Lassa virus glycoprotein complex review: insights into its unique fusion machinery.
Lassa virus (LASV), an arenavirus endemic to West Africa, causes Lassa fever-a lethal hemorrhagic fever. Entry of LASV into the host cell is mediated by the glycoprotein complex (GPC), which is the only protein located on the viral surface and comprises three subunits: glycoprotein 1 (GP1), glycoprotein 2 (GP2), and a stable signal peptide (SSP). The LASV GPC is a class one viral fusion protein, akin to those found in viruses such as human immunodeficiency virus (HIV), influenza, Ebola virus (EBOV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These viruses are enveloped and utilize membrane fusion to deliver their genetic material to the host cell. Like other class one fusion proteins, LASV-mediated membrane fusion occurs through an orchestrated sequence of conformational changes in its GPC. The receptor-binding subunit, GP1, first engages with a host cell receptor then undergoes a unique receptor switch upon delivery to the late endosome. The acidic pH and change in receptor result in the dissociation of GP1, exposing the fusion subunit, GP2, such that fusion can occur. These events ultimately lead to the formation of a fusion pore so that the LASV genetic material is released into the host cell. Interestingly, the mature GPC retains its SSP as a third subunit-a feature that is unique to arenaviruses. Additionally, the fusion domain contains two separate fusion peptides, instead of a standard singular fusion peptide. Here, we give a comprehensive review of the LASV GPC components and their unusual features.


Heart rate variability in time domain after acute myocardial infarction.
These results suggest that analysis of heart rate variability recorded even very early after acute myocardial infarction (1 to 2 days after onset of pain) is feasible in clinical routine and strongly related to subsequent arrhythmic events and cardiac mortality. Decreased HRV is considered not only a marker of impaired vagal activity of the heart but complete autonomic impairment, strongly associated with the degree of myocardial damage. HRV represents the integrated response of the cardiovascular system to a variety of different influences: the plasma level of catecholamines, the baroreflex activation and the direct sympathetic and vagal activity. The HRV profile is dynamic-HRV reduction caused by myocardial damage changes over time presenting a progressive increase up to normality over a 2-month follow-up. The observed early differences between anterior and inferior myocardial infarction disappear later in the healing phase. However, group analysis results of different HRV indices are stabile over time and highly reproducible, but presenting large individual variations. HRV parameters which are adjusted to heart rate (e. g. CV) seemed to be more stabile. The role of HRV analysis in risk stratification of patients after myocardial infarction is strongly related to the actual model of the genesis of ventricular arrhythmias. Multiple experimental and clinical studies described the development of life threatening ventricular arrhythmias as a multifactorial event which can not be described adequately using just one risk parameter for stratification. The arrhythmogenic substrate representing the underlying inhomogeneity of electrical behaviour of adjacent myocardial areas might be detectable by the analysis of ventricular late potentials or frequency disturbances from the signal averaged ECG. The autonomic modulation of this substrate is represented by an altered heart rate variability. Possible trigger factors to initiate arrhythmias in a modulated arrhythmogenic substrate like ventricular premature beats or transient myocardial ischemia can be detected by conventional arrhythmia and ST segment analysis from Holter tapes. The optimized combination of these non-invasive risk predictors together with well known evident clinical risk parameters, like left ventricular ejection fraction, may lead to a valid set of screening parameters for individual risk estimation after myocardial infarction.


Multiple risk intervention in high-risk hypertensive patients. A 3-year ultrasound study of intima-media thickness and plaques in the carotid artery. Risk Intervention Study (RIS) Group.
In spite of optimal blood pressure control, available data indicate that the risk of coronary heart disease remains high in many patients with hypertension. Multifactorial risk intervention programs have therefore been advocated. The aim of the present randomized study was to analyze whether a favorable change in risk factors caused by a comprehensive risk factor modification program (focused mainly on nonpharmacological intervention) might beneficially affect ultrasound-assessed far-wall common carotid intima-media thickness or plaques in the carotid artery in high-risk hypertensive patients (n=81) in comparison with those undergoing usual care (n=83). A further aim was to analyze whether risk factors measured at baseline or follow-up were related to the change recorded in intima-media thickness during follow-up. The results showed in the intervention group a favorable change in LDL cholesterol (-9%), in smoking habits (32% of smokers quit smoking), and in HbA1c (-17% in patients with diabetes mellitus) over the 3.5-year observation period. However, no difference between the two randomization groups could be observed for far-wall common carotid intima-media thickness or plaque status during follow-up. Of all tested potential risk factors, only fasting insulin at baseline (available in nondiabetic patients) was significantly related to the change in mean intima-media thickness during follow-up (r=.25, n=92, P<.01). The relationship (negative) between follow-up serum HDL and change in mean intima-media thickness during the preceding follow-up was of borderline significance. Patients with moderate to large plaques in the carotid artery region at baseline had a significantly larger increase in common carotid artery intima-media thickness during follow-up than patients with no or only small plaques. The results are disappointing and may indicate that either the change in risk factors occurred too late in life or a considerably larger change in concomitant risk factors than we observed is needed to favorably affect intima-media thickness during an observation period of around 3 years in high-risk hypertensive patients.


A malaria risk analysis in an irrigated area in Sri Lanka.
Malaria in Sri Lanka is unstable and epidemic, with large spatial and temporal differences in transmission dynamics. The disease is of great public health significance and identification of underlying risk factors is important in order to use the limited resources in a cost-effective way. The International Water Management Institute (IWMI) recently launched a project of GIS-based malaria risk mapping in Sri Lanka, to investigate whether this tool could be used for epidemic forecasting and for the planning of malaria control activities. This paper presents results for the Uda Walawe region in southern Sri Lanka, an irrigated agricultural area where malaria cases were mapped at the smallest administrative level for each month over a 10-year period. Malaria incidence rates were related to land- and water-use patterns, socio-economic features, and data on malaria control interventions in a multivariate analysis. Areas of high malaria risk were characterized by: (i) higher than average rainfall, (ii) greater forest coverage; (iii) slash and burn cultivation as a predominant agricultural activity; (iv) presence of many abandoned irrigation reservoirs; and (v) poor socio-economic status. Irrigated rice cultivation areas had a lower risk of malaria than non-irrigated areas. This difference could be due to socio-economic factors related to irrigation development and/or transmission dynamics related to vector density or species composition. Our findings call for malaria control strategies that are readily adapted to different ecological and epidemiological settings. Malaria risk maps are a convenient tool for discussing targeted and cost-effective interventions with disease control personnel.


Adjuvant effects of Lactobacillus casei added to a renutrition diet in a malnourished mouse model.
Nutritional deficiencies are associated with impaired immune response, affecting the body's defence mechanisms. It is also known that Lactic Acid Bacteria (LAB) and fermented products such us yogurt have immunopotentiator activity and nutritional properties, and could thus be used as a valuable supplement in a renutrition diet. The aim of this study was to determine, in a non-severe malnutrition model, the effective dose of Lactobacillus casei (L. casei), which when is used as an adjuvant in a renutrition diet, would modulate the mucosal immune system and induce recovery of the integrity of the intestinal barrier. The experiments were performed on groups of malnourished and renourished BALB/c mice. They received after milk renutrition a supplement of different doses and periods of L. casei feeding. We measured body weight; hematologic values and serum proteins. We also characterized small intestine immunoglobulin secreting cells, intraepithelial leukocytes, mastocytes and goblet cells. Structural and ultrastructural studies were performed. Our results suggest that impaired gut barrier and mucosal immune function produced by malnutrition can be reversed by L. casei and that the dose of 10(7) cfu/day/mouse administered during 5 consecutive days was the optimal one for recovery of the gut mucosal immune system. The clinical significance of these findings suggests ways for improving mucosal immunity, and generating protection against enteropathogens in hosts immunosuppressed by malnutrition.


Genetic Modifiers of Duchenne Muscular Dystrophy in Chinese Patients.
Background: Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive muscle disorder characterized by heterogeneous progression and severity. We aimed to study the effects of single nucleotide polymorphisms (SNPs) in SPP1 and LTBP4 on DMD progression in Chinese patients. Methods: We genotyped LTBP4 haplotypes and the SPP1 promoter SNPs rs28357094, rs11730582, and rs17524488 in 326 patients registered in the neuromuscular database of The First Affiliated Hospital of Sun Yat-sen University. Kaplan-Meier curves and log-rank tests were used to estimate and compare median age at loss of ambulation, while Cox proportional hazard regression models were used as to analyze the effects of glucocorticoids treatments, DMD genotype, and SPP1/LTBP4 SNPs on loss of ambulation. Results: The CC/CT genotype at rs11730582 was associated with a 1.33-year delay in ambulation loss (p = 0.006), with hazard ratio 0.63 (p = 0.008), in patients with truncated DMD genotype and undergoing steroid treatment. On the other hand, rs17524488 in SPP1 and the IAAM/IAAM haplotype in LTBP4 were not associated with time to ambulation loss. Conclusions: SPP1 rs11730582 is a genetic modifier of the long-term effects of steroid treatment in Chinese DMD patients. Thus, any future clinical study in DMD should adjust for glucocorticoids use, DMD genotype, and SPP1 polymorphisms.


Reconstruction of Near-Total Loss of the Upper and Lower Lips due to Purpura Fulminans with Local Tissue and a Dual-Skin Paddled Anterolateral Thigh Flap.
It is difficult to totally reconstruct the lip, achieving good functional and aesthetic results. There have been few reports of reconstructing complete lip defects. Moreover, upper and lower lip necrosis by purpura fulminans has not been reported. We present a case of a 60-year-old male purpura fulminans patient with upper and lower lip necrosis. Fortunately, our patient had retained his oral commissure function. We reconstructed this defect with an orbicularis oris muscle-skin-mucosal pedicled flap derived from the region between the nasolabial folds for upper lip; a similar bipedicled flap for the lower lip and the donor site was closed with a dual-skin paddled anterolateral thigh flap. Postoperative results were satisfactory, that is, no lip tightness or aperture restriction was seen, and symmetry had been achieved. The new lips exhibited complete sensory recovery. Drooling was minimal during rest and feeding. We could select a method that combined the advantages of local and free flaps. We consider our method for this defect is superior to those described in previous studies, in that the restoration of lip sensation and oral sphincter function can be achieved to some extent in 1 stage while preserving the oral commissure function.


Best practices for community gardening in a US-Mexico border community.
Minority communities such as those on the US-Mexico border are placed at disproportionate high risk for child and adult obesity, diabetes and cardiovascular diseases. A built environment characterized by an arid desert climate, lack of access to healthy foods, barriers to increasing physical activity, cultural and community norms which deter healthy eating and sustainable food production, shape obesity-related health disparities in these communities. Three pilot community gardens (implemented by two local governmental organizations and one community-based organization) were funded through the local Healthy Eating Active Living (HEAL) initiative in El Paso, Texas, and Las Cruces and Anthony, New Mexico (US-MX border communities with high obesity rates) in order to encourage healthy lifestyles among families in the region. A mixed-methods evaluation (n = 223) examined the implementation process, immediate outcomes and best practices of implementing and sustaining community gardens in these minority binational communities. In addition to nutrition-related outcomes, the potential for psychosocial outcomes from participating in community and school garden projects were observed. The best practices in relation to (i) assessing community norms related to growing food, (ii) increasing access to land and water for community/school gardening and (iii) enhancing social support for gardening are discussed. The implications of these best practices for obesity prevention and implementing community gardens in a minority US-MX border community characterized by cultural, geographical and socioeconomic barriers are examined.


meso-3,6-Dioxopiperazine-2,5-diacet-amide.
The title compound, C(8)H(12)N(4)O(4), was obtained by cyclization of the two l-asparagine mol-ecules and reveals a crystallographic inversion symmetry, and accordingly the two stereogenic centres are of opposite chirality. Thus, an asymmetric unit comprises a half of a mol-ecule. The mol-ecules are assembled into a three-dimensional hydrogen-bonding network by N-H⋯O hydrogen bonds.


Infrared refractive index of atmospheric aerosol substances.
The optical constants in the ir from lambda2.5 microm to 40 microm (4000-250 cm(-1)) of dry natural aerosol substances and of sea salt are presented. The aerosol substances were obtained from rain and snow water: dust and soot by sedimentation, and water soluble salts by evaporation. The spectra of the absorption index n' were derived from our published transmittance measurements of potassium bromide disks. The real part n of the refractive index was calculated from the specular reflectance at near normal incidence of disks of pure aerosol substance. The observed spectral features are being related to chemical constituents, notably sulfates and alcohol soluble organics. Optical constants of composite and wet aerosol are discussed. A simple model confirms the measured transmission of a coarse dry powder of water solubles and shows that the extinction by natural aerosol should have a minimum near 8 microm and a strong maximum near 9 microm.


Response of rat model of Pneumocystis carinii pneumonia to continuous infusion of deferoxamine.
The iron-chelating drug deferoxamine mesylate (DFO) is active against Pneumocystis carinii in vitro and in rat and mouse models of P. carinii pneumonia. Because DFO has a short half-life, daily divided or continuous dosage was expected to improve the dose response, as is the case with DFO treatment of malaria. Therefore, results of single daily intraperitoneal injections were compared with results of an evenly divided four-times-daily dosage and the efficacy of delivery with implanted infusion pumps. The highest bolus dosage (1,000 mg kg-1 of body weight day-1) was as effective as the standard combination of trimethoprim with sulfamethoxazole. Unexpectedly, very little improvement was observed with the divided or continuous dosage, and several mechanisms that could account for this are discussed.


Undertaking a research project improves confidence in research skills among student dietitians.
Research is a cornerstone of evidence-based dietetic practice. Research skills are often taught at university through experiential learning during a final-year research project. The present study aimed to investigate attitudes towards research and confidence in research skills among student dietitians before and after a research project. A questionnaire survey of student dietitians' attitudes to research and confidence in research skills was undertaken before and after completing a research project at two universities in London, UK. Dichotomous data were compared before and after the research project using a McNemar's test. Factors associated with 'high confidence' or 'improved confidence' in overall research skills at the end of the research project were investigated using multivariable logistic regression. In total, 160 student dietitians completed a questionnaire before and after their research project. The majority had positive attitudes to research both before and after their research project. There was an increase in numbers with 'high confidence' in overall research skills before (13; 8.1%) and after (79; 49.4%) the research project (p < 0.001), and 113 (70.6%) reported 'improved confidence' in overall research skills. The only factor associated with 'high confidence' in overall research skills was having 'high levels of involvement in the overall research process' (odds ratio = 6.13, 95% confidence interval = 2.03-18.49, p = 0.001). Student dietitians have positive attitudes towards research and undertaking a research project significantly improves confidence in their research skills. A higher level of involvement in the research project is the single most significant factor associated with high confidence in research skills.


The optic tectum of the dogfish Scyliorhinus canicula L.: a Golgi study.
The optic tectum of the dogfish Scyliorhinus canicula L. was studied by using the methods of Nissl, reduced silver nitrate, Golgi-aldehyde, and Golgi-Cox. Six layers and eight types of neurons were recognized. These cell types are not restricted to one layer; in fact some are found in all six tectal layers. The types of cells found are A) monopolar, B) triangular, C) radial bipolar, D) horizontal fusiform, E) large tectal, F) small tectal, G) pyriform, and H) stellate cells. In at least six of the cell types a series of dendritic specializations can be observed, such as spines in the form of "drumsticks" and thin varicose appendages, similar to those reported previously in the optic tecta of amphibians and teleosts. The optic tectum of the dogfish shows a degree of complexity comparable to that of amphibians and teleosts.


Semen parameters before and after transurethral surgery for ejaculatory duct obstruction.
We examined how transurethral resection of the ejaculatory ducts, performed for infertility, affects semen quality in patients with azoospermia and oligo-asthenospermia. A retrospective review was done of 46 cases of transurethral resection of the ejaculatory ducts for ejaculatory duct obstruction, confirmed by transrectal ultrasound. Clinical course and semen quality were assessed by semen parameter indications. In 65% of the patients transurethral resection of the ejaculatory ducts improved semen quality (greater than a 50% increase in total motile sperm count) and 20% initiated a pregnancy an average of 6.1 months postoperatively. Statistically significant increases in total motile sperm count were achieved in men with azoospermia and those treated for oligo-asthenospermic indications; the improvement also was shown to be sustainable. Complications occurred in 20% of the men. Significant and durable semen quality improvement can be achieved after transurethral resection of the ejaculatory ducts for all surgical indications. In most unsuccessful cases the reason for failure is unclear.


ATP-binding cassette transporter A1 (ABCA1) in macrophages: a dual function in inflammation and lipid metabolism?
Activated lipid-laden macrophages in the vascular wall are key modulators of the inflammatory processes underlying atherosclerosis. We demonstrate here that the ATP-binding cassette (ABC) transporter ABCA1 is induced during differentiation of human monocytes into macrophages. ABCA1 has been implicated in macrophage interleukin-1beta secretion and apoptosis. Moreover, ABCA1 mRNA and protein levels are strongly upregulated by uptake of modified LDL and downregulated by HDL(3)-mediated lipid efflux in macrophages. Mutation analysis in patients with the classical Tangier disease (TD), a monogenetic disorder characterized by hypersplenism, macrophage accumulation and deposition of cholesteryl esters in the reticuloendothelial system, low plasma HDL and premature atherosclerosis, revealed deleterious mutations in their ABCA1 gene. The localization pattern of the mutations within the ABCA1 protein appears to determine the tropism for either the reticuloendothelial system, as seen in the classical TD phenotype, or the artery wall, as in the case of HDL deficiency in the absence of splenomegaly. In a comprehensive analysis of the expression and regulation of all currently known human ABC transporters, we identified additional cholesterol-responsive genes that are induced during monocyte differentiation into macrophages. Our results indicate a dual regulatory function for ABCA1 in macrophage lipid metabolism and inflammation.


Mechanistic Studies and Expansion of the Substrate Scope of Direct Enantioselective Alkynylation of α-Ketiminoesters Catalyzed by Adaptable (Phebox)Rhodium(III) Complexes.
Mechanistic studies and expansion of the substrate scope of direct enantioselective alkynylation of α-ketiminoesters catalyzed by adaptable (phebox)rhodium(III) complexes are described. The mechanistic studies revealed that less acidic alkyne rather than more acidic acetic acid acted as a proton source in the catalytic cycle, and the generation of more active (acetato-κ(2)O,O')(alkynyl)(phebox)rhodium(III) complexes from the starting (diacetato)rhodium(III) complexes limited the overall reactivity of the reaction. These findings, as well as facile exchange of the alkynyl ligand on the (alkynyl)rhodium(III) complexes led us to use (acetato-κ(2)O,O')(trimethylsilylethynyl)(phebox)rhodium(III) complexes as a general precatalyst for various (alkynyl)rhodium(III) complexes. Use of the (trimethylsilylethynyl)rhodium(III) complexes as precatalysts enhanced the catalytic performance of the reactions with an α-ketiminoester derived from ethyl trifluoropyruvate at a catalyst loading as low as 0.5 mol % and expanded the substrate scope to unprecedented α-ketiminophosphonate and cyclic N-sulfonyl α-ketiminoesters.


Pantothenate is required in Neurospora crassa for assembly of subunit peptides of cytochrome c oxidase and ATPase/ATP synthase.
One polypeptide subunit of cytochrome c oxidase (EC 220.127.116.11) and two subunits of the ATPase/ATP synthase (EC 184.108.40.206) in mitochondria of Neurospora crassa are covalently modified with a derivative of pantothenic acid. In asexual spores of a pantothenate auxotroph of Neurospora, deprivation of pantothenic acid blocked the increase of the specific activities of cytochrome c oxidase and the ATPase above the basal activities in the dormant spores. Under cellular panthothenate deprivation, all the subunit peptides of these two enzymes apparently were synthesized and accumulated in the mitochondria, but these subunits were not assembled into normal complexes, and 55Fe-labeled heme a was incorporated into immunoprecipitable cytochrome c oxidase to a very low extent. In pantothenate-supplemented cells, the pantothenate derivative apparently is attached to the free unassembled subunits and appears not to be present in the assembled enzymes. It is likely that cellular deprivation of pantothenate, resulting in failure to modify the three subunit peptides, causes an interruption of the assembly pathway of cytochrome c oxidase and the ATPase/ATP synthase.


Lipid peroxidation as a component in trypanocidal drug action.
A representative range of trypanocides was examined for ability to induce lipid peroxidation in Trypanosoma rhodesiense in vitro. Because of drug interference, thiobarbituric acid (TBA) chromogen production and diene conjugation U.V. absorbance assay methods were less satisfactory that GLC analysis of polyenoic fatty acid loss. Docosohexanoic acid (22:6) content was specifically reduced to a highly significant degree by treatment with Ethidium or the lipid-soluble 4-demethoxydaunorubicin.


Morpho-functional cardiovascular adaptation in hypertensive patients: two-dimensional speckle tracking echocardiographic study.
Twenty-four-hour blood pressure (BP) variability is an important predictor of organ damage and cardiovascular events. Although epidemiological data are widely based on evaluation of office (clinic) BP, 24-hour ambulatory BP monitoring (ABPM) accurately assess the severity of hypertension to predict cardiovascular events in hypertensive patients, because it more accurately reflects BP load on heart and blood vessels. Conventional transthoracic echocardiography (TTE), such as M-mode and two-dimensional (2D), and more advanced techniques, such as tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE), are used to identify pathological changes of the hypertensive heart disease. In addition, the study of systemic arterial compliance (SAC) predicts the impact of the arterial stiffness on the LV remodeling. Fifty-eight patients (34 males and 24 females, aged 53±12 years) with hypertension for at least one year were studied using Ambulatory Blood Pressure Monitoring (ABPM), with evaluation of 24-hour, day time, night time and sleep and awake average systolic and diastolic BP, and subsequently with TTE, to evaluate the influence of the 24-hour average BP, integrated with echocardiographic parameters, on cardiovascular adaptations in hypertensive patients. ECHO parameters examined were: left ventricle (LV) mass indexed to body surface area (LVMi), LV ejection fraction (EF), left atrial volume indexed to body surface area (LAVi), mitral inflow velocities (E, A and E/A), mitral annulus velocities (S' and E') and E/E' ratio by TDI, LV global longitudinal strain (GLS) using 2D STE. SAC was derived by the ratio SVi/PP, using echocardiographic stroke volume index to body surface area (SVi) and pulse pressure (PP). LVMi showed a correlation with the 24-hour average BP (SBP r=0.32; DBP r=0.26), SBPd (r=0.32), DBPd (r=0.28) and SBPn (r=0.29). GLS was correlated with the 24-hour average BP (SBP r=0.30; DBP r=0.32), SBPd (r=0.32), DBPd (r=0.32) and with LVMi (r=0.42), LAVi with 24 hour SBP (r=0.28), while SAC with LVMi (r=0.29) and LAVi (r=0.33). ABPM and TTE evaluation can be particularly useful in hypertensive patients, even with normal office BP, to highlight the influence of 24-hour blood pressure profile on LVM, and to a lesser extent, on LAV. SAC, instead, seems to be correlated both to LVM and LAV, independently of BP levels.


Genetic insights into schizophrenia.
To outline new insights into the genetic etiology of schizophrenia. We discuss several commonly held beliefs about the genetic issues in schizophrenia. The complex genetic nature of the illness poses a challenge for investigators seeking causative genetic mutations. Multiple independent research findings are, however converging to identify a relatively small number of chromosomal locations that appear to contain schizophrenia susceptibility genes. Also, a clinically relevant genetic subtype of schizophrenia (22qDS) has been identified. We are developing a better understanding of how schizophrenia relates to other psychiatric disorders. While investigations into the possible roles of dopaminergic and serotonergic systems continue, other approaches that do not require theories of the mechanism of illness are also being used to identify candidate susceptibility genes. Research to date suggests that our understanding of the pathophysiology of schizophrenia will soon be fundamentally altered by genetic approaches to this complex disease.


Brain activation deficit in increased-load working memory tasks among adults with ADHD using fMRI.
Working memory (WM) is impaired among adults with attention-deficit hyperactivity disorder (ADHD). This study aimed to investigate the brain activation deficit for low-level or increased-load WM among adults with ADHD. A total of 20 adults with ADHD and controls were recruited according to diagnostic interviewing by a psychiatrist. Phonological and visual-spatial 2-back and 3-back tasks were performed under functional magnetic resonance scanning. The results demonstrated that both the adults with ADHD and the controls exhibited activation of the fronto-parietal network for WM, and the intensity was greater in the adult ADHD group. The ADHD group had higher brain activation over the bilateral anterior cingulate, left inferior frontal lobe, hippocampus, and supplementary motor area (SMA) for phonological WM than the control group. When the task loading increased from 2-back to 3-back tasks, the adults with ADHD perceived greater difficulty. The control group exhibited increased brain activation over the frontal-parietal network in response to increased phonological WM load. However, the ADHD group showed decreased brain activation over the left precuneus, insula, and SMA. Further analysis demonstrated that the ADHD group exhibited a greater decrease in brain activation over the left fronto-parietal network, including the precuneus, SMA, insula/inferior frontal lobe, and dorsolateral prefrontal cortex, than the control group. These results suggest that adults with ADHD pay more effort to low demanding phonological WM. On the other hand, brain activation of the left fronto-parietal network is impaired when the demands of WM exceed the capacity of adults with ADHD.


Serum Immune-Inflammation Index Assessment in the Patients with Ulcerative Colitis.
Radiologic and endoscopic diagnostic methods are used to determine disease activity in ulcerative colitis (UC). In order for endoscopic procedures to be invasive and to prevent radiation exposure, especially in young people, studies have been carried out frequently to determine a simple, fast, and reliable activity marker with laboratory methods. Our aim in this study is to determine the usefulness of serum immune-inflammatory index as a noninvasive marker of activation in patients with ulcerative colitis. A total of 82 consecutive patients treated with a diagnosis of ulcerative colitis were included in the study. The disease activation was assessed using the Mayo endoscopic subscore. The site of involvement was grouped into two as left colitis and extensive colitis. Patients were divided into two groups as those who had active disease based on clinical and endoscopic findings and those who were in remission. C-reactive protein (CRP) levels, platelets, neutrophils, and lymphocytes were recorded in all participants. The systemic immune-inflammation index (SII) and CRP values were compared between UC patients with active disease or remission. The correlations between CRP, SII, and Mayo endoscopic subscores were analyzed. In addition, ROC curve analysis for SII was performed to determine the cut-off value, sensitivity, and specificity in determining ulcerative colitis activity. The value of SII was significantly higher in the active group than the remission group (respectively, 1497 ± 1300 and 495 ± 224, p < 0.001). In the correlation analysis, a significant correlation was found between SII and Mayo subscore. In ROC curve analysis, SII was found to be significantly effective in determining activity in ulcerative colitis patients. For 0.860 area under the curve, the sensitivity was 68.1% and the specificity was 91.2% at a cut-off value of 781.5. SII is significantly higher in patients with active ulcerative colitis than those in remission. It shows promise for use as a noninvasive marker of active ulcerative colitis.


Neuronal migration disorders. Part I: Terminology, classification, pathophysiology, EEG and epilepsy.
Intractable epilepsies and partial epilepsies, which make up a great majority of epileptic disorders, are not better recognized and their etiologies unveiled with the help of the new imaging techniques. The development of magnetic resonance imaging (MRI) permits the accurate diagnosis while the patients are alive of the neuronal migration disorders (NMD), which constitute an important group of intractable epilepsies. Previously, NMD cases were described by neuropathologists from autopsy materials, and many of these developmental disorders were not considered compatible with prolonged survival. Cerebral malformations due to neuronal migration anomalies are described in association with motor and mental retardation, learning disabilities, microcephaly, dysmorphic features and epilepsy. Neuronal migration takes place in all parts of the central nervous system (CNS) during the shaping process of the CNS; it actually includes both the central and peripheral nervous systems. However, in common usage the meaning of "neuronal migration disorders" is restricted to the neocortex.


Linnaea borealis L. var. borealis-In Vitro Cultures and Phytochemical Screening as a Dual Strategy for Its Ex Situ Conservation and a Source of Bioactive Compounds of the Rare Species.
Linnaea borealis L. (Twinflower)-a dwarf shrub in the Linnaeeae tribe of Caprifoliaceae family-is distributed across the Northern Hemisphere. By means of this study, a reliable protocol for efficient micropropagation of uniform L. borealis L. var. borealis plantlets has been provided for the first time; callus culture was also established. Different initial explants, types of cultures, media systems, and plant growth regulators in Murashige and Skoog (MS) media were tested. Agitated shoot cultures in the liquid media turned out to be the best system for the production of sustainable plant biomass. After stabilization of the callus lines, the highest growth index (c.a. 526%) was gained for callus maintained on MS enriched with picloram. TLC and UHPLC-HESI-HRMS analysis confirmed the presence of phenolic acids and flavonoids, and for the first time, the presence of iridoids and triterpenoid saponins in this species. Multiplication of L. borealis shoot culture provides renewable raw material, allowing for the assessment of the phytochemical profile, and, in the future, for the quantitative analyses and the studies of the biological activity of extracts, fractions, or isolated compounds. This is the first report on in vitro cultures of traditionally used L. borealis rare taxon and its biosynthetic potential.


Restoration of the CEJ level and root coverage after gingival augmentation procedure on mandibular teeth: a case presentation.
The aim of this article is to present a clinical case of a 54-year-old patient where the cementoenamel junction (CEJ) level was restored and a root coverage procedure carried out after gingival augmentation on the mandibular teeth. A very thin buccal keratinized tissue (KT) was detected apical to the recessions. The restorative approach consisted of identifying the lost CEJ, thus differentiating the area of restoration from the area of root coverage of the abraded teeth. Subsequently, a free gingival graft (FGG) was applied. A coronally advanced flap procedure was performed 3 months later. The clinical outcomes obtained through combined restorative/ periodontal treatment were maintained at the 4-year follow-up.


Tackling multidrug resistance mediated by efflux transporters in tumor-initiating cells.
Expression of the multifunctional ATP-binding cassette (ABC) efflux transporter gene family is a well-established mechanism for protecting cancer stem cells (CSCs) from damage or death due to toxins. The outcome of such protection makes CSCs innately multidrug resistant (MDR) to conventional chemotherapy. While research has focused on gaining better insight into the role of ABC transporters in CSC drug resistance, various strategies to circumvent the function of these transporters have been proposed, including inhibition of transporter function through targeted tyrosine kinase inhibitors, competitive and allosteric modulators, shRNA-mediated inhibition, nanoparticle-mediated delivery of inhibitors, and modulating the regulation of transcriptional and signaling pathways involving ABC transporters. This review highlights the role of MDR mediated by ABC transporters, particularly in CSCs, and the current progress and pitfalls of strategies to circumvent MDR in CSCs. Cancer stem cells are now a subject of intense research, as it is hypothesized that these progenitors predominantly beget tumorigenesis, chemoresistance, and metastasis. Consequently, the design and synthesis of more effective ABC transporter inhibitors, to increase cytotoxic drug concentrations in CSCs (thus increasing their eradication), is a promising approach for the field of oncology.


Anti-SARS-CoV Natural Products With the Potential to Inhibit SARS-CoV-2 (COVID-19).
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), known to cause the disease COVID-19, was declared a pandemic in early 2020. The objective of this review was to collate information regarding the potential of plants and natural products to inhibit coronavirus and targets associated with infection in humans and to highlight known drugs, which may have potential activity against SARS-CoV-2. Due to the similarity in the RNA genome, main proteases, and primary host receptor between SARS-CoV and SARS-CoV-2, a review was conducted on plants and secondary metabolites, which have shown activity against SARS-CoV. Numerous scientific reports on the potential of plants and secondary metabolites against SARS-CoV infection were found, providing important information on their possible activity against SARS-CoV-2. Based on current literature, 83 compounds have been identified with the potential to inhibit COVID-19. The most prominent selectivity was found for the alkaloid, lycorine, the lignan, savinin, and the abietane terpenoid, 8-beta-hydroxyabieta-9(11),13-dien-12-one with selectivity index values greater than 945, 667, and 510, respectively. Plants and their secondary metabolites, with activity against targets associated with the SARS-CoV infection, could provide valuable leads for the development into drugs for the novel SARS-CoV-2. The prospects of using computational methods to screen secondary metabolites against SARS-CoV targets are briefly discussed, and the drawbacks have been highlighted. Finally, we discuss plants traditionally used in Southern Africa for symptoms associated with respiratory viral infections and influenza, such as coughs, fever, and colds. However, only a few of these plants have been screened against SARS-CoV. Natural products hold a prominent role in discovering novel therapeutics to mitigate the current COVID-19 pandemic; however, further investigations regarding in vitro, in vivo, pre-clinical, and clinical phases are still required.


The role of mitochondrial dysfunction in psychiatric disease.
Mitochondrial respiratory chain disorders are a group of genetically and clinically heterogeneous disorders caused by the biochemical complexity of mitochondrial respiration and the fact that two genomes, one mitochondrial and one nuclear, encode the components of the respiratory chain. These disorders can manifest at birth or present later in life. They result, at least in part, in defective production of ATP. Typically, mitochondrial disorders affect tissues with high energetic demands such as skeletal muscle, cardiac muscle, and the central nervous system. Neurological dysfunction is the most frequent clinical presentation of these disorders. The central nervous system is highly dependent on oxidative metabolism, and particular mitochondrial disorders are accompanied by focal brain necrosis (Leigh disease), dementia, or static encephalopathy. Furthermore, many children with mitochondrial encephalomyopathies present with more subtle and indolent signs including focal cognitive deficits of memory, perception, and language. Some subjects with mitochondrial disorders may also exhibit nonverbal cognitive impairment, compromised visuospatial abilities, and short-term memory deficits associated with working memory that likely reflect defects in synaptic plasticity. Psychiatric features are found within the clinical spectrum of mitochondrial syndromes. It is increasingly recognized that mitochondrial dysfunction may be associated with neuropsychiatric abnormalities such as dementia, major depression, and bipolar disorder. Furthermore, several lines of evidence suggest that there is involvement of mitochondrial dysfunction in schizophrenia, including documented alterations in brain energy metabolism, electron transport chain activity, and expression of genes involved in mitochondrial function. The purpose of this review article is to summarize the psychiatric features observed in mitochondrial cytopathies and discuss possible mechanisms of dysfunctional cellular energy metabolism that underlie the pathophysiology of major subsets of psychiatric disorders.


Phosphorylation of right open reading frame 2 (Rio2) protein kinase by polo-like kinase 1 regulates mitotic progression.
Polo-like kinase 1 (Plk1) plays essential roles during multiple stages of mitosis by phosphorylating a number of substrates. Here, we report that the atypical protein kinase Rio2 is a novel substrate of Plk1 and can be phosphorylated by Plk1 at Ser-335, Ser-380, and Ser-548. Overexpression of Rio2 causes a prolonged mitotic exit whereas knockdown of Rio2 accelerates mitotic progression, suggesting that Rio2 is required for the proper mitotic progression. Overexpression of phospho-mimicking mutant Rio2 S3D but not the nonphosphorylatable mutant Rio2 S3A displays a profile similar to that of wild-type Rio2. These results indicate that the phosphorylation status of Rio2 correlates with its function in mitosis. Furthermore, time-lapse imaging data show that overexpression of Rio2 but not Rio2 S3A results in a slowed metaphase-anaphase transition. Collectively, these findings strongly indicate that the Plk1-mediated phosphorylation of Rio2 regulates metaphase-anaphase transition during mitotic progression.


Multiple primary cancers in patients with squamous cell carcinoma of the oral cavity.
During the 27 years between 1962 and 1988, 984 patients visited the National Cancer Center Hospital for previously untreated squamous cell carcinoma of the oral cavity and lip. The records of all these 984 patients were reviewed to determine the incidence of additional primary carcinoma. 1) One hundred and thirty-five additional carcinomas developed in 111 patients (11.2%) during 5,689.2 person-years of observation. The incidence of additional primary carcinoma was 23.7 per 1,000 person-years. 2) The cumulative rate of additional primary carcinoma during the first five years of observation showed a tendency to increase in the most recently treated patients (from 1980 to 1988). 3) The observed-to-expected ratio (O/E ratio) for all sites was 2.77 and this is significantly high (P less than 0.01). The calculation of the O/E ratio for each site revealed significantly high risks in the oral cavity and pharynx, esophagus and skin. The O/E ratio for the oral cavity and pharynx was extremely high (79.45). 4) The O/E ratio for all sites in each year of follow-up was the highest in the first year, stayed nearly constant from the second to 14th years, and decreased gradually afterwards. Significantly high risk was observed until the 13th year of follow-up. Patients with oral squamous cell carcinoma must be under frequent and regular examination for almost 15 years.


Publishing Identifiable Patient Photographs in Scientific Journals: Scoping Review of Policies and Practices.
Publishing identifiable patient data in scientific journals may jeopardize patient privacy and confidentiality if best ethical practices are not followed. Current journal practices show considerable diversity in the publication of identifiable patient photographs, and different stakeholders may have different opinions of and practices in publishing patient photographs. This scoping review aimed to identify existing evidence and map knowledge gaps in medical research on the policies and practices of publishing identifiable photographs in scientific articles. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL with Full Text, Database of Abstracts of Reviews of Effects, Ovid MEDLINE, and Scopus. The Open Science Framework, PROSPERO, BASE, Google Scholar, OpenGrey, ClinicalTrials.gov, the Campbell Collaboration Library, and Science.gov were also searched. After screening the initial 15,949 titles and abstracts, 98 (0.61%) publications were assessed for eligibility at the full-text level, and 30 (0.19%) publications were included in this review. The studies were published between 1994 and 2020; most had a cross-sectional design and were published in journals covering different medical disciplines. We identified 3 main topics. The first included ethical aspects of the use of facial photographs in publications. In different clinical settings, the consent process was not conducted properly, and health professionals did not recognize the importance of obtaining written patient consent for taking and using patient medical photographs. They often considered verbal consent sufficient or even used the photographs without consent. The second topic included studies that investigated the practices and use of medical photography in publishing. Both patients and doctors asked for confidential storage and maintenance of medical photographs. Patients preferred to be photographed by their physicians using an institutional camera and preferred nonidentifiable medical photographs not only for publication but also in general. Conventional methods of deidentification of facial photographs concealing the eye area were recognized as unsuccessful in protecting patient privacy. The third topic emerged from studies investigating medical photography in journal articles. These studies showed great diversity in publishing practices regarding consent for publication of medical photographs. Journal policies regarding the consent process and consent forms were insufficient, and existing ethical professional guidelines were not fully implemented in actual practices. Patients' photographs from open-access medical journals were found on public web-based platforms. This scoping review showed a diversity of practices in publishing identifiable patient photographs and an unsatisfactory level of knowledge of this issue among different stakeholders despite existing standards. Emerging issues include the availability of patients' photographs from open-access journals or preprints in the digital environment. There is a need to improve standards and processes to obtain proper consent to fully protect the privacy of patients in published articles.


Spread of Burn and Non-burn Pathologies, Anaesthetic Support and some Management Data.
In this article we present the surgical activity of the Burns Service in the University Hospital Centre in Tirana. Not only burn patients but also patients with trauma and soft tissue losses are hospitalized in a burns centre, as well as patients needing plastic surgery coming from similar specialities. In 2006, 1127 patients were subjected to surgery in our service. The techniques of anaesthesia used are general anaesthesia (endotracheal tube, laryngeal mask airway, intravenous) and regional anaesthesia. An anaesthesiologist acting in the role of physician manager can add significant value to the overall operating room process by improving efficiency in resource utilization and simultaneously quality of care. We have found that giving priority to burns, including burns sequelae and other hospitalized burn patients, if possible in day surgery, can optimize the bed occupancy rate.


Incorporation of MnO2-coated carbon nanotubes between graphene sheets as supercapacitor electrode.
Hierarchical graphene-based composite consisting of graphene sheets intercalated by MnO(2)-coated carbon nanotubes (MnC) was prepared for high-performance supercapacitor electrode. The highly negatively charged graphene oxides reduced by urea (RGO) and the positively charged MnC functionalized with poly(diallyldimethylammonium chloride) created a strong electrostatic interaction, forming a hierarchical nanostructure. The elelctrocapacitive behaviors of MnC/RGO (MnC-G) were systematically investigated by cyclic voltammetry, galvanostatic charge-discharge and electrochemical impedance spectroscopy. A maximum specific capacitance of 193 F/g was achieved for the MnC-G composite with 37% RGO, which was almost 3-fold higher than 69 F/g of carbon nanotubes/RGO and 2-fold higher than 89 F/g of MnO(2)/RGO composite. Moreover, an excellent rate performance, a good capacitance retention (~70%) and a superior Coulombic efficiency (94-96%) were also observed during the continuous 1300 cycles of galvanostatic charge-discharge.


Regulation of development of leucine uptake activity by glutamine in the scutellum of germinating barley grain.
Scutella from ungerminated grains of barley (Hordeum vulgare L. cv Pirkka) take up leucine at a slow rate, which increases rapidly during germination. When endosperms were removed from the grains after imbibition for 4 hours or after germination for 12 or 72 hours, the increase in the rate of leucine uptake was greatly accelerated during subsequent incubation of the embryos or scutella. These increases were rapidly inhibited by cordycepin and cycloheximide, suggesting that protein synthesis, probably synthesis of the carrier protein, was required for the development of the uptake activity.In separated embryos or scutella, the increases in the leucine uptake activity were inhibited by glutamine. The inhibitions caused by glutamine and cycloheximide were not additive, suggesting that glutamine did not interfere with the function of the carrier but repressed its synthesis. Glutamine did not inhibit the simultaneous increase in peptide uptake; in this respect, its effect was specific for leucine uptake, which appears to be due to a general amino acid uptake system.Some other protein amino acids also inhibited the increase in leucine uptake without inhibiting the increase in peptide uptake. However, these effects were smaller than that of glutamine.These results suggest that the transfer of leucine (and other amino acids) from the endosperm to the seedling in a germinating barley grain is regulated at the uptake step by repression of the synthesis of the amino acid carrier protein by glutamine and-possibly to a lesser extent-by some other amino acids taken up from the endosperm.


Evaluating the Interpersonal Needs Questionnaire: Comparison of the Reliability, Factor Structure, and Predictive Validity across Five Versions.
Five versions of the Interpersonal Needs Questionnaire (INQ), a self-report measure of perceived burdensomeness and thwarted belongingness, have been used in recent studies (including 10-, 12-, 15-, 18-, and 25-items). Findings regarding the associations between perceived burdensomeness, thwarted belongingness, and suicidal ideation using different versions have been mixed, potentially due to differences in measurement scales. This study evaluated factor structure, internal consistency, and concurrent predictive validity of these five versions in three samples. Samples 1 and 2 were comprised of 449 and 218 undergraduates, respectively; Sample 3 included 114 adolescent psychiatric inpatients. All versions demonstrated acceptable internal consistency. The 10-item version and 15-item version demonstrated the best, most consistent model fit in confirmatory factor analyses. Both perceived burdensomeness and thwarted belongingness consistently predicted concurrent suicidal ideation on the 10-item INQ only. Future research should consider using the 15-item or 10-item versions.


Photodissociation study of 1,3-dibromopropane at 234 nm via an ion velocity imaging technique.
The photodissociation of 1,3-dibromopropane has been studied at 234 nm using a 2D photofragment ion velocity imaging technique coupled with a [2 + 1] resonance-enhanced multiphoton ionization scheme. The velocity distributions for the Br (2P1/2) (denoted Br) and Br (2P3/2) (denoted Br) fragments are determined, and each can be fitted by a narrow single-peaked Gaussian curve, suggesting that bromine fragments are generated as a result of direct dissociation via repulsive potential energy surfaces. The recoil anisotropies were measured to be beta = 0.80 for Br and 1.31 for Br, and the product relative quantum yields at 234 nm is Phi234 nm(Br) = 0.21.


Effects of dexfenfluramine on glucose drinking and glucose-conditioned flavour preferences in rats: taste versus post-ingestive conditioning.
A comparison was made of the effects of dexfenfluramine (DF, 3-10 mg kg-1) on intake of and conditioning with glucose solutions varying in orostimulant properties (taste) and post-ingestive actions (calories), in rats. First, sham-feeding, using gastric-fistulated rats, was performed to assess the orostimulant properties of the solutions. Then, two experiments were done. In the first experiment, we examined the effects of DF, given at doses of 13 and 10 mg kg-1, on the intake of two glucose solutions having different orostimulant properties and different caloric values. The solutions were a mix of 1% glucose plus 0.125% saccharin (low caloric, more orostimulant), and 4% glucose (high caloric, less orostimulant). At doses of 10 mg kg-1, DF administration markedly reduced intake of both solutions (P < 0.05 vs Control Group, respectively). In second experiment, we examined the effects of DF (10 mg kg-1) on flavour preference conditioning in two parts. In the first part of the experiment, rats consumed two distinctively flavoured solutions having equal orostimulant properties but different caloric value for a conditioning period of 16 days. The solutions were a mix of 1% glucose plus 0.125% saccharin (low caloric), and 6.1% glucose (high caloric). At the end of the conditioning period, the flavour paired with ingestion of more calories was subsequently preferred (P < 0.05 vs low caloric glucose-saccharin mix). DF, when given during and after the conditioning period, attenuated this flavour-calorie conditioning (P < 0.05 vs Control Group). In the second part of the experiment, rats were conditioned with flavours associated with a mix of 20% glucose plus 0.4% citric acid and 20% glucose solutions. These solutions were equally caloric but differed in orostimulant properties. The flavour paired with better orostimulant properties was subsequently preferred (P < 0.05 vs less orostimulant glucose-citric acid mix). DF, when given during and after the conditioning period, also attenuated this flavour-flavour conditioning (P < 0.05 vs Control Group). These results suggest that DF may impair flavour preference learning.


Complete Genome Sequence of Escherichia Phage OSYSP.
Bacteriophage OSYSP is a new anti-Escherichia coli O157:H7 phage isolated from municipal wastewater in Ohio. OSYSP is potent against enterohemorrhagic E. coli and is a candidate biocontrol agent for food and therapeutic applications. In this paper, we present the important genetic features of this phage based on its complete genome sequence.


Isoxazole Derivatives against Carbonic Anhydrase: Synthesis, Molecular Docking, MD Simulations, and Free Energy Calculations Coupled with In Vitro Studies.
Heterocyclic compounds with a five-membered ring as a core, particularly those containing more than one heteroatom, have a wide spectrum of biological functions, especially in enzyme inhibition. In this study, we present the synthesis of five-membered heterocyclic isoxazole derivatives via sonication of ethyl butyrylacetate with aromatic aldehyde in the presence of a SnII-Mont K10 catalyst. The synthesized compounds were characterized using sophisticated spectroscopic methods. In vitro testing of the compounds reveals three derivatives with significant inhibitory action against carbonic anhydrase (CA) enzyme. The compound AC2 revealed the most promising inhibitory activity against CA among the entire series, with an IC50 = 112.3 ± 1.6 μM (%inh = 79.5) followed by AC3 with an IC50 = 228.4 ± 2.3 μM (%inh = 68.7) compared to the standard with 18.6 ± 0.5 μM (%inh = 87.0). Molecular docking (MD) study coupled with extensive MD simulations (400 ns) and MMPBSA study fully supported the in vitro enzyme inhibition results, evident from the computed ΔG bind (AC2 = -13.53 and AC3 = -12.49 kcal/mol). The in vitro and in silico studies are also augmented by a fluorescence-based enzymatic assay in which compounds AC2 and AC3 showed significant fluorescence enhancement. Therefore, on the basis of the present study, it is inferred that AC2 and AC3 may serve as a new framework for designing effective CA inhibitors.


The chloroplast and cytoplasmic ribosomes of euglena: I. Stability of chloroplast ribosomes prepared by an improved procedure.
A new isolation procedure has resulted in an improved yield of stable 68S chloroplast ribosomes from Euglena gracilis var. bacillaris. Chloroplasts are isolated by suspending the cells in buffer I (sorbitol, 250 mm; sucrose, 250 mm; Ficoll, 2.5% [w/v]; magnesium acetate, 1 mm; bovine serum albumin, 0.01% [w/v]; mercaptoethanol, 14 mm; N-2-hydroxyethyl-piperazine-N'-2-ethanesulfonic acid, pH 7.6, 5 mm) and passing through a French press at less than 1500 pounds per square inch. The crude chloroplasts are purified by three washings with buffer II (sorbitol, 150 mm; sucrose, 150 mm; Ficoll, 2.5% [w/v]; magnesium acetate, 1 mm; bovine serum albumin, 0.01% [w/v]; mercaptoethanol, 14 mm; N-2-hydroxyethyl-piperazine-N'-2-ethanesulfonic acid, pH 7.6, 5 mm). Stable 68S chloroplast ribosomes are obtained when the isolated chloroplasts are resuspended in ribosome buffer (tris-HCI, pH 7.6, 10 mm; magnesium acetate, 12 mm; KCI, 60 mm) containing spermidine, 0.5 mm; mercaptoethanol, 14 mm; sucrose, 8% (w/w), passed through a French press at 4000 pounds per square inch and extracted with either 0.1% (w/v) sodium deoxycholate or 1.0% (v/v) Triton X-100. At 0 to 4 C in ribosome buffer, the purified 68S chloroplast monosome forms a 53S particle while the 35S particle, an expected product of monosome dissociation, cannot be detected. Spermidine and mercaptoethanol prevent the formation of 53S particles from 68S monosomes. The purified 53S particles derived from 68S monosomes contain 23S RNA as well as a significant amount of 16S RNA, suggesting that this particle may not be a true ribosomal subunit.


[Intravenous light sedation with midazolam by dentists].
Approximately 800,000 Dutch people refrain from going to the dentist because of fear. Behavioural therapy, a psychological approach to treating anxiety, is taught extensively at the various Dutch universities and is used in dental practice in the Netherlands. For medicinal treatment, dentists in the Netherlands use nitrous oxide sedation and orally administered benzodiazepines. For the intravenous administration of sedatives Dutch dentists are almost entirely dependent on an anaesthesiologist. Light intravenous sedation with midazolam can be used to make anxious patients more comfortable. Dutch dentists can apply light sedation with midazolam intravenously in adult patients themselves, subject to a wide range of conditions.


Clinical wear of overdenture ball attachments after 1, 3 and 8 years.
Implant-supported overdentures have become the treatment of choice in restoring complete edentulism, but the types of attachment to assure durable retention are a subject of debate. Ball attachments were reported as a simple treatment, but wear of components was responsible for a decrease in retention. The aim of this retrospective study was to measure the wear of the ball abutment or patrix after three different periods of clinical wear. Sixty-nine specimens of three groups of patrix that were in use for a mean of 12.3 months (group A), 39 months (group B) and 95.6 months (group C) were retrieved from 35 patients and measured on a coordinate measuring machine equipped with a touch trigger probe. Ten unused ball abutments were added as a control (group D). The patrix diameters and any deviation from circularity in different axes were measured. The diameters of groups A, B and C were significantly different from that of group D (control). No statistically significant differences were found between diameter and circularity variations between groups B and C. The maximal amount of diameter reduction was limited to approximately 30 μm, and 90% of diameter loss at the equator due to wear was reached in group B. One, 3 and 8 years of clinical wear reduced significantly the diameters of the ball abutments tested, and the maximal amount of wear was reached after 3 years of clinical use.


Glioblastoma treated with concurrent radiation therapy and temozolomide chemotherapy: differentiation of true progression from pseudoprogression with quantitative dynamic contrast-enhanced MR imaging.
To explore the role of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the differentiation of true progression from pseudoprogression in patients with glioblastoma on the basis of findings in entirely newly developed or enlarged enhancing lesions after concurrent radiation therapy and chemotherapy with temozolomide and to evaluate the diagnostic performance of the quantitative pharmacokinetic parameters obtained at dynamic contrast-enhanced MR imaging, such as the volume transfer constant (K(trans)), the extravascular extracellular space per unit volume of tissue(ve), and the blood plasma volume per unit volume of tissue(vp). This prospective study had institutional review board approval; written informed consent was obtained from all patients. Thirty-three patients with histopathologically proven glioblastoma who had undergone concurrent radiation therapy and chemotherapy with temozolomide were included. Dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters, including K(trans), ve, and vp, were calculated for newly developed or enlarged enhancing lesions. Pharmacokinetic parameters were compared between the true progression (n = 17) and pseudoprogression (n = 16) groups by using unpaired t tests and then multivariable analysis. The mean K(trans) and ve were higher in the true progression group than in the pseudoprogression group (mean K(trans), 0.44 min(-1) ± 0.25 [standard deviation] and 0.23 min(-1) ± 0.10 for true progression and pseudoprogression groups, respectively, P = .004; and mean ve, 1.26 ± 0.78 and 0.75 ± 0.49 for true progression and pseudoprogression groups, respectively, P = .034). Multivariable analysis showed that mean K(trans) was the only independently differentiating variable (P = .004). Dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters, including K(trans) and ve, in the entire newly developed or enlarged enhancing lesion may be useful objective diagnostic tools in the differentiation of true progression from pseudoprogression in patients with glioblastoma who have undergone concurrent radiation therapy and chemotherapy with temozolomide.


CD spectroscopy of peptides and proteins bound to large unilamellar vesicles.
Circular dichroism (CD) spectroscopy is an essential tool for determining the conformation of proteins and peptides in membranes. It can be particularly useful for measuring the free energy of partitioning of peptides into lipid vesicles. The belief is broadly held that such CD measurements can only be made using sonicated small unilamellar vesicles (SUVs) because light scattering associated with extruded large unilamellar vesicles (LUVs) is unacceptably high. We have examined this issue using several experimental approaches in which a chiral object (i.e., peptide or protein) is placed both on the membrane and outside the membrane. We show that accurate CD spectra can be collected in the presence of LUVs. This is important because SUVs, unlike LUVs, are metastable and consequently unsuitable for equilibrium thermodynamic measurements. Our data reveal that undistorted CD spectra of peptides can be measured at wavelengths above 200 nm in the presence of up to 3 mM LUVs and above 215 nm in the presence of up to 7 mM LUVs. We introduce a simple way of characterizing the effect on CD spectra of light scattering and absorption arising from suspensions of vesicles of any diameter. Using melittin as an example, we show that CD spectroscopy can be used to determine the fractional helical content of peptides in LUVs and to measure their free energy of partitioning of into LUVs.


Platelets stored in whole blood at 4°C: in vivo posttransfusion platelet recoveries and survivals and in vitro hemostatic function.
Ordinarily, whole blood (WB) is separated into components before storage. We assessed the posttransfusion viability and function of platelets (PLTs) if they were stored within WB at 4°C. Whole blood was obtained from 30 normal subjects and stored at 4°C without agitation for 12 days and for 10, 15, or 22 days with agitation. After WB storage, a PLT concentrate was prepared, and a fresh PLT sample was obtained from each donor. The stored PLTs were labeled with 111 In and the fresh with 51 Cr, and both were simultaneously transfused into their donor. Blood samples were obtained after transfusion to determine PLT recoveries and survivals. PLT samples from WB before and after storage were also assayed for PLT function and biochemistry. After storage for 12 days without WB rotation, poststorage PLT counts averaged only 49 ± 12% of baseline values. After storage for 10, 15, or 22 days with end-over-end WB rotation, PLT counts averaged 76 ± 14% of baseline values. Fifteen-day poststorage radiolabeled PLT recoveries averaged 27 ± 11% (49 ± 16% of fresh), and survivals averaged 1.2 ± 0.4 days (16 ± 6% of fresh). in vitro assays demonstrated marked PLT activation after any storage time, and although PLT function decreased over time, stored PLTs were still considered acceptable. These data suggest that, during rotated WB storage at 4°C for up to 15 days, PLT yields, poststorage PLT recoveries and survivals, and PLT function should be sufficient to support the short-term hemostatic needs of traumatized patients.


[Multiphase Spatial Distribution Characteristics of Cd Morphology in Typical Intertidal Zones in the Guangdong-Hong Kong-Macao Greater Bay Area and Its Influencing Factors].
Simultaneous sampling and observation were conducted at 14 stations in typical intertidal zones of the Guangdong-Hong Kong-Macao greater bay area. The spatial distribution characteristics of Cd morphology in surface water, pore water, suspended matters, and sediments at each sampling site were analyzed, and the influencing factors of Cd morphology changes in each medium were discussed using statistical analyses based on environmental factors. The results showed that the total contents of Cd in surface water, pore water, suspended matters, and sediments in each intertidal zone ranged from 0.41-15.03 μg·L-1, 0.41-27.54 μg·L-1, 0.41-4.88 mg·kg-1, and 0.20-5.30 mg·kg-1, respectively. The contents of Cd in Shajiao Bay were significantly higher than those in other sampling sites, which should be related to the developed electronics and manufacturing industries in Dongguan. The concentration of Cd in surface water was slightly lower than that in pore water, whereas the content of Cd in suspended matter was comparable to that in sediment at the same sampling site. The results of morphological analysis showed that the ionic-state Cd was dominant in both surface water and pore water, accounting for 67.23%-97.56% and 33.33%-97.16%, respectively. In suspended matter and sediment, Cd was mainly in the residual state, accounting for 45.45%-96.36% and 45.80%-97.27%, respectively. Pearson correlation analysis showed that the complex-state Cd in the aqueous phase was negatively correlated with oxidation reduction potential (ORP) and pH and positively correlated with total organic carbon. The bioavailable Cd in solid sediment was significantly positively correlated with the proportion of clay, ORP, and solid organic carbon and significantly negatively correlated with pH. The single factor linear regression analysis showed that ORP had the greatest effect on the complex-state Cd in the aqueous phase, with regression coefficients of 0.864 and 0.824, respectively. The bioavailable Cd in solid sediment at different depths was significantly affected by the proportion of clay, and the regression coefficients were 0.968, 0.980, 0.977, and 0.877, respectively. The above results indicate that the distribution of total Cd content in the typical intertidal environment of the Greater Bay Area was affected by the characteristics of urban economic development, whereas the allocation of Cd morphology was closely related to environmental factors.


Torsion of the spermatic cord: An exemplary early presentation.
Torsion of the spermatic cord may lead to loss of the testis when presentation is delayed. In our environment, a high premium is placed on the male child and his ability to procreate. Hence, torsion of the spermatic cord is a true surgical emergency. Here, we report a case of torsion of the spermatic cord in a 19-year-old student that exemplifies early presentation and short presentation-detorsion time. Immediately after the operation, the clinical information in the patient's case file was summarized. A literature search was conducted on the subject matter, and the findings were compared with those of the present patient. The determinants of outcome include presentation time and the time between presentation and operation. Unfortunately, in many series, late presentation is still the norm. In the index patient, the presentation time was very short. In our environment, patients with torsion of the spermatic cord can present early and be operated promptly if we can provide public health education, mobile phones, commercial taxis, and good road networks.


Long-lived mitochondrial (Mit) mutants of Caenorhabditis elegans utilize a novel metabolism.
The Caenorhabditis elegans mitochondrial (Mit) mutants have disrupted mitochondrial electron transport chain (ETC) functionality, yet, surprisingly, they are long lived. We have previously proposed that Mit mutants supplement their energy needs by exploiting alternate energy production pathways normally used by wild-type animals only when exposed to hypoxic conditions. We have also proposed that longevity in the Mit mutants arises as a property of their new metabolic state. If longevity does arise as a function of metabolic state, we would expect to find a common metabolic signature among these animals. To test these predictions, we established a novel approach monitoring the C. elegans exometabolism as a surrogate marker for internal metabolic events. Using HPLC-ultraviolet-based metabolomics and multivariate analyses, we show that long-lived clk-1(qm30) and isp-1(qm150) Mit mutants have a common metabolic profile that is distinct from that of aerobically cultured wild-type animals and, unexpectedly, wild-type animals cultured under severe oxygen deprivation. Moreover, we show that 2 short-lived mitochondrial ETC mutants, mev-1(kn1) and ucr-2.3(pk732), also share a common metabolic signature that is unique. We show that removal of soluble fumarate reductase unexpectedly increases health span in several genetically defined Mit mutants, identifying at least 1 alternate energy production pathway, malate dismutation, that is operative in these animals. Our study suggests long-lived, genetically specified Mit mutants employ a novel metabolism and that life span may well arise as a function of metabolic state.


Experience of implementing a quality management system in an Ontario hospital laboratory.
This article describes the process of building and implementing a quality management system in the Department of Laboratory Medicine at St. Michael's Hospital in Toronto. This was done in part to fulfill the requirements of the Ontario Laboratory Accreditation program. During the process, we revised and created new procedure manuals and documents through the use of focus groups and inter-departmental committees. The entire project took approximately two-and-a-half years to complete and required teamwork, personal commitment, and professional sacrifices by key personnel.


Immune function and dysfunction are determined by lymphoid tissue efficacy.
Lymphoid tissue returns to a steady state once each immune response is resolved, and although this occurs multiple times throughout life, its structural integrity and functionality remain unaffected. Stromal cells orchestrate cellular interactions within lymphoid tissue, and any changes to the microenvironment can have detrimental outcomes and drive disease. A breakdown in lymphoid tissue homeostasis can lead to a loss of tissue structure and function that can cause aberrant immune responses. This Review highlights recent advances in our understanding of lymphoid tissue function and remodelling in adaptive immunity and in disease states. We discuss the functional role of lymphoid tissue in disease progression and explore the changes to lymphoid tissue structure and function driven by infection, chronic inflammatory conditions and cancer. Understanding the role of lymphoid tissues in immune responses to a wide range of pathologies allows us to take a fuller systemic view of disease progression.


Effects of E2 and E1 glycosylation on specific membrane fusion in rubella virus strain JR23.
To explore the effects of glycosylation in glycoprotein on membrane fusion in rubella virus strain JR23. The N-linked glycosylation sites in glycoproteins were mutated individually or in combination. Total expression and cell surface expression efficiencies of mutant proteins were assayed with Western blot and FACS. The fusion functions were assayed with Giemsa staining and reporter gene method. Binding activity of mutant proteins was detected with hemadsorption assays. We observed that total expression levels of all the mutant proteins in cells were unchanged, but the cell surface expression efficiencies of all the mutant proteins except E2 S131V were lower than wild-type protein. When effects of reduced cell surface expression were eliminated, mutant proteins N53G, S73I, S131V and T78A had lower fusion activities than wild-type protein, and binding abilities of E2 S73I and E1 T78A decreased slightly. But in all the combined mutants, no cell fusion was detected, and only a minor hemadsorption was observed in N53G-S131V, N53G-T78A and N53G-T211A. Glycosylation of glycoproteins were involved in cell surface expression synergistically. Glycosylation on E2 N53, N71, N129 and E1 N76 altered the specific membrane fusion, whereas no effects were detected on E1 N177 and N209 individually.


[Clinical experience with cefoperazone in the pediatric field (author's transl)].
Cefoperazone (CPZ) was given intravenously to 23 children with the following acute bacterial infections; 10 cases of pneumonia, 4 cases of urinary tract infection, 2 cases of purulent cervical lymphadenitis, 2 cases of pertussis pneumonia, 2 cases of septicemia, 1 case of osteomyelitis, 1 case of perforative peritonitis and 1 case of bacterial meningitis. Clinical effectiveness was obtained in 20 cases out of 23 cases and bacteriological effectiveness in 14 cases out of 17 cases. With CPZ, the following side effects developed; transient diarrhea in 1 case, asymptomatic eosinophilia in 2 cases. From the above clinical results, it is apparent that CPZ is a useful antibiotic for treating pediatric patients with various kinds of bacterial infections.


Antiviral-resistant fulminant herpes hepatitis in pregnancy.
Fulminant herpes hepatitis with disseminated extrahepatic involvement in pregnancy is rare and carries a high mortality risk. Although acyclovir remains standard first-line therapy, effective management of acyclovir-resistant disseminated herpes simplex virus (HSV) in pregnancy remains elusive. We present a case of disseminated HSV resistant to both acyclovir and foscarnet, the first double-agent resistant case in pregnancy reported in the literature to date. In this case, therapeutic delivery was the ultimate treatment resulting in full recovery.


[Treatment of snoring by a Herbst-activator. Satisfaction of patient and bedfellow].
Snoring is primarily a social problem which for instance brings considerable pressure on someone's conjugal relationship. Often treatment is demanded by the bedfellow. Patient as well as bedfellow needs to be involved in the treatment of the problem. In this study, twenty-three habitual snorers and their bedfellows completed a questionnaire concerning the effect of the treatment of snoring by a Herbst-activator before treatment and 3 and 6 months after treatment. Two-thirds of the patients and bedfellows were satisfied with the therapy results. The bedfellows exhibited an even more positive therapy effect than the patients.


Endogenous cytokinin in developing kiwifruit is implicated in maintaining fruit flesh chlorophyll levels.
Green kiwifruit (Actinidia deliciosa) retain high concentrations of chlorophyll in the fruit flesh, whereas in gold-fleshed kiwifruit (A. chinensis) chlorophyll is degraded to colourless catabolites during fruit development, leaving yellow carotenoids visible. The plant hormone group the cytokinins has been implicated in the delay of senescence, and so the aim of this work was to investigate the link between cytokinin levels in ripening fruit and chlorophyll de-greening. The expression of genes related to cytokinin metabolism and signal transduction and the concentration of cytokinin metabolites were measured. The regulation of gene expression was assayed using transient activation of the promoter of STAY-GREEN2 (SGR2) by cytokinin response regulators. While the total amount of cytokinin increased in fruit of both species during maturation and ripening, a high level of expression of two cytokinin biosynthetic gene family members, adenylate isopentenyltransferases, was only detected in green kiwifruit fruit during ripening. Additionally, high levels of O-glucosylated cytokinins were detected only in green kiwifruit, as was the expression of the gene for zeatin O-glucosyltransferase, the enzyme responsible for glucosylating cytokinin into a storage form. Season to season variation in gene expression was seen, and some de-greening of the green kiwifruit fruit occurred in the second season, suggesting environmental effects on the chlorophyll degradation pathway. Two cytokinin-related response regulators, RRA17 and RRB120, showed activity against the promoter of kiwifruit SGR2. The results show that in kiwifruit, levels of cytokinin increase markedly during fruit ripening, and that cytokinin metabolism is differentially regulated in the fruit of the green and gold species. However, the causal factor(s) associated with the maintenance or loss of chlorophyll in kiwifruit during ripening remains obscure.


Mechanisms of differential activation of target gene promoters by p53 hinge domain mutants with impaired apoptotic function.
Suppression of tumor cell growth by p53 results from the activation of both apoptosis and cell cycle arrest functions that have been shown to be separable activities of p53. We report here that some mutants in the p53 hinge domain, a short linker between the DNA binding and tetramerization domains, differentially activated the promoters of p53 target genes and possessed an impaired apoptotic function. Our results indicate that the hinge domain may play an important role in differentially regulating p53 cell cycle arrest and apoptotic functions. However, the mechanisms by which p53 hinge domain mutants differentially activate its target genes, e.g. p21(WAF1/CIP1) and Bax, remain unknown. To investigate the possible mechanisms, recombinant p21(WAF1/CIP1) and Bax promoters were constructed, resulting in rearrangement of the existing p53 binding sites within a given promoter or actually swapping p53 binding sites between the two promoters. Our results suggest that multiple mechanisms of differential transactivation occur, depending on the molecular nature of the relevant hinge domain mutant, such as the possibility that dual separate DNA binding sites in the p21(WAF1/CIP1) promoter are responsible for the selective transactivation activity of p53 hinge domain mutant del300-327, which has a large deletion in the hinge domain. Lack of ideal p53 binding sites in the Bax promoter results in less potent activation than that seen with the p21(WAF1/CIP1) promoter when it is transactivated by hinge domain point mutant mutR306P or short deletion mutant del300-308 proteins. How the single mutation or the short deletion affect the conformation of p53 and consequently the transactivation of the Bax promoter will require further investigation of the relevant p53 protein: DNA-binding domain by NMR and x-ray crystallographic techniques.


Juvenile xanthogranuloma with clonal proliferation in the bone marrow.
The triple association between juvenile xanthogranuloma (JXG), juvenile myelomonocytic leukemia and neurofibromatosis was described in literature in about 20 cases. In this paper, the case of an 11-month-old infant boy with a disseminated JXG with unusual cytogenetic representation in the bone marrow was reported. Neurofibromatosis and juvenile myelomonocytic leukemia were excluded, just the same as other leukemias. Bone marrow and peripheral blood cytogenetic analysis revealed a karyotype with many rearrangements 46,XY,-6,der(12)t(6;12)(p21;p13),del(7)(p13p22),+9 once described in the literature as a B-acute lymphoblastic leukemia case. On the contrary, in our patient immunologic testing demonstrated a high activity of T lymphocytes, however, inflammation was excluded. To the best of our knowledge this is the first described case of systemic JXG with determined karyotype representing unusual chromosomal aberrations.


[The importance of plasma B-type natriuretic peptide levels in cardiovascular diseases].
Natriuretic peptide type B (brain natriuretic peptide, BNP) is a neurohormone released by cardiac ventricles in response to volume and pressure load. Recent studies have demonstrated that BNP level measured in the plasma plays an important role in cardiovascular diseases especially in the diagnosis and treatment of heart failure and acute coronary syndrome. This article summarizes the physiology of the brain natriuretic peptide, diagnosis of heart failure and acute coronary syndrome and use of BNP in the treatment and determining the prognosis of cardiovascular diseases.


Resistant hypertension: who and how to evaluate.
Resistant hypertension is found in an important and rapidly growing subset of the hypertensive population, and data characterizing this group of patients are limited. The purpose of this review is to present the latest evidence on resistant hypertension, its risk factors, patient characteristics, and approach to diagnosis. We focus on important associations between resistant hypertension and primary aldosteronism and with obstructive sleep apnea. Resistant hypertension comprises 20-35% of the general hypertensive population. It is important to ascertain that a patient has true resistant hypertension and not merely uncontrolled hypertension. Twenty-four-hour ambulatory blood pressure monitoring can reliably rule out a white-coat effect and may have prognostic significance in patients with resistant hypertension. Patients should be screened for secondary causes of hypertension. Primary aldosteronism is common among patients with resistant hypertension, as is obstructive sleep apnea. A plasma aldosterone to renin ratio is a useful screening tool for primary aldosteronism. Aldosterone has been found to accelerate the increase in left ventricular mass in patients with hypertension. Patients with resistant hypertension comprise a unique subset, with risk factors and associations that are distinct or pronounced compared with the general hypertensive population. It is important to bear these associations in mind when dealing with patients with true resistant hypertension.


Popliteal Artery Entrapment Syndrome (PAES) in a 17-Year-Old Adolescent.
Popliteal artery entrapment syndrome (PAES) is caused by compression of the popliteal artery (PA) due to deranged myotendinous structures. It can be asymptomatic or may present with exercise intolerance, claudication, or even limb-threatening ischemia. The clinical picture depends on the anatomy and degree of vascular compromise. We report a case of a 17-year-old Caucasian male with PAES Type II presenting with intermittent claudication and progression towards acute limb ischemia. MRI and MRA helped identifying the aberrant anatomy and thrombotic occlusion. Doppler ultrasound and conventional angiography have also been employed in a stepwise approach. The thrombus at the site of occlusion was removed by the use of catheter-directed lysis. Subsequently, popliteal artery release was achieved by myotomy of the aberrant medial head of gastrocnemius muscle (MHGM) and muscle transfer to the medial femoral condyle. A three-month regimen of 60mg edoxaban was recommended after surgery. Surgical correction of the anomalous anatomy and postoperative anticoagulation led to freedom of symptoms. Clinical presentation of PAES mimicking peripheral artery occlusive disease is very rare but potentially limb-threatening. PAES should be considered in young and otherwise healthy individuals.


Relative refractoriness of breast cancer cells to tumour necrosis factor-α induced necroptosis.
Necroptosis, a recently identified programmed cell death pathway, has attracted attention as an alternative route to target apoptosis-resistant cancer cells. The status of the necroptosis pathway in different subtypes of breast cancer has not been well explored. Stimulating the cells by TNF-α can trigger cell survival or death depending on the combination of downstream players involved. In this work, we attempted to induce necroptosis in them using a combination of TNF-α and Z-VAD-FMK with and without chemotherapy. Cell viability, apoptosis, and necroptosis were assessed using MTT and Annexin-V/PI assays, respectively. Gene and protein expression was analysed by qPCR and immunophenotyping. Both the cell lines were resistant to induction of cell death by necroptosis. There was no enhancement in cell death when chemotherapeutic drugs were combined with necroptosis induction. Expression studies showed reduced translational expression of key necroptosis molecules like RIP kinases and MLKL in breast cancer cells compared to positive control cell line L929. Also, cell survival molecules were expressed more in MDA-MB-231 in contrast to death pathway molecules which were expressed more in T47D cells. In this work, the two breast cancer cell lines were observed to be resistant to TNF-α induced necroptosis with or without chemotherapy. Expression of key necroptosis players revealed relative insufficiency of the molecular machinery involved in the above pathway. In our opinion this may be the cause for resistance to necroptosis and novel strategies to upregulate these molecules need to be developed to sensitize the breast cancer cells towards cell death by necroptosis.


Effect of iron oxide nanoparticles on vascular function and nitric oxide production in acute stress-exposed rats.
We investigated whether polyethylene glycol-coated Fe3O4 nanoparticles (IONs), acute stress and their combination modifies vascular functions, nitric oxide synthase (NOS) activity, mean arterial pressure (MAP) as well as hepcidin and ferritin H gene expressions in Wistar-Kyoto rats. Rats were divided into control, ION-treated rats (1 mg Fe/kg i.v.), repeated acute air-jet stress-exposed rats and IONs-and-stress co-exposed rats. Maximal acetylcholine (ACh)-induced and sodium nitroprusside (SNP)-induced relaxations in the femoral arteries did not differ among the groups. IONs alone significantly elevated the N?-nitro-L-arginine methyl ester (L-NAME)-sensitive component of ACh-induced relaxation and reduced the sensitivity of vascular smooth muscle cells to SNP. IONs alone also elevated NOS activity in the brainstem and hypothalamus, reduced NOS activity in the kidneys and had no effect in the liver. Acute stress alone failed to affect vascular function and NOS activities in all the tissues investigated but it elevated ferritin H expression in the liver. In the ION-and-stress group, NOS activity was elevated in the kidneys and liver, but reduced in the brainstem and hypothalamus vs. IONs alone. IONs also accentuated air-jet stress-induced MAP responses vs. stress alone. Interestingly, stress reduced ION-originated iron content in blood and liver while it was elevated in the kidneys. In conclusion, the results showed that 1) acute administration of IONs altered vascular function, increased L-NAME-sensitive component of ACh-induced relaxation and had tissue-dependent effects on NOS activity, 2) ION effects were considerably reduced by co-exposure to repeated acute stress, likely related to decrease of ION-originated iron in blood due to elevated decomposition and/or excretion.


Comparison of Three Anaesthetic Options to Reduce Acute Pain Response in Kid Goats.
Three options for anesthetizing the skin around the horn bud of dairy goat kids were explored. Forty-five <10-day-old Saanen goat kids from were randomly split into five treatment groups (topical anesthetic cream (TA), vapocoolant spray (VS), local anesthetic applied by jet injector (JI), control - no treatment but painful stimulus applied (C), sham - no treatment and touching sites with a finger. The painful stimulus was multiple needle pricks on the skin around the horn bud. The outcome variables measured were heart rate movement, and vocalization during treatment application and administration of a painful stimulus around the horn bud. Heart rates were greater during application of a VS compared to TA.Neither the TA nor the VS appeared to have any effect on the response to the painful stimulus. Kids in the JI group had a 96% reduced odds of expressing a marked pain response in comparison to TA group and an 83% reduction in the odds of a high movement grade during a painful procedure in comparison to the combined results of the other three treatment groups.


3-Methylcrotonyl-CoA carboxylase deficiency: Mutational spectrum derived from comprehensive newborn screening.
The deficiency of 3-methycrotonyl-CoA carboxylase (3-MCC; EC 220.127.116.11) is an autosomal recessive organic aciduria that is included in the newborn screening programs of several countries. This study reports data mainly obtained from the Portuguese newborn screening program collected over a ten-year period. Analysis of the MCCC1 and MCCC2 genes yielded 26 previously unreported mutations and a variant of clinically unknown significance. These mutations are discussed in the context of their likely impact on the function of the 3-MCC enzyme, with a view to exploring whether a phenotype-genotype correlation might be discerned. Further, these mutations were analysed in the context of what is known of the MCCC1 and MCCC2 mutational spectra, information that will be useful in both clinical and laboratory practice.


Fast solubilization of recalcitrant cellulosic biomass by the basidiomycete fungus Laetisaria arvalis involves successive secretion of oxidative and hydrolytic enzymes.
Enzymatic breakdown of lignocellulosic biomass is a known bottleneck for the production of high-value molecules and biofuels from renewable sources. Filamentous fungi are the predominant natural source of enzymes acting on lignocellulose. We describe the extraordinary cellulose-deconstructing capacity of the basidiomycete Laetisaria arvalis, a soil-inhabiting fungus. The L. arvalis strain displayed the capacity to grow on wheat straw as the sole carbon source and to fully digest cellulose filter paper. The cellulolytic activity exhibited in the secretomes of L. arvalis was up to 7.5 times higher than that of a reference Trichoderma reesei industrial strain, resulting in a significant improvement of the glucose release from steam-exploded wheat straw. Global transcriptome and secretome analyses revealed that L. arvalis produces a unique repertoire of carbohydrate-active enzymes in the fungal taxa, including a complete set of enzymes acting on cellulose. Temporal analyses of secretomes indicated that the unusual degradation efficiency of L. arvalis relies on its early response to the carbon source, and on the finely tuned sequential secretion of several lytic polysaccharide monooxygenases and hydrolytic enzymes targeting cellulose. The present study illustrates the adaptation of a litter-rot fungus to the rapid breakdown of recalcitrant plant biomass. The cellulolytic capabilities of this basidiomycete fungus result from the rapid, selective and successive secretion of oxidative and hydrolytic enzymes. These enzymes expressed at critical times during biomass degradation may inspire the design of improved enzyme cocktails for the conversion of plant cell wall resources into fermentable sugars.


[Novel study and applications of CT angiography derived fractional flow reserve in China].
CT angiography derived fractional flow reserve (CT-FFR) has been an important tool for evaluating functional significance of coronary stenosis since 2011, promoting coronary CT angiography (CCTA) from the era of traditional anatomical evaluation to a new era of functional evaluation,playing a key role in guiding clinical decisions and prognostic evaluation of coronary artery disease. This review focuses on the innovative research and contributions of Chinese scholars' in CT-FFR filed, including homemade techniques, extending clinical applications and generalization of CT-FFR.


Progress on Genetic Basis of Primary Aldosteronism.
Primary aldosteronism (PA) is a heterogeneous group of disorders caused by the autonomous overproduction of aldosterone with simultaneous suppression of plasma renin activity (PRA). It is considered to be the most common endocrine cause of secondary arterial hypertension (HT) and is associated with a high rate of cardiovascular complications. PA is most often caused by a bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenoma (APA); rarer causes of PA include genetic disorders of steroidogenesis (familial hyperaldosteronism (FA) type I, II, III and IV), aldosterone-producing adrenocortical carcinoma, and ectopic aldosterone-producing tumors. Over the last few years, significant progress has been made towards understanding the genetic basis of PA, classifying it as a channelopathy. Recently, a growing body of clinical evidence suggests that mutations in ion channels appear to be the major cause of aldosterone-producing adenomas, and several mutations within the ion channel encoding genes have been identified. Somatic mutations in four genes (KCNJ5, ATP1A1, ATP2B3 and CACNA1D) have been identified in nearly 60% of the sporadic APAs, while germline mutations in KCNJ5 and CACNA1H have been reported in different subtypes of familial hyperaldosteronism. These new insights into the molecular mechanisms underlying PA may be associated with potential implications for diagnosis and therapy.


Some properties and applications of thin self-supporting polymer membranes.
Membranes as thin as 500 A were produced from many plastic materials and transferred to frames with dimensions of several centimeters. The self-supporting membranes were obtained using simple-dip-coating techniques. In some cases additional plasma polymerized layers were applied. These membranes can withstand several procedures of photolithography and chemical processing. The mechanical properties of the membranes are similar to that of the bulk material. Some typical applications are described. These applications include the use of the membranes as substrates for thermoelectric detectors and also as beamsplitters and windows for cells employed in CO(2) laser spectroscopy.


Convenient and Efficient Fabrication of Colloidal Crystals Based on Solidification-Induced Colloidal Assembly.
The simple yet efficient and versatile fabrication of colloidal crystals was investigated based on the solidification-induced colloidal crystallization process with particle/water suspension as precursor. The resulting colloidal crystals were constituted by crystal grains with sizes ranging from several tens of micrometers to a few millimeters. Each of the grains had a close-hexagonal array of colloids, which endowed the bulk colloidal crystal powders with some specific optical properties. The freezing of water was shown as the major driving force to form colloidal crystal grains, which supersaturated the solution with nanoparticles and thus induced the formation and growth of colloidal crystal seeds. This process is intrinsically different from those conventional methods based on shearing force, surface tension, columbic interaction or magnetic interaction, revealing a new strategy to fabricate colloidal crystals in a convenient and efficient way.