there is clear evidence that manipulated or misleading photos are associated with false memories for personal events and fake news, but no evidence of broader effects on susceptibility to memory distortion. Further study of the impact of media and technology on the memory sins is a fruitful pursuit for interdisciplinary studies.


Reconstruction of the pulmonary artery by a novel biodegradable conduit engineered with perinatal stem cell-derived vascular smooth muscle cells enables physiological vascular growth in a large animal model of congenital heart disease.
Lack of growth potential of available grafts represents a bottleneck in the correction of congenital heart defects. Here we used a swine small intestinal submucosa (SIS) graft functionalized with mesenchymal stem cell (MSC)-derived vascular smooth muscle cells (VSMCs), for replacement of the pulmonary artery in piglets. MSCs were expanded from human umbilical cord blood or new-born swine peripheral blood, seeded onto decellularized SIS grafts and conditioned in a bioreactor to differentiate into VSMCs. Results indicate the equivalence of generating grafts engineered with human or swine MSC-derived VSMCs. Next, we conducted a randomized, controlled study in piglets (12-15 kg), which had the left pulmonary artery reconstructed with swine VSMC-engineered or acellular conduit grafts. Piglets recovered well from surgery, with no casualty and similar growth rate in either group. After 6 months, grafted arteries had larger circumference in the cellular group (28.3 ± 2.3 vs 18.3 ± 2.1 mm, P < 0.001), but without evidence of aneurism formation. Immunohistochemistry showed engineered grafts were composed of homogeneous endothelium covered by multi-layered muscular media, whereas the acellular grafts exhibited a patchy endothelial cell layer and a thinner muscular layer. RESULTS: show the feasibility and efficacy of pulmonary artery reconstruction using clinically available grafts engineered with allogeneic VSMCs in growing swine.


Current and future treatment of anaplastic lymphoma kinase-rearranged cancer.
Aberrant forms of the anaplastic lymphoma kinase (ALK) are involved in the pathogenesis of several types of cancer, including anaplastic large cell lymphoma, non-small-cell lung cancer (NSCLC), inflammatory myofibroblastic tumors, colorectal cancer, neuroblastoma and others. In general, the ALK catalytic domain is rearranged and fused to a dimerization domain encoded by an unrelated gene. Less frequently, full-length ALK is activated by point mutations. The common theme is unregulated firing of ALK downstream signalling, leading to uncontrolled cell division and increased cell survival. ALK-driven tumors can be treated with Crizotinib, an orally available dual ALK/MET inhibitor, currently approved for advanced ALK-positive NSCLCs. Crizotinib-treated patients achieve high response rates, with an excellent toxicity profile. However, drug-resistant disease often develops, particularly in NSCLC patients. The processes leading to drug resistance include both ALK-dependent (point mutations or gene amplification), as well as ALK-independent mechanisms, which are here briefly discussed. Recently, Ceritinib has been approved for Crizotinib-refractory NSCLC, further extending patients' survival, but resistance again emerged. Novel ALK kinase inhibitors are currently under clinical development, showing great promise for improved efficacy in drug-resistance disease. It is opinion of the author that drug-resistance is likely to arise under any treatment, due to intrinsic heterogeneity and adaptability of cancer. To prevent or delay this phenomenon, we need to treat less advanced disease, with drugs that are rapidly effective in order not to allow enough time for tumor evolution, and we want to have more and more drugs with non-overlapping resistance profiles, for subsequent lines of targeted therapy. Finally, the use of drug combinations may exponentially decrease the chances of resistance.


The role of positron computed tomography (PET/CT) in lung cancer staging.
Lung cancer is the leading cause of cancer-related mortalities with the rate of incidence reaching about 1.5 million cases per year worldwide. Approximately 350 people die each day from lung cancer in USA-nearly 2.5 times more than the number of people who die from colorectal cancer (CRC), which is the second leading cause of cancer death overall. In 2023, an estimated 238,340 people (117,550 men and 120,790 women) will be diagnosed with lung cancer, and 127,070 people will die from the disease. Although approximately 80% of lung cancers are caused by cigarette smoking, the toll among people who have never smoked is substantial, ranking among the top 10 causes of cancer death when categorized separately. Lung cancer encompasses a variety of biologically distinct tumours. The two primary types of lung cancer are non-small cell lung cancer (NSCLC), which accounts for 81% of cases, and small cell lung cancer (SCLC), which accounts for 14% of cases. NSCLC is further categorized as adenocarcinoma, which is slightly more common in women, followed by squamous cell carcinoma and large cell carcinoma.


Unsupervised contrastive graph learning for resting-state functional MRI analysis and brain disorder detection.
Resting-state functional magnetic resonance imaging (rs-fMRI) helps characterize regional interactions that occur in the human brain at a resting state. Existing research often attempts to explore fMRI biomarkers that best predict brain disease progression using machine/deep learning techniques. Previous fMRI studies have shown that learning-based methods usually require a large amount of labeled training data, limiting their utility in clinical practice where annotating data is often time-consuming and labor-intensive. To this end, we propose an unsupervised contrastive graph learning (UCGL) framework for fMRI-based brain disease analysis, in which a pretext model is designed to generate informative fMRI representations using unlabeled training data, followed by model fine-tuning to perform downstream disease identification tasks. Specifically, in the pretext model, we first design a bi-level fMRI augmentation strategy to increase the sample size by augmenting blood-oxygen-level-dependent (BOLD) signals, and then employ two parallel graph convolutional networks for fMRI feature extraction in an unsupervised contrastive learning manner. This pretext model can be optimized on large-scale fMRI datasets, without requiring labeled training data. This model is further fine-tuned on to-be-analyzed fMRI data for downstream disease detection in a task-oriented learning manner. We evaluate the proposed method on three rs-fMRI datasets for cross-site and cross-dataset learning tasks. Experimental results suggest that the UCGL outperforms several state-of-the-art approaches in automated diagnosis of three brain diseases (i.e., major depressive disorder, autism spectrum disorder, and Alzheimer's disease) with rs-fMRI data.


Episcleritis; and posterior uveitis misdiagnosed as orbital cellulitis in a child patient with Behçet's disease.
Behçet's disease is a chronic multisystem vasculitis that presented with several manifestations. Episcleritis is a benign inflammation of the episcleral tissue and is rarely reported in Behçet's disease. We reported an 11-year-old girl who was admitted due to pain and swelling around the left eye with initial diagnosis of preseptal cellulitis. The patient had a history of recurrent oral aphthous ulcers and genital ulcers. Episcleritis and posterior uveitis were reported in ophthalmic examination and ultrasonography. Pathergy skin test and human leukocyte antigens (HLA) B5 and HLA-B51 were positive, consistent with the diagnosis of Behcet's disease. This case report emphasizes that various pathological causes may cause episcleritis and uveitis in children, one of which is rheumatic diseases, that should always be considered.


Participation of Runx2 in mandibular condylar cartilage development.
The purpose of this study was to investigate the expression pattern of Runx2 in mandibular condylar cartilage, a type of secondary cartilage. Mandibular condyle of ddY mice were fixed from embryonic day 14 (E14) through just after birth (equivalent to E19). Samples were cut into 4 micro m serial sections through the central area of the mandibular condyle at the sagittal plane. Serial sections were examined using histological, immunohistochemical (IHC) and in situ hybridization (ISH) techniques. There are no developmental features of mandibular condyle. At the distal upper portion of developmental mandibular bone, mesenchymal cell proliferation and condensation without metacholomatic reaction to Toluidine blue (TB) were seen at E14. At E15, mandibular condylar cartilage was clearly evident, as TB metacholomasia. In IHC specimens at E14, expression of Runx2 peptide was observed in the nuclei and the cytoplasms cells of coagulating mesenchymal cells, both in the cytoplasm and nucleus. After E17, Runx2 appeared in the cells of the condylar cartilage sheath. In ISH examination at E14 and E15, expressions of Runx2 mRNA appeared in the cytoplasms of proliferating chondrocytes. From E16 to E18, Runx2 mRNA was detected throughout almost all cytoplasm in all layers. These IHC and ISH results suggest that Runx2 plays an essential role for mandibular condylar cartilage development, especially that Runx2 is essential for the onset of secondary cartilage differentiation.


Membrane depolarization-induced contraction of rat caudal arterial smooth muscle involves Rho-associated kinase.
Depolarization of the sarcolemma of smooth muscle cells activates voltage-gated Ca2+ channels, influx of Ca2+ and activation of cross-bridge cycling by phosphorylation of myosin catalysed by Ca2+/calmodulin-dependent myosin light-chain kinase (MLCK). Agonist stimulation of smooth muscle contraction often involves other kinases in addition to MLCK. In the present study, we address the hypothesis that membrane depolarization-induced contraction of rat caudal arterial smooth muscle may involve activation of Rho-associated kinase (ROK). Addition of 60 mM K+ to de-endothelialized muscle strips in the presence of prazosin and propranolol induced a contraction that peaked rapidly and then declined to a steady level of force corresponding to approx. 30% of the peak contraction. This contractile response was abolished by the Ca2+-channel blocker nicardipine or the removal of extracellular Ca2+. An MLCK inhibitor (ML-9) inhibited both the phasic and tonic components of K+-induced contraction. On the other hand, the ROK inhibitors Y-27632 and HA-1077 abolished the tonic component of K+-induced contraction, and slightly reduced the phasic component. Phosphorylation levels of the 20-kDa light chain of myosin increased rapidly in response to 60 mM K+ and subsequently declined to a steady-state level significantly greater than the resting level. Y-27632 abolished the sustained and reduced the phasic elevation of the phosphorylation of the 20-kDa light chain of myosin, without affecting the K+-induced elevation of cytosolic free Ca2+ concentration. These results indicate that ROK activation plays an important role in the sustained phase of K+-induced contraction of rat caudal arterial smooth muscle, but has little involvement in the phasic component of K+-induced contraction. Furthermore, these results are consistent with inhibition of myosin light-chain phosphatase by ROK, which would account for the sustained elevation of myosin phosphorylation and tension in response to membrane depolarization.


An ADAMTS17 splice donor site mutation in dogs with primary lens luxation.
To identify the genetic cause of isolated canine ectopia lentis, a well-characterized veterinary disease commonly referred to as primary lens luxation (PLL) and to compare the canine disease with a newly described human Weill-Marchesani syndrome (WMS)-like disease of similar genetic etiology. Genomewide association analysis and fine mapping by homozygosity were used to identify the chromosomal segment harboring the PLL locus. The resequencing of a regional candidate gene was used to discover a mutation in a splice donor site predicted to cause exon skipping. Exon skipping was confirmed by reverse transcription-polymerase chain reaction amplification of RNA isolated from PLL-affected eyes and from skin fibroblast cultures from PLL-affected dogs. An allelic discrimination assay was used to genotype individual dogs at the splice donor site mutation. The PLL locus was mapped to a 664-kb region of canine chromosome 3 containing regional candidate gene ADAMTS17. Resequencing ADAMTS17 revealed a GT-->AT splice-donor-site mutation at the 5' end of intron 10. The predicted exon 10 skipping and resultant frame shift were confirmed with RNA derived from PLL-affected dogs. The ADAMTS17 mutation was significantly associated with clinical PLL in three different dog breeds. A truncating mutation in canine ADAMTS17 causes PLL, a well-characterized veterinary disease, which can now be compared to a recently described rare WMS-like disease caused by truncating mutations of the human ADAMTS17 ortholog.


Electrochemically generated acid and its containment to 100 micron reaction areas for the production of DNA microarrays.
An addressable electrode array was used for the production of acid at sufficient concentration to allow deprotection of the dimethoxytrityl (DMT) protecting group from an overlaying substrate bound to a porous reaction layer. Containment of the generated acid to an active electrode of 100 micron diameter was achieved by the presence of an organic base. This procedure was then used for the production of a DNA array, in which synthesis was directed by the electrochemical removal of the DMT group during synthesis. The product array was found to have a detection sensitivity to as low as 0.5 pM DNA in a complex background sample.


Herbicides: Combination Enhances Selectivity.
The herbicides N-(3-chloro-4-methyphenyl)-2-methylpentamamide (solan) and 1, 1'-dimethyl-4, 4'dipyridylium dichloride (paraquat) were less toxic to tomato plants when applied together than either one alone. However, the combination was more toxic to crabgrass and eggplant. This phenomenon may result from the interaction of the herbicides with photosynthesis.


1H-Benzimidazole derivatives as mammalian DNA topoisomerase I inhibitors.
Benzimidazole is one of the most important heterocyclic groups manifesting various biological properties, such as antibacterial, antifungal, antimicrobial, antiprotozoal and antihelmintic activities. Several benzimidazole derivatives are also active as inhibitors of type I DNA topoisomerases. In this study, three 1H-benzimidazole derivatives with different electronic characteristics at position 5-, namely 5-chloro-4-(1H-benzimidazole-2-yl)phenol (Cpd I), 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) and 4-(1H-benzimidazole-2-yl)phenol (Cpd III), were synthesized and evaluated for their effects on mammalian type I DNA topoisomerase activity using quantitative in vitro plasmid supercoil relaxation assays. For the structure elucidation of the compounds, melting points, UV, IR, 1H NMR, 13C NMR, mass spectral data and elemental analyses were interpreted. Among the compounds, 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) manifested relatively potent topoisomerase I inhibition.


[Gunshot bladder trauma: case report and literature review].
To report one case of gunshot bladder trauma and to review its diagnosis and treatment in the related literature. We report the case of a 43-year-old-male with an abdominal firearm wound and gross haematuria. Imaging diagnosis by abdominal and pelvic CT and CT-cystography. Surgical treatment. CT-cystography showed extraperitoneal bladder rupture. Exploratory laparotomy to evaluate for other associated injuries. Bladder wall surgical closure and ureteroneocystostomy with transvesical technique because of complete distal ureter tear. Broad spectrum antibiotherapy. Favourable progress. The patient was discharged at 14th day. Firearm bladder traumas are a rare entity. Surgical exploration and closure is mandatory. In haemodynamicaly stable patients, abdomen and pelvis CT and CT-cystography allow us to rule out associated injuries and to classify the bladder trauma type. Ureteral damage associated in 5-8,9%, diagnosed during surgical exploration. Broad-spectrum antibiotherapy in all patients.


Peritoneovenous shunting for ascites in cancer patients.
Twenty patients with malignant ascites were treated by insertion of a peritoneovenous shunt. Twelve had a LeVeen shunt, 7 a Denver shunt and 1 patient had a LeVeen shunt subsequently replaced by a Denver shunt. Overall survival was poor, which reflects the advanced stage of the patients' disease. Function of the Denver shunt seemed to be better than that of the LeVeen shunt. None of the 8 Denver shunts inserted was a complete failure, while 4 out of 13 LeVeen shunts were of no benefit. With a satisfactorily functioning shunt, good palliation was always achieved. A Denver shunt has become our first choice.


Influence of an oscillating circuit on the radiation of transient acoustic waves by an electroelastic cylinder.
The problem of nonstationary wave radiation in an infinitely long thick-wall piezoelectric cylinder in fluid medium is considered. The influence of an oscillating circuit with lumped parameters on characteristics of transient process is taken into consideration. Problem formulation is executed within the forced electrostatic theory, acoustic approximations, and quasistatic theory for electric circuit. The solution method is based on the integral Laplace transform in time. This allows analytically reducing the problem to solving a system of Volterra integral equations with retarded arguments. The numerical results of calculations are presented and analyzed.


Cardiopulmonary function following post-cardiac surgical mediastinitis.
Eleven survivors of bacterial mediastinitis, which followed cardiac surgery through a median sternotomy approach, underwent noninvasive cardiopulmonary evaluation to determine whether clinically apparent mediastinal fibrosis had developed. Compared to preoperative values, forced vital capacity was reduced by 9.75 percent of predicted; the greatest reduction occurred in those patients with Gram-negative mediastinitis. In one patient, an abnormal jugular venous wave form and apex cardiogram were consistent with constrictive cardiac physiology, but this was not associated with an abnormal echocardiogram or impaired functional status. In this small series, no serious abnormalities in cardiopulmonary function were detected which could be attributed to prior mediastinal infection.


Genetic Characterization of Periphyton Communities Associated with Selenium Bioconcentration and Trophic Transfer in a Simple Food Chain.
A major source of uncertainty in predicting selenium (Se) distribution in aquatic food webs lies in the enrichment factor (EF), the ratio of Se bioconcentration in primary producers and microorganisms relative to the concentration of Se in the surrounding water. It has been well demonstrated that EFs can vary dramatically among individual algal taxa, but data are lacking regarding the influence of periphyton community composition on EFs for a given geochemical form of Se. Therefore, the goals of this study were first to assess whether different periphyton communities could be established in aquaria with the same starting inoculum using different light and nutrient regimes, and second, to determine if the periphyton assemblage composition influences the uptake of waterborne Se (as selenite) and subsequent Se transfer to a model macroinvertebrate primary consumer. Periphyton biofilms were grown in aquaria containing filtered pond water (from Saskatoon, SK) spiked with approximately 20 μg Se/L (mean measured concentration 21.0 ± 1.2 μg Se/L), added as selenite. Five different light and nutrient regimes were applied to the aquaria (three replicates per treatment) to influence biofilm community development. After 6 weeks of biofilm maturation, 40 to 80 immature cultured snails (Stagnicola elodes) were added to each aquarium. The bacterial and algal members of the periphyton community were characterized by targeted metagenomic analyses before and after addition of snails to ensure the snails themselves did not significantly alter the biofilm community. Samples were collected for Se analysis of water, periphyton, and whole-body snail. The nutrient and light treatments resulted in substantially different compositions of the periphytic biofilms, with each being relatively consistent across replicates and throughout the study. Although the aqueous concentration of dissolved Se administered to treatments was constant, uptake by the different periphytic biofilms differed significantly. Both the low-light (61.8 ± 12.1 μg Se/g d.w.) and high-light (30.5 ± 4.7 μg Se/g d.w.) biofilms, which were found to have high proportions of cyanobacteria, contained statistically higher concentrations of Se relative to the other treatments. Furthermore, the concentration of Se in bulk periphyton was predictive of Se bioaccumulation in grazing snails but as an inverse relationship, opposite to expectations. The trophic transfer factor was inversely correlated with periphyton enrichment factor (r = -0.841). A number of different bacterial and algal taxa were correlated (either positively or negatively) with Se accumulation in periphyton biofilm and snails. Recent advancements in genetic methods make it possible to conduct detailed characterization of periphyton assemblages and begin to understand the influence that periphyton composition has on Se biodynamics in aquatic systems.


Clustering in music: an appraisal of task factors.
The pitch and temporal intervals of tune fragments, taken from folk music, were analyzed in terms of gestalt similarity principles and studied as determinants of music grouping structure. In experiment 1, the listeners were required to divide each tune into its 'natural' parts. Their ability to segment the tunes closely matched the boundaries generated by the clustering determinants under study, this consistency being particularly high for musicians. In experiment 2, a probe recognition task was used in which subjects were presented with a tune fragment followed by a true or false probe; true probes fell either within or across the boundaries studied in experiment 1. Since the probe was presented after the tune fragment, the differential ease of verifying within and across probes was taken to reflect the part structure of the tune held in memory. In order to study the part structure representation that is being built during music listening, a third experiment was devised by presenting the probe prior to the tune fragment and having subjects monitor the probe while listening to the fragment. Of the last two paradigms, only the latter was found to be sensitive to cluster boundaries, as defined along the temporal dimension. The entire set of results suggests that there does not seem to be a basic format of musical representation that is uniquely specified from the output of the clustering process.


Genomics in the neonatal nursery: Focus on ROP.
Retinopathy of prematurity (ROP) is a complex disease that is influenced by both genetic and environmental factors. Several small studies have found genetic variants in EPAS1, VEGF, SOD, and members of the WNT family in association with ROP. Design in genetic studies is challenging because of changing recommendations for the management of prematurity and ROP, the fact ROP is rare, and that availability of resources for managing premature infants can vary throughout the world. In addition, there is a shortage of ophthalmologists with the ability to diagnose and characterize severe ROP. Careful determination of the degree of prematurity is important when evaluating genetic studies. Controlling for significant epidemiologic factors and multiple comparisons is also important to consider when evaluating genetic studies. One large candidate gene study controlled for degree of prematurity, significant epidemiologic factors, and multiple comparisons and found variants within the intron of BDNF associated with severe ROP. Future studies using unbiased techniques to assess genetic risk are important as are in-depth study of BDNF through deep sequencing and associated mechanistic studies using appropriate experimental models.


Providing health care for lesbian clients.
Health and nursing care for lesbian clients should be culturally congruent with their values and lifestyle. Barriers that lesbian clients encounter in the health care system are discussed, along with strategies that health care providers can use to overcome these barriers. Professional literature is reviewed that incorporates health promotion and maintenance issues influencing lesbian health care. Culturally appropriate services that are available in one women's health center are described, and resources for interested health care providers are provided.


Management of hip disorders in patients with cerebral palsy.
Hip disorders are common in patients with cerebral palsy and cover a wide clinical spectrum, from the hip at risk to subluxation, dislocation, and dislocation with degeneration and pain. Although the hip is normal at birth, a combination of muscle imbalance and bony deformity leads to progressive dysplasia. The spasticity or contracture usually involves the adductor and iliopsoas muscles; thus, the majority of hips subluxate in a posterosuperior direction. Many patients with untreated dislocations develop pain by early adulthood. Because physical examination alone is unreliable, an anteroposterior radiograph of the pelvis is required for diagnosis. Soft-tissue lengthening is recommended for children as soon as discernable hip subluxation (hip abduction <30 degrees, migration index >25%) is recognized. One-stage comprehensive hip reconstruction is effective treatment for children 4 years of age or older who have a migration index >60% but who have not yet developed advanced degenerative changes of the femoral head. Salvage options for the skeletally mature patient with a neglected hip are limited.


Catalytic transport of molecular cargo using diffusive binding along a polymer track.
Transport at the molecular scale is a prerequisite for the development of future molecular factories. Here, we have designed oligoanionic molecular sliders on polycationic tracks that exploit Brownian motion and diffusive binding to transport cargo without using a chemical fuel. The presence of the polymer tracks increases the rate of bimolecular reactions between modified sliders by over two orders of magnitude. Molecular dynamics simulations showed that the sliders not only diffuse, but also jump and hop surprisingly efficiently along polymer tracks. Inspired by acetyl-coenzyme A transporting and delivering acetyl groups in many essential biochemical processes, we developed a new and unconventional type of catalytic transport involving sliders (including coenzyme A) picking up, transporting and selectively delivering molecular cargo. Furthermore, we show that the concept of diffusive binding can also be utilized for the spatially controlled transport of chemical groups across gels. This work represents a new concept for designing functional nanosystems based on random Brownian motion.


Endotheliitis-like changes in chronic hepatitis C.
Liver biopsies in hepatitis C frequently show bile duct damage, lymphoid follicles, large and small droplet fat, hepatocyte multinucleation. Mallory body-like material, and activation of sinusoidal inflammatory cells. Even though these lesions are useful parameters in the diagnosis of hepatitis C, their specificity remains uncertain. Endotheliitis-like changes of small portal veins have been described for various liver diseases, including viral hepatitis. The aim of the present study was to investigate the prevalence and severity of endotheliitis-like changes in chronic hepatitis C in comparison with chronic hepatitis B. For this purpose, liver biopsies of 50 patients with chronic hepatitis C and 48 patients which chronic hepatitis B were systematically analyzed for the presence of endotheliitis-like changes. Endotheliitis-like changes were defined as lymphocytic infiltration of venous walls, subendothelial lymphocyte accumulation, adherence of lymphocytes to the endothelium, and endothelial cell damage. Endotheliitis-like change severity was graded (borderline/questionable; slight to moderate; severe), and endotheliitis-like changes were analyzed in small portal veins and in central veins. Endotheliitis-like changes were significantly more frequent in chronic hepatitis C than in chronic hepatitis B (41.5% vs. 6.9%; p < 0.05). In chronic hepatitis C, endotheliitis-like changes predominated in small portal veins, but 27% of small hepatic veins were involved as well. The findings indicate that endotheliitis-like changes may represent a useful histological parameter in the diagnosis of chronic hepatitis C.


A Systematic Review and Meta-Analysis of Outcomes Following Mitral Valve Surgery in Patients with Significant Functional Mitral Regurgitation and Left Ventricular Dysfunction.
The surgical correction of functional mitral regurgitation (MR) remains challenging and controversial. The study aim was to systematically review the outcomes of surgical mitral valve repair (MVRpr) and mitral valve replacement (MVR) in patients with significant functional MR and left ventricular (LV) dysfunction. A meta-analysis was performed of published data acquired from patients with moderate to severe functional MR and LV ejection fraction (LVEF) <40% who underwent surgical MVRpr or MVR. The data were meta-analyzed across studies using Bayesian hierarchical models when feasible. The search yielded 36 observational studies. The pooled proportion of operative mortality following MVRpr was 5% (33 studies; 2,231 patients; 95% credible interval (CrI) 4-7%), while that following MVR was 10% (10 studies; 389 patients; 95% CrI 5-18%). For patients undergoing MVRpr, pooled proportions of postoperative cerebrovascular accidents and renal failure were 2% (11 studies; 750 patients; 95% CrI 1-3%) and 9% (11 studies; 756 patients; 95% CrI 5-16%), respectively. The five-year actuarial survival rates following MVRpr across 12 studies ranged from 47% to 78% (median 66%). In selected patients with significant functional MR and LV dysfunction, surgical MVRpr and MVR can be performed with acceptable intermediate operative mortality risks.


Fast-Response and Flexible Nanocrystal-Based Humidity Sensor for Monitoring Human Respiration and Water Evaporation on Skin.
We develop a fast-response and flexible nanocrystal-based humidity sensor for real-time monitoring of human activity: respiration and water evaporation on skin. A silicon-nanocrystal film is formed on a polyimide film by spin-coating the colloidal solution and is used as a flexible and humidity-sensitive material in a humidity sensor. The flexible nanocrystal-based humidity sensor shows a high sensitivity; current through the nanocrystal film changes by 5 orders of magnitude in the relative humidity range of 8-83%. The response/recovery time of the sensor is 40 ms. Thanks to the fast response and recovery time, the sensor can monitor human respiration and water evaporation on skin in real time. Due to the flexibility and the fast response/recovery time, the sensor is promising for application in personal health monitoring as well as environmental monitoring.


Effects of a peer educator program for HIV status disclosure and health system strengthening: Findings from a clinic-based disclosure support program in Mozambique.
In Mozambique, HIV counseling and testing (HCT) rates are low and the cascade (or continuum) of care is poor. Perhaps more importantly, low disclosure rates and low uptake of joint testing are also related to both (1) limitations on access to services and (2) the availability of trained staff. We describe the implementation and impact of a disclosure support implemented by peer educators (PE). Ten PEs, previously trained in basic HIV and post-test counseling, completed additional training on providing disclosure support for newly-diagnosed persons living with HIV (PLH). Of the 6,092 persons who received HCT, 677 (11.1%) tested positive. Any newly-diagnosed PLH who was tested when PEs were present (606 / 677) was approached about participating in the disclosure program; of these, 94.2% of PLH (n = 574) agreed to participate. Of these, at follow-up (between 1 day and 3 months later, depending on client inclination and availability) 91.9% (n = 528) said that they had disclosed their HIV infection, of whom 66.9% (n = 384) were female and 24.1% (n = 144) male. In turn, 92.7% of partners (n = 508) who had received HIV-related exposure information were tested; of these, 78.7% (n = 400) were found to be HIV-positive. Of the latter, 96.3% (n = 385) were then seen by health care providers and referred for further diagnosis and treatment. Supporting newly-diagnosed PLH is important both for their own health and that of others. For the newly-diagnosed, there are extensive challenges related to understanding the implications of their illness; social support from clinical care teams can be vital in planning and coping. Our study has shown that such support of PLH is also crucial to disclosure, in part via improving awareness of positive health implications for (and from) family, friends and other support networks.


Nomad scientists and the ones left behind.
To improve the diversity of the scientific workforce, we should not penalize researchers who are unable to move abroad for long periods.


A Nickel Dithiolate Water Reduction Catalyst Providing Ligand-Based Proton-Coupled Electron-Transfer Pathways.
A nickel pyrazinedithiolate ([Ni(dcpdt)2 ]2- ; dcpdt=5,6-dicyanopyrazine-2,3-dithiolate), bearing a NiS4 core similar to the active center of [NiFe] hydrogenase, is shown to serve as an efficient molecular catalyst for the hydrogen evolution reaction (HER). This catalyst shows effectively low overpotentials for HER (330-400 mV at pH 4-6). Moreover, the turnover number of catalysis reaches 20 000 over the 24 h electrolysis with a high Faradaic efficiency, 92-100 %. The electrochemical and DFT studies reveal that diprotonated one-electron-reduced species (i.e., [NiII (dcpdt)(dcpdtH2 )]- or [NiII (dcpdtH)2 ]- ) forms at pH<6.4 via ligand-based proton-coupled electron-transfer (PCET) pathways, leading to electrocatalytic HER without applying the highly negative potential required to generate low-valent nickel intermediates. This is the first example of catalysts exhibiting such behavior.


Young Children Want to See Others Get the Help They Need.
Children's instrumental helping has sometimes been interpreted as a desire to complete action sequences or to restore the physical order of things. Two-year-old children (n = 51) selectively retrieved for an adult the object he needed rather than one he did not (but which equally served to restore the previous order of things), and those with greater internal arousal (i.e., pupil dilation) were faster to help. In a second experiment (n = 64), children's arousal increased when they witnessed an adult respond inappropriately to another adult's need. This was not the case in a nonsocial control condition. These findings suggest that children's helping is not aimed at restoring the order of things but rather at seeing another person's need fulfilled.


Organic substrates as electron donors in permeable reactive barriers for removal of heavy metals from acid mine drainage.
This research was conducted to select suitable natural organic substrates as potential carbon sources for use as electron donors for biological sulphate reduction in a permeable reactive barrier (PRB). A number of organic substrates were assessed through batch and continuous column experiments under anaerobic conditions with acid mine drainage (AMD) obtained from an abandoned lignite coal mine. To keep the heavy metal concentration at a constant level, the AMD was supplemented with heavy metals whenever necessary. Under anaerobic conditions, sulphate-reducing bacteria (SRB) converted sulphate into sulphide using the organic substrates as electron donors. The sulphide that was generated precipitated heavy metals as metal sulphides. Organic substrates, which yielded the highest sulphate reduction in batch tests, were selected for continuous column experiments which lasted over 200 days. A mixture of pig-farm wastewater treatment sludge, rice husk and coconut husk chips yielded the best heavy metal (Fe, Cu, Zn and Mn) removal efficiencies of over 90%.


[Whole body magnetic resonance imaging].
Magnetic resonance imaging (MRI) has a growing number of applications in the whole body area. Its role cannot be properly considered without comparing it to the diagnostic capabilities and availability of sonography and the high standard of newest-generation CT. MRI is an accepted diagnostic modality for diseases involving the pelvis and the musculoskeletal system. It is equal or superior to other modalities in examination of the neck, the cardiovascular system, the upper abdomen and the retroperitoneum.


Two growth factor signalling pathways in fibroblasts distinguished by pertussis toxin.
The primary action of a family of mitogens including bombesin, bradykinin, vasopressin and alpha-thrombin is to activate the hydrolysis of polyphosphoinositides. Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) by phospholipase C is mediated through coupling of surface receptors to a GTP-binding protein (Gp protein) which, in some cells, is inactivated by the toxin of Bordetella pertussis. It is not known whether this signalling pathway is involved in initiating DNA replication, whereas it has been firmly established that reinitiation of DNA synthesis can be triggered without activation of PtdIns(4,5)P2 hydrolysis by, for example, EGF (epidermal growth factor), FGF (fibroblast growth factor) and insulin/IGF-I (insulin-like growth factor-I), members of a class of mitogens known to activate receptor tyrosine kinases. Taking advantage of the fact that Chinese hamster lung fibroblasts respond to either class of mitogens and that their Gp protein appears to be sensitive to pertussis toxin, we have now analysed the toxin's effect on reinitiation of DNA synthesis and find that it inhibits up to 95% of thrombin-induced mitogenicity without affecting EGF- or FGF-induced DNA synthesis and proliferation. These findings strongly suggest that activation of PtdIns(4,5)P2-phospholipase C has a determinant function in growth control, and confirm the existence of alternative growth factor-signalling pathways independent of polyphosphoinositide breakdown.


Prevalence and Genetic Characterization of Histomonas meleagridis in Chickens in Vietnam.
This study was performed to investigate the prevalence and to characterize the genetic diversity of Histomonas meleagridis isolates in chickens in southern Vietnam. A total of 194 chickens, randomly selected from 18 backyard and 18 commercial flocks, were screened for H. meleagridis infection using both macroscopic diagnosis and an 18S rRNA gene-based PCR method. Overall, 12.9% of birds, representing 19 flocks, showed gross lesions typical for histomonosis whereas 25.3% of the birds from 29 flocks were positive by PCR assay. Following initial diagnostic approaches, H. meleagridis-positive samples were further analyzed by sequencing three different genomic loci; the 18S rRNA, alpha-actinin1, and rpb1. Thirteen samples from 12 flocks were genetically identified as H. meleagridis, demonstrating a flock and sample prevalence of 33.3% and 6.7%, respectively. There was no significant difference in prevalence between different farm types, age groups, and seasonality. Genetic analysis demonstrated minor heterogeneity of Vietnamese isolates with 99% homology to H. meleagridis sequences from the database. This is the first survey of the prevalence and genetic characterization of H. meleagridis in chickens in Vietnam.


Curative Effect of Foraminal Endoscopic Surgery and Efficacy of the Wearable Lumbar Spine Protection Equipment in the Treatment of Lumbar Disc Herniation.
Lumbar disc herniation is a common and frequently-occurring disease in pain clinics. The incidence rate of affliction is increasing with every passing year. Besides the aged, young people also suffer from long-term pain, which not only affects their daily routines but may also lead to serious impairment. The causes of chronic low back and leg pain caused by lumbar disc herniation are mainly related to mechanical compression, the adhesion of epidural space, intervertebral space, and aseptic inflammatory reaction. The treatment of lumbar disc herniation should follow the principle of step-by-step treatment. An appropriate treatment scheme needs to be adopted according to the patient's condition. About 80% of patients received nonsurgical treatment to get relief from the pain symptoms. However, 10% to 15% of patients still need traditional open surgery. Spinal foraminal surgery is a new method for the treatment of lumbar disc herniation, lumbar surgery failure syndrome, and lumbar spinal stenosis. However, there are only scattered clinical reports on the efficacy of spinal foraminal surgery. Based on it, this paper proposes a method to explore the efficacy of spinal foraminal mirror surgery in the treatment of lumbar disc herniation. Besides, postoperative wearable lumbar protective equipment is proposed to ensure a seamless rehabilitation effect on the patients. Statistical analysis performed using a t-test revealed that there was a significant difference between the visual analog scales (VAS) scores of the two groups after 3 and 6 months of treatment (P < 0.05). The paper analyzes and summarizes the cases with definite and poor curative effects, which not only provides the basis for clinical practice but also paves the way to multicenter clinical research.


[The organization of mental health care in community].
Integration of the psychiatry in primary care is beneficial for the early detection of mental disorder, better outcome of mental disorder and reduction of stigma. Psychiatry is a leading profession in organisation of mental health services. General practitioners (GPs) in Europe deal with mental disorders in their everyday practice, so the same is expected in Croatia. Graduate and postgraduate education of our GPs is insufficient for this new role. The paper compares actual situation in Croatia with forthcoming needs. The paper suggests that community psychiatry, anti-stigma program, continuing medical education of GPs and network of consultant psychiatrists give the best results in the early detection and treatment of mental disorder.


In vitro and in vivo assessment of inhibitory effect of stevioside on pro-inflammatory cytokines.
Stevioside is a natural non-caloric sweetener which has been reported to have anti-inflammatory activity. The aim of the present study was to examine in vitro and in vivo effects of stevioside on rats plasma levels of tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), TNF-α and IL-1β release from lipopolysaccharide(LPS)-stimulated rat peripheral blood mononuclear cells (PBMCs). Male wistar rats weighing between 170-220 g were given stevioside (0, 500 and 1000 mg/kg BW/day) for 6 weeks. Mononuclear cells were separated from peripheral blood samples. TNF-α and IL-1β levels in plasma and the release of TNF-α and IL-1β from PBMCs were determined using rat enzyme-linked immunosorbent assay (ELISA) kits. Plasma levels of TNF-α and IL-1β were found to be non-detectable in control and groups treated with 500 and 1000 mg/kg of stevioside. Regarding TNF-α release from LPS-stimulated PBMCs, rats that were orally fed with 500 and 1000 mg/kg of stevioside were significantly different (p<0.05) from those in LPS-treated control group (186.8+18.6 and 151.4 + 15.4 vs 248.6+21.4 pg/ml). Additionally, IL-1β levels in rats treated with 500 and 1000 mg/kg of stevioside were significantly different (p<0.05) from those in LPS-treated control group (220.0+12.1 and 158.1 + 22.6 vs 294.4+16.1 pg/ml). Consumption of stevioside has an inhibitory effect on the release of TNF-α and IL-1β from LPS-stimulated PBMCs in rats.


Ultrastructural lesions induced by neptunium-237: apoptosis or necrosis?
In this study, we are concerned with the 237 isotope of neptunium (237Np), which is a by-product of uranium in nuclear reactors. To study ultrastructural lesions induced by this element, a group of rats were injected with a solution of 237Np-nitrate once a day for 14 weeks. Lesions observed in liver and kidney are described using electron microscopy. Ultrastructural alterations of cellular membranes and intracellular organelles demonstrated the existence of neptunium toxicity. This toxicity was characterized by various lesions, such as cytoplasmic clarification, disappearance of mitochondrial cristae, swollen mitochondria, abnormal condensation of nuclear chromatin, and nuclear fragmentations. This study demonstrated the probable induction of apoptosis by neptunium both in liver and kidneys.


MRI-Derived Myocardial Strain Measures in Normal Subjects.
The aim of this study was to perform a systematic review and meta-analysis to estimate the normal ranges of magnetic resonance imaging (MRI)-based feature tracking (FT) and to identify sources of variations. Similar analyses were also performed for strain encoding, displacement encoding with stimulated echoes, and myocardial tagging. MRI-FT is a novel technique for quantification of myocardial deformation using MRI cine images. However, the reported 95% confidence intervals (CIs) from the 2 largest studies have no overlaps. Four databases (EMBASE, SCOPUS, PUBMED, and Web of Science) were systematically searched for MRI strains of the left (LV) and right (RV) ventricles. The key terms for MRI-FT were "tissue tracking," "feature tracking," "cardiac magnetic resonance," "cardiac MRI," "CMR," and "strain." A random effects model was used to pool LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and RVGLS. Meta-regressions were used to identify the sources of variations. 659 healthy subjects were included from 18 papers for MRI-FT. Pooled mean of LVGLS was -20.1% (95% CI: -20.9% to -19.3%), LVGCS -23% (95% CI: -24.3% to -21.7%), LVGRS 34.1% (95% CI: 28.5% to 39.7%), and RVGLS -21.8% (95% CI: -23.3% to -20.2%). Although there were no publication biases except for LVGCS, significant heterogeneities were found. Meta-regression showed that variation of LVGCS was associated with field strength (β = 3.2; p = 0.041). Variations of LVGLS, LVGRS, and RVGLS were not associated with any of age, sex, software, field strength, sequence, LV ejection fraction, or LV size. LVGCS seems the most robust in MRI-FT. Among the MRI-derived strain techniques, the normal ranges were mostly concordant in LVGLS and LVGCS but varied substantially in LVGRS and RVGLS. The pooled means of 4 MRI-derived myocardial strain methods in normal subjects are demonstrated. Differences in field strength were attributed to variations of LVGCS.


Taxonomic review of Athliini (Coleoptera: Scarabaeidae: Melolonthinae), a new tribe of scarab beetles endemic to South America.
Athliini Smith Evans, new tribe (Coleoptera: Scarabaeidae: Melolonthinae) includes four genera that occur from southern South America through to the southeastern regions of Brazil: Apteroathlia Smith Evans, new genus, Athlia Erichson, 1835, Dihymenonyx Gutiérrez, 1949, and Ulata Saylor, 1945. Justifications are provided for the new tribe and for the placement each genus in the new tribe. Keys to genera and species are presented along with distributional data and maps for all species. Apteroathlia translucida Smith Evans, new species and Apteroathlia nox Smith Evans, new species are described. Lectotypes are designated for Athlia bruchi Moser, 1924 and Athlia rustica Erichson, 1835. A neotype is designated for Ulata argentina Saylor, 1945.


F-actin involvement in guinea pig sperm motility.
Sperm motility is a must for natural fertilization to occur. During their travel through the epididymis, mammalian spermatozoa gradually acquire the ability to move. This is accomplished through a sliding movement of the outer doublet microtubules of the axoneme which is energized by the dynein ATPase. Within its complex structure, the mammalian sperm flagellum contains F-actin and thus, we decided to test in the guinea pig sperm flagellum the role of F-actin in motility. During maturation, capacitation, and the acrosome reaction, a gradual decrease of the relative concentration of F-actin was observed. Motility increased as spermatozoa became able to fertilize. Gelsolin, phalloidin, and KI inhibited sperm motility. Gelsolin canceled sperm motility within 20 min of treatment while 0.6 M KI had immediate effects. Phalloidin diminished hyperactive sperm motility slightly. All three compounds significantly increased the relative concentration of F-actin. Latrunculins are conventional drugs that destabilize the F-actin cytoskeleton. Latrunculin A (LAT A) did not affect sperm motility; but significantly increased F-actin relative concentration. The results suggested that in guinea pig spermatozoa, randomly severing F-actin filaments inhibits flagellar motility; while end filament alteration does not. Thus, specific filament regions seem to be important for sperm motility.


Regulation of proximal-distal intercalation during limb regeneration in the axolotl (Ambystoma mexicanum).
Intercalation is the process whereby cells located at the boundary of a wound interact to stimulate proliferation and the restoration of the structures between the boundaries that were lost during wounding. Thus, intercalation is widely considered to be the mechanism of regeneration. When a salamander limb is amputated, the entire cascade of regeneration events is activated, and the missing limb segments and their boundaries (joints) as well as the structures within each segment are regenerated. Therefore, in an amputated limb it is not possible to distinguish between intersegmental regeneration (formation of new segments/joints) and intrasegmental regeneration (formation of structures within a given segment), and it is not possible to study the differential regulation of these two processes. We have used two models for regeneration that allow us to study these two processes independently, and report that inter- and intrasegmental regeneration are different processes regulated by different signaling pathways. New limb segments/joints can be regenerated from cells that dedifferentiate to form blastema cells in response to signaling that is mediated in part by fibroblast growth factor.


[First isolate of Encephalitozoon intestinalis from stools of a Colombian patient with AIDS].
Microsporidia are obligate intracellular parasites that are recognized as important opportunistic pathogens of immunocompromised and transplanted patients. Enterocytozoon bieneusi and, less frequently, Encephalitozoon intestinalis are the most prevalent species in humans; both of them are associated with enteric infections. Cell cultures have been useful in the study of microsporidia biology. In Colombia, however, no isolates of microsporidia from patients with AIDS have been obtained. A cell culture of intestinal microsporidia was established from stools of positive patients in order to isolate a native strain. Stool from a single AIDS patient was concentrated with the water-ether technique, and the sediment was treated with a mixture of antibiotics and antifungal agents for 18 hours at 37 degrees C. Vero cells were cultivated in 24-well plates with Gibco RPMI medium supplemented with 10% bovine fetal serum and antibiotics. The culture was subsequently inoculated with previously concentrated spores. The medium was changed every second day and the presence of spores was evaluated with the Quick Hot Gram chromotrope stain. Two weeks post-infection, microsporidial spores were identified with characteristic morphology and staining properties. PCR results showed that Encephalitozoon intestinalis was the isolated species. A cell culture of microsporidia was established from a stool sample. This protocol is important to isolate and maintain additional native Colombian strains and it will contribute to biochemical, immunological and epidemiological studies of the currently established strain.


Theoretical insights, in the liquid phase, into the antioxidant mechanism-related parameters in the 2-monosubstituted phenols.
The paper describes a DFT/B3LYP study, in the liquid phase, [using the PCM continuum model] on the O-H bond dissociation enthalpy (BDE) and ionization energy (IE) parameter values of the 2-monosubstituted phenols (2-X-ArOH), related to the H-atom transfer (HAT) and single-electron transfer (SET) mechanisms. The solvent and substituent effects on the conformers, the BDEs, and the IEs were studied using four electron-donating (EDG) and five electron-withdrawing (EWG) groups, in seven different solvents. In both the EDG- and/or EWG-substituted species of the parent compounds, radicals, and/or cation radicals, the most stable conformer is varied, depending on the medium and the substitution. The EWG-substituents increase IEs, resulting in a weaker antioxidant activity than the EDG ones; the effect appears stronger on the IEs than on BDEs. However, although the liquid-phase IEs, which are related to solution-phase oxidation potentials, decrease with the polarity and/or the hydrogen-bonding ability of the solvent, the opposite holds true for the BDEs, exhibiting a weaker effect. The gas-phase-calculated IE for benzene is among the most accurate ones in the field, compared to the experiment, that for phenol being the most accurate. In addition, calculated IEs for the 2-X-ArOH are in close agreement with the very few existing experimental ones. It is shown that the oxidation potentials are (a) highly correlated with the gas-phase ones, and (b) strongly solvent dependent. The stabilization/destabilization of the cation radical (SPC) contribution, in all media, is the decisive factor in the DeltaIE calculation. The reasonable correlations found between the DeltaBDE and DeltaIE could account well for the assumption of the simultaneous action of both mechanisms in the 2-X-ArOH, in both the gas and the liquid phase. It seems, however, that the presence of a particular solvent by itself is not sufficient enough for the HAT to SET transition. The involvement of specific ED and/or EW groups in the 2-X-ArOH seems also necessary. It appears that our theoretical approach is not only generally applicable to the set of substituents important to antioxidant activity but also useful in (a) the rational design of phenolic antioxidants and (b) affording accurate BDE and IE parameter values related to both possible antioxidant mechanisms.


An update on mobility assessment of dogs with musculoskeletal disease.
Mobility impairments associated with musculoskeletal diseases, such as osteoarthritis and degenerative joint disease, affect approximately 200,000 dogs annually and pose a notable challenge to canine health and welfare. Osteoarthritis causes the remodelling of synovial joints, alongside inflammation and impaired mechanical function which can be extremely debilitating. Secondary osteoarthritis commonly affects dogs and can be exacerbated by previous joint abnormalities, such as patellar luxation or cranial cruciate ligament rupture. Although musculoskeletal diseases can affect dogs of any age, the early subtle signs of gait abnormalities are perhaps missed by owners, thus, dogs may be in the latter stages of osteoarthritis progression when they are presented to veterinarians. Dogs showing subtle signs of gait abnormalities must be presented to veterinary practices for acute diagnosis to prevent long-term deterioration. Musculoskeletal diseases, such as osteoarthritis and degenerative joint disease, are commonly diagnosed via visible radiographic changes. However, veterinarians can use a combination of subjective and objective clinical scoring systems, such as clinical metrology instruments and gait assessment in conjunction with radiography to aid their diagnosis and longitudinal monitoring of musculoskeletal diseases. These scoring systems may be more sensitive to earlier signs of mobility impairments in dogs, ultimately, promoting increased canine health and welfare by enabling pain reduction, improvement of muscle strength and preservation of joint function. Current canine mobility scoring systems available to veterinarians will be discussed in turn throughout this review for implementation into clinical practice.


Effect of pre-planting irrigation, maize planting pattern and nitrogen on weed seed bank population.
Pre-planting irrigation and planting patterns are important factors in weed management that effect on seed bank. Additionally, the nitrogen is the most important factor in plant growth that affects weed-crop competition and ultimately, seed rain into the soil. A field experiment was conducted to study the effect of nitrogen application rates, pre-planting irrigation and maize planting patterns on weed seed bank population. Experimental factors were nitrogen rates at 4 levels (200, 300, 400 and 500 kg per hectare) as main plot; and pre-planting irrigation at 2 levels (irrigation before planting plus weeding emerged seedlings and, irrigation after sowing), and maize planting patterns (one-row and two-row planting of maize with same density per square of row length) that were assigned in a factorial arrangement to the sub plots. Soil samples were taken at the beginning of the season (before planting of maize) and at the end of the season (after harvest) at depth of 0-5 cm in the fixed quadrates (60 cm x 60 cm). The weed seeds were extracted from the soil samples and were identified using standard methods. The majority of weed seed bank populations included 6 weed species: Portulaca oleracea, Chenopodium album, Amaranthus retroflexus, Sorghum halepense, Daturea stramonium, Xanthium strumarium. Results showed that population of weed seed bank increased significantly with increasing nitrogen rate. The increasing rate was different between one-row and two-row planting patterns. The parameters indicated that seed bank population was much higher in a one row planting pattern of maize. With two-row planting, seed bank was decreased by 34, 26, 20 and 5% at 200, 300, 400 and 500 kg N/ha, respectively. Pre-planting irrigation was also found an effective implement to reduce the weed seed bank. When pre-planting irrigation was applied, seed bank was decreased by 57, 43, 34 and 9% at 200, 300, 400 and 500 kg N/ha. Increasing nitrogen because of weed's better growth and higher seed production neutralized the decreasing effect of pre-planting irrigation and two-row planting of maize on weed seed bank population.


Synthesis and cholera toxin binding properties of a lactose-2-aminothiazoline conjugate.
[structure: see text] During the search for improved monovalent ligands for cholera toxin (CT), a new lactose-2-aminothiazoline conjugate was discovered. In a fluorescence binding assay the compound was found to be one of the strongest relatively simple CT ligands to date with a K(d) of 23 microM.